Sample records for human beta s
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DEFF Research Database (Denmark)
Wewer, U M; Gerecke, D R; Durkin, M E
1994-01-01
or other known laminin genes. Immunostaining showed that the beta 2 chain is localized to the smooth muscle basement membranes of the arteries, while the homologous beta 1 chain is confined to the subendothelial basement membranes. The beta 2 chain was found in the basement membranes of ovarian carcinomas......Overlapping cDNA clones that encode the full-length human laminin beta 2 chain, formerly called the S chain, were isolated. The cDNA of 5680 nt contains a 5391-nt open reading frame encoding 1797 amino acids. At the amino terminus is a 32-amino-acid signal peptide that is followed by the mature...... beta 2 chain polypeptide of 1765 amino acids with a calculated molecular mass of 192,389 Da. The human beta 2 chain is predicted to have all of the seven structural domains typical of the beta chains of laminin, including the short cysteine-rich alpha region. The amino acid sequence of human beta 2...
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LHCb: $2\\beta_s$ measurement at LHCb
Conti, G
2009-01-01
A measurement of $2\\beta_s$, the phase of the $B_s-\\bar{B_s}$ oscillation amplitude with respect to that of the ${\\rm b} \\rightarrow {\\rm c^{+}}{\\rm W^{-}}$ tree decay amplitude, is one of the key goals of the LHCb experiment with first data. In the Standard Model (SM), $2\\beta_s$ is predicted to be $0.0360^{+0.0020}_{-0.0016} \\rm rad$. The current constraints from the Tevatron are: $2\\beta_{s}\\in[0.32 ; 2.82]$ at 68$\\%$CL from the CDF experiment and $2\\beta_{s}=0.57^{+0.24}_{-0.30}$ from the D$\\oslash$ experiment. Although the statistical uncertainties are large, these results hint at the possible contribution of New Physics in the $B_s-\\bar{B_s}$ box diagram. After one year of data taking at LHCb at an average luminosity of $\\mathcal{L}\\sim2\\cdot10^{32}\\rm cm^{-2} \\rm s^{-1}$ (integrated luminosity $\\mathcal{L}_{\\rm int}\\sim 2 \\rm fb^{-1}$), the expected statistical uncertainty on the measurement is $\\sigma(2\\beta_s)\\simeq 0.03$. This uncertainty is similar to the $2\\beta_s$ value predicted by the SM.
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Specific radioimmunoassay of human. beta. -endorphin in unextracted plasma
Energy Technology Data Exchange (ETDEWEB)
Wiedemann, E. (Univ. of California, Berkeley); Saito, T.; Linfoot, J.A.; Li, C.H.
1979-09-01
With an antiserum against human ..beta..-endorphin (..beta..-EP) crossreacting <2% with human ..beta..-lipotropin (..beta..-LPH) by weight we have developed a radioimmunoassay that can detect 1 pg ..beta..-EP in diluted raw plasma. In a.m. fasting plasma of 14 normal subjects ..beta..-EP ranged from <5 to 45 pg/ml. ..beta..-EP was elevated in untreated, but normal in successfully treated Cushing's disease; undetectable in a patient with adrenal adenoma; extremely high in Nelson's syndrome; and elevated in a patient with bronchogenic carcinoma before, but undetectable after tumor resection. In subjects with intact hypothalamic-pituitary-adrenal axis, ..beta..-EP was undectectable after dexamethasone and increased after metyrapone administration and insulin-induced hypoglycemia. ..beta..-EP concentration was considerably lower in serum than in simultaneously collected plasma, but increased in serum left unfrozen for several hours after clot removal. Thus, ..beta..-EP behaves like a hormone responding to the same stimuli as ACTH and ..beta..-LPH and blood appears to contain enzymes both generating and destroying immunoreactive ..beta..-EP.
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Radioimmunoassay of human. beta. -lipotropin in unextracted plasma. [/sup 125/I tracer technique
Energy Technology Data Exchange (ETDEWEB)
Wiedemann, E. (Univ. of California, Berkeley); Saito, T.; Linfoot, J.A.; Li, C.H.
1977-11-01
A sensitive and specific radioimmunoassay for human ..beta..-lipotropin (..beta../sub h/-LPH) in unextracted plasma was developed using pure ..beta../sub h/-LPH as tracer and standard and an antiserum not cross-reacting with human ..beta..-MSH and hACTH. In healthy volunteers plasma ..beta../sub h/-LPH ranged from <20 to 150 pg/ml at 8:00 a.m. and rose after metyrapone administration. ..beta../sub h/-LPH was very low in panhypopituitarism, normal in most patients with untreated Cushing's disease, elevated in acromegaly and extremely high in Nelson's syndrome.
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In vitro proliferation of adult human beta-cells.
Directory of Open Access Journals (Sweden)
Sabine Rutti
Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.
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Energy Technology Data Exchange (ETDEWEB)
Wolff, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires
1957-07-01
{beta}-phenethyl-mercaptan ({sup 35}S) has been synthesized by action of elementary radioactive sulphur ({sup 35}S) on {beta}-phenethyl-magnesium-bromide, with a 90 per cent yield. (author) [French] Le {beta}-phenethylmercaptan ({sup 35}S) a ete synthetise par action du soufre radioactif elementaire ({sup 35}S) sur le bromure de {beta}-phenethylmagnesium, avec un rendement de 90 pour cent. (auteur)
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Human RECQL5beta stimulates flap endonuclease 1
DEFF Research Database (Denmark)
Speina, Elzbieta; Dawut, Lale; Hedayati, Mohammad
2010-01-01
devoid of RECQL1 and RECQL5 display increased chromosomal instability. Here, we report the physical and functional interaction of the large isomer of RECQL5, RECQL5beta, with the human flap endonuclease 1, FEN1, which plays a critical role in DNA replication, recombination and repair. RECQL5beta...... dramatically stimulates the rate of FEN1 cleavage of flap DNA substrates. Moreover, we show that RECQL5beta and FEN1 interact physically and co-localize in the nucleus in response to DNA damage. Our findings, together with the previous literature on WRN, BLM and RECQL4's stimulation of FEN1, suggests...
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Utsumi, J; Yamazaki, S; Kawaguchi, K; Kimura, S; Shimizu, H
1989-10-05
Human interferon-beta 1 is extremely stable is a low ionic strength solution of pH 2 such as 10 mM HCl at 37 degrees C. However, the presence of 0.15 M NaCl led to a remarkable loss of antiviral activity. The molecular-sieve high-performance liquid chromatography revealed that, whereas completely active human interferon-beta 1 eluted as a 25 kDa species (monomeric form), the inactivated preparation eluted primarily as a 90 kDa species (oligomeric form). The specific activity (units per mg protein) of the oligomeric form was approx. 10% of that of the monomeric form. This observation shows that oligomeric human interferon-beta 1 is apparently in an inactive form. When the oligomeric eluate was resolved by polyacrylamide gel containing sodium dodecyl sulphate (SDS), it appeared to be monomeric under non-reducing conditions. Monomerization of the oligomeric human interferon-beta 1 by treatment with 1% SDS, fully regenerated its antiviral activity. These results suggest that the inactivation of the human interferon-beta 1 preparation was caused by its oligomerization via hydrophobic interactions without the formation of intermolecular disulphide bonds. These oligomers can be dissociated by SDS to restore biological activity.
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Human APC sequesters beta-catenin even in the absence of GSK-3beta in a Drosophila model.
Rao, P R; Makhijani, K; Shashidhara, L S
2008-04-10
There have been conflicting reports on the requirement of GSK-3beta-mediated phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) vis-à-vis its ability to bind and degrade beta-catenin. Using a unique combination of loss of function for Shaggy/GSK-3beta and a gain of function for human APC in Drosophila, we show that misexpressed human APC (hAPC) can still sequester Armadillo/beta-catenin. In addition, human APC could suppress gain of Wnt/Wingless phenotypes associated with loss of Shaggy/GSK-3beta activity, suggesting that sequestered Armadillo/beta-catenin is non-functional. Based on these studies, we propose that binding per se of beta-catenin by APC does not require phosphorylation by GSK-3beta.
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DEFF Research Database (Denmark)
Durkin, M E; Gautam, M; Loechel, F
1996-01-01
We have determined the structural organization of the human and mouse genes that encode the laminin beta2 chain (s-laminin), an essential component of the basement membranes of the neuromuscular synapse and the kidney glomerulus. The human and mouse genes have a nearly identical exon-intron organ......We have determined the structural organization of the human and mouse genes that encode the laminin beta2 chain (s-laminin), an essential component of the basement membranes of the neuromuscular synapse and the kidney glomerulus. The human and mouse genes have a nearly identical exon...
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DEFF Research Database (Denmark)
Reimers, J; Wogensen, L D; Welinder, B
1991-01-01
Based upon in vivo rat experiments it was recently suggested that interleukin 1 in the circulation may be implicated in the initial events of beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to estimate half-lives of distribut......Based upon in vivo rat experiments it was recently suggested that interleukin 1 in the circulation may be implicated in the initial events of beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to estimate half......-lives of distribution (T1/2 alpha) and elimination phases (T1/2 beta) of human recombinant interleukin 1 beta (rIL-1 beta), and its tissue distribution and cellular localization by means of mono-labelled, biologically active 125I-rIL-1 beta. After intravenous (i.v.) injection, 125I-rIL-1 beta was eliminated from.......v., intraperitoneal (i.p.) and subcutaneous (s.c.) injections, as demonstrated by high performance size exclusion chromatography, trichloracetic acid precipitation and SDS-PAGE until 5 h after tracer injection. Pre-treatment with 'cold' rIL-1 beta enhanced degradation of a subsequent injection of tracer. The route...
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Directional and balancing selection in human beta-defensins.
Hollox, Edward J; Armour, John A L
2008-04-16
In primates, infection is an important force driving gene evolution, and this is reflected in the importance of infectious disease in human morbidity today. The beta-defensins are key components of the innate immune system, with antimicrobial and cell signalling roles, but also reproductive functions. Here we examine evolution of beta-defensins in catarrhine primates and variation within different human populations. We show that five beta-defensin genes that do not show copy number variation in humans show evidence of positive selection in catarrhine primates, and identify specific codons that have been under selective pressure. Direct haplotyping of DEFB127 in humans suggests long-term balancing selection: there are two highly diverged haplotype clades carrying different variants of a codon that, in primates, is positively selected. For DEFB132, we show that extensive diversity, including a four-state amino acid polymorphism (valine, isoleucine, alanine and threonine at position 93), is present in hunter-gatherer populations, both African and non-African, but not found in samples from agricultural populations. Some, but not all, beta-defensin genes show positive selection in catarrhine primates. There is suggestive evidence of different selective pressures on these genes in humans, but the nature of the selective pressure remains unclear and is likely to differ between populations.
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Directional and balancing selection in human beta-defensins
Directory of Open Access Journals (Sweden)
Armour John AL
2008-04-01
Full Text Available Abstract Background In primates, infection is an important force driving gene evolution, and this is reflected in the importance of infectious disease in human morbidity today. The beta-defensins are key components of the innate immune system, with antimicrobial and cell signalling roles, but also reproductive functions. Here we examine evolution of beta-defensins in catarrhine primates and variation within different human populations. Results We show that five beta-defensin genes that do not show copy number variation in humans show evidence of positive selection in catarrhine primates, and identify specific codons that have been under selective pressure. Direct haplotyping of DEFB127 in humans suggests long-term balancing selection: there are two highly diverged haplotype clades carrying different variants of a codon that, in primates, is positively selected. For DEFB132, we show that extensive diversity, including a four-state amino acid polymorphism (valine, isoleucine, alanine and threonine at position 93, is present in hunter-gatherer populations, both African and non-African, but not found in samples from agricultural populations. Conclusion Some, but not all, beta-defensin genes show positive selection in catarrhine primates. There is suggestive evidence of different selective pressures on these genes in humans, but the nature of the selective pressure remains unclear and is likely to differ between populations.
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Radioimmunological evidence for beta-endorphin in human cerebrospinal fluid
International Nuclear Information System (INIS)
Graf, M.
1982-01-01
Both-endomorphin-like immunoreactivity in human cerebrospinal fluid was determined by two different radioimmunoassays. Measurements made using a bought RIA-kit (Immuno Nuclear Corporation) produced results which were too high compared to results from the literature. The procedure for the beta-endophin radioimmunoassay of Hoellt et al. was followed, the various steps studied and in part modified. Here both beta endorphin and beta-lipotropin were labelled with I-125 and a new method introduced for separating I - -125 following labelling. Studies on the specificity of the method revealed that, in addition to beta-endorphin, beta-lipotropin and two further non-identified fluid fractions were also determined but that the specificity of the RIA's could be significantly increased by prior extraction of the fluid with silicic acid. Determinations of beta-endorphin-like immunoreactivity in 28 different human fluids using this RIA gave values from below 20 pg/ml to 70 pg/ml thus confirming literature values. (orig.) [de
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DEFF Research Database (Denmark)
Pedersen, L O; Stryhn, A; Holter, T L
1995-01-01
of class I molecules are involved in peptide binding, whereas most of class I molecules are involved in beta 2m binding. We propose that mouse beta 2m interacts with the minor peptide binding (i.e. the "empty") fraction with a lower affinity than human beta 2m does, whereas mouse and human beta 2m interact......The function of major histocompatibility complex (MHC) class I molecules is to sample peptides derived from intracellular proteins and to present these peptides to CD8+ cytotoxic T lymphocytes. In this paper, biochemical assays addressing MHC class I binding of both peptide and beta 2-microglobulin...... (beta 2m) have been used to examine the assembly of the trimolecular MHC class I/beta 2m/peptide complex. Recombinant human beta 2m and mouse beta 2ma have been generated to compare the binding of the two beta 2m to mouse class I. It is frequently assumed that human beta 2m binds to mouse class I heavy...
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Energy Technology Data Exchange (ETDEWEB)
Sato, H.; Sugiyama, Y.; Sawada, Y.; Iga, T.; Hanano, M.
1985-10-07
Binding of immunoreactive radioiodinated human ..beta..-endorphin (/sup 125/I-..beta..-EP) to rat serum was demonstrated by gel filtration of /sup 125/I-..beta..-EP in pooled rat serum on Sephadex G-200. Two radioactive peaks associated with proteins eluted from the column. The first peak eluted at the void volume containing lipoproteins, ..cap alpha../sub 2/- and ..beta../sub 2/-macroglobulins, and the second peak at the fraction of albumin. Binding of /sup 125/I-..beta..-EP to albumin was directly proved by gel filtration of /sup 125/I-..beta..-EP in buffer containing 4% human serum albumin on Sephadex G-200. Equilibrium dialysis was not applicable to investigating the interaction of /sup 125/I-..beta..-EP with serum proteins, because of the intense nonspecific adsorption to the semi-permeable membrane and the degradation of the peptide during dialysis. Therefore, in order to quantitatively evaluate the binding of /sup 125/I-..beta..-EP in sera from rats and humans, the authors utilized four other methods (ultrafiltration, charcoal adsorption, polyethylene glycol precipitation and equilibrium gel filtration). These methods corresponded well with each other and indicated 35-44% binding of /sup 125/I-..beta..-EP in rat serum. Binding of /sup 125/I-..beta..-EP in normal human serum was 36%, determined by ultrafiltration. Serum protein binding of /sup 125/I-..beta..-EP was concentration independent over the concentration range studied (1-1000 nM). 23 references, 4 figures, 1 table.
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Kim, Jaewon; Lee, Jihun; Brych, Stephen R; Logan, Timothy M; Blaber, Michael
2005-02-01
The beta-turn is the most common type of nonrepetitive structure in globular proteins, comprising ~25% of all residues; however, a detailed understanding of effects of specific residues upon beta-turn stability and conformation is lacking. Human acidic fibroblast growth factor (FGF-1) is a member of the beta-trefoil superfold and contains a total of five beta-hairpin structures (antiparallel beta-sheets connected by a reverse turn). beta-Turns related by the characteristic threefold structural symmetry of this superfold exhibit different primary structures, and in some cases, different secondary structures. As such, they represent a useful system with which to study the role that turn sequences play in determining structure, stability, and folding of the protein. Two turns related by the threefold structural symmetry, the beta4/beta5 and beta8/beta9 turns, were subjected to both sequence-swapping and poly-glycine substitution mutations, and the effects upon stability, folding, and structure were investigated. In the wild-type protein these turns are of identical length, but exhibit different conformations. These conformations were observed to be retained during sequence-swapping and glycine substitution mutagenesis. The results indicate that the beta-turn structure at these positions is not determined by the turn sequence. Structural analysis suggests that residues flanking the turn are a primary structural determinant of the conformation within the turn.
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Kim, Nam-Hee; Kim, Yeong-Su; Kim, Hye-Jung; Oh, Deok-Kun
2008-01-01
The formation of beta-carotene detergent micelles and their conversion into retinal by recombinant human beta,beta-carotene 15,15'-monooxygenase was optimized under aqueous conditions. Toluene was the most hydrophobic among the organic solvents tested; thus, it was used to dissolve beta-carotene, which is a hydrophobic compound. Tween 80 was selected as the detergent because it supported the highest level of retinal production among all of the detergents tested. The maximum production of retinal was achieved in detergent micelles containing 200 mg/L of beta-carotene and 2.4% (w/v) Tween 80. Under these conditions, the recombinant enzyme produced 97 mg/L of retinal after 16 h with a conversion yield of 48.5% (w/w). The amount of retinal produced, which is the highest ever reported, is a result of the ability of our system to dissolve large amounts of beta-carotene.
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Energy Technology Data Exchange (ETDEWEB)
Guenther, Ilonka; Hall, Haakan; Halldin, Christer; Swahn, Carl-Gunnar; Farde, Lars; Sedvall, Goeran
1997-10-01
The binding of the three dopamine transporter radioligands ([{sup 125}I]{beta}-CIT, [{sup 125}I]{beta}-CIT-FE, and [{sup 125}I]{beta}-CIT-FP) was studied using whole-hemisphere autoradiography on postmortem human brains. The autoradiograms revealed an intense and homogeneous labeling of the nucleus caudatus and putamen but also to varying extent to serotonergic and noradrenergic transporters of neocortex and thalamus. The order of specificity estimated (striatum over neocortex ratios) was {beta}-CIT-FP > {beta}-CIT-FE >> {beta}-CIT, suggesting that {beta}-CIT-FE and {beta}-CIT-FP should be preferred for in vivo studies of the dopamine transporter in the human brain.
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Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene
Energy Technology Data Exchange (ETDEWEB)
Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (USA)); Birkenmeier, E.H.; Gwynn, B. (Jackson Laboratory, Bar Harbor, ME (USA))
1990-05-01
The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.
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Beta adrenergic receptors in human cavernous tissue
Energy Technology Data Exchange (ETDEWEB)
Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.
1985-04-01
Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.
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Energy Technology Data Exchange (ETDEWEB)
Perl, S; Kushner, J A; Buchholz, B A; Meeker, A K; Stein, G M; Hsieh, M; Kirby, M; Pechhold, S; Liu, E H; Harlan, D M; Tisdale, J F
2010-03-15
Diabetes mellitus results from an absolute or relative deficiency of insulin producing pancreatic beta-cells. The adult human beta-cell's turnover rate remains unknown. We employed novel techniques to examine adult human islet beta-cell turnover and longevity in vivo. Subjects enrolled in NIH clinical trials received thymidine analogues [iododeoxyuridine (IdU) or bromodeoxyuridine (BrdU)] 8-days to 4-years prior to death. Archival autopsy samples from ten patients (aged 17-74 years) were employed to assess beta-cell turnover by scoring nuclear analog labeling within insulin staining cells. Human adult beta-cell longevity was determined by estimating the cells genomic DNA integration of atmospheric carbon-14 ({sup 14}C). DNA was purified from pancreatic islets isolated from cadaveric donors; whole islet prep DNA was obtained from a 15 year old donor, and purified beta-cell DNA was obtained from two donors (age 48 and 80 years). {sup 14}C levels were then determined using accelerator mass spectrometry (AMS). Cellular 'birth date' was determined by comparing the subject's DNA {sup 14}C content relative to a well-established {sup 14}C atmospheric prevalence curve. In the two subjects less than age 20 years, 1-2% of the beta-cell nuclei co-stained for BrdU/IdU. No beta-cell nuclei co-stained in the eight patients more than 30 years old. Consistent with the BrdU/IdU turnover data, beta-cell DNA {sup 14}C content indicated the cells 'birth date' occurred within the subject's first 30 years of life. Under typical circumstances, adult human beta-cells and their cellular precursors are established by young adulthood.
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Determination of $\\gamma$ and $-2\\beta_s$ from charmless two-body decays of beauty mesons
Aaij, Roel; Adeva, Bernardo; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassen, Rolf; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Belogurov, Sergey; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Bjørnstad, Pål Marius; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borgia, Alessandra; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Brambach, Tobias; Bressieux, Joël; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Brown, Henry; Bursche, Albert; Busetto, Giovanni; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Ciba, Krzystof; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cojocariu, Lucian; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Counts, Ian; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pascal; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Di Canto, Angelo; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gavrilov, Gennadii; Geraci, Angelo; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Gianì, Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, Vladimir; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Hunt, Philip; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jaton, Pierre; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kaballo, Michael; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kelsey, Matthew; Kenyon, Ian; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kozlinskiy, Alexandr; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leo, Sabato; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lopez-March, Neus; Lowdon, Peter; Lu, Haiting; Lucchesi, Donatella; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Machikhiliyan, Irina V; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martens, Aurelien; Martín Sánchez, Alexandra; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathe, Zoltan; Matteuzzi, Clara; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; McSkelly, Ben; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Moggi, Niccolò; Molina Rodriguez, Josue; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Katharina; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Nicol, Michelle; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Oggero, Serena; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Orlandea, Marius; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Arantza; Pal, Bilas Kanti; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parkes, Christopher; Parkinson, Christopher John; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pazos Alvarez, Antonio; Pearce, Alex; Pellegrino, Antonio; Pepe Altarelli, Monica; Perazzini, Stefano; Perez Trigo, Eliseo; Perret, Pascal; Perrin-Terrin, Mathieu; Pescatore, Luca; Pesen, Erhan; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Poluektov, Anton; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz, Hugo; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrie, Mauro; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Seco, Marcos; Semennikov, Alexander; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Sparkes, Ailsa; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Subbiah, Vijay Kartik; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szilard, Daniela; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Tran, Minh Tâm; Tresch, Marco; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ubeda Garcia, Mario; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; Voss, Helge; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Whitehead, Mark; Wicht, Jean; Wiedner, Dirk; Wilkinson, Guy; Williams, Matthew; Williams, Mike; Wilschut, Hans; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Wen Chao; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zvyagin, Alexander
2015-01-01
Using the latest LHCb measurements of time-dependent $C\\!P$ violation in the $B^0_s \\to K^+K^-$ decay, a U-spin relation between the decay amplitudes of $B^0_s \\to K^+K^-$ and $B^0\\to \\pi^+\\pi^-$ decay processes allows constraints to be placed on the angle $\\gamma$ of the unitarity triangle and on the $B^0_s$ mixing phase $-2\\beta_s$. Results from an extended approach, which uses additional inputs on $B^0\\to \\pi^0\\pi^0$ and $B^+\\to \\pi^+\\pi^0$ decays from other experiments and exploits isospin symmetry, are also presented. The dependence of the results on the maximum allowed amount of U-spin breaking is studied. At 68% probability, the value $\\gamma = \\left( 63.5^{\\,+\\, 7.2}_{\\,-\\,6.7} \\right)^\\circ~\\mathrm{modulo}~180^\\circ$ is determined. In an alternative analysis, the value $-2\\beta_s = -0.12 ^{\\,+\\,0.14}_{\\,-\\,0.16}\\,\\,\\mathrm{rad}$ is found. In both measurements, the uncertainties due to U-spin breaking effects up to 50% are included.
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Determination of $\\gamma$ and $-2\\beta_s$ from charmless two-body decays of beauty mesons
Aaij, Roel; Adeva, Bernardo; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassen, Rolf; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Belogurov, Sergey; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Bjørnstad, Pål Marius; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borgia, Alessandra; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Brambach, Tobias; Bressieux, Joël; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Brown, Henry; Bursche, Albert; Busetto, Giovanni; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Ciba, Krzystof; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cojocariu, Lucian; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Counts, Ian; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pascal; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Di Canto, Angelo; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gavrilov, Gennadii; Geraci, Angelo; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Gianì, Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Hunt, Philip; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jaton, Pierre; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kaballo, Michael; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kelsey, Matthew; Kenyon, Ian; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kozlinskiy, Alexandr; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leo, Sabato; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lopez-March, Neus; Lowdon, Peter; Lu, Haiting; Lucchesi, Donatella; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Machikhiliyan, Irina V; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martens, Aurelien; Martín Sánchez, Alexandra; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathe, Zoltan; Matteuzzi, Clara; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; McSkelly, Ben; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Moggi, Niccolò; Molina Rodriguez, Josue; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Katharina; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Nicol, Michelle; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Oggero, Serena; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Orlandea, Marius; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Arantza; Pal, Bilas Kanti; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parkes, Christopher; Parkinson, Christopher John; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pazos Alvarez, Antonio; Pearce, Alex; Pellegrino, Antonio; Pepe Altarelli, Monica; Perazzini, Stefano; Perez Trigo, Eliseo; Perret, Pascal; Perrin-Terrin, Mathieu; Pescatore, Luca; Pesen, Erhan; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Poluektov, Anton; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz, Hugo; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrie, Mauro; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Seco, Marcos; Semennikov, Alexander; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Sparkes, Ailsa; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Subbiah, Vijay Kartik; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szilard, Daniela; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Tran, Minh Tâm; Tresch, Marco; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ubeda Garcia, Mario; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; Voss, Helge; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Whitehead, Mark; Wicht, Jean; Wiedner, Dirk; Wilkinson, Guy; Williams, Matthew; Williams, Mike; Wilschut, Hans; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Wen Chao; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zvyagin, Alexander
2015-02-04
Using the latest LHCb measurements of time-dependent $C\\!P$ violation in the $B^0_s \\to K^+K^-$ decay, a U-spin relation between the decay amplitudes of $B^0_s \\to K^+K^-$ and $B^0\\to \\pi^+\\pi^-$ decay processes allows constraints to be placed on the angle $\\gamma$ of the unitarity triangle and on the $B^0_s$ mixing phase $-2\\beta_s$. Results from an extended approach, which uses additional inputs on $B^0\\to \\pi^0\\pi^0$ and $B^+\\to \\pi^+\\pi^0$ decays from other experiments and exploits isospin symmetry, are also presented. The dependence of the results on the maximum allowed amount of U-spin breaking is studied. At 68% probability, the value $\\gamma = \\left( 63.5^{\\,+\\, 7.2}_{\\,-\\,6.7} \\right)^\\circ~\\mathrm{modulo}~180^\\circ$ is determined. In an alternative analysis, the value $-2\\beta_s = -0.12 ^{\\,+\\,0.14}_{\\,-\\,0.16}\\,\\,\\mathrm{rad}$ is found. In both measurements, the uncertainties due to U-spin breaking effects up to 50% are included.
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Biotinylated human. beta. -endorphins as probes for the opioid receptor
Energy Technology Data Exchange (ETDEWEB)
Hochhaus, G.; Gibson, B.W.; Sadee, W.
1988-01-05
The reaction of human ..beta..-endorphin and biotinyl N-hydroxysuccinimide with or without spacer arm, afforded a series of products that were separated by high performance liquid chromatography (HPLC). Liquid secondary ion mass spectrometry of the biotinylated products and their tryptic digests produced abundant protonated molecular ions (MH/sup +/), which specified the number and location of biotinylation. Between 1 and 4 biotinyl residues were incorporated per human ..beta..-endorphin molecule, at Lys-9, -19, -24, -28, and -29, but not at the amino-terminal Try-1. Three HPLC fractions were isolated for receptor binding studies monobiotinylation of Lys-9, Lys-19, and a mixture of Lys-24, Lys-28, and Lys-29 derivatives. IC/sub 50/ values for binding to ..mu.. and delta opioid receptor sites were 3-8 times higher for monobiotinylated derivatives than for the parent human ..beta..-endorphin. Association with avidin decreased opioid receptor affinities for the C/sub 6/ spacer derivative biotinylated at position Lys-9, which is close to the (1-5) enkephalin receptor region. In contrast, avidin did not affect or even increased apparent affinities to ..mu.. and delta sites for derivatives biotinylated at the ..cap alpha..-helical part of the molecule (Lys-19, -24, -28, and -29). Biotinylated human ..beta..-endorphins also bound to low affinity nonopioid binding sites on NG-108-15 cells; however, affinities to these sites were considerably reduced when derivatives were bound to avidin. The ability of biotinylated human ..beta..-endorphin to cross-link the ..mu.. and delta opioid receptors to avidin allows application of the biotin-avidin system as a molecular probe of the opioid receptor.
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Human amyloid beta protein gene locus: HaeIII RFLP
Energy Technology Data Exchange (ETDEWEB)
Taylor, J E; Gonzalez-DeWhitt, P A; Fuller, F; Cordell, B; Frossard, P M [California Biotechnology Inc., Mountain View (USA); Tinklenberg, J R; Davies, H D; Eng, L F; Yesavage, J A [Stanford Univ. School of Medicine, Palo Alto, CA (USA)
1988-07-25
A 2.2 kb EcoRI-EcoRI fragment from the 5{prime} end of the human amyloid beta protein cDNA was isolated from a human fibroblast cDNA library and subcloned into pGEM3. HaeIII (GGCC) detects 6 invariant bands at 0.5 kb, 1.0 kb, 1.1 kb, 1.3 kb, 1.4 kb and 1.6 kb and a two-allele polymorphism with bands at either 1.9 kb or 2.1 kb. Its frequency was studied in 50 North Americans. Human amyloid beta protein gene mapped to the long arm of chromosome 21 (21q11.2-21q21) by Southern blot analysis of human-rodent somatic cell hybrids. Co-dominant segregation was observed in two families (15 individuals).
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MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting {beta}-catenin
Energy Technology Data Exchange (ETDEWEB)
Sun, Jian-Yong [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Huang, Yi [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, 710032 Xi' an (China); Li, Ji-Peng [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Zhang, Xiang; Wang, Lei [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Meng, Yan-Ling [Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Yan, Bo [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Bian, Yong-Qian [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Wang, Wei-Zhong, E-mail: weichang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi' an (China); and others
2012-04-20
Highlights: Black-Right-Pointing-Pointer miR-320a is downregulated in human colorectal carcinoma. Black-Right-Pointing-Pointer Overexpression of miR-320a inhibits colon cancer cell proliferation. Black-Right-Pointing-Pointer {beta}-Catenin is a direct target of miR-320a in colon cancer cells. Black-Right-Pointing-Pointer miR-320a expression inversely correlates with mRNA expression of {beta}-catenin's target genes in human colon carcinoma. -- Abstract: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and {beta}-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and {beta}-catenin's downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting {beta}-catenin, suggesting its application in prognosis prediction and cancer treatment.
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Raftopoulos, H; Ward, M; Bank, A
1998-06-30
Insertion of a normally functioning human beta-globin gene into the hematopoietic stem cells (HSC) of patients with beta-thalassemia may be an effective approach to the therapy of this disorder. Safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models are prerequisites for HSC somatic gene therapy. We have recently shown for the first time that, using a modified beta-globin retroviral vector in a mouse transplant model, long-term, high-level expression of a transferred human beta-globin gene is possible. The human beta-globin gene continues to be detected up to eight months post-transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice. The transferred human beta-globin gene is detected in three of five mice surviving long-term (> 4 months) transplanted with bone marrow cells transduced with high-titer virus. The unrearranged 5.1 kb human beta-globin gene-containing provirus is seen by Southern blotting in two of these mice. More importantly, long-term expression of the transferred gene is seen in two mice at levels of 5% and 20% that of endogenous murine beta-globin. We document stem cell transduction by showing continued high-level expression of the human beta-globin gene in secondarily transplanted recipient mice. These results provide evidence of HSC transduction with a human beta-globin gene in animals and demonstrate that retroviral-mediated unrearranged human beta-globin gene transfer leads to a high level of human beta-globin gene expression in the long term for the first time. A gene therapy strategy may be a feasible therapeutic approach to the beta-thalassemias if consistent human beta-globin gene transfer and expression into HSC can be achieved.
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A human beta cell line with drug inducible excision of immortalizing transgenes
Benazra, Marion; Lecomte, Marie-José; Colace, Claire; Müller, Andreas; Machado, Cécile; Pechberty, Severine; Bricout-Neveu, Emilie; Grenier-Godard, Maud; Solimena, Michele; Scharfmann, Raphaël; Czernichow, Paul; Ravassard, Philippe
2015-01-01
Objectives Access to immortalized human pancreatic beta cell lines that are phenotypically close to genuine adult beta cells, represent a major tool to better understand human beta cell physiology and develop new therapeutics for Diabetes. Here we derived a new conditionally immortalized human beta cell line, EndoC-βH3 in which immortalizing transgene can be efficiently removed by simple addition of tamoxifen. Methods We used lentiviral mediated gene transfer to stably integrate a tamoxifen inducible form of CRE (CRE-ERT2) into the recently developed conditionally immortalized EndoC βH2 line. The resulting EndoC-βH3 line was characterized before and after tamoxifen treatment for cell proliferation, insulin content and insulin secretion. Results We showed that EndoC-βH3 expressing CRE-ERT2 can be massively amplified in culture. We established an optimized tamoxifen treatment to efficiently excise the immortalizing transgenes resulting in proliferation arrest. In addition, insulin expression raised by 12 fold and insulin content increased by 23 fold reaching 2 μg of insulin per million cells. Such massive increase was accompanied by enhanced insulin secretion upon glucose stimulation. We further observed that tamoxifen treated cells maintained a stable function for 5 weeks in culture. Conclusions EndoC βH3 cell line represents a powerful tool that allows, using a simple and efficient procedure, the massive production of functional non-proliferative human beta cells. Such cells are close to genuine human beta cells and maintain a stable phenotype for 5 weeks in culture. PMID:26909308
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Energy Technology Data Exchange (ETDEWEB)
Zhao, Yong, E-mail: yongzhao@uic.edu [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Guo, Chengshan; Hwang, David; Lin, Brian; Dingeldein, Michael; Mihailescu, Dan; Sam, Susan; Sidhwani, Seema [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Zhang, Yongkang [Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Jain, Sumit [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Skidgel, Randal A. [Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Prabhakar, Bellur S. [Department of Immunology and Microbiology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Mazzone, Theodore [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Holterman, Mark J. [Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612 (United States)
2010-09-03
Research highlights: {yields} Establish a human immune-mediated type 1 diabetic model in NOD-scid IL2r{gamma}{sup null} mice. {yields} Using the irradiated diabetic NOD mouse spleen mononuclear cells as trigger. {yields} The islet {beta} cells were selectively destroyed by infiltrated human T cells. {yields} The model can facilitate translational research to find a cure for type 1 diabetes. -- Abstract: Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that leads to the loss of insulin-producing {beta} cells. The optimal preclinical testing of promising therapies would be aided by a humanized immune-mediated T1D model. We develop this model in NOD-scid IL2r{gamma}{sup null} mice. The selective destruction of pancreatic islet {beta} cells was mediated by human T lymphocytes after an initial trigger was supplied by the injection of irradiated spleen mononuclear cells (SMC) from diabetic nonobese diabetic (NOD) mice. This resulted in severe insulitis, a marked loss of total {beta}-cell mass, and other related phenotypes of T1D. The migration of human T cells to pancreatic islets was controlled by the {beta} cell-produced highly conserved chemokine stromal cell-derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor (CXCR) 4, as demonstrated by in vivo blocking experiments using antibody to CXCR4. The specificity of humanized T cell-mediated immune responses against islet {beta} cells was generated by the local inflammatory microenvironment in pancreatic islets including human CD4{sup +} T cell infiltration and clonal expansion, and the mouse islet {beta}-cell-derived CD1d-mediated human iNKT activation. The selective destruction of mouse islet {beta} cells by a human T cell-mediated immune response in this humanized T1D model can mimic those observed in T1D patients. This model can provide a valuable tool for translational research into T1D.
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International Nuclear Information System (INIS)
Li, Xiaoou; Liu, Lian; Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan; Wen, Fuqiang
2014-01-01
Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis
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Energy Technology Data Exchange (ETDEWEB)
Li, Xiaoou [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Liu, Lian [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Wen, Fuqiang, E-mail: wenfuqiang.scu@gmail.com [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China)
2014-11-28
Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis.
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DEFF Research Database (Denmark)
Hée, P.; Klinken, Leif; Ballegaard, Martin
1992-01-01
Neuropathology, analgesics - intrathecal, central nervous system, histology, human beta-endorphin, toxicity......Neuropathology, analgesics - intrathecal, central nervous system, histology, human beta-endorphin, toxicity...
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Abulencia, A; Acosta, D; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J-F; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Bachacou, H; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Belloni, A; Haim, E Ben; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carron, S; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chapman, J; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Chu, P H; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciljak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Cresciolo, F; Cruz, A; Almenar, C Cuenca; Cuevas, J; Culbertson, R; Cyr, D; Daronco, S; D'Auria, S; D'Onofrio, M; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; Dell'orso, M; Paoli, F Delli; Demers, S; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Dionisi, C; Dittmann, J R; Dituro, P; Dörr, C; Donati, S; Donega, M; Dong, P; Donini, J; Dorigo, T; Dube, S; Ebina, K; Efron, J; Ehlers, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Flores-Castillo, L R; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Sciveres, M Garcia; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Ginsburg, C; Giokaris, N; Giolo, K; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Gotra, Y; Goulianos, K; Gresele, A; Griffiths, M; Grinstein, S; Grosso-Pilcher, C; Grundler, U; da Costa, J Guimaraes; Gunay-Unalan, Z; Haber, C; Hahn, S R; Hahn, K; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, M; Harper, S; Harr, R F; Harris, R M; Hatakeyama, K; Hauser, J; Hays, C; Heijboer, A; Heinemann, B; Heinrich, J; Herndon, M; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jensen, H; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Junk, T R; Kamon, T; Kang, J; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kobayashi, H; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kovalev, A; Kraan, A; Kraus, J; Kravchenko, I; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kuhlmann, S E; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; Macqueen, D; Madrak, R; Maeshima, K; Maki, T; Maksimovic, P; Malde, S; Manca, G; Margaroli, F; Marginean, R; Marino, C; Martin, A; Martin, V; Martínez, M; Maruyama, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; von der Mey, M; Miao, T; Miladinovic, N; Miles, J; Miller, R; Miller, J S; Mills, C; Milnik, M; Miquel, R; Mitra, A; Mitselmakher, G; Miyamoto, A; Moggi, N; Mohr, B; Moore, R; Morello, M; Fernandez, P Movilla; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Nachtman, J; Naganoma, J; Nahn, S; Nakano, I; Napier, A; Naumov, D; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nigmanov, T; Nodulman, L; Norniella, O; Nurse, E; Ogawa, T; Oh, S H; Oh, Y D; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Paoletti, R; Papadimitriou, V; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Rakitin, A; Rappoccio, S; Ratnikov, F; Reisert, B; Rekovic, V; van Remortel, N; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robertson, W J; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Rott, C; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Sabik, S; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Saltzberg, D; Sanchez, C; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfiligoi, I; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Sjolin, J; Skiba, A; Slaughter, A J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spezziga, M; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; Denis, R St; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sumorok, K; Sun, H; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tanimoto, N; Tecchio, M; Teng, P K; Terashi, K; Tether, S; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Tönnesmann, M; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuchiya, R; Tsuno, S; Turini, N; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vaiciulis, A; Vallecorsa, S; Varganov, A; Vataga, E; Velev, G; Veramendi, G; Veszpremi, V; Vidal, R; Vila, I; Vilar, R; Vine, T; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, W; Wallny, R; Walter, T; Wan, Z; Wang, S M; Warburton, A; Waschke, S; Waters, D; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zetti, F; Zhang, X; Zhou, J; Zucchelli, S
2006-06-16
We report the first observation of B(0)(s)-->Psi(2S)Phi decay in p(p_) collisions at square root of 8=1.96 TeV using 360 pb(-1) of data collected by the CDF II detector at the Fermilab Tevatron. We observe 20.2 +/- 5.0 and 12.3 +/- 4.1 B(0)(s)-->Psi(2S)Phi candidates, in Psi(2S)-->mu(+)mu(-) and Phi(2S)-->J/Phipi(+)pi(-) decay modes, respectively. We present a measurement of the relative branching fraction Beta(B(0)(s)-->Psi(2S)Phi)/Beta(B(0)(s)-->J/PsiPhi)=0.52 +/- 0.13(stat) +/- 0.04(syst) +/- 0.06(BR) using the Psi(2S)-->mu(+)mu(-) decay mode.
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Energy Technology Data Exchange (ETDEWEB)
Ploos van Amstel, H.; Reitsma, P.H.; van der Logt, C.P.; Bertina, R.M. (University Hospital, Leiden (Netherlands))
1990-08-28
The human protein S locus on chromosome 3 consists of two protein S genes, PS{alpha} and PS{beta}. Here the authors report the cloning and characterization of both genes. Fifteen exons of the PS{alpha} gene were identified that together code for protein S mRNA as derived from the reported protein S cDNAs. Analysis by primer extension of liver protein S mRNA, however, reveals the presence of two mRNA forms that differ in the length of their 5{prime}-noncoding region. Both transcripts contain a 5{prime}-noncoding region longer than found in the protein S cDNAs. The two products may arise from alternative splicing of an additional intron in this region or from the usage of two start sites for transcription. The intron-exon organization of the PS{alpha} gene fully supports the hypothesis that the protein S gene is the product of an evolutional assembling process in which gene modules coding for structural/functional protein units also found in other coagulation proteins have been put upstream of the ancestral gene of a steroid hormone binding protein. The PS{beta} gene is identified as a pseudogene. It contains a large variety of detrimental aberrations, viz., the absence of exon I, a splice site mutation, three stop codons, and a frame shift mutation. Overall the two genes PS{alpha} and PS{beta} show between their exonic sequences 96.5% homology. Southern analysis of primate DNA showed that the duplication of the ancestral protein S gene has occurred after the branching of the orangutan from the African apes. A nonsense mutation that is present in the pseudogene of man also could be identified in one of the two protein S genes of both chimpanzee and gorilla. This implicates that silencing of one of the two protein S genes must have taken place before the divergence of the three African apes.
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DEFF Research Database (Denmark)
Nissen, Mogens Holst; Claësson, M H
1987-01-01
the endogenous production of interleukin 2 in the MLC culture; monoclonal antibody which reacts with both the native beta 2-m and M-beta 2-m molecule blocks the augmentation of cytotoxic T lymphocyte production induced by M-beta 2-m; murine as well as human MLC responder cells can proteolytically modify native......A proteolytically modified form of beta 2-microglobulin (beta 2-m) present in the serum of patients suffering from autoimmune, immunodeficient diseases and cancer has been reported in the literature. In the present study we show that human beta 2-m as well as the proteolytically modified human form...... (M-beta 2-m) bind to murine lymphocytes expressing H-2 class I antigens; M-beta 2-m, when added at day 0 and 1 of culture in nanomolar concentrations to a one-way murine allogeneic mixed lymphocyte culture (MLC) augments the generation of specific cytotoxic T lymphocytes; M-beta 2-m increases...
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Long-term transfer and expression of the human beta-globin gene in a mouse transplant model.
Raftopoulos, H; Ward, M; Leboulch, P; Bank, A
1997-11-01
Somatic gene therapy of hemoglobinopathies depends initially on the demonstration of safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models. We have used a beta-globin gene/beta-locus control region retroviral vector containing several modifications to optimize gene transfer and expression in a mouse transplant model. In this report we show that transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice leads to the continued presence of the gene up to 8 months posttransplantation. The transferred human beta-globin gene is detected in 3 of 5 mice surviving long term (>4 months) transplanted with bone marrow cells transduced with high-titer virus. Southern blotting confirms the presence of the unrearranged 5.1-kb human beta-globin gene-containing provirus in 2 of these mice. In addition, long-term expression of the transferred gene is seen in 2 mice at levels of 5% and 20% that of endogenous murine beta-globin at 6 and 8 months posttransplantation. We further document stem cell transduction by the successful transfer and high-level expression of the human beta-globin gene from mice transduced 9 months earlier into irradiated secondary recipient mice. These results demonstrate high-level, long-term somatic human beta-globin gene transfer into the hematopoietic stem cells of an animal for the first time, and suggest the potential feasibility of a retroviral gene therapy approach to sickle cell disease and the beta thalassemias.
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Anodic Aluminum Oxide Membrane-Assisted Fabrication of beta-In(2)S(3) Nanowires.
Shi, Jen-Bin; Chen, Chih-Jung; Lin, Ya-Ting; Hsu, Wen-Chia; Chen, Yu-Cheng; Wu, Po-Feng
2009-06-06
In this study, beta-In(2)S(3) nanowires were first synthesized by sulfurizing the pure Indium (In) nanowires in an AAO membrane. As FE-SEM results, beta-In(2)S(3) nanowires are highly ordered, arranged tightly corresponding to the high porosity of the AAO membrane used. The diameter of the beta-In(2)S(3) nanowires is about 60 nm with the length of about 6-8 mum. Moreover, the aspect ratio of beta-In(2)S(3) nanowires is up to 117. An EDS analysis revealed the beta-In(2)S(3) nanowires with an atomic ratio of nearly S/In = 1.5. X-ray diffraction and corresponding selected area electron diffraction patterns demonstrated that the beta-In(2)S(3) nanowire is tetragonal polycrystalline. The direct band gap energy (E(g)) is 2.40 eV from the optical measurement, and it is reasonable with literature.
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BENIGN EPITHELIAL NEOPLASIA ASSOCIATED WITH BETA-HUMAN PAPILLOMA VIRUS
Directory of Open Access Journals (Sweden)
V. A. Molochkov
2014-01-01
Full Text Available Aim: To study an association between acrochordon and human papilloma virus (HPV using quantitative analysis of viral desoxyribonucleic acid (DNA; to detect different phenotypes of beta-HPV. Materials and methods: We examined 52 patients (22 immuno-suppressed patients and 30 immunocompetent subjects in the Dermatovenereology and Dermato-Oncology Department and Chronic Dialysis and Kidney Transplantation Department of the Moscow Regional Research and Clinical Institute (MONIKI. Control group included 49 healthy donors. Burr biopsy samples (micro-samples of acrochordon and intact skin (apper arm were collected in sterile conditions. After sample procession and DNA isolation using DNK-sorb-C kit (Central Research Institute for Epidemiology – CRIE, polymerase chain reaction for HPV was performed with real-time fluorescent hybridization detection. For DNA amplification and detection we used RotorGene 3000 analyzer (Corbett Research, Australia. In the beta-HPV assay, recombinant plasmids were used as positive controls and control human beta-globin gene fragments (CRIE. 4 oligo-nucleotide systems (group-specific primers and probes were used for the detection of beta-HPV DNA. Results: Preliminary data indicated that acrochordons of open and covered skin regions were common in renal transplant recipients. Beta-HPV DNA was more frequent in acrochordons and intact skin (64% and 54% of renal transplant recipients compared to healthy donors (47%. 57% of renal transplant recipients demonstrated mixed infection in acrochordons. Conclusion: HPV DNA was frequently detected in acrochordons and intact skin of renal transplant recipients. In immunocompetent patients prevalence of HPV DNA in acrochordons was significantly higher compared to intact skin.
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International Nuclear Information System (INIS)
Hayashida, D.N.; Leung, R.; Goldfien, A.; Roberts, J.M.
1982-01-01
The radioactive beta-adrenergic antagonist [ 3 H] dihydroalprenolol (DHA) binds to particulate preparations of human myometrium in a manner compatible with binding to the beta-adrenergic receptor. The binding of DHA is rapid (attaining equilibrium in 12 minutes), readily reversible (half time = 16 minutes), high affinity (K/sub D/ = 0.50 nM), low capacity (Bmax = 70 fmoles/mg of protein), and stereoselective ([-]-propranolol is 100 times as potent as [+] -propranolol in inhibiting DHA binding). Adrenergic agonists competed for DHA binding sites in a manner compatible with beta-adrenergic interactions and mirrored β 2 pharmacologic potencies: isoproterenol > epinephrine >> norepinephrine. Studies in which zinterol, a β 2 -adrenergic agonist, competed for DHA binding sites in human myometrial particulate indicated that at least 87% of the beta-adrenergic receptors present are β 2 -adrenergic receptors. Binding of DHA to human myometrial beta-adrenergic receptors provides a tool which may be used in the examination of gonadal hormonal modification of adrenergic response in human uterus as well as in the analysis of beta-adrenergic agents as potentially useful tocolytic agents
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VANWAARDE, A; ANTHONIO, RL; ELSINGA, PH; POSTHUMUS, H; WEEMAES, AMA; BLANKSMA, PK; PAANS, AMJ; VAALBURG, W; Visser, Ton J.; Visser, Gerben
1995-01-01
beta-Adrenoceptors in human lungs and heart can be imaged with the radioligand 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1 ,3-dihydro-2H-benzimidazol-2-C-11-one (CGP 12177, [C-11]I). For quantification of receptor density with compartment models by adjustment of rate constants, an 'input
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The function of the human interferon-beta 1a glycan determined in vivo
DEFF Research Database (Denmark)
Dissing-Olesen, Lasse; Thaysen-Andersen, Morten; Meldgaard, Michael
2008-01-01
Recombinant human interferon-beta (rhIFN-beta) is the leading therapeutic intervention shown to change the cause of relapsing-remitting multiple sclerosis, and both a nonglycosylated and a significantly more active glycosylated variant of rhIFN-beta are used in treatment. This study investigates...... into the role of the rhIFN-beta1a glycan and its carbohydrate residues. The possibilities of improving the pharmacological properties of rhIFN-beta1a using glycoengineering are discussed...
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Regulation of laminin beta2 chain gene expression in human cancer cell lines
DEFF Research Database (Denmark)
Durkin, M E; Nielsen, F C; Loechel, F
2001-01-01
of the human laminin beta2 chain gene generates two isoforms of the 5' untranslated region of the beta2 chain mRNA. The translational efficiencies of the two laminin beta2 chain leaders did not differ significantly, when assayed by polysome profile analysis of endogenous clone A cell beta2 chain m......RNA, transient transfection of chimeric beta2 chain leader/luciferase expression plasmids in clone A cells, and translation of in vitro synthesized RNAs in rabbit reticulocyte lysates....
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Himelstein, A; Ward, M; Podda, S; de la Flor Weiss, E; Costantini, F; Bank, A
1993-03-01
When the human beta-globin gene is transferred into the bone marrow cells of live mice, its expression is very low. To investigate the reason for this, we transferred the bone marrow of transgenic mice containing and expressing the human beta-globin into irradiated recipients. We demonstrate that long-term high level expression of the human beta-globin gene can be maintained in the marrow and blood of irradiated recipients following transplantation. Although expression decreased over time in most animals because of host marrow reconstitution, the ratio of human beta-globin transgene expression to endogenous mouse beta-globin gene expression in donor-derived erythroid cells remained constant over time. We conclude that there is no inherent limitation to efficient expression of an exogenous human beta-globin gene in mouse bone marrow cells following marrow transplantation.
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Crystal structure of the human beta2 adrenergic G-protein-coupled receptor
DEFF Research Database (Denmark)
Rasmussen, Søren Gøgsig Faarup; Choi, Hee-Jung; Rosenbaum, Daniel M
2007-01-01
Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and neurotransmitters has been hindered by their low natural abundance, inherent structural flexibility, and instability in detergent solutions. Here we report a structure of the human beta2 adrenoceptor (beta2AR), which was ...
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Beta 3 and PDI proteins isolated from human platelets bind with ECwt rotavirus in vitro
International Nuclear Information System (INIS)
Mayorga, Diana; Rubio, Linda; Guerrero-Fonseca, Carlos A; Acosta-Losada, Orlando
2010-01-01
Commercial integrin Beta 3 is currently not available and commercial PDI is too expensive, which is making access difficult to these proteins needed for conducting experiments aimed at the establishment of possible interactions between integrin Beta 3 and PDI and wild type rotavirus strains. Objective. To explore a methodology allowing isolation of proteins Beta 3 and PDI from human platelets to be used as antigens in the generation of rabbit polyclonal antibodies useful in the assessment of interactions between these proteins and rotavirus ECwt. Materials and methods. Proteins Beta 3 and PDI from human platelet lysates were separated using preparative electrophoresis under reducing conditions and then eluted. Interactions of these proteins with rotavirus ECwt were analyzed using co-immunoprecipitation, Western blotting and capture ELISA. Results. Proteins from human platelet lysates were separated by preparative electrophoresis under reducing conditions. The identification of proteins Beta 3 and PDI present in a gel slice was performed through their reaction with commercial antibodies in a Western blotting analysis. Protein purity was established after electro elution from a gel slice. Polyclonal antibodies against protein Beta 3 were generated in rabbit. Incubation of eluted proteins Beta 3 and PDI with rotavirus ECwt showed in co-immunoprecipitation and ELISA assays that these proteins bound virus in vitro. The same binding was showed to occur when rotavirus was incubated with isolated small intestinal villi from suckling mice. Conclusions. Relatively high amounts of proteins Beta 3 and PDI were partially purified from human platelets by preparative electrophoresis. The isolation of these proteins allowed the generation of polyclonal antibodies against Beta 3 in addition to the establishment of the in vitro interaction of proteins Beta 3 and PDI with rotavirus ECwt. This interaction was also demonstrated in vivo after incubating the virus with isolated small
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DEFF Research Database (Denmark)
Sung, Jongmin; Nag, Suman; Vestergaard, Christian L.
2014-01-01
human beta cardiac myosin S1. We also compare load-velocity curves for wild-type motors with load-velocity curves of mutant forms that cause hypertrophic or dilated-cardiomyopathy (HCM or DCM), in order to understand the effects of mutations on the contractile cycle at the single molecule level....
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vanWaarde, A; Posthumus, H; Elsinga, PH; Anthonio, RL; van Loenen - Weemaes, Anne-miek; Beaufort-Krol, Gertie C. M.; Paans, AMJ; Vaalburg, W; Visser, Thomas; Visser, Gerben
1996-01-01
Myocardial and pulmonary beta-adrenoceptors can be imaged with 2-(S)-(-)-(9H-carbazol-4-yl-oxy)-3-[1-(fluoromethyl)ethyl]amino-2-propanol (S-1'-[F-18]fluorocarazolol, I). Quantification of unmodified fluorocarazolol in plasma is necessary for analysis of PET images in terms of receptor densities. We
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Measurement of gross alpha and gross beta activity concentrations in human tooth
International Nuclear Information System (INIS)
Soeguet, Omer; Aydin, Mehmet Fatih; Kuecuekoender, Erdal; Zorer, Ozlem Selcuk; Dogru, Mahmut
2010-01-01
The gross alpha and gross beta activity concentrations were measured in human tooth taken from 3 to 6 age-groups to 40 and over ones. Accumulated teeth samples are investigated in two groups as under and above 18 years. The gross alpha and beta radioactivity of human tooth samples was measured by using a gas-flow proportional counter (PIC-MPC 9604-α/β counter). In tooth samples, for female age-groups, the obtained results show that the mean gross alpha and gross beta activity concentrations varied between 0.534-0.203 and 0.010-0.453 Bq g -1 and the same concentrations for male age-groups varied between 0.009-1.168 and 0.071-0.204 Bq g -1 , respectively.
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Specific binding of beta-endorphin to normal human erythrocytes
Energy Technology Data Exchange (ETDEWEB)
Chenet, B.; Hollis, V. Jr.; Kang, Y.; Simpkins, C.
1986-03-05
Beta-endorphin (BE) exhibits peripheral functions which may not be mediated by interactions with receptors in the brain. Recent studies have demonstrated binding of BE to both opioid and non-opioid receptors on lymphocytes and monocytes. Abood has reported specific binding of /sup 3/H-dihydromorphine in erythrocytes. Using 5 x 10/sup -11/M /sup 125/I-beta-endorphin and 10/sup -5/M unlabeled BE, they have detected 50% specific binding to human erythrocytes. This finding is supported by results from immunoelectron microscopy using rabbit anti-BE antibody and biotinylated secondary antibody with avidin-biotin complexes horseradish peroxidase. Binding is clearly observed and is confined to only one side of the cells. Conclusions: (1) BE binding to human erythrocytes was demonstrated by radioreceptor assay and immunoelectron microscopy, and (2) BE binding sites exist on only one side of the cells.
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Tissue-specific methylation of human insulin gene and PCR assay for monitoring beta cell death.
Directory of Open Access Journals (Sweden)
Mohamed I Husseiny
Full Text Available The onset of metabolic dysregulation in type 1 diabetes (T1D occurs after autoimmune destruction of the majority of pancreatic insulin-producing beta cells. We previously demonstrated that the DNA encoding the insulin gene is uniquely unmethylated in these cells and then developed a methylation-specific PCR (MSP assay to identify circulating beta cell DNA in streptozotocin-treated mice prior to the rise in blood glucose. The current study extends to autoimmune non-obese diabetic (NOD mice and humans, showing in NOD mice that beta cell death occurs six weeks before the rise in blood sugar and coincides with the onset of islet infiltration by immune cells, demonstrating the utility of MSP for monitoring T1D. We previously reported unique patterns of methylation of the human insulin gene, and now extend this to other human tissues. The methylation patterns of the human insulin promoter, intron 1, exon 2, and intron 2 were determined in several normal human tissues. Similar to our previous report, the human insulin promoter was unmethylated in beta cells, but methylated in all other tissues tested. In contrast, intron 1, exon 2 and intron 2 did not exhibit any tissue-specific DNA methylation pattern. Subsequently, a human MSP assay was developed based on the methylation pattern of the insulin promoter and human islet DNA was successfully detected in circulation of T1D patients after islet transplantation therapy. Signal levels of normal controls and pre-transplant samples were shown to be similar, but increased dramatically after islet transplantation. In plasma the signal declines with time but in whole blood remains elevated for at least two weeks, indicating that association of beta cell DNA with blood cells prolongs the signal. This assay provides an effective method to monitor beta cell destruction in early T1D and in islet transplantation therapy.
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DEFF Research Database (Denmark)
Hasman, Henrik; Mevius, D.; Veldman, K.
2005-01-01
Objectives: The purpose of this work was to study the genetic determinants responsible for extended-spectrum beta-lactamase (ESBL) resistance of Salmonella isolated from Dutch poultry, poultry meat and hospitalized humans. Methods: Thirty-four ESBL-resistant Salmonella isolates from The Netherlands...... were tested towards 21 antimicrobial agents. PCR and sequencing were used to determine the underlying genetic determinants responsible for the ESBL phenotypes. The transferability of the ESBL phenotypes was tested by conjugation to a susceptible Salmonella enterica serovar Dublin and plasmid....... Finally, the bla(ACC-1) gene was cloned from a S. Bareilly isolate and was found to be present on indistinguishable plasmids in all S. Bareilly isolates examined as well as in a S. Braenderup isolate and a S. Infantis isolate. Conclusions: Our data underscore the diversity of ESBL genes in Salmonella...
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Biologic activities of recombinant human-beta-defensin-4 toward cultured human cancer cells.
Gerashchenko, O L; Zhuravel, E V; Skachkova, O V; Khranovska, N N; Filonenko, V V; Pogrebnoy, P V; Soldatkina, M A
2013-06-01
The aim of the study was in vitro analysis of biological activity of recombinant human beta-defensin-4 (rec-hBD-4). hBD-4 cDNA was cloned into pGEX-2T vector, and recombinant plasmid was transformed into E. coli BL21(DE3) cells. To purify soluble fusion GST-hBD-4 protein, affinity chromatography was applied. Rec-hBD-4 was cleaved from the fusion protein with thrombin, and purified by reverse phase chromatography on Sep-Pack C18. Effects of rec-hBD-4 on proliferation, viability, cell cycle distribution, substrate-independent growth, and mobility of cultured human cancer cells of A431, A549, and TPC-1 lines were analyzed by direct cell counting technique, MTT assay, flow cytofluorometry, colony forming assay in semi-soft medium, and wound healing assay. Rec-hBD-4 was expressed in bacterial cells as GST-hBD-4 fusion protein, and purified by routine 3-step procedure (affine chromatography on glutathione-agarose, cleavage of fusion protein by thrombin, and reverse phase chromatography). Analysis of in vitro activity of rec-hBD-4 toward three human cancer cell lines has demonstrated that the defensin is capable to affect cell behaviour in concentration-dependent manner. In 1-100 nM concentrations rec-hBD-4 significantly stimulates cancer cell proliferation and viability, and promotes cell cycle progression through G2/M checkpoint, greatly enhances colony-forming activity and mobility of the cells. Treatment of the cells with 500 nM of rec-hBD-4 resulted in opposite effects: significant suppression of cell proliferation and viability, blockage of cell cycle in G1/S checkpoint, significant inhibition of cell migration and colony forming activity. Recombinant human beta-defensin-4 is biologically active peptide capable to cause oppositely directed effects toward biologic features of cancer cells in vitro dependent on its concentration.
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Bouman, Annechien; Schipper, Martin; Heineman, Maas Jan; Faas, Marijke
2004-01-01
OBJECTIVE: To test whether 17beta-estradiol or progesterone influence the cytokine productive capacity of lipopolysaccharide (LPS)-stimulated monocytes in humans. DESIGN: Prospective study. SETTING: Academic research institution. PATIENT(S): Seven women in the luteal phase of a normal ovarian cycle,
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Schipper, M; Heineman, MJ; Faas, M; Bouman, A.
2004-01-01
Objective: To test whether 17beta-estradiol or progesterone influence the cytokine productive capacity of lipopolysaccharide (LPS)-stimulated monocytes in humans. Design: Prospective study. Setting: Academic research institution. Patient(s): Seven women in the luteal phase of a normal ovarian cycle,
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Energy Technology Data Exchange (ETDEWEB)
Kuikka, J.T. [Dept. of Clinical Physiology, Kuopio Univ. Hospital (Finland); Bergstroem, K.A. [Dept. of Clinical Physiology, Kuopio Univ. Hospital (Finland); Ahonen, A. [Dept. of Clinical Chemistry, Oulu Univ. Central Hospital (Finland); Hiltunen, J. [MAP Medical Technologies Oy, Tikkakoski (Finland); Haukka, J. [MAP Medical Technologies Oy, Tikkakoski (Finland); Laensimies, E. [Dept. of Clinical Physiology, Kuopio Univ. Hospital (Finland); Wang Shaoyin [Research Biochemicals International (RBI), Natick, MA (United States); Neumeyer, J.L. [Research Biochemicals International (RBI), Natick, MA (United States)
1995-04-01
Several cocaine congeners are of potential for imaging the dopamine transporter (DAT). Previous studies have shown that iodine-123 labelled 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane ([{sup 123}I]{beta}-CIT) is a promising radiotracer for imaging the serotonin (5-HT) and dopamine (DA) transporters in the living human brain with single-photon emission tomography (SPET). [{sup 123}I]{beta}-CIT was found to be not very practical for 1-day DAT imaging protocols since peak DAT uptake occurs later than 8 h. Here we report a pilot comparison of [{sup 123}I]{beta}-CIT and 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ([{sup 123}I]{beta}-CIT-FP), using SPET imaging in four healthy male subjects. Peak uptake of [{sup 123}I]{beta}-CIT-FP into the basal ganglia occurred earlier (3-4 h after injection of tracer) than that of [{sup 123}I]{beta}-CIT (>8 h). However, the specific DAT binding of [{sup 123}I]{beta}-CIT-FP in the basal ganglia was somewhat less (0.813{+-}0.047) than that of [{sup 123}I]{beta}-CIT (0.922{+-}0.004). Imaging quality is excellent with both tracers and they are potentially of value for brain imaging in various neuropsychiatric disorders. (orig.)
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Perimovement decrease of alpha/beta oscillations in the human nucleus accumbens.
Stenner, Max-Philipp; Dürschmid, Stefan; Rutledge, Robb B; Zaehle, Tino; Schmitt, Friedhelm C; Kaufmann, Jörn; Voges, Jürgen; Heinze, Hans-Jochen; Dolan, Raymond J; Schoenfeld, Mircea Ariel
2016-10-01
The human nucleus accumbens is thought to play an important role in guiding future action selection via an evaluation of current action outcomes. Here we provide electrophysiological evidence for a more direct, i.e., online, role during action preparation. We recorded local field potentials from the nucleus accumbens in patients with epilepsy undergoing surgery for deep brain stimulation. We found a consistent decrease in the power of alpha/beta oscillations (10-30 Hz) before and around the time of movements. This perimovement alpha/beta desynchronization was observed in seven of eight patients and was present both before instructed movements in a serial reaction time task as well as before self-paced, deliberate choices in a decision making task. A similar beta decrease over sensorimotor cortex and in the subthalamic nucleus has been directly related to movement preparation and execution. Our results support the idea of a direct role of the human nucleus accumbens in action preparation and execution. Copyright © 2016 the American Physiological Society.
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Sherman, Maxwell A.; Lee, Shane; Law, Robert; Haegens, Saskia; Thorn, Catherine A.; Hämäläinen, Matti S.; Moore, Christopher I.; Jones, Stephanie R.
2016-01-01
Human neocortical 15–29-Hz beta oscillations are strong predictors of perceptual and motor performance. However, the mechanistic origin of beta in vivo is unknown, hindering understanding of its functional role. Combining human magnetoencephalography (MEG), computational modeling, and laminar recordings in animals, we present a new theory that accounts for the origin of spontaneous neocortical beta. In our MEG data, spontaneous beta activity from somatosensory and frontal cortex emerged as noncontinuous beta events typically lasting drive targeting proximal and distal dendrites of pyramidal neurons, where the defining feature of a beta event was a strong distal drive that lasted one beta period (∼50 ms). This beta mechanism rigorously accounted for the beta event profiles; several other mechanisms did not. The spatial location of synaptic drive in the model to supragranular and infragranular layers was critical to the emergence of beta events and led to the prediction that beta events should be associated with a specific laminar current profile. Laminar recordings in somatosensory neocortex from anesthetized mice and awake monkeys supported these predictions, suggesting this beta mechanism is conserved across species and recording modalities. These findings make several predictions about optimal states for perceptual and motor performance and guide causal interventions to modulate beta for optimal function. PMID:27469163
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Directory of Open Access Journals (Sweden)
Holger A Russ
Full Text Available Expansion of beta cells from the limited number of adult human islet donors is an attractive prospect for increasing cell availability for cell therapy of diabetes. However, attempts at expanding human islet cells in tissue culture result in loss of beta-cell phenotype. Using a lineage-tracing approach we provided evidence for massive proliferation of beta-cell-derived (BCD cells within these cultures. Expansion involves dedifferentiation resembling epithelial-mesenchymal transition (EMT. Epigenetic analyses indicate that key beta-cell genes maintain open chromatin structure in expanded BCD cells, although they are not transcribed. Here we investigated whether BCD cells can be redifferentiated into beta-like cells.Redifferentiation conditions were screened by following activation of an insulin-DsRed2 reporter gene. Redifferentiated cells were characterized for gene expression, insulin content and secretion assays, and presence of secretory vesicles by electron microscopy. BCD cells were induced to redifferentiate by a combination of soluble factors. The redifferentiated cells expressed beta-cell genes, stored insulin in typical secretory vesicles, and released it in response to glucose. The redifferentiation process involved mesenchymal-epithelial transition, as judged by changes in gene expression. Moreover, inhibition of the EMT effector SLUG (SNAI2 using shRNA resulted in stimulation of redifferentiation. Lineage-traced cells also gave rise at a low rate to cells expressing other islet hormones, suggesting transition of BCD cells through an islet progenitor-like stage during redifferentiation.These findings demonstrate for the first time that expanded dedifferentiated beta cells can be induced to redifferentiate in culture. The findings suggest that ex-vivo expansion of adult human islet cells is a promising approach for generation of insulin-producing cells for transplantation, as well as basic research, toxicology studies, and drug
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RFLP for the human retinoic acid receptor gene RAR-. beta
Energy Technology Data Exchange (ETDEWEB)
Datson, N A; Oostra, B A [Erasmus Univ., Rotterdam (Netherlands); van der Saag, P T [Netherlands Institute for Developmental Biology, Utrecht (Netherlands)
1989-11-11
1.4 kb Mae I fragment containing the entire RAR-{beta} ORF was cloned into the Sma I site of pTZ18U, yielding the plasmid pCOD20. Msp I digestion of genomic DNA and hybridization with the pCOD20 probe detects a two allele polymorphism with allelic fragments of 8.1 and 7.7 kb. The human RAR-{beta} gene has been localized to the p24 band of chromosome 3. Co-dominant segregation of the alleles was observed in 4 Caucasian families.
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Energy Technology Data Exchange (ETDEWEB)
Andarawewa, Kumari L.; Erickson, Anna C.; Chou, William S.; Costes, Sylvain; Gascard, Philippe; Mott, Joni D.; Bissell, Mina J.; Barcellos-Hoff, Mary Helen
2007-04-06
Transforming growth factor {beta}1 (TGF{beta}) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGF{beta}, activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGF{beta}-mediated epithelial to mesenchymal transition (EMT). Non-malignant HMEC (MCF10A, HMT3522 S1 and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture, or treated with a low concentration of TGF{beta} (0.4 ng/ml), or double-treated. All double-treated (IR+TGF{beta}) HMEC underwent a morphological shift from cuboidal to spindle-shaped. This phenotype was accompanied by decreased expression of epithelial markers E-cadherin, {beta}-catenin and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin and vimentin. Furthermore, double-treatment increased cell motility, promoted invasion and disrupted acinar morphogenesis of cells subsequently plated in Matrigel{trademark}. Neither radiation nor TGF{beta} alone elicited EMT, even though IR increased chronic TGF{beta} signaling and activity. Gene expression profiling revealed that double treated cells exhibit a specific 10-gene signature associated with Erk/MAPK signaling. We hypothesized that IR-induced MAPK activation primes non-malignant HMEC to undergo TGF{beta}-mediated EMT. Consistent with this, Erk phosphorylation were transiently induced by irradiation, persisted in irradiated cells treated with TGF{beta}, and treatment with U0126, a Mek inhibitor, blocked the EMT phenotype. Together, these data demonstrate that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression.
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Zheng, Xiaofen; De Paiva, Cintia S; Rao, Kavita; Li, De-Quan; Farley, William J; Stern, Michael; Pflugfelder, Stephen C
2010-09-01
To develop a new bioassay method using human lung epithelial cells (CCL-185) to assess activity of transforming growth factor beta (TGF-beta) in human tear fluid from normal subjects and patients with dry eye. Two epithelial cell lines, mink lung cells (CCL-64) and human lung cells (CCL-185), were compared to detect the active form of TGF-beta by BrdU incorporation (quantitation of cell DNA synthesis) and WST assay (metabolic activity of viable cells). The effect of TGF-beta on the growth of CCL-185 cells was observed microscopically. Human tears from normal control subjects and patients with dry eye (DE) with and without Sjögren syndrome were evaluated for TGF-beta concentration by Luminex microbead assay, and TGF-beta activity by the CCL-185 cell growth inhibition bioassay. The metabolic activity of viable CCL-185 cells, measured by WST, was shown to be proportional to the TGF-beta1 concentration (R = 0.919) and confirmed by BrdU assay (R = 0.969). Compared with CCL-185, metabolic activity of viable cells and DNA synthesis, measured by WST and BrdU incorporation assays, were shown to be less proportional to the TGF-beta1 concentration in the CCL-64 line (R = 0.42 and 0.17, respectively). Coincubation with human anti-TGF-beta1 antibody (MAB-240) yielded a dose-dependent inhibition of TGF-beta1 (0.3 ng/mL) activity. CCL-185 cell growth observed microscopically was noted to decrease in response to increasing TGF-beta1 concentrations. Levels of immuodetectable TGF-beta1 and TGF-beta2 were similar in normal and DE tears. TGF-beta bioactivity in DE human tears measured by the CCL-185 cells assay was found to be higher (9777.5 +/- 10481.9 pg/mL) than those in normal controls (4129.3 +/- 1342.9 pg/mL) (P tears and 37.6% TGF-beta in normal tears were found to be biologically active. The CCL-185 cell assay was found to be a suitable tool for assessing TGF-beta activity in human tears. Tear TGF-beta bioactivity increases in DE, particularly in Sjögren syndrome, where
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Anti-Proliferative and Apoptotic Effects of Beta-Ionone in Human Leukemia Cell Line K562
Directory of Open Access Journals (Sweden)
Zohreh Faezizadeh
2016-06-01
Full Text Available Background Beta-ionone is an aroma compound found in the Rosaceae family. Some evidence supported that beta-ionone has a great potential for cancer prevention. To date, the anti-proliferative and apoptotic effects of beta-ionone in human leukemia cell line K562 were not studied. Objectives Hence, we investigated whether beta-ionone could inhibit cell growth and induce apoptosis in the K562 cells. Materials and Methods In this experimental study, human leukemia cell line K562 was cultured and anti-proliferation effect of beta-ionone with different doses (25 - 400 µm at different times (24 - 96 hours on treated cells was evaluated by the MTT assay. To determine apoptosis rate, the Hoechst 33342 staining and flow cytometry was performed. Results The MTT assay showed that beta-ionone inhibited proliferation of K562 cells in a dose-dependent manner significantly (P = 0.0008. Moreover, the increased apoptotic rate was found after incubation of K562 cells with 200 µm beta-ionone. The Hoechst staining and flow cytometry analysis indicated that beta-ionone could increase apoptosis of K562 cells in a dose-dependent manner. Conclusions The results demonstrated that beta-ionone has anti-proliferative and apoptotic effects on K562 cells, and in the future may be used in the treatment of some leukemia sub-types.
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[Application of the polymerase chain reaction (PCR) in the diagnosis of Hb S-beta(+)-thalassemia].
Harano, K; Harano, T; Kushida, Y; Ueda, S
1991-08-01
Isoelectric focusing of the hemolysate prepared from a two-year-old American black boy with microcytic hypochromia showed the presence of a high percentage (63.3%) of such Hb variant as Hb S, while the levels of Hb A, Hb F and Hb A2 were 20.0%, 12.7%, and 4.0%, respectively. The ratio of the non-alpha-chain to the alpha-chain of the biosynthesized globin chains was 0.49. The variant was identified as Hb S by amino acid analysis of the abnormal peptide (beta T-1) and digestion of DNA amplified by the polymerase chain reaction with enzyme Eco 81 I. This was further confirmed by DNA sequencing. DNA sequencing of a beta-gene without the beta s-mutation revealed a nucleotide change of T to C in the polyadenylation signal sequence AATAAA 3' to the beta-gene, resulting in beta(+)-thalassemia. These results are consistent with the existence of a beta s-gene and a beta(+)-thalassemia gene in trans.
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DEFF Research Database (Denmark)
Wogensen, L D; Welinder, B; Hejnaes, K R
1991-01-01
-lives of distribution (T1/2 alpha) and elimination phases (T1/2 beta) of human recombinant interleukin 1 beta (rIL-1 beta), and its tissue distribution and cellular localization by means of mono-labelled, biologically active 125I-rIL-1 beta. After intravenous (i.v.) injection, 125I-rIL-1 beta was eliminated from...... the circulation with a T1/2 alpha of 2.9 min and a T1/2 beta of 41.1 min. The central and peripheral volume of distribution was 20.7 and 19.1 ml/rat, respectively, and the metabolic clearance rate was 16.9 ml/min/kg. The kidney and liver showed the highest accumulation of tracer, and autoradiography demonstrated...
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Directory of Open Access Journals (Sweden)
Ansaya Thonpho
Full Text Available Pyruvate carboxylase (PC is an enzyme that plays a crucial role in many biosynthetic pathways in various tissues including glucose-stimulated insulin secretion. In the present study, we identify promoter usage of the human PC gene in pancreatic beta cells. The data show that in the human, two alternative promoters, proximal and distal, are responsible for the production of multiple mRNA isoforms as in the rat and mouse. RT-PCR analysis performed with cDNA prepared from human liver and islets showed that the distal promoter, but not the proximal promoter, of the human PC gene is active in pancreatic beta cells. A 1108 bp fragment of the human PC distal promoter was cloned and analyzed. It contains no TATA box but possesses two CCAAT boxes, and other putative transcription factor binding sites, similar to those of the distal promoter of rat PC gene. To localize the positive regulatory region in the human PC distal promoter, 5'-truncated and the 25-bp and 15-bp internal deletion mutants of the human PC distal promoter were generated and used in transient transfections in INS-1 832/13 insulinoma and HEK293T (kidney cell lines. The results indicated that positions -340 to -315 of the human PC distal promoter serve as (an activator element(s for cell-specific transcription factor, while the CCAAT box at -71/-67, a binding site for nuclear factor Y (NF-Y, as well as a GC box at -54/-39 of the human PC distal promoter act as activator sequences for basal transcription.
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Energy Technology Data Exchange (ETDEWEB)
Kuikka, J T [Kuopio Univ. Hospital (Finland). Dept. of Clinical Physiology; Bergstroem, K A [Kuopio Univ. Hospital (Finland). Dept. of Clinical Physiology; Vanninen, E [Kuopio Univ. Hospital (Finland). Dept. of Clinical Physiology; Laulumaa, V [Kuopio Univ. Hospital (Finland). Dept. of Neurology; Hartikainen, P [Kuopio Univ. Hospital (Finland). Dept. of Neurology; Laensimies, E [Kuopio Univ. Hospital (Finland). Dept. of Clinical Physiology
1993-09-01
The iodinated cocaine analogue 2[beta]-carbomethoxy-3[beta]-(4-iodophenyl)tropane ([sup 123]I[beta]-CIT), a new dopamine transporter, was preliminarily tested in human brain. Two normal volunteers and two patients with Parkinson's disease were imaged with a high-resolution single-photon emission tomography scanner. The specific binding of [sup 123]I[beta]-CIT in the basal ganglia and thalamus was high in normal volunteers. In addition, there was relatively intense uptake in the medial prefrontal area. Patients with Parkinson's disease who were older than controls showed significantly lower specific binding in the basal ganglia and thalamus and no uptake in the medial prefrontal cortex. This decrease in the dopamine transporter may be age related. (orig.)
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International Nuclear Information System (INIS)
Krutmann, J.; Koeck, A.S.; Schauer, E.; Parlow, F.; Moeller, A.K.; Kapp, A.; Foerster, E.S.; Schoepf, E.L.; Luger, T.A.
1990-01-01
Intercellular adhesion molecule-1 (ICAM-1) functions as a ligand of leukocyte function-associated antigen-1 (LFA-1), as well as a receptor for human picorna virus, and its regulation thus affects various immunologic and inflammatory reactions. The weak, constitutive ICAM-1 expression on human keratinocytes (KC) can be up-regulated by cytokines such as interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha). In order to further examine the regulation of KC ICAM-1 expression, normal human KC or epidermoid carcinoma cells (KB) were incubated with different cytokines and/or exposed to ultraviolet (UV) radiation. Subsequently, ICAM-1 expression was monitored cytofluorometrically using a monoclonal anti-ICAM-1 antibody. Stimulation of cells with recombinant human (rh) interleukin (IL) 1 alpha, rhIL-4, rhIL-5, rhIL-6, rh granulocyte/macrophage colony-stimulating factor (GM-CSF), rh interferon alpha (rhIFN alpha), and rh transforming growth factor beta (TGF beta) did not increase ICAM-1 surface expression. In contrast, rhTNF beta significantly up-regulated ICAM-1 expression in a time- and dose-dependent manner. Moreover, the combination of rhTNF beta with rhIFN gamma increased the percentage of ICAM-1-positive KC synergistically. This stimulatory effect of rhTNF beta was further confirmed by the demonstration that rhTNF beta was capable of markedly enhancing ICAM-1 mRNA expression in KC. Finally, exposure of KC in vitro to sublethal doses of UV radiation (0-100 J/m2) prior to cytokine (rhIFN tau, rhTNF alpha, rhTNF beta) stimulation inhibited ICAM-1 up-regulation in a dose-dependent fashion. These studies identify TNF beta and UV light as potent regulators of KC ICAM-1 expression, which may influence both attachment and detachment of leukocytes and possibly viruses to KC
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Furimsky, Anna M; Green, Carol E; Sharp, Lewanne E Hunt; Catz, Paul; Adjei, Araba A; Parman, Toufan; Kapetanovic, Izet M; Weinshilboum, Richard M; Iyer, Lalitha V
2008-01-01
The purpose of this study was to investigate the sulfation of resveratrol (3,5,4'-trihydroxystilbene) and its potential to exhibit drug-drug interactions via sulfation. The possible interaction of resveratrol with 17beta-estradiol (E2), a major estrogen hormone and prototypic substrate for sulfate conjugation, was studied. Resveratrol and E2 are both known to undergo sulfate conjugation catalyzed by human sulfotransferases (SULTs). Resveratrol is a phytoestrogen with mixed estrogen agonist/antagonist properties that is being developed as a chemopreventive agent. The sulfate conjugation of E2 and resveratrol were studied individually using S9 fractions from human liver and jejunum as well as recombinant human SULT isoforms. The sulfation of E2 (3-20 nM) was then investigated in the presence of various concentrations (0, 0.5, 1, and 2 microM) of resveratrol using the two S9 preparations as well as recombinant SULT1E1, the major isoform responsible for E2 sulfation. Resveratrol inhibited E2 sulfation with estimated K(i) values of 1.1 microM (liver), 0.6 microM (jejunum), and 2.3 microM (SULT1E1), concentrations that could be pharmacologically relevant. The results suggest that these phytoestrogens can potentially alter the homeostasis of estrogen levels. These findings also imply that resveratrol may inhibit the metabolism of other estrogen analogs or therapeutic agents such as ethinylestradiol or dietary components that are also substrates for SULT1E1.
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DEFF Research Database (Denmark)
Wogensen, L D; Reimers, J; Nerup, J
1992-01-01
It is unknown whether interleukin-1 exerts a bimodal effect on Beta-cell function in vivo, and whether interleukin-1 has a diabetogenic action in normal animals. We therefore studied: (a) acute effects 2 h after an intraperitoneal bolus injection of 4 micrograms of recombinant human interleukin-1...
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Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle
Sakhnini, Lama
2003-05-01
In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.
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Rabbitt, E H; Ayuk, J; Boelaert, K; Sheppard, M C; Hewison, M; Stewart, P M; Gittoes, N J L
2003-03-20
The physiological effects of glucocorticoids (GCs) are, at least in part, mediated by inhibition of cell proliferation. Two isozymes of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) interconvert cortisol (F) and inactive cortisone (E), and are thus able to modulate GC action at an autocrine level. Previously, we have demonstrated absent expression of 11 beta-HSD2 in normal pituitaries; however, in a small number of pituitary tumors analysed, 11 beta-HSD2 was readily demonstrable. Here we have used real-time RT-PCR to quantify expression of mRNA for 11 beta-HSD1 and 2 in 105 human pituitary tumors and have performed enzyme expression and activity studies in primary pituitary cultures. Overall, pituitary tumors expressed lower levels of 11 beta-HSDl mRNA compared with normals (0.2-fold, Pprotein (mean+/-s.d.)) but no detectable 11 beta-HSDl activity. Proliferation assays showed that addition of glycyrrhetinic acid (an 11 beta-HSD2 inhibitor) resulted in a 30.3+/-7.7% inhibition of cell proliferation. In summary, we describe a switch in expression from 11 beta-HSDl to 11 beta-HSD2 in neoplastic pituitary tissue. We propose that abnormal expression of 11 beta-HSD2 acts as a proproliferative prereceptor determinant of pituitary cell growth, and may provide a novel target for future tumor therapy.
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International Nuclear Information System (INIS)
Bidart, J.M.; Troalen, F.; Salesse, R.; Bousfield, G.R.; Bohuon, C.J.; Bellet, D.H.
1987-01-01
We describe a first attempt to study the antibody-combining sites recognized by monoclonal antibodies raised against the beta-subunit of human choriogonadotropin (hCG). Two groups of antibodies were first defined by their ability to recognize only the free beta-subunit or the free and combined subunit. Antibodies FBT-11 and FBT-11-L bind only to hCG beta-subunit but not to hCG, whereas antibodies FBT-10 and D1E8 bind to both the beta-subunit and the hormone. In both cases, the antigenic determinants were localized to the core of the protein (residues 1-112), indicating the weak immunogenicity of the specific carboxyl-terminal extension of hCG-beta. Nine synthetic peptides spanning different regions of hCG-beta and lutropin-beta were assessed for their capacity to inhibit antibody binding. A synthetic peptide inclusive of the NH2-terminal region (residues 1-7) of the hCG beta-subunit was found to inhibit binding to the radiolabeled subunit of a monoclonal antibody specific for free hCG-beta (FBT-11). Further delineation of the antigenic site recognized by this antibody provided evidence for the involvement of fragment 82-92. Moreover, monoclonal antibody FBT-11 inhibited the recombination of hCG-beta to hCG-alpha, indicating that its antigenic determinant might be located nearby or in the hCG-beta portion interacting with the alpha-subunit. Binding of monoclonal antibody FBT-10, corresponding to the second antigenic determinant, was weakly inhibited by fragment 82-105 and did not impair the recombination of the hCG beta-subunit to the hCG alpha-subunit. Its combining site appeared to be located in a region of the intact native choriogonadotropin present at the surface of the hormone-receptor complex
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DEFF Research Database (Denmark)
Kassem, M; Kveiborg, Marie; Eriksen, E F
2000-01-01
Transforming growth factor beta (TGF-beta) plays an important role in skeletal remodelling. However, few studies have examined its effects on cultured human osteoblasts. Our aim is to characterise the biological effects of TGF-beta1 on human osteoblasts and to examine the interaction between TGF-...
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Innate-like control of human iNKT cell autoreactivity via the hypervariable CDR3beta loop.
Directory of Open Access Journals (Sweden)
Gediminas Matulis
2010-06-01
Full Text Available Invariant Natural Killer T cells (iNKT are a versatile lymphocyte subset with important roles in both host defense and immunological tolerance. They express a highly conserved TCR which mediates recognition of the non-polymorphic, lipid-binding molecule CD1d. The structure of human iNKT TCRs is unique in that only one of the six complementarity determining region (CDR loops, CDR3beta, is hypervariable. The role of this loop for iNKT biology has been controversial, and it is unresolved whether it contributes to iNKT TCR:CD1d binding or antigen selectivity. On the one hand, the CDR3beta loop is dispensable for iNKT TCR binding to CD1d molecules presenting the xenobiotic alpha-galactosylceramide ligand KRN7000, which elicits a strong functional response from mouse and human iNKT cells. However, a role for CDR3beta in the recognition of CD1d molecules presenting less potent ligands, such as self-lipids, is suggested by the clonal distribution of iNKT autoreactivity. We demonstrate that the human iNKT repertoire comprises subsets of greatly differing TCR affinity to CD1d, and that these differences relate to their autoreactive functions. These functionally different iNKT subsets segregate in their ability to bind CD1d-tetramers loaded with the partial agonist alpha-linked glycolipid antigen OCH and structurally different endogenous beta-glycosylceramides. Using surface plasmon resonance with recombinant iNKT TCRs and different ligand-CD1d complexes, we demonstrate that the CDR3beta sequence strongly impacts on the iNKT TCR affinity to CD1d, independent of the loaded CD1d ligand. Collectively our data reveal a crucial role for CDR3beta for the function of human iNKT cells by tuning the overall affinity of the iNKT TCR to CD1d. This mechanism is relatively independent of the bound CD1d ligand and thus forms the basis of an inherent, CDR3beta dependent functional hierarchy of human iNKT cells.
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Clusters of conserved beta cell marker genes for assessment of beta cell phenotype
DEFF Research Database (Denmark)
Martens, Geert A; Jiang, Lei; Hellemans, Karine H
2011-01-01
The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture...... microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators....
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Energy Technology Data Exchange (ETDEWEB)
Mark, Brian L.; Mahuran, Don J.; Cherney, Maia M.; Zhao, Dalian; Knapp, Spencer; James, Michael N.G.
2010-12-01
In humans, two major {beta}-hexosaminidase isoenzymes exist: Hex A and Hex B. Hex A is a heterodimer of subunits {alpha} and {beta} (60% identity), whereas Hex B is a homodimer of {beta}-subunits. Interest in human {beta}-hexosaminidase stems from its association with Tay-Sachs and Sandhoff disease; these are prototypical lysosomal storage disorders resulting from the abnormal accumulation of G{sub M2}-ganglioside (G{sub M2}). Hex A degrades G{sub M2} by removing a terminal N-acetyl-D-galactosamine ({beta}-GalNAc) residue, and this activity requires the G{sub M2}-activator, a protein which solubilizes the ganglioside for presentation to Hex A. We present here the crystal structure of human Hex B, alone (2.4 {angstrom}) and in complex with the mechanistic inhibitors GalNAc-isofagomine (2.2 {angstrom}) or NAG-thiazoline (2.5 {angstrom}). From these, and the known X-ray structure of the G{sub M2}-activator, we have modeled Hex A in complex with the activator and ganglioside. Together, our crystallographic and modeling data demonstrate how {alpha} and {beta}-subunits dimerize to form either Hex A or Hex B, how these isoenzymes hydrolyze diverse substrates, and how many documented point mutations cause Sandhoff disease ({beta}-subunit mutations) and Tay-Sachs disease ({alpha}-subunit mutations).
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Labelling of. beta. -endorphin (. beta. -END) and. beta. -lipotropin (. beta. -LPH) by /sup 125/I
Energy Technology Data Exchange (ETDEWEB)
Deby-Dupont, G.; Joris, J.; Franchimont, P. (Universite de Liege (Belgique)); Reuter, A.M.; Vrindts-Gevaert, Y. (Institut des Radioelements, Fleurus (Belgique))
1983-01-01
5 ..mu..g of human ..beta..-endorphin were labelled with 2 mCi /sup 125/I by the chloramine T technique. After two gel filtrations on Sephadex G-15 and on Sephadex G-50 in phosphate buffer with EDTA, Trasylol and mercapto-ethanol, a pure tracer was obtained with a specific activity about 150 ..mu..Ci/..mu..g.Kept at + 4/sup 0/C, the tracer remained utilizable for 30 days without loss of immunoreactivity. The labelling with lactoperoxydase and the use of another gel filtration method (filtration on Aca 202) gave a /sup 125/I ..beta..-END tracer with the same immunoreactivity. The binding of this tracer to the antibody of an anti-..beta..-END antiserum diluted at 1/8000 was 32% with a non specific binding of 2%. 5 ..mu..g of human ..beta..-lipotropin were labelled with 0.5 mCi /sup 125/I by the lactoperoxydase method. After two gel filtrations on Sephadex G-25 and on Sephadex G-75 in phosphate buffer with EDTA, Trasylol and mercapto-ethanol, a pure tracer with a specific activity of 140 ..mu..Ci/..mu..g was obtained. It remained utilizable for 30 days when kept at + 4/sup 0/C. Gel filtration on Aca 202 did not give good purification, while gel filtration on Aca 54 was good but slower than on Sephadex G-75. The binding to antibody in absence of unlabelled ..beta..-LPH was 32% for an anti-..beta..-LPH antiserum diluted at 1/4000. The non specific binding was 2.5%.
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International Nuclear Information System (INIS)
Darvin, M E; Gersonde, I; Meinke, M; Sterry, W; Lademann, J
2005-01-01
Resonance Raman spectroscopy was used as a fast and non-invasive optical method of measuring the absolute concentrations of beta-carotene and lycopene in living human skin. Beta-carotene and lycopene have different absorption values at 488 and 514.5 nm and, consequently, the Raman lines for beta-carotene and lycopene have different scattering efficiencies at 488 and 514.5 nm excitations. These differences were used for the determination of the concentrations of beta-carotene and lycopene. Using multiline Ar + laser excitation, clearly distinguishable carotenoid Raman spectra can be obtained which are superimposed on a large fluorescence background. The Raman signals are characterized by two prominent Stokes lines at 1160 and 1525 cm -1 , which have nearly identical relative intensities. Both substances were detected simultaneously. The Raman spectra are obtained rapidly, i.e. within about 10 s, and the required laser light exposure level is well within safety standards. The disturbance of the measurements by non-homogeneous skin pigmentation was avoided by using a relatively large measuring area of 35 mm 2 . It was shown that beta-carotene and lycopene distribution in human skin strongly depends upon the skin region studied and drastically changed inter-individually. Skin beta-carotene and lycopene concentrations are lower in smokers than in non-smokers and higher in the vegetarian group
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Energy Technology Data Exchange (ETDEWEB)
Darvin, M E [Center of Experimental and Applied Cutaneous Physiology (CCP), Department of Dermatology, Charite University Hospital, Berlin (Germany); Gersonde, I [Institute of Medical Physics and Laser Medicine, Charite University Hospital, Berlin (Germany); Meinke, M [Institute of Medical Physics and Laser Medicine, Charite University Hospital, Berlin (Germany); Sterry, W [Center of Experimental and Applied Cutaneous Physiology (CCP), Department of Dermatology, Charite University Hospital, Berlin (Germany); Lademann, J [Center of Experimental and Applied Cutaneous Physiology (CCP), Department of Dermatology, Charite University Hospital, Berlin (Germany)
2005-08-07
Resonance Raman spectroscopy was used as a fast and non-invasive optical method of measuring the absolute concentrations of beta-carotene and lycopene in living human skin. Beta-carotene and lycopene have different absorption values at 488 and 514.5 nm and, consequently, the Raman lines for beta-carotene and lycopene have different scattering efficiencies at 488 and 514.5 nm excitations. These differences were used for the determination of the concentrations of beta-carotene and lycopene. Using multiline Ar{sup +} laser excitation, clearly distinguishable carotenoid Raman spectra can be obtained which are superimposed on a large fluorescence background. The Raman signals are characterized by two prominent Stokes lines at 1160 and 1525 cm{sup -1}, which have nearly identical relative intensities. Both substances were detected simultaneously. The Raman spectra are obtained rapidly, i.e. within about 10 s, and the required laser light exposure level is well within safety standards. The disturbance of the measurements by non-homogeneous skin pigmentation was avoided by using a relatively large measuring area of 35 mm{sup 2}. It was shown that beta-carotene and lycopene distribution in human skin strongly depends upon the skin region studied and drastically changed inter-individually. Skin beta-carotene and lycopene concentrations are lower in smokers than in non-smokers and higher in the vegetarian group.
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Lee, Seung-Hee; Hao, Ergeng; Savinov, Alexei Y; Geron, Ifat; Strongin, Alex Y; Itkin-Ansari, Pamela
2009-04-15
Islet transplantation is limited by the need for chronic immunosuppression and the paucity of donor tissue. As new sources of human beta-cells are developed (e.g., stem cell-derived tissue), transplanting them in a durable device could obviate the need for immunosuppression, while also protecting the patient from any risk of tumorigenicity. Here, we studied (1) the survival and function of encapsulated human beta-cells and their progenitors and (2) the engraftment of encapsulated murine beta-cells in allo- and autoimmune settings. Human islets and human fetal pancreatic islet-like cell clusters were encapsulated in polytetrafluorethylene devices (TheraCyte) and transplanted into immunodeficient mice. Graft survival and function was measured by immunohistochemistry, circulating human C-peptide levels, and blood glucose levels. Bioluminescent imaging was used to monitor encapsulated neonatal murine islets. Encapsulated human islet-like cell clusters survived, replicated, and acquired a level of glucose responsive insulin secretion sufficient to ameliorate hyperglycemia in diabetic mice. Bioluminescent imaging of encapsulated murine neonatal islets revealed a dynamic process of cell death followed by regrowth, resulting in robust long-term allograft survival. Further, in the non-obese diabetic (NOD) mouse model of type I diabetes, encapsulated primary beta-cells ameliorated diabetes without stimulating a detectable T-cell response. We demonstrate for the first time that human beta-cells function is compatible with encapsulation in a durable, immunoprotective device. Moreover, our study suggests that encapsulation of beta-cells before terminal differentiation will be a successful approach for new cell-based therapies for diabetes, such as those derived from stem cells.
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International Nuclear Information System (INIS)
Monopoli, A.; Forlani, A.; Bevilacqua, M.; Vago, T.; Norbiato, G.; Bertora, P.; Biglioli, P.; Alamanni, F.; Ongini, E.
1989-01-01
beta- And alpha 1-adrenoceptor antagonist properties of bufuralol, carvedilol, celiprolol, dilevalol, labetalol, and pindolol were investigated in human myocardium and mammary artery using binding techniques and functional studies. In myocardial membranes, beta-adrenoceptor antagonists showed monophasic competition isotherms for [125I]pindolol binding with high affinity (Ki from 1-100 nM), except for celiprolol which displayed a biphasic competition isotherm (pKi = 6.4 +/- 0.06 for beta 1- and 4.8 +/- 0.07 for beta 2-adrenoceptors). Drug interactions with alpha 1-adrenoceptors were evaluated in human mammary artery by [3H]prazosin binding and by measuring contractile responses to norepinephrine (NE). Labetalol and carvedilol showed a moderate affinity for alpha 1-adrenoceptors (pKi = 6.2 +/- 0.01 and 6.1 +/- 0.06, respectively), and inhibited NE-induced contractions (pA2 = 6.93 +/- 0.23 and 8.64 +/- 0.24, respectively). Dilevalol, bufuralol, and pindolol displayed weak effect both in binding (Ki in micromolar range) and functional experiments (pA2 = 5.98, 5.54, and 6.23, respectively). Celiprolol did not show antagonist properties up to 100 microM in functional studies, but displayed a slight affinity for alpha 1-adrenoceptors in binding studies. The data indicate that the vasodilating activity of these beta-adrenoceptor antagonists is caused in some instances by an alpha 1-adrenoceptor antagonism (labetalol, carvedilol), whereas for the others alternative mechanisms should be considered
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Energy Technology Data Exchange (ETDEWEB)
Zhou, Shuxia; Zhou, Hua; Walian, Peter J.; Jap, Bing K.
2005-04-06
, such as APP, CD44, DCC, ErbB4, E-cadherin, LRP, N-cadherin, Nectin-1, and Notch, within their transmembranous regions (2-11); therefore, in addition to its role in AD, {gamma}-secretase has been found to participate in other important biological functions, such as intracellular signaling. {gamma}-secretase processing of APP requires prior removal of a major fragment of the APP extracellular domain (sAPP{sub {beta}}) by {beta}-secretase to yield a membrane bound fragment (APP CTF{sub {beta}}). Subsequent cleavage of this membrane bound fragment by {gamma}-secretase results in the release of the Alzheimer's disease (AD) associated amyloid {beta}-peptides (12). The proteolytic activity of {gamma}-secretase is found not to be critically dependent on the specific sequence, but instead on the size of the extracellular domain (13); such sequence independent characteristics of the substrate are reminiscent of those of the 26S proteasome complex that cleaves substrates in a non-sequence specific manner. {gamma}-secretase is present in almost all animal species, vertebrates and invertebrates; it is expressed in many human organs and tissues.
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Clusters of conserved beta cell marker genes for assessment of beta cell phenotype
DEFF Research Database (Denmark)
Martens, Geert A; Jiang, Lei; Hellemans, Karine H
2011-01-01
The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture...
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The Yin and Yang of human beta defensins in health and disease
Directory of Open Access Journals (Sweden)
Aaron eWeinberg
2012-10-01
Full Text Available Rapidly evolving research examining the extended role of human beta-defensins (hBDs in chemoattraction, innate immune-mediated response and promotion of angiogenesis suggest that the collective effects of hBDs extend well beyond their antimicrobial mechanism(s. Indeed, the numerous basic cellular functions associated with hBDs demonstrate that these peptides have dual impact on health, as they may be advantageous under certain conditions, but potentially detrimental in others. The consequences of these functions are reflected in the overexpression of hBDs in diseases, such as psoriasis, and recently the association of hBDs with pro-tumoral signaling. The mechanisms regulating hBD response in health and disease are still being elucidated. Clearly the spectrum of function now attributed to hBD regulation identifies these molecules as important cellular regulators, whose appropriate expression is critical for proper immune surveillance; i.e., expression of hBDs in proximity to areas of cellular dysregulation may inadvertently exacerbate disease progression. Understanding the mechanism(s that regulate contextual signaling of hBDs is an important area of concentration in our laboratories. Using a combination of immunologic, biochemical and molecular biologic approaches, we have identified signaling pathways associated with hBD promotion of immune homeostasis and have begun to dissect the inappropriate role that beta-defensins may assume in disease.
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Beta cell adaptation in pregnancy
DEFF Research Database (Denmark)
Nielsen, Jens Høiriis
2016-01-01
Pregnancy is associated with a compensatory increase in beta cell mass. It is well established that somatolactogenic hormones contribute to the expansion both indirectly by their insulin antagonistic effects and directly by their mitogenic effects on the beta cells via receptors for prolactin...... and growth hormone expressed in rodent beta cells. However, the beta cell expansion in human pregnancy seems to occur by neogenesis of beta cells from putative progenitor cells rather than by proliferation of existing beta cells. Claes Hellerström has pioneered the research on beta cell growth for decades...... in the expansion of the beta cell mass in human pregnancy, and the relative roles of endocrine factors and nutrients....
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Shimojo, M; Ricketts, M L; Petrelli, M D; Moradi, P; Johnson, G D; Bradwell, A R; Hewison, M; Howie, A J; Stewart, P M
1997-03-01
11 beta-Hydroxysteroid dehydrogenase (11 beta HSI) is an enzyme complex responsible for the conversion of hormonally active cortisol to inactive cortisone; two isoforms of the enzyme have been cloned and characterized. Clinical observations from patients with the hypertensive syndrome apparent mineralocorticoid excess, recently explained on the basis of mutations in the human 11 beta HSD2 gene, suggest that it is the 11 beta HSD2 isoform that serves a vital role in dictating specificity upon the mineralocorticoid receptor (MR). We have raised a novel antibody in sheep against human 11 beta HSD2 using synthetic multiantigenic peptides and have examined the localization and subcellular distribution of 11 beta HSD2 in mineralocorticoid target tissues. The immunopurified antibody recognized a single band of approximately 44 kDa in placenta, trophoblast, and distal colon. In kidney tissue, two bands of approximately 44 and 48 kDa were consistently observed. No signal was seen in decidua, adrenal, or liver. Immunoperoxidase studies on the mineralocorticoid target tissues, kidney, colon, and parotid gland indicated positive staining in epithelial cells known to express the MR: respectively, renal collecting ducts, surface and crypt colonic epithelial cells, and parotid duct epithelial cells. No staining was seen in these tissues in other sites. The intracellular localization of 11 beta HSD2 in kidney and colon epithelial cells was addressed using confocal laser microscopy. Parallel measurements of 11 beta HSD2 and nuclear propidium iodide fluorescence on sections scanned through an optical section of approximately 0.1 micron indicated significant 11 beta HSD2 immunofluorescence in the nucleus. In human kidney, colon, and salivary gland, 11 beta HSD2 protects the MR from glucocorticoid excess in an autocrine fashion. Furthermore, within these tissues, 11 beta HSD2, which had been considered to be a microsomal enzyme, is also found in the nucleus, suggesting that the
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Bugnon, C; Bloch, B; Lenys, D; Fellmann, D
1979-06-27
In man, discrete neurons of the infundibular (arcuate) nucleus contain compounds that can be stained with anti-endorphin (alpha and beta), anti-ACTH, anti-MSH (alpha and beta) and anti-beta-LPH immune sera (I.S.). In the fetus, certain neurons stain with anti-beta-endorphin or anti((17--39)ACTH starting from the 11th week of fetal life. At the ultrastructural level, these neurons contain elementary granules that are immunoreactive with anti-beta-endorphin. In the adult, neurons immunoreactive with anti-beta-endorphin are found in the infundibular nucleus. Their axonal fibers terminate around blood vessels in the neurovascular zone and in the pituitary stalk, or establish contacts with non-immunoreactive perikarya of the infundibular nucleus. These neurons can be stained with anti(17--39)ACTH and anti-beta-endorphin I.S. The most reactive are also stained moderately with anti-alpha-MSH, anti-beta-MSH, anti-beta-LPH, anti-alpha-endorphin, or anti(1--24)ACTH I.S. These results indicate that, in man, compound(s) identical with or immunologically related to endorphins, beta-LPH, ACTH and MSH are secreted by certain hypothalamic neurons. These agents probably originate from a common precursor molecula similar to the so-called pro-opiocortin.
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New additions to the National Plant Germplasm System’s Beta collection: Southern Morocco expedition
The USDA Agricultural Research Service’s National Plant Germplasm System’s (NPGS) Beta collection is comprised of 2,541 accessions from 14 species. The largest number of accessions is from Beta vulgaris ssp. vulgaris, (domesticated beet crops – table, leaf (Swiss chard), fodder and, primarily, sugar...
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Energy Technology Data Exchange (ETDEWEB)
Goni, S.; Guerrero, A.; Puertas, F.; Hernandez, M. S.; Palacios, M.; Dolado, J. S.; Zhu, W.; Howind, T.
2011-07-01
The textural and mechanical characterization of C-S-H gels formed from the hydration of pure T1-C{sub 3}S, {beta}-C{sub 2}S and their blends are studied by Nitrogen sorption and nano indentation experiments. The surface area and nano porosity of C-S-H gels formed from the hydration of {beta}-C{sub 2}S and the 30-70 (T1-C{sub 3}S and {beta}-C{sub 2}S mixture) are higher than those from hydration of T1-C{sub 3}S, and 70-30, with the difference decreasing with hydration age. Such changes are well supported by findings of nano indentation study, which shows the greater relative volume of C-S-H phases with lower densities in the {beta}-C{sub 2}S and the 30-70 pastes. With the increase in hydration age, the relative volume of C-S-H phases with higher densities increased at the expenses of those with lower density. Important quantitative correlations were found among these textural characteristics and the mean chain length, determined from {sup 2}9Si magic-angle-spinning (MAS) NMR, of the C-S-H gels. (Author) 36 refs.
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Directory of Open Access Journals (Sweden)
Giribaldi Giuliana
2008-08-01
Full Text Available Abstract Background It has been shown previously that human monocytes fed with haemozoin (HZ or trophozoite-parasitized RBCs displayed increased matrix metalloproteinase-9 (MMP-9 enzyme activity and protein/mRNA expression and increased TNF production, and showed higher matrix invasion ability. The present study utilized the same experimental model to analyse the effect of phagocytosis of: HZ, delipidized HZ, beta-haematin (lipid-free synthetic HZ and trophozoites on production of IL-1beta and MMP-9 activity and expression. The second aim was to find out which component of HZ was responsible for the effects. Methods Native HZ freshly isolated from Plasmodium falciparum (Palo Alto strain, Mycoplasma-free, delipidized HZ, beta-haematin (lipid-free synthetic HZ, trophozoites and control meals such as opsonized non-parasitized RBCs and inert latex particles, were fed to human monocytes. The production of IL-1beta by differently fed monocytes, in presence or absence of specific MMP-9 inhibitor or anti-hIL-1beta antibodies, was quantified in supernatants by ELISA. Expression of IL-1beta was analysed by quantitative real-time RT-PCR. MMP-9 activity and protein expression were quantified by gelatin zymography and Western blotting. Results Monocytes fed with HZ or trophozoite-parasitized RBCs generated increased amounts of IL-1beta and enhanced enzyme activity (in cell supernatants and protein/mRNA expression (in cell lysates of monocyte MMP-9. The latter appears to be causally related to enhanced IL-1beta production, as enhancement of both expression and enzyme activity were abrogated by anti-hIL-1beta Abs. Upregulation of IL-1beta and MMP-9 were absent in monocytes fed with beta-haematin or delipidized HZ, indicating a role for HZ-attached or HZ-generated lipid components. 15-HETE (15(S,R-hydroxy-6,8,11,13-eicosatetraenoic acid a potent lipoperoxidation derivative generated by HZ from arachidonic acid via haem-catalysis was identified as one mediator
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Characterization of DNA polymerase. beta. mRNA: cell-cycle growth response in cultured human cells
Energy Technology Data Exchange (ETDEWEB)
Zmudzka, B Z; Fornace, A; Collins, J; Wilson, S H
1988-10-25
DNA polymerase ..beta.. (..beta..-polymerase) is a housekeeping enzyme involved in DNA repair in vertebrate cells. The authors used a cDNA probe to study abundance of ..beta..-polymerase mRNA in cultured human cells. The mRNA level in synchronized HeLa cells, representing different stages of the cell-cycle, varied only slightly. Contact inhibited fibroblasts AG-1522 contained the same level of mRNA as growing cells. The steady-state level of mRNA in fibroblasts is equivalent to 6 molecules per cell. The results indicate that the ..beta..-polymerase transcript is low abundance and is neither cell-cycles nor growth phase responsive.
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Energy Technology Data Exchange (ETDEWEB)
Diamant, M.; Henricks, P.A.J.; Nijkamp, F.P.; de Wied, D. (Univ. of Utrecht (Netherlands))
1989-01-01
In the present study, the immunomodulatory effect of {beta}-endorphin ({beta}-E) and shorter pro-opiomelancortin (POMC) fragments was evaluated by assessing their influence on respiratory burst in human polymorphonuclear leukocytes (PMN). The effect of the peptides on phorbol myristate acetate (PMA)-stimulated production of reactive oxygen metabolites was measured in a lucigenin-enhanced chemiluminescence (CL) assay. Both POMC peptides with opiate-like activity and their non-opioid derivatives were tested. With the exception of {alpha}-E, PMA-stimulated respiratory burst was suppressed by all POMC fragments tested. A U-shaped dose-response relation was observed. Doses lower than 10{sup {minus}17}M and higher than 10{sup {minus}8}M were without effect. {beta}-E and dT{beta}E both suppressed PMA-induced oxidative burst in human PMN at physiological concentrations. {gamma}-E and dT{gamma}E proved to be less potent inhibitors, reaching maximal effect at higher concentrations. DE{gamma}E exerted an even less pronounced but still significant suppressive effect at the concentration of 10{sup {minus}10}M. None of the endorphins tested was shown to affect resting oxidative metabolism in the PMN. The modulatory effects of the opioid peptides could not be blocked by the opioid antagonist naloxone.
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Lee, I Y; Nissen, S L; Rosazza, J P
1997-01-01
beta-Hydroxy-beta-methylbutyric acid (HMB) has been shown to increase strength and lean mass gains in humans undergoing resistance-exercise training. HMB is currently marketed as a calcium salt of HMB, and thus, environmentally sound and inexpensive methods of manufacture are being sought. This study investigates the microbial conversion of beta-methylbutyric acid (MBA) to HMB by cultures of Galactomyces reessii. Optimal concentrations of MBA were in the range of 5 to 20 g/liter for HMB produ...
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Characterization of GLP-1 effects on beta-cell function after meal ingestion in humans
DEFF Research Database (Denmark)
Ahrén, Bo; Holst, Jens Juul; Mari, Andrea
2003-01-01
OBJECTIVE: Glucagon-like peptide 1 (GLP-1) is an incretin that augments insulin secretion after meal intake and is developed for treatment of type 2 diabetes. As a novel therapeutic agent, characteristics of its beta-cell effects are important to establish. Previously, beta-cell effects of GLP-1...... have been characterized in humans during graded intravenous infusions of glucose, whereas its effects after more physiological stimuli, like meal intake, are not known. RESEARCH DESIGN AND METHODS: Eight women (aged 69 years, fasting glucose 3.7-10.3 mmol/l, BMI 22.4-43.9 kg/m(2)) who had fasted...... meal augments insulin secretion in humans by a dose...
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Human parvovirus B19 in patients with beta thalassemia major from Tehran, Iran.
Arabzadeh, Seyed Ali Mohammad; Alizadeh, Farideh; Tavakoli, Ahmad; Mollaei, Hamidreza; Bokharaei-Salim, Farah; Karimi, Gharib; Farahmand, Mohammad; Mortazavi, Helya Sadat; Monavari, Seyed Hamidreza
2017-03-01
Due to the tropism of human parvovirus B19 to erythroid progenitor cells, infection in patients with an underlying hemolytic disorder such as beta-thalassemia major leads to suppression of erythrocyte formation, referred to as transient aplasia crisis (TAC), which may be life-threatening. We investigated the prevalence of parvovirus B19 among patients with beta thalassemia major attending the Zafar Adult Thalassemia Clinic in Tehran, Iran. This cross-sectional study was performed to determine the presence of parvovirus B19 DNA in blood samples and parvovirus B19 genotypes in plasma samples of patients with thalassemia major. The population consisted of 150 patients with beta-thalassemia major who attended the Zafar clinic in Tehran. Specimens were studied using a real-time polymerase chain reaction assay. The prevalence of parvovirus B19 in our study population was 4%. Of 150 patients with thalassemia, six (4%) were positive for B19 DNA. There was no significant correlation between blood transfusion frequency and B19 DNA positivity. Finally, phylogenetic analysis of human parvovirus B19 revealed genotype I in these six patients. In this study, acute B19 infections were detected in patients with beta thalassemia major. Screening of such high-risk groups can considerably reduce the incidence and prevalence of B19 infection; thus, screening is required for epidemiologic surveillance and disease-prevention measures.
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Response of E. coli Bsub(s-1) to tritium-. beta. particles under aerated and anoxic conditions
Energy Technology Data Exchange (ETDEWEB)
Lunec, J; Cramp, W A [Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit
1978-12-01
E.coli Bsub(s-1) cells were exposed to acute doses of tritium-..beta.. particles by suspension in tritiated water for known lengths of time. The resulting survival rate was compared with that obtained for external irradiation with 7 MeV electrons. The o.e.r. measured for tritium-..beta..s was not significantly different from the value of 2.15 measured for 7 MeV electrons. The r.b.e. of the tritium ..beta..s relative to 7 MeV electrons was 1.21 in both air and nitrogen. These results were compared with existing data for low voltage electron irradiations and with track segment studies of the effect of varying LET on the radiosensitivity of E.coli Bsub(s-1).
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DEFF Research Database (Denmark)
Damstrup, L; Rygaard, K; Spang-Thomsen, M
1993-01-01
A panel of 21 small cell lung cancer cell (SCLC) lines were examined for the presence of Transforming growth factor beta receptors (TGF beta-r) and the expression of TGF beta mRNAs. By the radioreceptor assay we found high affinity receptors to be expressed in six cell lines. scatchard analysis......(r) = 65,000 and 90,000 and the betaglycan (type III) with M(r) = 280,000. Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines. Our results provide, for the first time, evidence that a large proportion of a broad panel of SCLC cell...... lines express TGF beta-receptors and also produce TGF beta mRNAs....
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Reeder, A Y; Joannou, G E
1995-12-01
In recent years several 15 beta-hydroxysteroids have emerged pathognomonic of adrenal disorders in human neonates of which 3 alpha,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (2) was the first to be identified in the urine of newborn infants affected with congenital adrenal hyperplasia. In this investigation we report the synthesis of the three remaining 3 xi,5 xi-isomers, namely 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (3), 3 beta,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (7) and 3 beta,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (8) for their definitive identification in pathological conditions in human neonates. 3 beta,15 beta-Diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (11), a product of chemical synthesis was converted to the isomeric 3 and 7, while conversion of 15 beta,17 alpha-dihydroxy-4-pregnen-3,20-dione (4), a product of microbiological transformation, resulted in the preparation of 8. In brief, selective acetate hydrolysis of 11 gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5-pregnen-20-one (12) which on catalytic hydrogenation gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5 alpha-pregnan-20-one (13) a common intermediate for the synthesis of the 3 beta(and alpha),5 alpha-isomers. Hydrolysis of the 15 beta-acetate gave 7, whereas oxidation with pyridinium chlorochromate gave 15 beta-acetoxy-17 alpha-hydroxy-5 alpha-pregnan-3,20-dione (14) which on reduction with L-Selectride and hydrolysis of the 15 beta-acetate gave 3. Finally, hydrogenation of 4 gave 15 beta, 17 alpha-dihydroxy-5 beta-pregnan-3,20-dione (10) which on reduction with L-Selectride gave 8.
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Energy Technology Data Exchange (ETDEWEB)
Han, Xiangzi [Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Department of Preventive Medicine, Yanbian University College of Medicine, Yanji (China); Ju, Ji-hyun [Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Shin, Incheol, E-mail: incheol@hanyang.ac.kr [Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)
2012-06-29
Highlights: Black-Right-Pointing-Pointer Novel S/T-P-S/T domains were identified in NICD. Black-Right-Pointing-Pointer Phosphorylation of NICD on the S/T-P-S/T domains induced nuclear localization. Black-Right-Pointing-Pointer GSK-3{beta} phosphorylated S and T residues in NICD S/T-P-S/T domains. -- Abstract: We identified two S/T-P-S/T domains (2122-2124, 2126-2128) inducing Notch intracellular domain (NICD) nuclear localization. The GFP-NICD (1963-2145) fusion protein deletion mutant without classical NLS was localized in the nucleus like the full length GFP-NICD. However, quadruple substitution mutant (T2122A T2124A S2126A T2128A) showed increased cytoplasmic localization. GSK-3{beta} enhanced nuclear localization and transcriptional activity of WT NICD but not of quadruple substitution mutant. In vitro kinase assays revealed that GSK-3{beta} phosphorylated S and T residues in NICD S/T-P-S/T domains. These results suggest that the novel S/T-P-S/T domain, phosphorylated by GSK-3{beta} is also involved in the nuclear localization of NICD as well as classical NLS.
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Energy Technology Data Exchange (ETDEWEB)
Park, Catherine C.; Park, Catherine C.; Zhang, Hui J.; Yao, Evelyn S.; Park, Chong J.; Bissell, Mina J.
2008-06-02
{beta}1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of {beta}1 integrin signaling. We showed previously that {beta}1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix (3D lrECM) cultures and in vivo. Here we asked whether AIIB2 could synergize with IR to modify Akt-mediated IR resistance. We used 3D lrECM cultures to test the optimal combination of AIIB2 with IR treatment of two breast cancer cell lines, MCF-7 and HMT3522-T4-2, as well as T4-2 myr-Akt breast cancer colonies or HMT3522-S-1, which form normal organotypic structures in 3D lrECM. Colonies were assayed for apoptosis and {beta}1 integrin/Akt signaling pathways were evaluated using western blot. In addition, mice bearing MCF-7 xenografts were used to validate the findings in 3D lrECM. We report that AIIB2 increased apoptosis optimally post-IR by down regulating Akt in breast cancer colonies in 3D lrECM. In vivo, addition of AIIB2 after IR significantly enhanced tumor growth inhibition and apoptosis compared to either treatment alone. Remarkably, the degree of tumor growth inhibition using AIIB2 plus 2 Gy radiation was similar to that of 8 Gy alone. We showed previously that AIIB2 had no discernible toxicity in mice; here, its addition allowed for a significant reduction in the IR dose that was necessary to achieve comparable growth inhibition and apoptosis in breast cancer xenografts in vivo.
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Cloning and characterization of human liver cytosolic beta-glycosidase
De Graaf, M; Van Veen, IC; Van Der Meulen-Muileman, IH; Gerritsen, WR; Pinedo, HM; Haisma, HJ
2001-01-01
Cytosolic beta -glucosidase (EC 3.2.1.21) from mammalian liver is a member of the family 1 glycoside hydrolases and is known for its ability to hydrolyse a range of beta -D-glycosides. including beta -D-glucoside acid beta -D-galactoside. We therefore refer to this enzyme as cytosolic beta
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Classic and molecular cytogenetic analysis regarding human reactivity to beta radiation
International Nuclear Information System (INIS)
Usurelu Daniela; Radu Irina; Gavrila Lucian; Cimponeriu Danut; Apostol Pompilia; Ahmadi Elham
2007-01-01
Complete text of publication follows. One of the most important mutagen agents in developing different types of cancer is the action of ionizing radiation. The main events induced by irradiation are: chromosome breakage, chromosome rearrangements and genomic instability. The chromosomal aberrations are very useful biomarkers as intermediate end points in evaluating harmful biological effects of ionizing radiation. So, the main objectives of this work were: the study of human genome reactivity to beta radiation by classic microscopy; the study of the integrity/modification of the telomeres after irradiation and the analysis of the amplification of the RNA telomerase compound by FISH technique. Irradiations were performed at Electron Accelerators Laboratory, National Institute for Laser, Plasma and Radiation Physics, Magurele-Bucharest, Romania. The samples were irradiated using an ALIN 10 linear electron accelerator. ALIN 10 is a travelling wave type linac operating at 2.998 GHz, 6.5 MeV mean energy, with a 0.1 mm Al foil exit window. Improved Fricke, ferrous sulphate, cupric sulphate and sulphuric acid in triple distilled water dosimetry system has been used to perform preliminary dose measurements. The conventional Hungerford method on short-term cultures for 72 hrs was adapted for human chromosome investigation. The peripheral blood was collected from aged 27, healthy, non-smoker donor. The doses used to irradiate human blood cultures were: 4, 6, 8 and 10 Gy. The slides for optic microscopy were prepared by air-drying and stained with a 10% Giemsa solution. For FISH technique was used Chromosome In Situ Hybridization Kit. The probes were: one satellite probe - for revealing the telomere and the second one for the RNA telomerase compound. A large spectrum of chromosomal rearrangements was induced by beta irradiation in humans in vitro: complex chromosomal interchange involving at least two nonhomologous chromosomes, double minutes (DM), acentric fragments
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DEFF Research Database (Denmark)
Pedersen, L O; Hansen, A S; Olsen, A C
1994-01-01
been generated recently and this paper reports on a similar assay for the interaction between beta 2m and class I. As a model system human beta 2m binding to mouse class I was used. The assay is strictly biochemical using purified reagents which interact in solution and complex formation is determined...... by size separation. It is specific and highly sensitive. The observed affinity of the interaction, KD, is close to 0.4 nM. The rate of association at 37 degrees C is very fast (the ka is around 5 x 10(4)/M/s) whereas the dissociation is slow (the kd is around 8 x 10(-6)/s); the ratio of dissociation...
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Energy Technology Data Exchange (ETDEWEB)
Woo, Yeon I; Park, Bong Joo; Kim, Hye-Lee; Lee, Mi Hee; Kim, Jungsung; Park, Jong-Chul [Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yang, Young-Il [Department of Pathology, School of Medicine, Paik Institute for Clinical Research, Inje University, 633-165 Gae-dong, Busan-jin-gu, Busan 614-735 (Korea, Republic of); Kim, Jung Koo [Department of Biomedical Engineering, College of Biomedical Science and Engineering, Inje University, Kimhae 621-749 (Korea, Republic of); Tsubaki, Kazufumi [R and D division, Asahi Denka Co. Ltd, 7-2-35 Higashi-ogu, Arakawa-ku, Tokyo 116-8554 (Japan); Han, Dong-Wook, E-mail: parkjc@yuhs.a [Department of Nanomedical Engineering, College of Nanoscience and Nanotechnology, Pusan National University, geumjeong-gu, Busan 609-735 (Korea, Republic of)
2010-08-01
In this study, we investigated the possible roles of (1,3)-(1,6)-{beta}-d-glucan ({beta}-glucan) and porous electrospun poly-lactide-co-glycolide (PLGA) membranes containing {beta}-glucan for skin wound healing, especially their effect on adult human dermal fibroblast (aHDF) and adipose tissue-derived stem cell (ADSC) activation, proliferation, migration, collagen gel contraction and biological safety tests of the prepared membrane. This study demonstrated that {beta}-glucan and porous PLGA membranes containing {beta}-glucan have enhanced the cellular responses, proliferation and migration, of aHDFs and ADSCs and the result of a collagen gel contraction assay also revealed that collagen gels contract strongly after 4 h post-gelation incubation with {beta}-glucan. Furthermore, we confirmed that porous PLGA membranes containing {beta}-glucan are biologically safe for wound healing study. These results indicate that the porous PLGA membranes containing {beta}-glucan interacted favorably with the membrane and the topical administration of {beta}-glucan was useful in promoting wound healing. Therefore, our study suggests that {beta}-glucan and porous PLGA membranes containing {beta}-glucan may be useful as a material for enhancing wound healing.
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DEFF Research Database (Denmark)
Hokland, M; Heron, I; Berg, K
1982-01-01
Normal human peripheral blood lymphocytes were incubated in the presence of different concentrations of interferon for various incubation periods. Subsequently, the amount of beta 2-Microglobulin and HLA-A, B and C surface antigens was estimated by means of quantitative immunofluorescence (flow...... cytofluorometry) and by a radioimmunoassay for beta 2-Microglobulin. It was found that the amounts of these MHC antigens increased in a dose and time-dependent way after interferon treatment. Furthermore, the influence of different temperatures on this IFN-induced increase in beta 2-Microglobulin was gradually...
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Cortisone Dissociates the Shaker Family K Channels from their Beta Subunit
Energy Technology Data Exchange (ETDEWEB)
Pan, Y.; Weng, J; Kabaleeswaran, V; Li, H; Cao, Y; Bholse, R; Zhou, M
2008-01-01
The Shaker family voltage-dependent potassium channels (Kv1) are expressed in a wide variety of cells and are essential for cellular excitability. In humans, loss-of-function mutations of Kv1 channels lead to hyperexcitability and are directly linked to episodic ataxia and atrial fibrillation. All Kv1 channels assemble with {Beta} subunits (Kv{Beta}s), and certain Kv{Beta}s, for example Kv{Beta}1, have an N-terminal segment that closes the channel by the N-type inactivation mechanism. In principle, dissociation of Kv{Beta}1, although never reported, should eliminate inactivation and thus potentiate Kv1 current. We found that cortisone increases rat Kv1 channel activity by binding to Kv{Beta}1. A crystal structure of the K{Beta}v-cortisone complex was solved to 1.82-{angstrom}resolution and revealed novel cortisone binding sites. Further studies demonstrated that cortisone promotes dissociation of Kv{Beta}. The new mode of channel modulation may be explored by native or synthetic ligands to fine-tune cellular excitability.
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Beta-lipotropin is the major component of the plasma opioid response to surgical stress in humans
Energy Technology Data Exchange (ETDEWEB)
Porro, C.A.; Facchinetti, F.; Bertellini, E.; Petraglia, F.; Stacca, R.; Barbieri, G.C.; Genazzani, A.R.
1987-12-07
There is growing experimental evidence that beta-endorphin immunoreactivity is raised by surgical stress in patients undergoing general anesthesia. As the assay methods employed to date did not allow to fully discriminate between beta-endorphin and its immediate precursor, beta-lipotropin, the authors have investigated in the present study plasma levels of these two peptides by separating them by chromatography on plasma extracts prior to radioimmunoassay. Beta-lipotropin, but not beta-endorphin, plasma levels were found to be significantly elevated during surgery in the general anesthesia group, while no change was found in either peptide concentration in the spinal one. Cortisol plasma levels also increased significantly 90 minutes after the beginning of surgery. Although the sampling time they adopted may have prevented them from detecting an early peak of beta-endorphin during the first 30 minutes of surgery, the major component of the pituitary opioid response to surgical stress appears to be related to beta-lipotropin. This is in agreement with results of experimental work on various kinds of stress in animals and humans and seems to rule out a role for plasma beta-endorphin in post-operative analgesia. 38 references, 1 figure, 1 table.
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Energy Technology Data Exchange (ETDEWEB)
Gillings, N.M.; Gee, A.D. [PET Centre, Aarhus University Hospital, Aarhus C (Denmark); Inoue, O. [School of Allied Health Sciences, Osaka University Medical School, Osaka (Japan)
1999-04-01
In an attempt to elucidate the contribution of the extent of nitrogen protonation on the in vivo binding of methamphetamine in the brain, the enantiomers of [N-methyl-{sup 11}C]{beta},{beta}-difluoroamphetamine (4) were prepared for use in positron emission tomography (PET) studies. Thus, the enantiomers of {beta},{beta}-difluoroamphetamine were prepared from trans-{beta}-methylstyrene, via bromination, conversion into the azirine, fluorination and resolution as the tartrate salts. (R)- and (S)-{beta},{beta}-difluoroamphetamine (3) were then each labelled with carbon-11 (t{sub 1/2}=20.4 min) by N-methylation of the corresponding homochiral {beta},{beta}-difluoroamphetamine with [{sup 11}C]methyl iodide. The labelled products were each synthesised, purified and formulated in 35 min, starting from [{sup 11}C]carbon dioxide in 15-16% decay-corrected radiochemical yield, with a radiochemical purity of >99% and specific radioactivity of 50-150 GBq {mu}mol{sup -1} at end of synthesis.
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Effects of transforming growth factor-beta on long-term human cord blood monocyte cultures
International Nuclear Information System (INIS)
Orcel, P.; Bielakoff, J.; De Vernejoul, M.C.
1990-01-01
Transforming growth factor-beta (TGF-beta) modulates growth and differentiation in many cell types and is abundant in bone matrix. We recently showed that human cord blood monocytes cultured in the presence of 1,25(OH)2D3 acquire some features of osteoclast precursors. Since TGF-beta has been shown to influence bone resorption in organ culture, we have studied the effect of TGF-beta (1-1,000 pg/ml) on cord blood monocyte cultures. These cells were cultured on plastic substrate during 3 weeks in the presence of 20% horse serum and 10(-9) M 1,25(OH)2D3. TGF-beta, from a concentration of 10 pg/ml in the culture medium, decreased in a dose dependent manner the formation of multinucleated cells. At a concentration of TGF-beta of 1 ng/ml, the multinucleated cells were reduced to 2.1% +/- 0.3%, compared to 19.3% +/- 1.5% in control cultures. TGF-beta inhibited in a dose-dependent manner the proliferation of cord blood monocytes as assessed by 3H-thymidine incorporation at 7 and 14 days of culture. The fusion index was also decreased by 3 weeks of treatment with TGF-beta. Indomethacin did not reverse the inhibitory effects of TGF-beta. The expression of the osteoclastic phenotype was assessed using two different antibodies: 23C6, a monoclonal antibody directed against the vitronectin receptor, which is highly expressed by osteoclasts but not by adult monocytes, and an antibody to HLA-DR, which is not present on osteoclast. TGF-beta decreased the expression of HLA-DR and increased in a dose-dependent manner the proportion of 23C6-labeled cells; these results suggest that TGF-beta could modulate a differentiation effect to the osteoclastic phenotype. However, when cord blood monocytes were cultured on devitalized rat calvariae prelabeled with 45Ca, TGF-beta did not induce any 45Ca release from bone cultured with monocytes
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DEFF Research Database (Denmark)
Frazzini, Andrea; Heje Pedersen, Lasse
We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model’s five central predictions: (1) Since constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for U...... of the BAB factor is low; (4) Increased funding liquidity risk compresses betas toward one; (5) More constrained investors hold riskier assets........S. equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures; (2) A betting-against-beta (BAB) factor, which is long leveraged low beta assets and short high-beta assets, produces significant positive risk-adjusted returns; (3) When funding constraints tighten, the return...
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Measurement of the CP-Violating Phase beta_s in B0s -> J/Psi Phi Decays with the CDF II Detector
Energy Technology Data Exchange (ETDEWEB)
Aaltonen, T. [Helsinki Institute of Physics (Finland); et al.
2012-04-01
We present a measurement of the \\CP-violating parameter \\betas using approximately 6500 $\\BsJpsiPhi$ decays reconstructed with the CDF\\,II detector in a sample of $p\\bar p$ collisions at $\\sqrt{s}=1.96$ TeV corresponding to 5.2 fb$^{-1}$ integrated luminosity produced by the Tevatron Collider at Fermilab. We find the \\CP-violating phase to be within the range $\\betas \\in [0.02, 0.52] \\cup [1.08, 1.55]$ at 68% confidence level where the coverage property of the quoted interval is guaranteed using a frequentist statistical analysis. This result is in agreement with the standard model expectation at the level of about one Gaussian standard deviation. We consider the inclusion of a potential $S$-wave contribution to the $\\Bs\\to J/\\psi K^+K^-$ final state which is found to be negligible over the mass interval $1.009 < m(K^+K^-)<1.028 \\gevcc$. Assuming the standard model prediction for the \\CP-violating phase \\betas, we find the \\Bs decay width difference to be $\\deltaG = 0.075 \\pm 0.035\\,\\textrm{(stat)} \\pm 0.006\\,\\textrm{(syst)} \\ps$. We also present the most precise measurements of the \\Bs mean lifetime $\\tau(\\Bs) = 1.529 \\pm 0.025\\,\\textrm{(stat)} \\pm 0.012\\,\\textrm{(syst)}$ ps, the polarization fractions $|A_0(0)|^2 = 0.524 \\pm 0.013\\,\\textrm{(stat)} \\pm 0.015\\,\\textrm{(syst)}$ and $|A_{\\parallel}(0)|^2 = 0.231 \\pm 0.014\\,\\textrm{(stat)} \\pm 0.015\\,\\textrm{(syst)}$, as well as the strong phase $\\delta_{\\perp}= 2.95 \\pm 0.64\\,\\textrm{(stat)} \\pm 0.07\\,\\textrm{(syst)} \\textrm{rad}$. In addition, we report an alternative Bayesian analysis that gives results consistent with the frequentist approach.
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DEFF Research Database (Denmark)
Boldyreff, B; James, P; Staudenmann, W
1993-01-01
Human casein kinase-2 (CK-2) subunits alpha and beta were bicistronically expressed in bacteria. The recombinant holoenzyme shared all investigated properties with the native CK-2 from mammalian sources (rat liver, Krebs II mouse ascites tumour cells). Contrary to recombinant human CK-2 produced...
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Directory of Open Access Journals (Sweden)
Julio A. da Luz
2006-01-01
Full Text Available Hemoglobinopathies are the most common monogenic disorders worldwide; however, they have never been systematically studied from a genetic perspective in Uruguay. In this study, we determined the frequencies of hemoglobin variants in Afro-Uruguayans. A sample of 52 healthy unrelated Afro-Uruguayans from the northern (N = 28 and southern (N = 24 regions of the country was analyzed. Eight individuals (15.4% were heterozygous for -alpha3,7thalassemia; seven of them (29.2% were originally from the southern region, whereas one of them (3.6% was from the northern region; the differences between both regions were statistically significant (p = 0.016 +/-0.003. The only structural mutation detected was betaS, which is typical of African populations. Four individuals (10% were heterozygous for betaS, three of them (13.6% from the South, and one (5.6% from the North. The betaS haplotypes were analyzed in eight individuals: two were homozygous betaS/betaS, two were heterozygous betaS/betathal, and four were heterozygous betaS/betaª. This haplotype distribution (60% Bantu, 20% Benin, and 20% Bantu A2 is in agreement with historical records reporting a predominantly Bantu origin for the enslaved Africans brought to Uruguay. Even though this is a preliminary study, due to the small sample size, our results are suggestive of a relatively high incidence of hemoglobinopathies in the Afro-Uruguayan population.
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Characterization of stimulus-secretion coupling in the human pancreatic EndoC-βH1 beta cell line.
Directory of Open Access Journals (Sweden)
Lotta E Andersson
Full Text Available Studies on beta cell metabolism are often conducted in rodent beta cell lines due to the lack of stable human beta cell lines. Recently, a human cell line, EndoC-βH1, was generated. Here we investigate stimulus-secretion coupling in this cell line, and compare it with that in the rat beta cell line, INS-1 832/13, and human islets.Cells were exposed to glucose and pyruvate. Insulin secretion and content (radioimmunoassay, gene expression (Gene Chip array, metabolite levels (GC/MS, respiration (Seahorse XF24 Extracellular Flux Analyzer, glucose utilization (radiometric, lactate release (enzymatic colorimetric, ATP levels (enzymatic bioluminescence and plasma membrane potential and cytoplasmic Ca2+ responses (microfluorometry were measured. Metabolite levels, respiration and insulin secretion were examined in human islets.Glucose increased insulin release, glucose utilization, raised ATP production and respiratory rates in both lines, and pyruvate increased insulin secretion and respiration. EndoC-βH1 cells exhibited higher insulin secretion, while plasma membrane depolarization was attenuated, and neither glucose nor pyruvate induced oscillations in intracellular calcium concentration or plasma membrane potential. Metabolite profiling revealed that glycolytic and TCA-cycle intermediate levels increased in response to glucose in both cell lines, but responses were weaker in EndoC-βH1 cells, similar to those observed in human islets. Respiration in EndoC-βH1 cells was more similar to that in human islets than in INS-1 832/13 cells.Functions associated with early stimulus-secretion coupling, with the exception of plasma membrane potential and Ca2+ oscillations, were similar in the two cell lines; insulin secretion, respiration and metabolite responses were similar in EndoC-βH1 cells and human islets. While both cell lines are suitable in vitro models, with the caveat of replicating key findings in isolated islets, EndoC-βH1 cells have the
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Covarelli, R
2003-01-01
The present model-independent measurements of the branching fractions BETA(B sup 0 -> D* sub s sup + D* sup -) and BETA(D sub s sup + -> phi pi sup +) based on 19.3 fb sup - sup 1 of data collected by the BABAR detector at the PEP-II e sup + e sup - B Factory. Neutral B-meson decays to the D* sub s sup + D* sup - final state are selected with a partial reconstruction of the D* sub s sup +; that is, only the D* sup - and the soft photon from the decay D* sub s sup + -> D sub s sup +gamma are reconstructed. The branching fraction BETA(B sup 0 -> D* sub s sup + D* sup -) is extracted from these event yields, while BETA(D sub s sup + -> phi pi sup +) is determined by combining this result with a previous measurement of the product BETA(B sup 0 -> D* sub s sup + D* sup -) x BETA(D sub s sup + -> phi pi sup +) with partial reconstruction of the D* sup -. They obtain the following preliminary results: BETA(B sup 0 -> D* sub s sup + D* sup -) = (1.50 +- 0.16 +- 0.12)%, BETA(D sub s sup + -> phi pi sup +) = (4.7 +- 0....
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Honke, K; Tsuda, M; Koyota, S; Wada, Y; Iida-Tanaka, N; Ishizuka, I; Nakayama, J; Taniguchi, N
2001-01-05
A novel sulfotransferase gene (designated GP3ST) was identified on human chromosome 2q37.3 based on its similarity to the cerebroside 3'-sulfotransferase (CST) cDNA (Honke, K., Tsuda, M., Hirahara, Y., Ishii, A., Makita, A., and Wada, Y. (1997) J. Biol. Chem. 272, 4864-4868). A full-length cDNA was obtained by reverse transcription-polymerase chain reaction and 5'- and 3'-rapid amplification of cDNA ends analyses of human colon mRNA. The isolated cDNA clone predicts that the protein is a type II transmembrane protein composed of 398 amino acid residues. The amino acid sequence indicates 33% identity to the human CST sequence. A recombinant protein that is expressed in COS-1 cells showed no CST activity, but did show sulfotransferase activities toward oligosaccharides containing nonreducing beta-galactosides such as N-acetyllactosamine, lactose, lacto-N-tetraose (Lc4), lacto-N-neotetraose (nLc4), and Gal beta 1-3GalNAc alpha-benzyl (O-glycan core 1 oligosaccharide). To characterize the cloned sulfotransferase, a sulfotransferase assay method was developed that uses pyridylaminated (PA) Lc4 and nLc4 as enzyme substrates. The enzyme product using PA-Lc4 as an acceptor was identified as HSO(3)-3Gal beta 1-3GlcNAc beta 1-3Gal beta 1- 4Glc-PA by two-dimensional (1)H NMR. Kinetics studies suggested that GP3ST is able to act on both type 1 (Gal beta 1-3GlcNAc-R) and type 2 (Gal beta 1-4GlcNAc-R) chains with a similar efficiency. In situ hybridization demonstrated that the GP3ST gene is expressed in epithelial cells lining the lower to middle layer of the crypts in colonic mucosa, hepatocytes surrounding the central vein of the liver, extravillous cytotrophoblasts in the basal plate and septum of the placenta, renal tubules of the kidney, and neuronal cells of the cerebral cortex. The results of this study indicate the existence of a novel beta-Gal-3'-sulfotransferase gene family.
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Plasma beta-endorphin, beta-lipotropin and corticotropin in polycystic ovarian disease.
Laatikainen, T; Salminen, K; Virtanen, T; Apter, D
1987-04-01
In 9 women with polycystic ovarian disease (PCOD) and in 11 control subjects at the follicular phase of the normal cycle, blood samples were collected at 15-min intervals during a 2 h period of bed rest for the assay of beta-endorphin, beta-lipotropin, corticotropin, cortisol and prolactin. During the study period, the plasma levels of these hormones decreased more significantly in the PCOD than in the control group, suggesting that the PCOD patients had a more significant stress response to the puncture of the vein than the control subjects. The second hour of the study period was considered to represent resting levels of hormones. The mean resting levels (+/- S.E.) of the hormones between the PCOD and control groups, respectively, were as follows: beta-E, 2.0 +/- 0.4 vs. 1.1 +/- 0.1 pmol/l, p less than 0.05; beta-LPH, 3.4 +/- 0.6 vs. 2.1 +/- 0.5 pmol/l, N.S.; corticotropin, 2.0 +/- 0.3 vs. 1.1 +/- 0.5 pmol/l, p less than 0.05; cortisol, 176 +/- 24 vs. 128 +/- 16, N.S.; and prolactin; 3.9 +/- 0.6 vs. 5.6 +/- 1.2 ng/ml, N.S. These results confirm the previous findings on increased circulating levels of beta-E in PCOD. A concomitant increase of the plasma level of corticotropin suggests that the basal secretion of both beta-E and corticotropin from the anterior pituitary gland is increased in women with PCOD.
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Ghosal, Abhisek; Sekar, Thillai V.
2014-01-01
Biotin is essential for the normal function of pancreatic beta cells. These cells obtain biotin from their surroundings via transport across their cell membrane. Little is known about the uptake mechanism involved, how it is regulated, and how it is affected by internal and external factors. We addressed these issues using the mouse-derived pancreatic beta-TC-6 cells and freshly isolated mouse and human primary pancreatic beta cells as models. The results showed biotin uptake by pancreatic beta-TC-6 cells occurs via a Na+-dependent, carrier-mediated process, that is sensitive to desthiobiotin, as well as to pantothenic acid and lipoate; the process is also saturable as a function of concentration (apparent Km = 22.24 ± 5.5 μM). These cells express the sodium-dependent multivitamin transporter (SMVT), whose knockdown (with doxycycline-inducible shRNA) led to a sever inhibition in biotin uptake. Similarly, uptake of biotin by mouse and human primary pancreatic islets is Na+-dependent and carrier-mediated, and both cell types express SMVT. Biotin uptake by pancreatic beta-TC-6 cells is also adaptively regulated (via transcriptional mechanism) by extracellular substrate level. Chronic treatment of pancreatic beta-TC-6 cells with bacterial lipopolysaccharides (LPS) leads to inhibition in biotin uptake. This inhibition is mediated via a Toll-Like receptor 4-mediated process and involves a decrease in membrane expression of SMVT. These findings show, for the first time, that pancreatic beta cells/islets take up biotin via a specific and regulated carrier-mediated process, and that the process is sensitive to the effect of LPS. PMID:24904078
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International Nuclear Information System (INIS)
Chavaudra, N.; Halimi, M.; Parmentier, C.; Gaillard, N.; Grinfeld, S.; Malaise, E.P.
1989-01-01
The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors
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Energy Technology Data Exchange (ETDEWEB)
Chavaudra, N.; Halimi, M.; Parmentier, C.; Gaillard, N.; Grinfeld, S.; Malaise, E.P.
1989-05-01
The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors.
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DEFF Research Database (Denmark)
Lambert, J-C; Ferreira, S; Gussekloo, J
2007-01-01
independent populations. Moreover, we detected a significant association of this SNP with increased risk of developing dementia or Alzheimer's disease (AD) in six independent populations, especially in women and in the oldest. Furthermore, we characterised a new primate-specific exon within intron 2 (the...... corresponding mRNA isoform was called S100beta2). S100beta2 expression was increased in AD brain compared with controls, and the rs2300403 SNP was associated with elevated levels of S100beta2 mRNA in AD brains, especially in women. Therefore, this genetic variant in S100beta increases the risk of low cognitive...
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Synthetic alleles at position 121 define a functional domain of human interleukin-1 beta.
Ambrosetti, D C; Palla, E; Mirtella, A; Galeotti, C; Solito, E; Navarra, P; Parente, L; Melli, M
1996-06-01
The non-conservative substitution of the tyrosine residue at position 121 of human interleukin-1 beta (IL-1 beta) generates protein mutants showing strong reduction of the capacity to induce (a) prostaglandin E2 (PGE2) release from fibroblasts and smooth muscle cells, (b) murine T-cells proliferation and (c) activation of interleukin-6 (IL-6) gene expression. It is generally accepted that these functions are mediated by the type-I interleukin-1 receptor (IL-1RI). However, the mutant proteins maintain the binding affinity to the types-I and II IL-1 receptors, which is the same as the control IL-1 beta, suggesting that this amino acid substitution does not alter the structure of the molecule, except locally. Thus we have identified a new functional site of IL-1 beta different from the known receptor binding region, responsible for fundamental IL-1 beta functions. Moreover, we show that the same mutants maintain at least two hypothalamic functions, that is, the in vitro short-term PGE2 release from rat hypothalamus and the induction of fever in rabbits. This result suggests that there is yet another site of the molecule responsible for the hypothalamic functions, implying that multiple active sites on the IL-1 beta molecule, possibly binding to more than one receptor chain, trigger different signals.
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ALK and TGF-Beta Resistance in Breast Cancer
2017-10-01
Award Number: W81XWH‐15‐1‐0650 TITLE: ALK and TGF-Beta Resistance in Breast Cancer PRINCIPAL INVESTIGATOR: Xin-Hua Feng CONTRACTING...and TGF-Beta Resistance in Breast Cancer 5b. GRANT NUMBER W81XWH‐15‐1‐0650 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Xin-Hua Feng...response is a hallmark in human cancer . However, the mechanisms underlying TGF- resistance in breast cancer have not been elucidated. Anaplastic
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Neuhaus, Jochen; Heinrich, Marco; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe
2009-02-01
Human detrusor smooth muscle cells (hBSMCs) are coupled by connexin 43 (Cx43)-positive gap junctions to form functional syncytia. Gap junctional communication likely is necessary for synchronised detrusor contractions and is supposed to be altered in voiding disturbances. Other authors have shown that the pleiotropic cytokine TGF-beta1 upregulates Cx43 expression in human aortic smooth muscle cells. In this study, we examined the TGF-beta1 effects on Cx43 expression in cultured hBSMCs. hBSMC cultures, established from patients undergoing cystectomy, were treated with recombinant human TGF-beta1. Cx43 expression was then examined by Western blotting, real-time PCR, and immunocytochemistry. Dye-injection experiments were used to study the size of functional syncytia. Dye-coupling experiments revealed stable formation of functional syncytia in passaged cell cultures (P1-P4). Stimulation with TGF-beta1 led to significant reduction of Cx43 immunoreactivity and coupling. Cx43 protein expression was significantly downregulated and Cx43 mRNA was only 30% of the control level. Interestingly, low phosphorylation species of Cx43 were particularly affected. Our experiments demonstrated a significant down regulation of connexin 43 by TGF-beta1 in cultured hBSMCs. These findings support the view that TGF-beta1 is involved in the pathophysiology of urinary bladder dysfunction.
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Effect of beta-agonists on LAM progression and treatment.
Le, Kang; Steagall, Wendy K; Stylianou, Mario; Pacheco-Rodriguez, Gustavo; Darling, Thomas N; Vaughan, Martha; Moss, Joel
2018-01-30
Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM. We observed stabilization of forced expiratory volume in 1 s over time in patients receiving sirolimus and long-acting beta-agonists with short-acting rescue inhalers compared with patients receiving only sirolimus. Because beta-agonists increase cAMP and PKA activity, we investigated effects of PKA activation on the mTOR pathway. Human skin TSC2 +/- fibroblasts or LAM lung cells incubated short-term with isoproterenol (beta-agonist) showed a sirolimus-independent increase in phosphorylation of S6, a downstream effector of the mTOR pathway, and increased cell growth. Cells incubated long-term with isoproterenol, which may lead to beta-adrenergic receptor desensitization, did not show increased S6 phosphorylation. Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus, activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an effect abrogated by beta-agonist-driven receptor desensitization. In agreement, retrospective clinical data from patients with LAM suggested that a combination of bronchodilators in conjunction with sirolimus may be preferable to sirolimus alone for stabilization of pulmonary function.
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Directory of Open Access Journals (Sweden)
Adela Banciu
2018-05-01
Full Text Available Voltage-gated calcium channels and estrogen receptors are essential players in uterine physiology, and their association with different calcium signaling pathways contributes to healthy and pathological conditions of the uterine myometrium. Among the properties of the various cell subtypes present in human uterine myometrium, there is increasing evidence that calcium oscillations in telocytes (TCs contribute to contractile activity and pregnancy. Our study aimed to evaluate the effects of beta-estradiol on voltage-gated calcium channels and estrogen receptors in TCs from human uterine myometrium and to understand their role in pregnancy. For this purpose, we employed patch-clamp recordings, ratiometric Fura-2-based calcium imaging analysis, and qRT-PCR techniques for the analysis of cultured human myometrial TCs derived from pregnant and non-pregnant uterine samples. In human myometrial TCs from both non-pregnant and pregnant uterus, we evidenced by qRT-PCR the presence of genes encoding for voltage-gated calcium channels (Cav3.1, Ca3.2, Cav3.3, Cav2.1, estrogen receptors (ESR1, ESR2, GPR30, and nuclear receptor coactivator 3 (NCOA3. Pregnancy significantly upregulated Cav3.1 and downregulated Cav3.2, Cav3.3, ESR1, ESR2, and NCOA3, compared to the non-pregnant condition. Beta-estradiol treatment (24 h, 10, 100, 1000 nM downregulated Cav3.2, Cav3.3, Cav1.2, ESR1, ESR2, GRP30, and NCOA3 in TCs from human pregnant uterine myometrium. We also confirmed the functional expression of voltage-gated calcium channels by patch-clamp recordings and calcium imaging analysis of TCs from pregnant human myometrium by perfusing with BAY K8644, which induced calcium influx through these channels. Additionally, we demonstrated that beta-estradiol (1000 nM antagonized the effect of BAY K8644 (2.5 or 5 µM in the same preparations. In conclusion, we evidenced the presence of voltage-gated calcium channels and estrogen receptors in TCs from non-pregnant and pregnant
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Banciu, Adela; Banciu, Daniel Dumitru; Mustaciosu, Cosmin Catalin; Radu, Mihai; Cretoiu, Dragos; Xiao, Junjie; Cretoiu, Sanda Maria; Suciu, Nicolae; Radu, Beatrice Mihaela
2018-05-09
Voltage-gated calcium channels and estrogen receptors are essential players in uterine physiology, and their association with different calcium signaling pathways contributes to healthy and pathological conditions of the uterine myometrium. Among the properties of the various cell subtypes present in human uterine myometrium, there is increasing evidence that calcium oscillations in telocytes (TCs) contribute to contractile activity and pregnancy. Our study aimed to evaluate the effects of beta-estradiol on voltage-gated calcium channels and estrogen receptors in TCs from human uterine myometrium and to understand their role in pregnancy. For this purpose, we employed patch-clamp recordings, ratiometric Fura-2-based calcium imaging analysis, and qRT-PCR techniques for the analysis of cultured human myometrial TCs derived from pregnant and non-pregnant uterine samples. In human myometrial TCs from both non-pregnant and pregnant uterus, we evidenced by qRT-PCR the presence of genes encoding for voltage-gated calcium channels (Cav3.1, Ca3.2, Cav3.3, Cav2.1), estrogen receptors (ESR1, ESR2, GPR30), and nuclear receptor coactivator 3 (NCOA3). Pregnancy significantly upregulated Cav3.1 and downregulated Cav3.2, Cav3.3, ESR1, ESR2, and NCOA3, compared to the non-pregnant condition. Beta-estradiol treatment (24 h, 10, 100, 1000 nM) downregulated Cav3.2, Cav3.3, Cav1.2, ESR1, ESR2, GRP30, and NCOA3 in TCs from human pregnant uterine myometrium. We also confirmed the functional expression of voltage-gated calcium channels by patch-clamp recordings and calcium imaging analysis of TCs from pregnant human myometrium by perfusing with BAY K8644, which induced calcium influx through these channels. Additionally, we demonstrated that beta-estradiol (1000 nM) antagonized the effect of BAY K8644 (2.5 or 5 µM) in the same preparations. In conclusion, we evidenced the presence of voltage-gated calcium channels and estrogen receptors in TCs from non-pregnant and pregnant human uterine
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Directory of Open Access Journals (Sweden)
Bhise NS
2013-12-01
Full Text Available Nupura S Bhise,1,* Karl J Wahlin,2,* Donald J Zack,2–4 Jordan J Green1,21Department of Biomedical Engineering, Translational Tissue Engineering Center, and Institute for Nanobiotechnology, 2Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, 3Solomon H Snyder Department of Neuroscience, Department of Molecular Biology and Genetics, and Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; 4Institut de la Vision, Paris, France*These authors contributed equally to this workBackground: Gene delivery can potentially be used as a therapeutic for treating genetic diseases, including neurodegenerative diseases, as well as an enabling technology for regenerative medicine. A central challenge in many gene delivery applications is having a safe and effective delivery method. We evaluated the use of a biodegradable poly(beta-amino ester nanoparticle-based nonviral protocol and compared this with an electroporation-based approach to deliver episomal plasmids encoding reprogramming factors for generation of human induced pluripotent stem cells (hiPSCs from human fibroblasts.Methods: A polymer library was screened to identify the polymers most promising for gene delivery to human fibroblasts. Feeder-independent culturing protocols were developed for nanoparticle-based and electroporation-based reprogramming. The cells reprogrammed by both polymeric nanoparticle-based and electroporation-based nonviral methods were characterized by analysis of pluripotency markers and karyotypic stability. The hiPSC-like cells were further differentiated toward the neural lineage to test their potential for neurodegenerative retinal disease modeling.Results: 1-(3-aminopropyl-4-methylpiperazine end-terminated poly(1,4-butanediol diacrylate-co-4-amino-1-butanol polymer (B4S4E7 self-assembled with plasmid DNA to form nanoparticles that were more effective than leading commercially available
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Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon
2006-10-01
Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.
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DEFF Research Database (Denmark)
Charrel-Dennis, Marie; Terrazzini, Nadia; McBride, Jeffrey D
2005-01-01
Wild-type human chorionic gonadotropin (hCG) has been used as a contraceptive vaccine. However, extensive sequence homology with LH elicits production of cross-reactive antibodies. Substitution of arginine(68) of the beta-subunit (hCG(beta)) with glutamic acid (R68E) profoundly reduces the cross...
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van de Merbel, Nico C.; Bronsema, Kees J.; van Hout, Mischa W. J.; Nilsson, Ralf; Sillen, Henrik
2011-01-01
A novel liquid chromatography-tandem mass spectrometry method is described for the quantitative determination of the endogenous CYP 3A4/5 marker 4 beta-hydroxycholesterol in human K(2)-EDTA plasma. It is based on alkaline hydrolysis to convert esterified to free 4 beta-hydroxycholesterol, followed
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Fejzić, Nihad; Begagić, Muris; Šerić-Haračić, Sabina; Smajlović, Muhamed
2014-01-01
Beta lactam antibiotics are widely used in therapy of cattle, particularly for the treatment of mastitis. Over 95% of residue testing in dairies in Bosnia and Herzegovina is for Beta lactams. The aim of this paper is to compare the efficacy of three most common screening tests for Beta lactam residues in cow’s milk in our country. The tests used in the study are SNAP β Lactam test (Idexx), Rosa Charm β Lactam test (Charm Sciences) and Inhibition MRL test (A&M). Study samples included: standardized concentrations of penicillin solution (0, 2, 3, 4, 5 and 6 ppb). In addition we tested milk samples from three equal size study groups (not receiving any antibiotic therapy, treated with Beta lactams for mastitis and treated with Beta lactams for diseases other than mastitis). Sensitivity and specificity were determined for each test, using standard penicillin concentrations with threshold value set at concentration of 4 ppb (Maximum residue level – MLR). Additionally we determined proportions of presumably false negative and false positive results for each test using results of filed samples testing. Agreement of test results for each test pair was assessed through Kappa coefficients interpreted by Landis-Koch scale. Detection level of all tests was shown to be well below MRL. This alongside with effects of natural inhibitors in milk contributed to finding of positive results in untreated and treated animals after the withholding period. Screening tests for beta lactam residues are important tools for ensuring that milk for human consumption is free from antibiotics residues. PMID:25172975
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DEFF Research Database (Denmark)
Paulsen, Søren Kildeberg; Pedersen, Steen Bønløkke; Fisker, Sanne
2007-01-01
of the metabolic syndrome. Our objective was to compare 11beta-HSD1 gene expression in different fat depots (visceral, subcutaneous abdominal, and subcutaneous gluteal) in lean and obese men and women. RESEARCH METHODS AND PROCEDURES: A cross-sectional study design was used for healthy patients undergoing minor...... women had lower 11beta-HSD1 gene expression in subcutaneous adipose tissue compared with men (62% lower, p difference was found between obese men and women. 11Beta-HSD1 mRNA in human adipose tissue was higher in obese subjects compared with lean subjects in both women...... and men and in both subcutaneous and visceral adipose tissue. No difference in mRNA expression of 11beta-HSD1 between visceral and subcutaneous adipose tissue or between subcutaneous adipose tissue from different depots was found. CONCLUSIONS: 11Beta-HSD1 in adipose tissue is increased in obesity in both...
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Directory of Open Access Journals (Sweden)
Park Raekil
2006-01-01
Full Text Available Abstract Background We recently showed that beta-defensins have antimicrobial activity against nontypeable Haemophilus influenzae (NTHi and that interleukin 1 alpha (IL-1 alpha up-regulates the transcription of beta-defensin 2 (DEFB4 according to new nomenclature of the Human Genome Organization in human middle ear epithelial cells via a Src-dependent Raf-MEK1/2-ERK signaling pathway. Based on these observations, we investigated if human middle ear epithelial cells could release IL-1 alpha upon exposure to a lysate of NTHi and if this cytokine could have a synergistic effect on beta-defensin 2 up-regulation by the bacterial components. Methods The studies described herein were carried out using epithelial cell lines as well as a murine model of acute otitis media (OM. Human cytokine macroarray analysis was performed to detect the released cytokines in response to NTHi exposure. Real time quantitative PCR was done to compare the induction of IL-1 alpha or beta-defensin 2 mRNAs and to identify the signaling pathways involved. Direct activation of the beta-defensin 2 promoter was monitored using a beta-defensin 2 promoter-Luciferase construct. An IL-1 alpha blocking antibody was used to demonstrate the direct involvement of this cytokine on DEFB4 induction. Results Middle ear epithelial cells released IL-1 alpha when stimulated by NTHi components and this cytokine acted in an autocrine/paracrine synergistic manner with NTHi to up-regulate beta-defensin 2. This synergistic effect of IL-1 alpha on NTHi-induced beta-defensin 2 up-regulation appeared to be mediated by the p38 MAP kinase pathway. Conclusion We demonstrate that IL-1 alpha is secreted by middle ear epithelial cells upon exposure to NTHi components and that it can synergistically act with certain of these molecules to up-regulate beta-defensin 2 via the p38 MAP kinase pathway.
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Shiina, T; Kawasaki, A; Nagao, T; Kurose, H
2000-09-15
The beta(1)-adrenergic receptor (beta(1)AR) shows the resistance to agonist-induced internalization. As beta-arrestin is important for internalization, we examine the interaction of beta-arrestin with beta(1)AR with three different methods: intracellular trafficking of beta-arrestin, binding of in vitro translated beta-arrestin to intracellular domains of beta(1)- and beta(2)ARs, and inhibition of betaAR-stimulated adenylyl cyclase activities by beta-arrestin. The green fluorescent protein-tagged beta-arrestin 2 translocates to and stays at the plasma membrane by beta(2)AR stimulation. Although green fluorescent protein-tagged beta-arrestin 2 also translocates to the plasma membrane, it returns to the cytoplasm 10-30 min after beta(1)AR stimulation. The binding of in vitro translated beta-arrestin 1 and beta-arrestin 2 to the third intracellular loop and the carboxyl tail of beta(1)AR is lower than that of beta(2)AR. The fusion protein of beta-arrestin 1 with glutathione S-transferase inhibits the beta(1)- and beta(2)AR-stimulated adenylyl cyclase activities, although inhibition of the beta(1)AR-stimulated activity requires a higher concentration of the fusion protein than that of the beta(2)AR-stimulated activity. These results suggest that weak interaction of beta(1)AR with beta-arrestins explains the resistance to agonist-induced internalization. This is further supported by the finding that beta-arrestin can induce internalization of beta(1)AR when beta-arrestin 1 does not dissociate from beta(1)AR by fusing to the carboxyl tail of beta(1)AR.
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White, Elizabeth A; Walther, Johanna; Javanbakht, Hassan; Howley, Peter M
2014-08-01
The genus beta human papillomaviruses (beta HPVs) cause cutaneous lesions and are thought to be involved in the initiation of some nonmelanoma skin cancers (NMSCs), particularly in patients with the genetic disorder epidermodysplasia verruciformis (EV). We have previously reported that at least two of the genus beta HPV E6 proteins bind to and/or increase the steady-state levels of p53 in squamous epithelial cells. This is in contrast to a well-characterized ability of the E6 proteins of cancer-associated HPVs of genus alpha HPV, which inactivate p53 by targeting its ubiquitin-mediated proteolysis. In this study, we have investigated the ability of genus beta E6 proteins from eight different HPV types to block the transactivation of p53 target genes following DNA damage. We find that the E6 proteins from diverse beta HPV species and types vary in their capacity to block the induction of MDM2, p21, and proapoptotic genes after genotoxic stress. We conclude that some genus beta HPV E6 proteins inhibit at least some p53 target genes, although perhaps not by the same mechanism or to the same degree as the high-risk genus alpha HPV E6 proteins. This study addresses the ability of various human papillomavirus E6 proteins to block the activation of p53-responsive cellular genes following DNA damage in human keratinocytes, the normal host cell for HPVs. The E6 proteins encoded by the high-risk, cancer-associated HPV types of genus alpha HPV have a well-established activity to target p53 degradation and thereby inhibit the response to DNA damage. In this study, we have investigated the ability of genus beta HPV E6 proteins from eight different HPV types to block the ability of p53 to transactivate downstream genes following DNA damage. We find that some, but not all, genus beta HPV E6 proteins can block the transactivation of some p53 target genes. This differential response to DNA damage furthers the understanding of cutaneous HPV biology and may help to explain the
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Lurton, J; Soto, H; Narayanan, A S; Raghu, G
1999-03-01
Transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) are two polypeptide mediators which are believed to play a role in the evolution of idiopathic pulmonary fibrosis (IPF). We have evaluated the effect of these two substances on the expression of receptors for collagen (cC1q-R) and globular (gC1q-R) domains of C1q and on type I collagen in human lung fibroblasts. Two fibroblast subpopulations differing in C1q receptor expression were obtained by culturing human lung explants in medium containing fresh human serum and heated plasma-derived serum and separating them based on C1q binding [Narayanan, Lurton and Raghu: Am J Resp Cell Mol Biol. 1998; 17:84]. The cells, referred to as HH and NL cells, respectively, were exposed to TGF-beta and TNF-alpha in serum-free conditions. The levels of mRNA were assessed by in situ hybridization and Northern analysis, and protein levels compared after SDS-polyacrylamide gel electrophoresis and Western blotting. NL cells exposed to TGF-beta and TNF-alpha contained 1.4 and 1.6 times as much cC1q-R mRNA, respectively, whereas in HH cells cC1q-R mRNA increased 2.0- and 2.4-fold. The gC1q-R mRNA levels increased to a lesser extent in both cells. These increases were not reflected in protein levels of CC1q-R and gC1q-R, which were similar to or less than controls. Both TGF-beta and TNF-alpha also increased procollagen [I] mRNA levels in both cells. Overall, TNF-alpha caused a greater increase and the degree of response by HH fibroblasts to both TGF-beta and TNF-alpha was higher than NL cells. These results indicated that TGF-beta and TNF-alpha upregulate the mRNA levels for cC1q-R and collagen and that they do not affect gC1q-R mRNA levels significantly. They also indicated different subsets of human lung fibroblasts respond differently to inflammatory mediators.
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Energy Technology Data Exchange (ETDEWEB)
Chakravarthy, Balu, E-mail: Balu.Chakravarthy@nrc-cnrc.gc.ca [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); Gaudet, Chantal; Menard, Michel; Brown, Leslie; Atkinson, Trevor [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); LaFerla, Frank M. [Department of Neurobiology and Behavior, University of California, Irvine, CA (United States); Ito, Shingo [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada); Armato, Ubaldo; Dal Pra, Ilaria [Department of Life and Reproduction Sciences, University of Verona Medical School, Verona (Italy); Whitfield, James [Human Health Therapeutics, National Research Council of Canada, Ottawa, ON (Canada)
2012-10-12
Highlights: Black-Right-Pointing-Pointer A{beta} and tau-induced neurofibrillary tangles play a key role in Alzheimer's disease. Black-Right-Pointing-Pointer A{beta}{sub 1-42} and mutant tau protein together reduce the primary cilium length. Black-Right-Pointing-Pointer This shortening likely reduces cilium-dependent neurogenesis and memory function. Black-Right-Pointing-Pointer This provides a model of an A{beta}/tau targeting of a neuronal signaling organelle. -- Abstract: The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis in adult rodents and humans. Virtually all dentate granule cells have a single immobile cilium with a microtubule spine or axoneme covered with a specialized cell membrane loaded with receptors such as the somatostatin receptor 3 (SSTR3), and the p75 neurotrophin receptor (p75{sup NTR}). The signals from these receptors have been reported to stimulate neuroprogenitor proliferation and the post-mitotic maturation of newborn granule cells into functioning granule cells. We have found that in 6-24-months-old triple transgenic Alzheimer's disease model mice (3xTg-AD) producing both A{beta}{sub 1-42} and the mutant human tau protein tau{sub P301L,} the dentate granule cells still had immunostainable SSTR3- and p75{sup NTR}-bearing cilia but they were only half the length of the immunostained cilia in the corresponding wild-type mice. However, the immunostainable length of the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large amounts of A{beta}{sub 1-42} or in mice accumulating only a mutant human tau protein. Thus it appears that a combination of A{beta}{sub 1-42} and tau protein accumulation affects the levels of functionally important receptors in 3xTg-AD mice. These observations raise the important possibility that structural and functional changes in granule cell cilia might have a role in AD.
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Directory of Open Access Journals (Sweden)
Jurczyk A
2013-12-01
Full Text Available Agata Jurczyk,1 Philip diIorio,1 Dean Brostowin,1 Linda Leehy,1 Chaoxing Yang,1 Fumihiko Urano,2 David M Harlan,3 Leonard D Shultz,4 Dale L Greiner,1 Rita Bortell1 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 2Department of Medicine, Washington University School of Medicine, St Louis, MO, 3Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 4The Jackson Laboratory, Bar Harbor, ME, USA Purpose: Dipeptidyl-peptidase-4 (DPP-4 inhibitors are known to increase insulin secretion and beta cell proliferation in rodents. To investigate the effects on human beta cells in vivo, we utilize immunodeficient mice transplanted with human islets. The study goal was to determine the efficacy of alogliptin, a DPP-4 inhibitor, to enhance human beta cell function and proliferation in an in vivo context using diabetic immunodeficient mice engrafted with human pancreatic islets. Methods: Streptozotocin-induced diabetic NOD-scid IL2rγnull (NSG mice were transplanted with adult human islets in three separate trials. Transplanted mice were treated daily by gavage with alogliptin (30 mg/kg/day or vehicle control. Islet graft function was compared using glucose tolerance tests and non-fasting plasma levels of human insulin and C-peptide; beta cell proliferation was determined by bromodeoxyuridine (BrdU incorporation. Results: Glucose tolerance tests were significantly improved by alogliptin treatment for mice transplanted with islets from two of the three human islet donors. Islet-engrafted mice treated with alogliptin also had significantly higher plasma levels of human insulin and C-peptide compared to vehicle controls. The percentage of insulin+BrdU+ cells in human islet grafts from alogliptin-treated mice was approximately 10-fold more than from vehicle control mice, consistent with a significant increase in human beta cell proliferation. Conclusion: Human islet-engrafted immunodeficient mice
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Energy Technology Data Exchange (ETDEWEB)
Sasaki, Shigekazu; Nakamura, Hirotoshi; Tagami, Tetsuya; Miyoshi, Yohzi; Nogimori, Tsuyoshi; Mitsuma, Terunori; Imura, Hiroo (Kyoto Univ. School of Medicine, Aichi (Japan))
1993-05-01
Point mutations in the human T[sub 3] receptor-[beta] (TR[beta]) gene causing single amino acid substitutions have been identified in several different kindred with generalized resistance to thyroid hormone. Until now, no study has been reported on the TR gene in cases of pituitary resistance (PRTH). In the present study, the authors analyzed the TR[beta] gene in a 30-yr-old Japanese female with PRTH. She exhibited clinical features of hyperthyroidism, elevated serum thyroid hormone levels accompanied by inappropriately increased secretion of TSH, mildly elevated basal metabolic rate, and increased urinary excretion of hydroxyproline. No pituitary tumor was detected. DNA fragments of exons 3-8 of the geonomic TR[beta] gene were generated by the polymerase chain reaction and analyzed by a single stranded conformation polymorphism method. Exon 7 of the patient's TR[beta] gene showed an abnormal band, suggesting the existence of mutation(s). By subcloning and sequencing the DNA, a point mutation was identified in one allele at nucleotide 1297 (C to T), which altered the 333rd amino acid, arginine, to tryptophan. Neither of her apparently normal parents had any mutations of the TR[beta] gene. In vitro translation products of the mutant TR[beta] gene showed remarkably decreased T[sub 3]-binding activity (K[sub a], 2.1 [times] 10[sup 8] M[sup [minus]1]; normal TR[beta] K[sub a], 1.1 [times] 10[sup 10] M[sup [minus]1]). Since the molecular defect detected in a patient with PRTH is similar to that seen in subjects with generalized resistance to thyroid hormone, both types of the syndrome may represent a continuous spectrum of the same etiological defect with variable tissue resistance to thyroid hormone.
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Beta-lactamases in Enterobacteriaceae in broilers
Dierikx, C.M.
2013-01-01
Resistance to cephalosprins due to the production of extended spectrum beta-lactamases (ESBLs) or plasmid mediated AmpC beta-lactamases is increasingly found in infections in humans outside the hospital. The genes encoding for these beta-lactamases are located on mobile DNA (plasmids), which can be
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Effect of beta-adrenoceptor blockers on human ether-a-go-go-related gene (HERG) potassium channels
DEFF Research Database (Denmark)
Dupuis, Delphine S; Klaerke, Dan A; Olesen, Søren-Peter
2005-01-01
Patients with congenital long QT syndrome may develop arrhythmias under conditions of increased sympathetic tone. We have addressed whether some of the beta-adrenoceptor blockers commonly used to prevent the development of these arrhythmias could per se block the cardiac HERG (Human Ether....... These data showed that HERG blockade by beta-adrenoceptor blockers occurred only at high micromolar concentrations, which are significantly above the recently established safe margin of 100 (Redfern et al., 2003).......-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) blocked the HERG channel with similar affinity, whereas the beta1-receptor antagonists metoprolol and atenolol showed weak effects. Further, the four compounds blocked HERG channels expressed in a mammalian HEK293 cell line...
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International Nuclear Information System (INIS)
Schier, W.A.; Couchell, G.P.
1993-01-01
A helium-jet/tape-transport system is employed in the study of beta-particle and gamma-ray energy spectra of aggregate fission products as a function of time after fission. During the initial nine months of this project we have investigated the following areas: Design, assembly and characterization of a beta-particle spectrometer; Measurement of 235 U(n th ff) beta spectra for delay times 0.2 s to 12,000 s; Assembly and characterization of a 5 x 5 Nal(Tl) gamma-ray spectrometer; Measurement of 235 U(n th ff) gamma-ray spectra for delay times 0.2s to 1 5,500s; Assembly and characterization of HPGe gamma-ray spectrometer with a Nal(Tl) Compton-and-background-suppression annulus; Measurement of 235 U(n th ,ff) high-resolution gamma-ray spectra for delay times 0.6 s to over 100,000 s; Comparison of individual gamma-line intensities with ENDF/B-VI; Adaptation to our computer of unfolding program FERDO for beta and gamma aggregate fission-product energy spectra and development of a spectrum-stripping program for analysis of HPGe gamma-ray spectra; Study of the helium-jet fission-fragment elemental transfer efficiency. This work has resulted in the publication of twelve BAPS abstracts of presentations at scientific meetings. There are currently four Ph.D. and two M.S. candidates working on dissertations associated with the project
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Litaker, J R; Pan, J; Cheung, Y; Zhang, D K; Liu, Y; Wong, S C; Wan, T S; Tsao, S W
1998-11-01
Senescence is a specific physiological stage of cells characterized by long population doubling time. It accounts for the inability of normal somatic cells to undergo indefinite cell division. As the number of population doublings increase, cell cycle regulatory mechanisms come into play and signal cells to exit the cell cycle and become senescent. Senescence has been implicated in the aging process and may function as a tumor suppressor mechanism in human cells. The ability to measure the degree of cellular senescence is important in understanding the biological processes regulating cell aging and immortalization. Senescent cells exhibit an enzyme termed senescence-associated histochemical staining. Cells immortalized by viral oncogenes often enter a stage of crisis at the early phase of immortalization. The cells at crisis have a long population doubling time. Cells at the crisis stage resemble senescent cells and the expression of SA- beta-Gal may be used to monitor the process of immortalization. In this study the expression profile of SA-beta-Gal was examined in human ovarian surface epithelial cells (HOSE 6-3) undergoing immortalization by the human papilloma viral oncogene E6 and E7 (HPV E6 and E7). Our results showed a low percentage (12.0%) of HOSE 6-3 cells expressing SA-beta-Gal activity at the pre-crisis stage. The percentage of HOSE 6-3 cells expressing SA-beta-Gal activity was highest (39.2%) at the crisis stage. When HOSE 6-3 cells achieved immortalized status there was a sharp decrease in cells (1. 3%) expressing SA-beta-Gal activity. In addition, an inverse relationship between the expression of SA-beta-Gal activity and telomerase activity was noted in cells undergoing immortalization. The results confirm that the SA-beta-Gal enzyme is a good marker for monitoring the population of cells undergoing senescence at different stages of immortalization and that telomerase activation is a characteristic feature of post-crisis cells.
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DEFF Research Database (Denmark)
Paulsen, Søren Kildeberg; Pedersen, Steen Bønløkke; Fisker, Sanne
2007-01-01
of the metabolic syndrome. Our objective was to compare 11beta-HSD1 gene expression in different fat depots (visceral, subcutaneous abdominal, and subcutaneous gluteal) in lean and obese men and women. RESEARCH METHODS AND PROCEDURES: A cross-sectional study design was used for healthy patients undergoing minor...... abdominal surgery (lean men, 10), minor gynecological surgery (lean woman, 10), or gastric banding operations (obese men, 10; and obese women, 10). Gene expressions of 11beta-HSD1 in adipose tissue samples were determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Lean...... women had lower 11beta-HSD1 gene expression in subcutaneous adipose tissue compared with men (62% lower, p women. 11Beta-HSD1 mRNA in human adipose tissue was higher in obese subjects compared with lean subjects in both women...
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Insulin Resistance as a Link between Amyloid-Beta and Tau Pathologies in Alzheimer’s Disease
Directory of Open Access Journals (Sweden)
Roger J. Mullins
2017-05-01
Full Text Available Current hypotheses and theories regarding the pathogenesis of Alzheimer’s disease (AD heavily implicate brain insulin resistance (IR as a key factor. Despite the many well-validated metrics for systemic IR, the absence of biomarkers for brain-specific IR represents a translational gap that has hindered its study in living humans. In our lab, we have been working to develop biomarkers that reflect the common mechanisms of brain IR and AD that may be used to follow their engagement by experimental treatments. We present two promising biomarkers for brain IR in AD: insulin cascade mediators probed in extracellular vesicles (EVs enriched for neuronal origin, and two-dimensional magnetic resonance spectroscopy (MRS measures of brain glucose. As further evidence for a fundamental link between brain IR and AD, we provide a novel analysis demonstrating the close spatial correlation between brain expression of genes implicated in IR (using Allen Human Brain Atlas data and tau and beta-amyloid pathologies. We proceed to propose the bold hypotheses that baseline differences in the metabolic reliance on glycolysis, and the expression of glucose transporters (GLUT and insulin signaling genes determine the vulnerability of different brain regions to Tau and/or Amyloid beta (Aβ pathology, and that IR is a critical link between these two pathologies that define AD. Lastly, we provide an overview of ongoing clinical trials that target IR as an angle to treat AD, and suggest how biomarkers may be used to evaluate treatment efficacy and target engagement.
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Energy Technology Data Exchange (ETDEWEB)
Liu Guangpeng [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Zhao Li [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Cui Lei [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Liu Wei [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Cao Yilin [National Tissue Engineering Research and Development Center, Shanghai 200235 (China)
2007-06-01
In this study we investigated not only the cellular proliferation and osteogenic differentiation of human bone marrow stromal cells (hBMSCs) on the novel {beta}-tricalcium phosphate ({beta}-TCP) scaffolds in vitro but also bone formation by ectopic implantation in athymic mice in vivo. The interconnected porous {beta}-TCP scaffolds with pores of 300-500 {mu}m in size were prepared by the polymeric sponge method. {beta}-TCP scaffolds with the dimension of 3 mm x 3 mm x 3 mm were combined with hBMSCs, and incubated with (+) or without (-) osteogenic medium in vitro. Cell proliferation and osteogenic differentiation on the scaffolds were evaluated by scanning electron microscopy (SEM) observation, MTT assay, alkaline phosphatase (ALP) activity and osteocalcin (OCN) content measurement. SEM observation showed that hBMSCs attached well on the scaffolds and proliferated rapidly. No significant difference in the MTT assay could be detected between the two groups, but the ALP activity and OCN content of scaffolds (+) were much higher than those of the scaffolds (-) (p < 0.05). These results indicated that the novel porous {beta}-TCP scaffolds can support the proliferation and subsequent osteogenic differentiation of hBMSCs in vitro. After being cultured in vitro for 14 days, the scaffolds (+) and (-) were implanted into subcutaneous sites of athymic mice. In {beta}-TCP scaffolds (+), woven bone formed after 4 weeks of implantation and osteogenesis progressed with time. Furthermore, tissue-engineered bone could be found at 8 weeks, and remodeled lamellar bone was also observed at 12 weeks. However, no bone formation could be found in {beta}-TCP scaffolds (-) at each time point checked. The above findings illustrate that the novel porous {beta}-TCP scaffolds developed in this work have prominent osteoconductive activity and the potential for applications in bone tissue engineering.
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Activation of Beta-Catenin Signaling in Androgen Receptor–Negative Prostate Cancer Cells
Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W.; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba S.; Troncoso, Patricia; Maity, Sankar N.; Navone, Nora M.
2012-01-01
Purpose To study Wnt/beta-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the beta-catenin–androgen receptor (AR) interaction. Experimental Design We performed beta-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of beta-catenin–mediated transcription), and sequenced the beta-catenin gene in MDA PCa 118a, MDA PCa 118b, MDA PCa 2b, and PC-3 prostate cancer (PCa) cells. We knocked down beta-catenin in AR-negative MDA PCa 118b cells and performed comparative gene-array analysis. We also immunohistochemically analyzed beta-catenin and AR in 27 bone metastases of human CRPCs. Results Beta-catenin nuclear accumulation and TOP-flash reporter activity were high in MDA PCa 118b but not in MDA PCa 2b or PC-3 cells. MDA PCa 118a and 118b cells carry a mutated beta-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA PCa 118b cells with downregulated beta-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant beta-catenin. Finally, we found nuclear localization of beta-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher’s exact test), suggesting that reduced AR expression enables Wnt/beta-catenin signaling. Conclusion We identified a previously unknown downstream target of beta-catenin, HAS2, in PCa, and found that high beta-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone-metastatic PCa. These findings may guide physicians in managing these patients. PMID:22298898
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Razeghi, Peter; Bruckner, Brian A; Sharma, Saumya; Youker, Keith A; Frazier, O H; Taegtmeyer, Heinrich
2003-01-01
Left ventricular assist device (LVAD) support of the failing human heart improves myocyte function and increases cell survival. One potential mechanism underlying this phenomenon is activation of the protein kinase B (PKB)/Akt/glycogen synthase kinase-3beta (GSK-3beta) survival pathway. Left ventricular tissue was obtained both at the time of implantation and explantation of the LVAD (n = 11). Six patients were diagnosed with idiopathic dilated cardiomyopathy, 4 patients with ischemic cardiomyopathy and 1 patient with peripartum cardiomyopathy. The mean duration of LVAD support was 205 +/- 35 days. Myocyte diameter and phosphorylation of ERK were used as indices for reverse remodeling. Transcript levels of genes required for the activation of PKB/Akt (insulin-like growth factor-1, insulin receptor substrate-1) were measured by quantitative RT-PCR. In addition, we measured the relative activity of PKB/Akt and GSK-3beta, and assayed for molecular and histological indices of PKB/Akt activation (cyclooxygenase mRNA levels and glycogen levels). Myocyte diameter and phosphorylation of ERK decreased with LVAD support. In contrast, none of the components of the PKB/Akt/GSK-3beta pathway changed significantly with mechanical unloading. The PKB/Akt/GSK-3beta pathway is not activated during LVAD support. Other signaling pathways must be responsible for the improvement of cellular function and cell survival during LVAD support. Copyright 2003 S. Karger AG, Basel
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High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor
DEFF Research Database (Denmark)
Cherezov, Vadim; Rosenbaum, Daniel M; Hanson, Michael A
2007-01-01
Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors constitute the largest family of eukaryotic signal transduction proteins that communicate across the membrane. We report the crystal structure of a human beta2-adrenergic receptor-T4 lysozyme fusion protein bound to t...
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Dehnavi, Ehsan; Soheili, Zahra-Soheila; Samiei, Shahram; Ataei, Zahra; Aryan, Hajar
2009-06-01
Transforming growth factor-beta (TGF-beta) superfamily regulates matrix metalloproteinases (MMP), which intrinsically regulate various cell behaviors leading to metastasis. We investigated the effect of TGF-beta(2) on MMP-2 regulation in human bladder carcinoma cell line 5637. Zymography, ELISA, and real-time polymerase chain reaction revealed that TGF-beta(2) stimulated MMP-2 production, but the transcription of its gene remained unchanged. Wortmannin could not inhibit MMP-2 secretion and activity and conversely the amount of the protein and its enzymatic activity were increased. These data suggest that TGF-beta(2) increased MMP-2 at the posttranscriptional level and this upregulation was independent of phosphatidylinositol 3-kinase signaling pathway.
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Activation of the human beta interferon gene by the adenovirus type 12 E1B gene
International Nuclear Information System (INIS)
Shiroki, K.; Toth, M.
1988-01-01
The transcription of endogenous beta interferon mRNA was activated in human embryo kidney (HEK) cells infected with adenovirus 12 (Ad12) but was activated only inefficiently or not at all in HEK cells infected with Ad5 and rc-1 (Ad5 dl312 containing the Ad12 E1A region). The analysis with Ad12 mutants showed that Ad12 E1B products, especially the 19K protein, were important for the expression of the endogenous beta interferon gene and Ad12 E1A products were not involved in the expression. The expression of exogeneously transfected pIFN-CAT (a hybrid plasmid having the human beta interferon promoter fused with the CAT gene) was activated in HEK and chicken embryo fibroblast (CEF) cells infected with either Ad12 or Ad5. The analysis of cotransfection of CEF cells with pIFN-CAT and plasmids containing fragments of Ad12 or Ad5 DNA showed that Ad12 or Ad5 E1B (possibly the 19K protein) was and E1A was not involved in the expression of the exogenous pIFN-CAT
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Cooper, E Jane; Hudson, Alan L; Parker, Christine A; Morgan, Noel G
2003-12-15
It is well known that certain imidazoline compounds can stimulate insulin secretion and this has been attributed to the activation of imidazoline I(3) binding sites in the pancreatic beta-cell. Recently, it has been proposed that beta-carbolines may be endogenous ligands having activity at imidazoline sites and we have, therefore, studied the effects of beta-carbolines on insulin secretion. The beta-carbolines harmane, norharmane and pinoline increased insulin secretion two- to threefold from isolated human islets of Langerhans. The effects of harmane and pinoline were dose-dependent (EC(50): 5 and 25 microM, respectively) and these agents also blocked the inhibitory effects of the potassium channel agonist, diazoxide, on glucose-induced insulin release. Stimulation of insulin secretion by harmane was glucose-dependent but, unlike the imidazoline I(3) receptor agonist efaroxan, it increased the rate of insulin release beyond that elicited by 20 mM glucose (20 mM glucose alone: 253+/-34% vs. basal; 20 mM glucose plus 100 microM harmane: 327+/-15%; P<0.01). Stimulation of insulin secretion by harmane was attenuated by the imidazoline I(3) receptor antagonist KU14R (2 (2-ethyl 2,3-dihydro-2-benzofuranyl)-2-imidazole) and was reduced when islets were treated with efaroxan for 18 h, prior to the addition of harmane. The results reveal that beta-carbolines can potentiate the rate of insulin secretion from human islets and suggest that these agents may be useful prototypes for the development of novel insulin secretagogues.
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Lifescience Database Archive (English)
Full Text Available 17913496 Immunoreceptor-like signaling by beta 2 and beta 3 integrins. Jakus Z, Fod...) Show Immunoreceptor-like signaling by beta 2 and beta 3 integrins. PubmedID 17913496 Title Immunoreceptor-...like signaling by beta 2 and beta 3 integrins. Authors Jakus Z, Fodor S, Abram CL
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DEFF Research Database (Denmark)
Ahlquist, P; Johansen, Torben; Friis, U G
1994-01-01
This study evaluates the effect of cryo-storage on beta 2-adrenoceptor number and formation of adenosine 3':5'-cyclic monophosphate (cAMP) in intact human lymphocytes as a measure of the beta 2-adrenoceptor responsiveness. Cryo-storage at -196 degrees C up to 12 months caused no significant......), but changed significantly after long-term storage (3-12 months). We can conclude that lymphocytes can be stored for months for later determination of beta-adrenoceptors. The cryo-storage method described in this paper are, however, only useful for measurements of very large changes in cAMP formation, and our...... results indicate that the method should be further modified in order to preserve the lymphocyte responsiveness after cryo-storage....
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Tributyltin alters secretion of interleukin 1 beta from human immune cells.
Brown, Shyretha; Whalen, Margaret
2015-08-01
Tributyltin (TBT) has been used as a biocide in industrial applications such as wood preservation, antifouling paint and antifungal agents. Owing to its many uses, it contaminates the environment and has been found in human blood samples. Interleukin-1 beta (IL-1β) is a pro-inflammatory cytokine that promotes cell growth, tissue repair and immune response regulation. Produced predominately by both monocytes and macrophages, IL-1β appears to increase the invasiveness of certain tumors. This study shows that TBT modifies the secretion of IL-1β from increasingly reconstituted preparations of human immune cells. IL-1β secretion was examined after 24-, 48-h or 6-day exposures to TBT in highly enriched human natural killer (NK) cells, monocyte-depleted peripheral blood mononuclear cells (MD-PBMCs), PBMCs, granulocytes and a preparation combining both PBMCs and granulocytes (PBMCs+granulocytes). TBT altered IL-1β secretion from all of the cell preparations. The 200 nM concentration of TBT normally blocked the secretion of IL-1β, whereas lower concentrations (usually 5-50 nM) elevated secretion of IL-1β. Examination of the signaling pathway(s) responsible for the elevated secretion of IL-1β was carried out in MD-PBMCs. Pathways examined were IL-1β processing (Caspase-1), mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NFκB). Results indicated that MAPK pathways (p44/42 and p38) appear to be the targets of TBT that lead to increased IL-1β secretion from immune cells. These results from human immune cells show IL-1β dysregulation by TBT is occurring ex vivo. Thus, the potential for in vivo effects on pro-inflammatory cytokine levels may possibly be a consequence of TBT exposures. Copyright © 2014 John Wiley & Sons, Ltd.
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Milk Intolerance, Beta-Casein and Lactose.
Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen
2015-08-31
True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows' milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows' milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows' milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.
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Milk Intolerance, Beta-Casein and Lactose
Directory of Open Access Journals (Sweden)
Sebely Pal
2015-08-01
Full Text Available True lactose intolerance (symptoms stemming from lactose malabsorption is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows’ milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.
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Proliferation of sorted human and rat beta cells
DEFF Research Database (Denmark)
Parnaud, G; Bosco, D; Berney, T
2008-01-01
The aim of the study was to determine whether purified beta cells can replicate in vitro and whether this is enhanced by extracellular matrix (ECM) and growth factors.......The aim of the study was to determine whether purified beta cells can replicate in vitro and whether this is enhanced by extracellular matrix (ECM) and growth factors....
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DEFF Research Database (Denmark)
Aarestrup, Frank Møller; Larsen, H.D.; Eriksen, N.H.R.
1999-01-01
The phenotypic expression of haemolysins and the presence of genes encoding alpha and beta-haemolysin were determined in 105 Sraphylococcus aureus isolates from bovine mastitis, 100 isolates from the nostrils of healthy humans, and 60 isolates from septicaemia in humans. Furthermore, the possible...... change in expression of haemolysins after subcultivation in human and bovine blood and milk was studied in selected isolates. alpha-haemolysin was expressed phenotypically in 39 (37%) of the bovine isolates, in 59 (59%) of the human carrier isolates, and in 40 (67%) of the isolates from septicaemia. beta......-haemolysin was expressed in 76 (72%) bovine, 11 (11%) carrier, and 8 (13%) septicaemia isolates. Significantly more bovine than human isolates expressed beta-haemolysin and significantly fewer expressed alpha-haemolysin. Genotypically, the gene encoding alpha-haemolysin was detected in all isolates. A significant...
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Directory of Open Access Journals (Sweden)
French Frank S
2004-08-01
Full Text Available Abstract Background The HE2 gene encodes a group of isoforms with similarities to the antimicrobial beta-defensins. We demonstrated earlier that the antimicrobial activity of HE2 proteins and peptides is salt resistant and structure dependent and involves permeabilization of bacterial membranes. In this study, we further characterize the antimicrobial properties of HE2 peptides in terms of the structural changes induced in E. coli and the inhibition of macromolecular synthesis. Methods E. coli treated with 50 micro g/ml of HE2alpha, HE2beta1 or HE2beta2 peptides for 30 and 60 min were visualized using transmission and scanning electron microscopy to investigate the impact of these peptides on bacterial internal and external structure. The effects of HE2alpha, HE2beta1 and HE2beta2 on E. coli macromolecular synthesis was assayed by incubating the bacteria with 2, 10 and 25 micro g/ml of the individual peptides for 0–60 min and measuring the incorporation of the radioactive precursors [methyl-3H]thymidine, [5-3H]uridine and L-[4,5-3H(N]leucine into DNA, RNA and protein. Statistical analyses using Student's t-test were performed using Sigma Plot software. Values shown are Mean ± S.D. Results E. coli treated with HE2alpha, HE2beta1 and HE2beta2 peptides as visualized by transmission electron microscopy showed extensive damage characterized by membrane blebbing, thickening of the membrane, highly granulated cytoplasm and appearance of vacuoles in contrast to the smooth and continuous membrane structure of the untreated bacteria. Similarly, bacteria observed by scanning electron microscopy after treating with HE2alpha, HE2beta1 or HE2beta2 peptides exhibited membrane blebbing and wrinkling, leakage of cellular contents, especially at the dividing septa, and external accumulation of fibrous materials. In addition, HE2alpha, HE2beta1 and HE2beta2 peptides inhibited E. coli DNA, RNA and protein synthesis. Conclusions The morphological changes observed
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DEFF Research Database (Denmark)
Jessen, H; Jacobsen, Christian
1997-01-01
1. The underlying mechanisms involved in the adaptive regulation of beta-amino acid uptake in the human proximal tubule were examined by use of an immortalized human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that the adaptive response to maintain whole-body taurine...
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Energy Technology Data Exchange (ETDEWEB)
Bruecke, T; Asenbaum, S; Frassine, H; Podreka, I [Vienna Univ. (Austria). Neurologische Klinik; Kornhuber, J [Wuerzburg Univ. (Germany); Angelberger, P [Oesterreichisches Forschungszentrum Seibersdorf GmbH (Austria)
1993-01-01
Single photon emission computerized tomography (SPECT) studies in non-human primates have previously shown that the cocaine derivative [[sup 123]I]-2-[beta]-carbomethoxy-3-[beta]-(4-iodophenyl)-tropane ([[sup 123]I][beta]-CIT) labels dopamine transporters in the striatum and serotonin transporters in the hypothalamus-midbrain area. Here, we report on the regional kinetic uptake of [[sup 123]I][beta]-CIT in the brain of 4 normal volunteers and 2 patients with Parkinson's disease. In healthy subjects striatal activity increased slowly to reach peak values at about 20 hours post injection. In the hypothalamus-midbrain area peak activities were observed at about 4 hours with a slow decrease thereafter. Low activity was observed in cortical and cerebellar areas. The striatal to cerebellar ratio was about 4 after 5 hours and 9 after 20 hours. In 2 patients with idiopathic Parkinson's disease striatal activity was markedly decreased while the activity in hypothalamus-midbrain areas was only diminished. Uptake into cortical and cerebellar areas appeared to be unchanged in Parkinson's disease. Consequently, in Parkinson's disease the striatal to cerebellar ratio was decreased to values around 2.5 after 20 hours. These preliminary methodological studies suggest that [[sup 123]I][beta]-CIT is a useful SPECT ligand for studying dopamine and possibly also serotonin transporters in the living human brain.
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Energy Technology Data Exchange (ETDEWEB)
Sato, H.; Sugiyama, Y.; Sawada, Y.; Iga, T.; Hanano, M.
1987-07-01
In order to simulate the distribution and elimination of radioiodinated human beta-endorphin (/sup 125/I-beta-EP) after iv bolus injection in rats, we proposed a physiologically based pharmacokinetic model incorporating diffusional transport of /sup 125/I-beta-EP across the capillary membrane. This model assumes that the distribution of /sup 125/I-beta-EP is restricted only within the blood and the tissue interstitial fluid, and that a diffusional barrier across the capillary membrane exists in each tissue except the liver. The tissue-to-blood partition coefficients were estimated from the ratios of the concentration in tissues to that in arterial plasma at the terminal (pseudoequilibrium) phase. The total body plasma clearance (9.0 ml/min/kg) was appropriately assigned to the liver and kidney. The transcapillary diffusion clearances of /sup 125/I-beta-EP were also estimated and shown to correlate linearly with that of inulin in several tissues. Numerically solving the mass-balance differential equations as to plasma and each tissue simultaneously, simulated concentration curves of /sup 125/I-beta-EP corresponded well with the observed data. It was suggested by the simulation that the initial rapid disappearance of /sup 125/I-beta-EP from plasma after iv injection could be attributed in part to the transcapillary diffusion of the peptide.
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Diversity of [beta]-globin mutations in Israeli ethnic groups reflects recent historic events
Energy Technology Data Exchange (ETDEWEB)
Filon, D.; Oron, V.; Krichevski, S.; Shaag, A.; Goldfarb, A.; Aker, M.; Rachmilewitz, E.A.; Rund, D.; Oppenheim, A. (Hebrew Univ. Hadassah-Medical School, Jerusalem (Israel)) (and others)
1994-05-01
The authors characterized nearly 500 [beta]-thalassemia genes from the Israeli population representing a variety of ethnic subgroups. They found 28 different mutations in the [beta]-globin gene, including three mutations ([beta][sup S], [beta][sup C], and [beta][sup O-Arab]) causing hemoglobinopathies. Marked genetic heterogeneity was observed in both the Arab (20 mutations) and Jewish (17 mutations) populations. On the other hand, two ethnic isolates - Druze and Samaritans - had a single mutation each. Fifteen of the [beta]-thalassemia alleles are Mediterranean in type, 5 originated in Kurdistan, 2 are of Indian origin, and 2 sporadic alleles came from Europe. Only one mutant allele-nonsense codon 37-appears to be indigenous to Israel. While human habitation in Israel dates back to early prehistory, the present-day spectrum of [beta]-globin mutations can be largely explained by migration events that occurred in the past millennium. 26 refs., 2 figs., 3 tabs.
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Expression pattern of thymosin beta 4 in the adult human liver
Directory of Open Access Journals (Sweden)
S. Nemolato
2011-09-01
Full Text Available Thymosin beta-4 (Tβ4 is a member of beta-thymosins, a family of small peptides involved in polymerization of G-actin, and in many critical biological processes including apoptosis, cell migration, angiogenesis, and fibrosis. Previous studies in the newborn liver did not reveal any significant reactivity for Tβ4 during the intrauterine life. The aim of the present study was to investigate by immunohistochemistry Tβ4 expression in the adult normal liver. Thirty-five human liver samples, including 11 needle liver biopsies and 24 liver specimens obtained at autopsy, in which no pathological change was detected at the histological examination, were immunostained utilizing an anti-Tβ4 commercial antibody. Tβ4 was detected in the hepatocytes of all adult normal livers examined. A zonation of Tβ4 expression was evident in the vast majority of cases. Immunostaining was preferentially detected in zone 3, while a minor degree of reactivity was detected in periportal hepatocytes (zone 1. At higher power, Tβ4-reactive granules appeared mainly localized at the biliary pole of hepatocytes. In cases with a strong immunostaining, even perinuclear areas and the sinusoidal pole of hepatocytes appeared interested by immunoreactivity for Tβ4. The current work first evidences a strong diffuse expression of Tβ4 in the adult human liver, and adds hepatocytes to the list of human cells able to synthesize large amounts of Tβ4 in adulthood. Moreover, Tβ4 should be added to the liver proteins characterized by a zonate expression pattern, in a descending gradient from the terminal vein to the periportal areas of the liver acinus. Identifying the intimate role played by this peptide intracellularly and extracellularly, in physiology and in different liver diseases, is a major challenge for future research focusing on Tβ4.
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Improved limits on beta(-) and beta(-) decays of Ca-48
Czech Academy of Sciences Publication Activity Database
Bakalyarov, A.; Balysh, A.; Barabash, AS.; Beneš, P.; Briancon, C.; Brudanin, V. B.; Čermák, P.; Egorov, V.; Hubert, F.; Hubert, P.; Korolev, NA.; Kosjakov, VN.; Kovalík, Alojz; Lebedev, NA.; Novgorodov, A. F.; Rukhadze, NI.; Štekl, NI.; Timkin, VV.; Veleshko, IE.; Vylov, T.; Umatov, VI.
2002-01-01
Roč. 76, č. 9 (2002), s. 545-547 ISSN 0021-3640 Institutional research plan: CEZ:AV0Z1048901 Keywords : beta decay * double beta decay * Ca-48 Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 1.483, year: 2002
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Using the NCBI Genome Databases to Compare the Genes for Human & Chimpanzee Beta Hemoglobin
Offner, Susan
2010-01-01
The beta hemoglobin protein is identical in humans and chimpanzees. In this tutorial, students see that even though the proteins are identical, the genes that code for them are not. There are many more differences in the introns than in the exons, which indicates that coding regions of DNA are more highly conserved than non-coding regions.
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Energy Technology Data Exchange (ETDEWEB)
A Kolyada; C Lee; A De Biasio; N Beglova
2011-12-31
{beta}2GPI is a major antigen for autoantibodies associated with antiphospholipid syndrome (APS), an autoimmune disease characterized by thrombosis and recurrent pregnancy loss. Only the dimeric form of {beta}2GPI generated by anti-{beta}2GPI antibodies is pathologically important, in contrast to monomeric {beta}2GPI which is abundant in plasma. We created a dimeric inhibitor, A1-A1, to selectively target {beta}2GPI in {beta}2GPI/antibody complexes. To make this inhibitor, we isolated the first ligand-binding module from ApoER2 (A1) and connected two A1 modules with a flexible linker. A1-A1 interferes with two pathologically important interactions in APS, the binding of {beta}2GPI/antibody complexes with anionic phospholipids and ApoER2. We compared the efficiency of A1-A1 to monomeric A1 for inhibition of the binding of {beta}2GPI/antibody complexes to anionic phospholipids. We tested the inhibition of {beta}2GPI present in human serum, {beta}2GPI purified from human plasma and the individual domain V of {beta}2GPI. We demonstrated that when {beta}2GPI/antibody complexes are formed, A1-A1 is much more effective than A1 in inhibition of the binding of {beta}2GPI to cardiolipin, regardless of the source of {beta}2GPI. Similarly, A1-A1 strongly inhibits the binding of dimerized domain V of {beta}2GPI to cardiolipin compared to the monomeric A1 inhibitor. In the absence of anti-{beta}2GPI antibodies, both A1-A1 and A1 only weakly inhibit the binding of pathologically inactive monomeric {beta}2GPI to cardiolipin. Our results suggest that the approach of using a dimeric inhibitor to block {beta}2GPI in the pathological multivalent {beta}2GPI/antibody complexes holds significant promise. The novel inhibitor A1-A1 may be a starting point in the development of an effective therapeutic for antiphospholipid syndrome.
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DEFF Research Database (Denmark)
Kiriy, N.; Kiriy, A.; Bocharova, V.
2004-01-01
by the pulse-radiolysis time-resolved microwave conductivity (PR-TRMC) technique was found to be Sigmamu(min) = 3.9 x 10(-3) cm(2) V-1 s(-1), which is comparable with the PR-TRMC mobility found for alpha,omega-DH6T. The field-effect mobility (FEM) of beta,beta'-DH6T was found to be on the order of 10(-5) cm(2......) V-1 s(-1), which is considerably less than the FEM of alpha,omega-DH6T. To understand the reason for such poor macroscopic electrical properties, the conformation and the molecular packing of beta,beta'-DH6T were systematically studied by means of UV-vis spectroscopy, scanning electron microscopy...... less dense crystalline packing than alpha,omega-DH6T. In contrast to the almost upright orientation of alpha,omega-DH6T molecules against the substrate (tilt angle about 68), the long axis of beta,beta'-DH6T molecules and the surface plane form an angle of similar to20degrees. Thus, the crystalline...
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Integrins beta 5, beta 3 and alpha v are apically distributed in endometrial epithelium.
Aplin, J D; Spanswick, C; Behzad, F; Kimber, S J; Vićovac, L
1996-07-01
Several adhesion molecules have been shown to occur at the surface of endometrial cells. One of these is the integrin alpha v subunit which associates with various beta chains including beta 5. We demonstrate the presence of integrin beta 5 polypeptide in human endometrial epithelial cells throughout the menstrual cycle using immunocytochemistry with monospecific antibodies, and at the mRNA level by thermal amplification from endometrial cDNA. Integrin beta 5 is also found in a population of bone marrow-derived cells. A notable feature of the distribution of the beta 5 subunit in the glandular and luminal epithelium is its apical localization, which may suggest an involvement in implantation. However, no evidence was found for regulated expression of epithelial beta 5. In mouse, the beta 5 subunit is found at both the apical and basal surface of epithelial cells and expression is essentially oestrous cycle-independent. Comparisons are made in both species with the distribution of the alpha v and beta 3 subunits which also localize to the apical epithelium.
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$\\sin(2\\beta)$ with $B^0 \\rightarrow\\!J/\\!\\psi K_\\text{S}$ at the LHCb experiment
Niet, Ramon
2015-01-01
The poster presents the recent measurement of $\\sin(2\\beta)$ using $B^0$ decays to the $J/\\!\\psi K_\\text{S}$ final state. The measurement is based on a dataset corresponding to an integrated luminosity of 3.0$\\,\\text{fb}^{-1}$ collected with the LHCb experiment in proton-proton collisions at center-of-mass energies of 7 and 8 TeV. To control penguin pollutions in the determination of $\\sin(2\\beta)$, $B_s^0$ decays to the same final state can be analysed. The results of the corresponding analysis are presented as well.
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Bhise, Nupura S; Wahlin, Karl J; Zack, Donald J; Green, Jordan J
2013-01-01
Gene delivery can potentially be used as a therapeutic for treating genetic diseases, including neurodegenerative diseases, as well as an enabling technology for regenerative medicine. A central challenge in many gene delivery applications is having a safe and effective delivery method. We evaluated the use of a biodegradable poly(beta-amino ester) nanoparticle-based nonviral protocol and compared this with an electroporation-based approach to deliver episomal plasmids encoding reprogramming factors for generation of human induced pluripotent stem cells (hiPSCs) from human fibroblasts. A polymer library was screened to identify the polymers most promising for gene delivery to human fibroblasts. Feeder-independent culturing protocols were developed for nanoparticle-based and electroporation-based reprogramming. The cells reprogrammed by both polymeric nanoparticle-based and electroporation-based nonviral methods were characterized by analysis of pluripotency markers and karyotypic stability. The hiPSC-like cells were further differentiated toward the neural lineage to test their potential for neurodegenerative retinal disease modeling. 1-(3-aminopropyl)-4-methylpiperazine end-terminated poly(1,4-butanediol diacry-late-co-4-amino-1-butanol) polymer (B4S4E7) self-assembled with plasmid DNA to form nanoparticles that were more effective than leading commercially available reagents, including Lipofectamine® 2000, FuGENE® HD, and 25 kDa branched polyethylenimine, for nonviral gene transfer. B4S4E7 nanoparticles showed effective gene delivery to IMR-90 human primary fibroblasts and to dermal fibroblasts derived from a patient with retinitis pigmentosa, and enabled coexpression of exogenously delivered genes, as is needed for reprogramming. The karyotypically normal hiPSC-like cells generated by conventional electroporation, but not by poly(beta-amino ester) reprogramming, could be differentiated toward the neuronal lineage, specifically pseudostratified optic cups. This
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DEFF Research Database (Denmark)
Grankowski, N; Boldyreff, B; Issinger, O G
1991-01-01
cDNA encoding the casein kinase II (CKII) subunits alpha and beta of human origin were expressed in Escherichia coli using expression vector pT7-7. Significant expression was obtained with E. coli BL21(DE3). The CKII subunits accounted for approximately 30% of the bacterial protein; however, most...
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Energy Technology Data Exchange (ETDEWEB)
Lin, K; Lin, Y; McPhie, P [Chang-Gung College of Medicine and Technology, Graduate Institute of Clinical Medicine, Taoyuan (Taiwan, Province of China); Cheng, S [National Cancer Inst., Bethesda, MD (United States)
1994-12-31
It is evaluated the expression of thyroid hormone nuclear receptors (TRs) and their possible roles in the carcinogenesis of human hepatocarcinoma. The expression of TR{beta}1 and TR{alpha} genes was evaluated at both the mRNA and protein levels. The expression of TR{beta}1 and TR{alpha}1 mRNAs is similar to those found in normal liver. However, the expression of TR isoform proteins depends on the cell-type. The expression of TRaplha1 protein is low in all cell lines examined. However, TR{Beta}1 protein is overexpressed in Mahlavu, SK-Hep-1, and HA22T, moderately expressed in J5, J7, and J328 and is very low HepG2, Hep3B, and PLC/PRF/5 cells. The proliferation of cells in which TR{beta}1 is overexpressed is stimulated by the thyroid hormone, 3,3`,5- triiodo-L-thyronine. These results suggest that TR{beta}1, not TR{alpha}1, is probably involved in the prolifaration of hepatoma cells.
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DEFF Research Database (Denmark)
Mandalari, G.; Adel-Patient, K.; Barkholt, Vibeke
2009-01-01
Initially the resistance to digestion of two cow's milk allergens, beta-casein, and beta-lactoglobulin (beta-Lg), was compared using a "high-protease assay" and a "low-protease assay" in a single laboratory. The low-protease assay represents an alternative standardised protocol mimicking conditions...... found in the gastrointestinal tract. For the high-protease assay, both proteins were incubated with either pepsin or pancreatin and digestion monitored by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and reverse phase-high performance liquid chromatography. The low-protease assay involved...... gastroduodenal digestion in the presence or absence of phosphatidylcholine (PC). Both beta-casein and beta-Lg were susceptible to hydrolysis by pepsin and pancreatin in the high-protease assay. In contrast, the kinetics of beta-casein digestion in the low-protease assay were slower, beta-Lg being pepsin...
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Creek, K E; Geslani, G; Batova, A; Pirisi, L
1995-01-01
Retinoids (vitamin A and its natural and synthetic derivatives) have shown potential as chemopreventive agents, and diets poor in vitamin A and/or its precursor beta-carotene have been linked to an increased risk of cancer at several sites including the cervix. Human papillomavirus (HPV) plays an important role in the etiology of cervical cancer. We have developed an in vitro model of cancer progression using human keratinocytes (HKc) immortalized by HPV16 DNA (HKc/HPV16). Although immortal, early passage HKc/HPV16, like normal HKc, require epidermal growth factor (EGF) and bovine pituitary extract (BPE) for proliferation and undergo terminal differentiation in response to serum and calcium. However, following prolonged culture, growth factor independent HKc/HPV16 lines that no longer require EGF and BPE can be selected (HKc/GFI). Further selection of HKc/GFI produces lines that are resistant to serum- and calcium- induced terminal differentiation (HKc/DR). HKc/DR, but not early passage HKc/HPV16, are susceptible to malignant conversion following transfection with viral Harvey ras or Herpes simplex virus type II DNA. We have investigated the sensitivity of low to high passage HKc/HPV16 and HKc/GFI to growth control by all-trans-retinoic acid (RA, an active metabolite of vitamin A). Early passage HKc/HPV16 are very sensitive to growth inhibition by RA, and in these cells RA decreases the expression of the HPV16 oncogenes E6 and E7. However, as the cells progress in culture they lose their sensitivity to RA. Growth inhibition by RA may be mediated through the cytokine transforming growth factor-beta (TGF-beta), a potent inhibitor of epithelial cell proliferation. RA treatment of HKc/HPV16 and HKc/GFI results in a dose-and time-dependent induction (maximal of 3-fold) in secreted levels of TGF-beta. Also, Northern blot analysis of mRNA isolated from HKc/HPV16 demonstrated that RA treatment induced TGF-beta 1 and TGF-beta 2 expression about 3- and 50-fold, respectively
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Directory of Open Access Journals (Sweden)
Tadesse Eguale
2017-01-01
Full Text Available Abstract Background Beta-lactam and quinolone antimicrobials are commonly used for treatment of infections caused by non-typhoidal Salmonella (NTS and other pathogens. Resistance to these classes of antimicrobials has increased significantly in the recent years. However, little is known on the genetic basis of resistance to these drugs in Salmonella isolates from Ethiopia. Methods Salmonella isolates with reduced susceptibility to beta-lactams (n = 43 were tested for genes encoding for beta-lactamase enzymes, and those resistant to quinolones (n = 29 for mutations in the quinolone resistance determining region (QRDR as well as plasmid mediated quinolone resistance (PMQR genes using PCR and sequencing. Results Beta-lactamase genes (bla were detected in 34 (79.1% of the isolates. The dominant bla gene was blaTEM, recovered from 33 (76.7% of the isolates, majority being TEM-1 (24, 72.7% followed by TEM-57, (10, 30.3%. The blaOXA-10 and blaCTX-M-15 were detected only in a single S. Concord human isolate. Double substitutions in gyrA (Ser83-Phe + Asp87-Gly as well as parC (Thr57-Ser + Ser80-Ile subunits of the quinolone resistance determining region (QRDR were detected in all S. Kentucky isolates with high level resistance to both nalidixic acid and ciprofloxacin. Single amino acid substitutions, Ser83-Phe (n = 4 and Ser83-Tyr (n = 1 were also detected in the gyrA gene. An isolate of S. Miami susceptible to nalidixic acid but intermediately resistant to ciprofloxacin had Thr57-Ser and an additional novel mutation (Tyr83-Phe in the parC gene. Plasmid mediated quinolone resistance (PMQR genes investigated were not detected in any of the isolates. In some isolates with decreased susceptibility to ciprofloxacin and/or nalidixic acid, no mutations in QRDR or PMQR genes were detected. Over half of the quinolone resistant isolates in the current study 17 (58.6% were also resistant to at least one of the beta-lactam antimicrobials
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Beta-human chorionic gonadotropin concentrations in cervicovaginal secretions in preterm delivery
Directory of Open Access Journals (Sweden)
Talip Gül
2010-05-01
Full Text Available Objectives: To investigate beta-human corionic gonadotropin (β-hCG levels in cervicovaginal secretions as an early marker for preterm delivery.Methods: The study included 55 patients at 25-36 of gestational weeks with preterm delivery risk factors including a history of preterm labor in a previous pregnancy or history of second trimester abortion. Beta-human chorionic gonadotropin (β-hCG levels of cervicovaginal secretions were measured in all patients by the radioimmunoassay method using a commercial kit.Results: Preterm delivery was observed in 25 patients and 30 patients gave term delivery. No significant differences were found between preterm and term delivery groups in age, gravidity and parity (P>0.05. APGAR scores and anthropometric measurements of newborns were significantly lower in preterm delivery group (P<0.001. Preterm delivery group had significantly higher cervicovaginal β-hCG levels compared with normal controls (94.7±37.7 vs. 35.5±14.8 mIU/ml, respectively, P<0.001. When 75 mIU/ml value of β-hCG level was taken as cut-off value; the sensitivity of the test was found as 76%, specifity 91.6%, positive predictive value 95.0% and negative predictive value as 79.9%.Conclusion: Concentrations of β-hCG in cervicovaginal secretions may be a useful early biochemical marker to detect preterm. Based on β-hCG levels in cervicovaginal secretions a closer follow-up may decrease some complications of preterm delivery. J Clin Exp Invest 2010; 1(1: 16-20
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Directory of Open Access Journals (Sweden)
Francisco Javier Gálvez-Gastélum
2004-08-01
Full Text Available El factor de crecimiento transformante beta (TGF-beta es una familia de proteínas que incluye al TGF-beta, activinas y a la proteína morfogénica de hueso (BMP, por sus siglas en inglés, citocinas que son secretadas y se relacionan estructuralmente en diferentes especies de metazoarios. Los miembros de la familia del TGF-beta regulan diferentes funciones celulares como proliferación, apoptosis, diferenciación, migración, y tienen un papel clave en el desarrollo del organismo. El TGF-beta está implicado en varias patologías humanas, incluyendo desórdenes autoinmunes y vasculares, así como enfermedades fibróticas y cáncer. La activación del receptor del TGF-beta propicia su fosforilación en residuos de serina/treonina y dispara la fosforilación de proteínas efectoras intracelulares (smad, que una vez activas se translocan al núcleo para inducir la transcripción de genes blanco, y así regular procesos y funciones celulares. Se están desarrollando novedosas estrategias terapéuticas encaminadas a corregir las alteraciones presentes en patologías que involucran al TGF-beta como actor principal.Transforming growth factor-beta (TGF-beta family members include TGF-beta, activins, and bone morphogenetic proteins (BMP. These proteins are structurally related cytokines secreted in diverse Metazoans. TGF-beta family members regulate cellular functions such as proliferation, apoptosis, differentiation, and migration, and play an important role in organism development. Deregulated TGF-beta family signaling participates in various human pathologies including auto-immune diseases, vascular disorders, fibrotic disease, and cancer. Ligand-induced activation of TGF-beta family receptors with intrinsic serine/threonine kinase activity, triggers phosphorylation of the intracellular effectors of TGF-beta signaling, the Smads proteins. Once these proteins are activated they translocate into the nucleus, where they induce transcription of target
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{beta} - amyloid imaging probes
Energy Technology Data Exchange (ETDEWEB)
Jeong, Jae Min [Seoul National University College of Medicine, Seoul (Korea, Republic of)
2007-04-15
Imaging distribution of {beta} - amyloid plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the {beta} -amyloid plaques includes using radiolabeled peptides which can be only applied for peripheral {beta} - amyloid plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging {beta} - amyloid plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for {beta} - amyloid imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for {beta} - amyloid imaging agent.
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DEFF Research Database (Denmark)
Nastainczyk, W; Schmidt-Spaniol, I; Boldyreff, B
1995-01-01
A murine monoclonal anti-protein kinase CK2 beta antibody was isolated and characterized. The antibody detects 1 pmol of purified recombinant CK2 beta-subunit after analysis on SDS-PAGE. Alternatively undenatured CK2 beta-subunit was detected by an ELISA assay either as recombinant CK2 beta......-subunit or in the CK2 holoenzyme (alpha 2 beta 2). Here, concentrations of the first antibody of 1 ng/ml still allowed the detection of the subunit. Immunoblotting of crude cellular extracts from various tissue cultures (man, mouse, and hamster), from human tumors, and the nonneoplastic tissue allowed the detection...... of the CK2 beta-subunit. The detected epitope of this antibody was, as determined by the epitope analysis technique, 123GLSDI127....
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Stabilization of beta-catenin induces pancreas tumor formation.
Heiser, Patrick W; Cano, David A; Landsman, Limor; Kim, Grace E; Kench, James G; Klimstra, David S; Taketo, Maketo M; Biankin, Andrew V; Hebrok, Matthias
2008-10-01
beta-Catenin signaling within the canonical Wnt pathway is essential for pancreas development. However, the pathway is normally down-regulated in the adult organ. Increased cytoplasmic and nuclear localization of beta-catenin can be detected in nearly all human solid pseudopapillary neoplasms (SPN), a rare tumor with low malignant potential. Conversely, pancreatic ductal adenocarcinoma (PDA) accounts for the majority of pancreatic tumors and is among the leading causes of cancer death. Whereas activating mutations within beta-catenin and other members of the canonical Wnt pathway are rare, recent reports have implicated Wnt signaling in the development and progression of human PDA. Here, we sought to address the role of beta-catenin signaling in pancreas tumorigenesis. Using Cre/lox technology, we conditionally activated beta-catenin in a subset of murine pancreatic cells in vivo. Activation of beta-catenin results in the formation of large pancreatic tumors at a high frequency in adult mice. These tumors resemble human SPN based on morphologic and immunohistochemical comparisons. Interestingly, stabilization of beta-catenin blocks the formation of pancreatic intraepithelial neoplasia (PanIN) in the presence of an activating mutation in Kras that is known to predispose individuals to PDA. Instead, mice in which beta-catenin and Kras are concurrently activated develop distinct ductal neoplasms that do not resemble PanIN lesions. These results demonstrate that activation of beta-catenin is sufficient to induce pancreas tumorigenesis. Moreover, they indicate that the sequence in which oncogenic mutations are acquired has profound consequences on the phenotype of the resulting tumor.
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International Nuclear Information System (INIS)
Murphree, S.S.; Saffitz, J.E.
1989-01-01
The density of beta-adrenergic receptors is reduced in crude membranes prepared from failing human myocardium. We used quantitative autoradiography of radioligand binding sites in intact tissue slices to determine whether the total tissue content of receptors is reduced and to characterize the transmural distribution of receptors in cardiac myocytes and the coronary vasculature in hearts obtained from nine cardiac transplant patients with severe congestive failure. Binding of [125Iodo]cyanopindolol to transmural slices of human myocardium was rapid, saturable, stereoselective, and displaceable by agonists and antagonists with an appropriate rank order of potency. Binding isotherms in four normal and nine failing ventricles showed a significant reduction in the total tissue content of beta-receptors in failing myocardium (38.3 +/- 2.0 fmol/mg protein) compared with normal tissue (52.4 +/- 1.7 fmol/mg protein, p = 0.038). In the normal ventricles, the greatest receptor density was observed autoradiographically in myocytic regions of the subendocardium. Receptor density of the coronary arterioles was approximately 70% of that in adjacent myocytic regions. The density of binding sites in both myocytic regions and arterioles was diminished in all regions of the failing ventricles, but down-regulation was due primarily to a selective reduction of beta-receptors of subendocardial myocytes (63 +/- 5% of subepicardial receptor density vs. 115 +/- 6% in controls, p less than 0.0001). These observations indicate that down-regulation occurs nonuniformly in the transmural distribution and thus is likely not related simply to elevated circulating catecholamine levels
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DEFF Research Database (Denmark)
Massumi, Mohammad; Pourasgari, Farzaneh; Nalla, Amarnadh
2016-01-01
developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems......The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have...... positive cells, 1% insulin and glucagon positive cells and 30% insulin and NKX6.1 co-expressing cells. Functionally, ES-DBCs were responsive to high glucose in static incubation and perifusion studies, and could secrete insulin in response to successive glucose stimulations. Mitochondrial metabolic flux...
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LENUS (Irish Health Repository)
Hogan, A M
2012-02-01
Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38\\/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta
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Fan, Jia-Ming; Liu, Ze-Hong; Li, Jing; Wang, Ya-Ping; Yang, Lv-Yuan; Huang, Jiang-Ju
2013-10-01
To observe the effect of ginseng polysaccharide (GPS) on the proliferation and apoptosis of human nasopharyngeal cancer cells CNE-2, and discuss the possible mechanism. The effect of GPS on the growth of CNE-2 cells was observed by CCK8 assay. CNE-2 cells in the logarithmic phase were collected and processed respectively with different concentrations (0, 0. 1, 0. 2, 0. 3. 0. 4 g L-1) of GPS for 48 h. The flow cytometry was used to detect its induction effect on CNE-2 cell apoptosis. Hoechst-33258 cell staining and electron microscope were used to observe the morphological changes of cells. The beta-catenin mRNA expression was detected by Real-time PCR. The protein localizations and expressions of beta-catenin and TCF4 were tested by the immunofluorescence staining. The expressions of beta-catenin, Bcl-2 and Bax proteins were detected by Western blot. CCK8 assay results showed that GPS could remarkably inhibit the proliferation of CNE-2 cells, with dose-time dependence. IC50 of cells induced with GPS for 48 h was 0. 39 g L-1. After being processed with GPS with concentrations of 0.1, 0. 2, 0. 3, 0. 4 g L-1 for 48 h, the cell apoptosis rates of human nasopharyngeal cancer cells CNE-2 were (5. 69 +/- 0. 29)% , (10. 3 +/- 0. 63)% , (15. 4 +/- 0. 74 ) % and (35. 7 +/- 1. 86)% , respectively. Significant difference was observed compared with the control group (2. 08 +/- 0. 11) % (P GPS with the concentration of 0. 4 g L -1 for 48 h. The results of Real-time PCR showed a significant reduction in beta-catenin mRNA expression. The results of laser confocal microscopy revealed notable decrease of beta-catenin and TCF4 expression in nucleus and transfer from nucleus to cell membranes in beta-catenin expression areas after being processed with GPS for 48 h. Western blot showed significant decrease in the expressions of beta-catenin and anti-apoptosis protein Bcl-2, with an increasing expression in apoptosis-promoting protein Bax (P GPS could significantly inhibit the
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Towards Alzheimer's beta-amyloid vaccination.
Frenkel, D; Solomon, B
2001-01-01
Beta-amyloid pathology, the main hallmark of Alzheimer's disease (AD), has been linked to its conformational status and aggregation. We recently showed that site-directed monoclonal antibodies (mAbs) towards the N-terminal region of the human beta-amyloid peptide bind to preformed beta-amyloid fibrils (Abeta), leading to disaggregation and inhibition of their neurotoxic effect. Here we report the development of a novel immunization procedure to raise effective anti-aggregating amyloid beta-protein (AbetaP) antibodies, using as antigen filamentous phages displaying the only EFRH peptide found to be the epitope of these antibodies. Due to the high antigenicity of the phage no adjuvant is required to obtain high affinity anti-aggregating IgG antibodies in animals model, that exhibit identity to human AbetaP. Such antibodies are able to sequester peripheral AbetaP, thus avoiding passage through the blood brain barrier (BBB) and, as recently shown in a transgenic mouse model, to cross the BBB and dissolve already formed beta-amyloid plaques. To our knowledge, this is the first attempt to use as a vaccine a self-anti-aggregating epitope displayed on a phage, and this may pave the way to treat abnormal accumulation-peptide diseases, such as Alzheimer's disease or other amyloidogenic diseases. Copyright 2001 The International Association for Biologicals.
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Compound list: transforming growth factor beta 1 [Open TG-GATEs
Lifescience Database Archive (English)
Full Text Available transforming growth factor beta 1 TGFB1 00182 ftp://ftp.biosciencedbc.jp/archive/op...en-tggates/LATEST/Human/in_vitro/transforming_growth_factor_beta_1.Human.in_vitro.Liver.zip ...
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Pierce Campbell, Christine M; Gheit, Tarik; Tommasino, Massimo; Lin, Hui-Yi; Torres, B Nelson; Messina, Jane L; Stoler, Mark H; Rollison, Dana E; Sirak, Bradley A; Abrahamsen, Martha; Carvalho da Silva, Roberto J; Sichero, Laura; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R
2016-10-01
Cutaneous human papillomaviruses (HPVs) increase the risk of non-melanoma skin cancer in sun-exposed skin. We examined the role of beta-HPV in the development of male external genital lesions (EGLs), a sun-unexposed site. In this nested case-control study (67 men with pathologically-confirmed EGLs and 134 controls), exfoliated cells collected from the surface of lesions and normal genital skin 0, 6, and 12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Beta-HPV prevalence was estimated and conditional logistic regression was used to evaluate the association with condyloma, the most common EGL. While beta-HPV prevalence among controls remained stable, the prevalence among cases was lowest on the surface of lesion. Detecting beta-HPV on the normal genital skin was not associated with the presence or development of condyloma. Cutaneous beta-HPV does not appear to be contributing to pathogenesis in male genital skin. Copyright © 2016. Published by Elsevier Inc.
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Energy Technology Data Exchange (ETDEWEB)
Pasek, Marta [Structural Glycobiology Section, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, Center for Cancer Research, NCI-Frederick, Frederick, MD 2170 (United States); Boeggeman, Elizabeth; Ramakrishnan, Boopathy [Structural Glycobiology Section, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, Center for Cancer Research, NCI-Frederick, Frederick, MD 2170 (United States); Basic Science Program, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, Center for Cancer Research, NCI-Frederick, Frederick, MD 2170 (United States); Qasba, Pradman K., E-mail: qasba@helix.nih.gov [Structural Glycobiology Section, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, Center for Cancer Research, NCI-Frederick, Frederick, MD 2170 (United States)
2010-04-09
The expression of recombinant proteins in Escherichia coli often leads to inactive aggregated proteins known as the inclusion bodies. To date, the best available tool has been the use of fusion tags, including the carbohydrate-binding protein; e.g., the maltose-binding protein (MBP) that enhances the solubility of recombinant proteins. However, none of these fusion tags work universally with every partner protein. We hypothesized that galectins, which are also carbohydrate-binding proteins, may help as fusion partners in folding the mammalian proteins in E. coli. Here we show for the first time that a small soluble lectin, human galectin-1, one member of a large galectin family, can function as a fusion partner to produce soluble folded recombinant human glycosyltransferase, {beta}-1,4-galactosyltransferase-7 ({beta}4Gal-T7), in E. coli. The enzyme {beta}4Gal-T7 transfers galactose to xylose during the synthesis of the tetrasaccharide linker sequence attached to a Ser residue of proteoglycans. Without a fusion partner, {beta}4Gal-T7 is expressed in E. coli as inclusion bodies. We have designed a new vector construct, pLgals1, from pET-23a that includes the sequence for human galectin-1, followed by the Tev protease cleavage site, a 6x His-coding sequence, and a multi-cloning site where a cloned gene is inserted. After lactose affinity column purification of galectin-1-{beta}4Gal-T7 fusion protein, the unique protease cleavage site allows the protein {beta}4Gal-T7 to be cleaved from galectin-1 that binds and elutes from UDP-agarose column. The eluted protein is enzymatically active, and shows CD spectra comparable to the folded {beta}4Gal-T1. The engineered galectin-1 vector could prove to be a valuable tool for expressing other proteins in E. coli.
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International Nuclear Information System (INIS)
Sahagia, M.
1978-01-01
The absolute standardization of radioactive solutions of low energy beta emitters and beta-gamma emitters with a high probability of disintegration to the ground state is described; the tracer and the efficiency extrapolation methods were used. Both types of radionuclides were mathematically and physically treated in an unified manner. The theoretical relations between different beta spectra were calculated according to Williams' model and experimentally verified for: 35 S + 60 Co, 35 S + 95 Nb, 147 Pm + 60 Co, 14 C + 95 Nb and two beta branches of 99 Mo. The optimum range of beta efficiency variation was indicated. The basic supposition that all beta efficieny tend to unity in the same time was experimentally verified, using two 192 Ir beta branches. Four computer programs, written in the FORTRAN IV language, were elaborated, for the adequate processing of the experimental data. Good precision coefficients according to international standards were obtained in the absolute standardization of 35 S, 147 Pm, 99 Mo solutions. (author)
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Eijnden-van Raaij, A.J.M. van den; Koornneef, I.; Zoelen, E.J.J. van
1988-01-01
A new method was developed for the purification of type beta transforming growth factor from human platelets. This method is a three-step procedure including gel filtration, weak cation exchange HPLC and reverse phase HPLC. All steps are carried out at low pH using exclusively volatile acidic buffer
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Directory of Open Access Journals (Sweden)
Elham Farrokhnazar
2016-07-01
Full Text Available Emergence of antibiotic resistance among pathogens, particularly in health centers and hospitals, has become a major public health problem. This study identified AmpC-type beta-lactamase against the antibiotic ceftazidime, cefotaxime and cefpodoxime in E.coli isolated from human and poultry and types of producing genes were studied by PCR. In this study, 500 clinical human samples of urine from hospitals of Tehran during 5 months as well as 300 poultry samples were collected and transferred to the microbiology laboratory. Biochemical tests such as TSI, Urea and IMViC were performed on suspected colonies with E.coli. To identify ESBL producing strains, beta-lactamase samples were cultured on Mueller-Hinton agar through antimicrobial susceptibility test by disk agar diffusion based on the standard CLSI for initial screening. PCR reactions were done using specific primers CITM, EBCM, DHAM and MOXM to identify the beta-lactamase AmpC. A number of 200 human and 55 poultry E.coli samples were screened. In human samples, 105 (52.5% were resistant and potential producers of ESBL and AmpC; out of those, 102 (51% produced ESBL and 3 (1.5% potentially produced AmpC. In the study on 55 E.coli isolates from poultry samples based on the results of disk agar diffusion test, 4 (7.2% samples were resistant and potential producers of ESBL. None of the samples were AmpC producers. Through PCR, 2 human samples (1% were CITM positive and one sample (0.5% was DHAM positive. Through the PCR carried out on poultry samples, there were no bands with 4 primers. There was AmpC in human samples; while further studies are required for poultry samples, because poultry significantly contribute in production of food for humans and can be an important source for dissemination of antibiotic resistance. Given the significance of Ampc in providing high levels of beta-lactam antibiotic resistance, particularly third generation cephalosporins which are very common treatments, more
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DEFF Research Database (Denmark)
Kveiborg, Marie; Flyvbjerg, Allan; Eriksen, E F
2001-01-01
While transforming growth factor-beta1 (TGF-beta1) regulates proliferation and differentiation of human osteoblast precursor cells, the mechanisms underlying these effects are not known. Several hormones and locally acting growth factors regulate osteoblast functions through changes in the insulin......-like growth factors (IGFs) and IGF-binding proteins (IGFBPs). Thus, we studied the effects of TGF-beta1 on IGFs and IGFBPs in human marrow stromal (hMS) osteoblast precursor cells. TGF-beta1 increased the steady-state mRNA level of IGF-I up to 8.5+/-0.6-fold (P...
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Gastrointestinal hyperplasia with altered expression of DNA polymerase beta.
Directory of Open Access Journals (Sweden)
Katsuhiko Yoshizawa
2009-08-01
Full Text Available Altered expression of DNA polymerase beta (Pol beta has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol beta over-expression has not yet been evaluated in a mouse model.We have recently developed a novel transgenic mouse model that over-expresses Pol beta. These mice present with an elevated incidence of spontaneous histologic lesions, including cataracts, hyperplasia of Brunner's gland and mucosal hyperplasia in the duodenum. In addition, osteogenic tumors in mice tails, such as osteoma and osteosarcoma were detected. This is the first report of elevated tumor incidence in a mouse model of Pol beta over-expression. These findings prompted an evaluation of human gastrointestinal tumors with regard to Pol beta expression. We observed elevated expression of Pol beta in stomach adenomas and thyroid follicular carcinomas, but reduced Pol beta expression in esophageal adenocarcinomas and squamous carcinomas.These data support the hypothesis that balanced and proficient base excision repair protein expression and base excision repair capacity is required for genome stability and protection from hyperplasia and tumor formation.
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Energy Technology Data Exchange (ETDEWEB)
Pellicci, Daniel G.; Patel, Onisha; Kjer-Nielsen, Lars; Pang, Siew Siew; Sullivan, Lucy C.; Kyparissoudis, Konstantinos; Brooks, Andrew G.; Reid, Hugh H.; Gras, Stephanie; Lucet, Isabelle S.; Koh, Ruide; Smyth, Mark J.; Mallevaey, Thierry; Matsuda, Jennifer L.; Gapin, Laurent; McCluskey, James; Godfrey, Dale I.; Rossjohn, Jamie; PMCI-A; Monash; UCHSC; Melbourne
2009-09-02
The semi-invariant natural killer T cell receptor (NKT TCR) recognizes CD1d-lipid antigens. Although the TCR{alpha} chain is typically invariant, the {beta} chain expression is more diverse, where three V{beta} chains are commonly expressed in mice. We report the structures of V{alpha}14-V{beta}8.2 and V{alpha}14-V{beta}7 NKT TCRs in complex with CD1d-{alpha}-galactosylceramide ({alpha}-GalCer) and the 2.5 {angstrom} structure of the human NKT TCR-CD1d-{alpha}-GalCer complex. Both V{beta}8.2 and V{beta}7 NKT TCRs and the human NKT TCR ligated CD1d-{alpha}-GalCer in a similar manner, highlighting the evolutionarily conserved interaction. However, differences within the V{beta} domains of the V{beta}8.2 and V{beta}7 NKT TCR-CD1d complexes resulted in altered TCR{beta}-CD1d-mediated contacts and modulated recognition mediated by the invariant {alpha} chain. Mutagenesis studies revealed the differing contributions of V{beta}8.2 and V{beta}7 residues within the CDR2{beta} loop in mediating contacts with CD1d. Collectively we provide a structural basis for the differential NKT TCR V{beta} usage in NKT cells.
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Haas, Michael J; Kurban, William; Shah, Harshit; Onstead-Haas, Luisa; Mooradian, Arshag D
Beta blockers are known to have favorable effects on endothelial function partly because of their capacity to reduce oxidative stress. To determine whether beta blockers can also prevent dextrose-induced endoplasmic reticulum (ER) stress in addition to their antioxidative effects, human coronary artery endothelial cells and hepatocyte-derived HepG2 cells were treated with 27.5 mM dextrose for 24 hours in the presence of carvedilol (a lipophilic beta blockers with alpha blocking activity), propranolol (a lipophilic nonselective beta blockers), and atenolol (a water-soluble selective beta blockers), and ER stress, oxidative, stress and cell death were measured. ER stress was measured using the placental alkaline phosphatase assay and Western blot analysis of glucose regulated protein 78, c-Jun-N-terminal kinase (JNK), phospho-JNK, eukaryotic initiating factor 2α (eIF2α), and phospho-eIF2α and measurement of X-box binding protein 1 (XBP1) mRNA splicing using reverse transcriptase-polymerase chain reaction. Superoxide (SO) generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride (MCLA) chemiluminescence. Cell viability was measured by propidium iodide staining method. The ER stress, SO production, and cell death induced by 27.5 mM dextrose were inhibited by all 3 beta blockers tested. The antioxidative and ER stress reducing effects of beta blockers were also observed in HepG2 cells. The salutary effects of beta blockers on endothelial cells in reducing both ER stress and oxidative stress may contribute to the cardioprotective effects of these agents.
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Directory of Open Access Journals (Sweden)
Akiko Takenaka
Full Text Available UNLABELLED: Adrenergic-receptor beta2 (ADRB2 and beta3 (ADRB3 are obesity genes that play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. The Glu27 allele in ADRB2 and the Arg64 allele in ADRB3 are associated with abdominal obesity and early onset of non-insulin-dependent diabetes mellitus (NIDDM in many ethnic groups. Peroxisome proliferator-activated receptor γ (PPARG is required for adipocyte differentiation. Pro12Ala mutation decreases PPARG activity and resistance to NIDDM. In humans, energy-expense alleles, Gln27 in ADRB2 and Trp64 in ADRB3, are at higher frequencies than Glu27 and Arg64, respectively, but Ala12 in PPARG is at lower frequency than Pro12. Adaptation of humans for lipolysis, thermogenesis, and reduction of fat accumulation could be considered by examining which alleles in these genes are dominant in non-human primates (NHP. All NHP (P. troglodytes, G. gorilla, P. pygmaeus, H. agilis and macaques had energy-thrifty alleles, Gly16 and Glu27 in ADRB2, and Arg64 in ADRB3, but did not have energy-expense alleles, Arg16, Gln27 and Trp64 alleles. In PPARG gene, all NHP had large adipocyte accumulating type, the Pro12 allele. CONCLUSIONS: These results indicate that a tendency to produce much more heat through the energy-expense alleles developed only in humans, who left tropical rainforests for savanna and developed new features in their heat-regulation systems, such as reduction of body hair and increased evaporation of water, and might have helped the protection of entrails from cold at night, especially in glacial periods.
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Directory of Open Access Journals (Sweden)
Pedro Andrade
2012-12-01
Full Text Available Insulin, a crucial therapeutic agent for diabetes mellitus, has been rarely associated with hypersensitivity events. We present a 69-year-old type-2 diabetic patient with urticariform lesions on the sites of subcutaneous injection of insulin. The patient denied any known allergies, except for an unspecific cutaneous reaction after intramuscular penicillin administration in childhood. Prick tests revealed positive reactions to all tested human insulins and insulin analogues. Serum IgE levels were above normal range and RAST tests were positive for human, bovine and porcine insulins, as well as beta-lactams. Type 1 IgEmediated allergy to insulin analogues demands a prompt diagnosis and represents a significant therapeutic challenge in diabetic patients.A insulina é um agente indispensável para o controlo da diabetes mellitus. Os efeitos adversos da sua administração, em particular fenómenos de hipersensibilidade, são raros. Apresentamos um doente de 69 anos, diabético do tipo 2, com episódios recorrentes de lesões urticariformes nos locais de administração subcutânea de insulina. Negava alergias medicamentosas, à excepção de reacção não especificada na infância após penicilina intramuscular. Foram realizados testes cutâneos por puntura (prick tests com diversos tipos de insulina humana e análogos, todos com reacções positivas, associando elevação dos níveis de IgE sérica e provas RAST positivas para as insulinas humana, bovina e porcina e para os antibióticos beta-lactâmicos. A alergia a análogos de insulina exige um diagnóstico precoce, originando um desafio terapêutico importante no doente diabético.
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Directory of Open Access Journals (Sweden)
Lisa Cadavez
Full Text Available In type 2 diabetes, beta-cell dysfunction is thought to be due to several causes, one being the formation of toxic protein aggregates called islet amyloid, formed by accumulations of misfolded human islet amyloid polypeptide (hIAPP. The process of hIAPP misfolding and aggregation is one of the factors that may activate the unfolded protein response (UPR, perturbing endoplasmic reticulum (ER homeostasis. Molecular chaperones have been described to be important in regulating ER response to ER stress. In the present work, we evaluate the role of chaperones in a stressed cellular model of hIAPP overexpression. A rat pancreatic beta-cell line expressing hIAPP exposed to thapsigargin or treated with high glucose and palmitic acid, both of which are known ER stress inducers, showed an increase in ER stress genes when compared to INS1E cells expressing rat IAPP or INS1E control cells. Treatment with molecular chaperone glucose-regulated protein 78 kDa (GRP78, also known as BiP or protein disulfite isomerase (PDI, and chemical chaperones taurine-conjugated ursodeoxycholic acid (TUDCA or 4-phenylbutyrate (PBA, alleviated ER stress and increased insulin secretion in hIAPP-expressing cells. Our results suggest that the overexpression of hIAPP induces a stronger response of ER stress markers. Moreover, endogenous and chemical chaperones are able to ameliorate induced ER stress and increase insulin secretion, suggesting that improving chaperone capacity can play an important role in improving beta-cell function in type 2 diabetes.
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Nilsson, Maria; Wasylik, Sylwia; Mörgelin, Matthias; Olin, Anders I.; Meijers, Joost C. M.; Derksen, Ronald H. W. M.; de Groot, Philip G.; Herwald, Heiko
2008-01-01
During the last years, the importance of antibacterial peptides has attracted considerable attention. We report here that peptides derived from the fifth domain of beta-2 glycoprotein I (beta(2)GPI), a human heparin binding plasma protein, have antibacterial activities against Gram-positive and
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Directory of Open Access Journals (Sweden)
Mohammad Massumi
Full Text Available The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have developed an abbreviated five-stage protocol (25-30 days to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs. We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems. The activation of FGF and Retinoic Acid along with the inhibition of BMP, SHH and TGF-beta led to the generation of 75% NKX6.1+/NGN3+ Endocrine Progenitors. The inhibition of Notch and tyrosine kinase receptor AXL, and the treatment with Exendin-4 and T3 in the final stage resulted in 35% mono-hormonal insulin positive cells, 1% insulin and glucagon positive cells and 30% insulin and NKX6.1 co-expressing cells. Functionally, ES-DBCs were responsive to high glucose in static incubation and perifusion studies, and could secrete insulin in response to successive glucose stimulations. Mitochondrial metabolic flux analyses using Seahorse demonstrated that the ES-DBCs could efficiently metabolize glucose and generate intracellular signals to trigger insulin secretion. In conclusion, targeting selected signaling pathways for 25-30 days was sufficient to generate ES-DBCs in vitro. The ability of ES-DBCs to secrete insulin in response to glucose renders them a promising model for the in vitro screening of drugs, small molecules or genes that may have potential to influence beta-cell function.
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Pavlikova, Nela; Smetana, Pavel; Halada, Petr; Kovar, Jan
2015-10-01
Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. Copyright © 2015 Elsevier Inc. All rights reserved.
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Fungal beta glucan protects radiation induced DNA damage in human lymphocytes.
Pillai, Thulasi G; Maurya, Dharmendra K; Salvi, Veena P; Janardhanan, Krishnankutty K; Nair, Cherupally K K
2014-02-01
Ganoderma lucidum (Ling Zhi), a basidiomycete white rot macrofungus has been used extensively for therapeutic use in China, Japan, Korea and other Asian countries for 2,000 years. The present study is an attempt to investigate its DNA protecting property in human lymphocytes. Beta glucan (BG) was isolated by standard procedure and the structure and composition were studied by infrared radiation (IR) and nuclear magnetic resonance (NMR) spectroscopy, gel filtration chromatography and paper chromatography. The radioprotective properties of BG isolated from the macro fungi Ganoderma lucidum was assessed by single cell gel electrophoresis (comet assay). Human lymphocytes were exposed to 0, 1, 2 and 4 Gy gamma radiation in the presence and absence of BG. The comet parameters were reduced by BG. The results indicate that the BG of G. lucidum possessed significant radioprotective activity with DNA repairing ability and antioxidant activity as the suggestive mechanism. The findings suggest the potential use of this mushroom for the prevention of radiation induced cellular damages.
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Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity
Energy Technology Data Exchange (ETDEWEB)
Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: sungy2004@sohu.com [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: rtliu@tsinghua.edu.cn [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)
2009-12-25
Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.
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DEFF Research Database (Denmark)
Abuyaman, Omar; Nexo, Ebba
2015-01-01
BACKGROUND: Cellular uptake of vitamin B12 (B12) demands binding of the vitamin to transcobalamin (TC) and recognition of TC-B12 (holoTC) by the receptor CD320. Recently, we identified a soluble form of CD320 (sCD320) in human plasma. Here we present data on the occurrence of this soluble receptor...... phospho-tau (181P) (p-tau), total tau (t-tau) and amyloid-beta 1-42 (Aβ) (n = 177) employing commercial ELISA kits (Innogenetics Company). Size exclusion chromatography was performed on a Superdex 200 column. RESULTS: The median sCD320 concentration in CSF (14 pmol/L) is around five times lower than...
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Sena-Esteves, M; Camp, S M; Alroy, J; Breakefield, X O; Kaye, E M
2000-03-20
Mutations in the lysosomal acid beta-galactosidase (EC 3.2.1.23) underlie two different disorders: GM1 gangliosidosis, which involves the nervous system and visceral organs to varying extents, and Morquio's syndrome type B (Morquio B disease), which is a skeletal-connective tissue disease without any CNS symptoms. This article shows that transduction of human GM1 gangliosidosis fibroblasts with retrovirus vectors encoding the human acid beta-galactosidase cDNA leads to complete correction of the enzymatic deficiency. The newly synthesized enzyme is correctly processed and targeted to the lysosomes in transduced cells. Cross-correction experiments using retrovirus-modified cells as enzyme donors showed, however, that the human enzyme is transferred at low efficiencies. Experiments using a different retrovirus vector carrying the human cDNA confirmed this observation. Transduction of human GM1 fibroblasts and mouse NIH 3T3 cells with a retrovirus vector encoding the mouse beta-galactosidase cDNA resulted in high levels of enzymatic activity. Furthermore, the mouse enzyme was found to be transferred to human cells at high efficiency. Enzyme activity measurements in medium conditioned by genetically modified cells suggest that the human beta-galactosidase enzyme is less efficiently released to the extracellular space than its mouse counterpart. This study suggests that lysosomal enzymes, contrary to the generalized perception in the field of gene therapy, may differ significantly in their properties and provides insights for design of future gene therapy interventions in acid beta-galactosidase deficiency.
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Additional beta-delayed protons from the T/sub z/ = -3/2 nuclei 21Mg, 25Si, 29S, and 41Ti
International Nuclear Information System (INIS)
Zhou, Z.Y.; Schloemer, E.C.; Cable, M.D.; Ahmed, M.; Reiff, J.E.; Cerny, J.
1985-01-01
Beta-delayed proton emission has proven to be a useful tool for understanding nuclei far from stability. Most of the beta decay strength is concentrated at and below the isobaric analog state (IAS) of the parent nucleus (precursor) ground state. Identification of beta strength to states above the IAS is important not only because it provides additional tests of nuclear models of beta decay, but also because proton emission from such beta daughter nuclei frequently constitutes an important component of the background in searches for more exotic nuclei. Therefore the authors have re-measured the beta-delayed proton spectra of four T/sub z/ = -3/2 nuclei: 21 Mg, 25 Si, 29 S, and 41 Ti. Fourteen previously unreported proton groups were observed and beta decay branching ratios were derived for each
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Simultaneous extraction of. beta. -endorphin and leu- and met-enkephalins from human and rat plasma
Energy Technology Data Exchange (ETDEWEB)
Bhathena, S.J.; Smith, P.M.; Kennedy, B.W. (Dept. of Agriculture, Beltsville, MD (USA)); Voyles, N.R.; Recant, L. (Diabetes Research Laboratory, Washington, DC (USA))
1989-01-01
A simple, rapid and reliable procedure is described to simultaneously concentrated and purify {beta}-endorphin, leu-and met-enkephalins from small volumes of human and rat plasma before radioimmunoassay is performed. It uses C{sub 18} Sep-Pak reverse phase cartridges. The effectiveness of different protease inhibitors in preventing degradation of opiates by plasma and different solvent systems for eluting opiates is also evaluated.
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International Nuclear Information System (INIS)
Ruzicka, F.J.; Schmid, S.M.; Groveman, D.S.; Cummings, K.B.; Borden, E.C.
1987-01-01
Studies of various established human bladder and renal carcinoma cell lines cultured in vitro demonstrated the presence of specific, saturable, high affinity binding sites for 125 I-labeled human interferon Beta ser IFN-beta ser). This recombinant produced interferon labeled with approximately one atom of 125 I/molecule of IFN expressed minimal or no loss of antiviral activity. A single class of binding sites (1000-2000/cell) with an affinity constant of 10(10)-10(11) L/M was measured at 4 degrees C for cells exhibiting widely different sensitivity to the antiproliferative effect of IFN-beta ser. Major fluctuations in the binding of 125 I-labeled IFN-beta ser to cellular receptors were observed during in vitro proliferation of four of five cell lines examined. A significant decrease (P less than 0.001) in specific binding was observed 48 h after cultures were established. Cell cycle analysis suggested that within the first 24 h and in the very late log and stationary phase of growth of ACHN (human renal carcinoma) cells, variations in the binding of 125 I-labeled IFN-beta ser were partially attributable to binding fluctuations during the mitotic cycle. The 2- to 3-fold decline 24 h following plating of ACHN cells corresponded to a 70% decrease in the number of cells in G0-G1. T24 (human transitional cell carcinoma) and ACHN cells, synchronized by serum starvation, demonstrated increased binding of 125 I-labeled IFN-beta ser 4-16 h following serum replenishment. This increase in receptor binding occurred prior to the onset of DNA and protein synthesis and was followed by a decline immediately prior to cell division. Binding site analysis indicated that the increased binding prior to DNA synthesis was due to a 5- to 6-fold increase in receptor affinity for the radiolabeled ligand
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DEFF Research Database (Denmark)
Lehrmann, E; Kiefer, R; Christensen, Thomas
1998-01-01
The potentially neurotrophic cytokine transforming growth factor-beta1 (TGF-beta1) is locally expressed following human stroke and experimental ischemic lesions, but the cellular source(s) and profile of induction have so far not been established in experimental focal cerebral ischemia. This stud...
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Andreas Bayer; Justus Lammel; Mersedeh Tohidnezhad; Sebastian Lippross; Peter Behrendt; Tim Klüter; Thomas Pufe; Jochen Cremer; Holger Jahr; Franziska Rademacher; Regine Gläser; Jürgen Harder
2017-01-01
Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF?)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting acti...
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Energy Technology Data Exchange (ETDEWEB)
Kuikka, J.T. [Dept. of Clinical Physiology, Kuopio Univ. Hospital (Finland); AAkerman, K. [Dept. of Clinical Physiology, Kuopio Univ. Hospital (Finland); Bergstroem, K.A. [Dept. of Clinical Physiology, Kuopio Univ. Hospital (Finland); Karhu, J. [Dept. of Clinical Neurophysiology, Kuopio Univ. Hospital (Finland); Hiltunen, J. [MAP Medical Technologies Oy, Tikkakoski (Finland); Haukka, J. [MAP Medical Technologies Oy, Tikkakoski (Finland); Heikkinen, J. [Dept. of Clinical Physiology, Kuopio Univ. Hospital (Finland); Tiihonen, J. [Dept. of Forensic Psychiatry, Niuvanniemi Hospital, Kuopio (Finland); Wang, S. [Research Biochemical International (RBI), Natick, MA (United States); Neumeyer, J.L. [Research Biochemical International (RBI), Natick, MA (United States)
1995-07-01
Here we report a pilot comparison of [{sup 123}I]{beta}-CIT and [{sup 123}I]{beta}-CIT-FP with a new tropane derivative, [{sup 123}I]N-(2-fluoroethyl)-2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane ([{sup 123}I]{beta}-CIT-FE), using SPET imaging in four healthy male subjects. Peak uptake of [{sup 123}I]{beta}-CIT-FE into the basal ganglia occurred very rapidly (0.5 h after injection of tracer), after which the striatal washout obeyed a bi-exponential form. The specific DAT binding of [{sup 123}I]{beta}-CIT-FE into the basal ganglia was somewhat less (0.785{+-}0.117) than that of [{sup 123}I]{beta}-CIT (0.922{+-}0.004) or [{sup 123}I]{beta}-CIT-FP (0.813{+-}0.047). All these tracers have excellent imaging quality in healthy control subjects. However, the relatively fast washout of [{sup 123}I]{beta}-CIT-FE and low temporal resolution of older SPET cameras may limit the use of this tracer to the measurement of the DAT density. (orig./UG)
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Energy Technology Data Exchange (ETDEWEB)
Pavlikova, Nela, E-mail: nela.pavlikova@lf3.cuni.cz [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Smetana, Pavel [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Halada, Petr [Laboratory of Molecular Structure Characterization, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague (Czech Republic); Kovar, Jan [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic)
2015-10-15
Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha-enolase, actin
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International Nuclear Information System (INIS)
Pavlikova, Nela; Smetana, Pavel; Halada, Petr; Kovar, Jan
2015-01-01
Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha-enolase, actin
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Energy Technology Data Exchange (ETDEWEB)
Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr. (Department of Biochemistry, Albany Medical College, New York, NY (USA))
1991-06-01
We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) induced uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.
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DEFF Research Database (Denmark)
Larsen, T.S.; Rasmussen, P.; Overgaard, M.
2008-01-01
Intense exercise decreases the cerebral metabolic ratio of oxygen to carbohydrates [O(2)/(glucose + (1/2)lactate)], but whether this ratio is influenced by adrenergic stimulation is not known. In eight males, incremental cycle ergometry increased arterial lactate to 15.3 +/- 4.2 mm (mean +/- s.......d.) and the arterial-jugular venous (a-v) difference from -0.02 +/- 0.03 mm at rest to 1.0 +/- 0.5 mm (P cerebral metabolic ratio decreased from 5.5 +/- 1.4 to 3.0 +/- 0.3 (P ... of a non-selective beta-adrenergic (beta(1) + beta(2)) receptor antagonist (propranolol) reduced heart rate (69 +/- 8 to 58 +/- 6 beats min(-1)) and exercise capacity (239 +/- 42 to 209 +/- 31 W; P
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Souazé, Frédérique; Viardot-Foucault, Véronique; Roullet, Nicolas; Toy-Miou-Leong, Mireille; Gompel, Anne; Bruyneel, Erik; Comperat, Eva; Faux, Maree C; Mareel, Marc; Rostène, William; Fléjou, Jean-François; Gespach, Christian; Forgez, Patricia
2006-04-01
Alterations in the Wnt/APC (adenomatous polyposis coli) signalling pathway, resulting in beta-catenin/T cell factor (Tcf)-dependent transcriptional gene activation, are frequently detected in familial and sporadic colon cancers. The neuropeptide neurotensin (NT) is widely distributed in the gastrointestinal tract. Its proliferative and survival effects are mediated by a G-protein coupled receptor, the NT1 receptor. NT1 receptor is not expressed in normal colon epithelial cells, but is over expressed in a number of cancer cells and tissues suggesting a link to the outgrowth of human colon cancer. Our results demonstrate that the upregulation of NT1 receptor occurring in colon cancer is the result of Wnt/APC signalling pathway activation. We first established the functionality of the Tcf response element within the NT1 receptor promoter. Consequently, we observed the activation of NT1 receptor gene by agents causing beta-catenin cytosolic accumulation, as well as a strong decline of endogenous receptor when wt-APC was restored. At the cellular level, the re-establishment of wt-APC phenotype resulted in the impaired functionality of NT1 receptor, like the breakdown in NT-induced intracellular calcium mobilization and the loss of NT pro-invasive effect. We corroborated the Wnt/APC signalling pathway on the NT1 receptor promoter activation with human colon carcinogenesis, and showed that NT1 receptor gene activation was perfectly correlated with nuclear or cytoplasmic beta-catenin localization while NT1 receptor was absent when beta-catenin was localized at the cell-cell junction in early adenomas of patients with familial adenomatous polyposis, hereditary non-polyposis colorectal cancer and loss of heterozygosity tumours. In this report we establish a novel link in vitro between the Tcf/beta-catenin pathway and NT1 receptor promoter activation.
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Zhang, Ling; Xiong, Wenqian; Xiong, Yao; Liu, Hengwei; Li, Na; Du, Yu; Liu, Yi
2016-03-01
Extracellular matrix remodeling is necessary for ectopic endometrium implantation. Many studies have shown an increased expression of matrix metalloproteinase 9 (MMP9) in the ectopic endometrium of endometriosis. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. The objective of our study was to investigate the association between MMP9 and the Wnt signaling pathway under the regulation of 17beta-estradiol (E2) in endometrial stromal cells. We found that MMP9 was elevated in tissues from women with endometriosis compared with normal women. Furthermore, MMP9 and beta-catenin increased concurrently in a time- and dose-dependent manner after E2 treatment. To clarify the relationship between MMP9 and beta-catenin, we performed luciferase promoter reporter and chromatin immunoprecipitation assays. A beta-catenin/TCF3/LEF1 complex bound to a specific site on the MMP9 promoter that promoted MMP9 gene and protein expression. The promotion of MMP9 by the Wnt signaling pathway under the regulation of E2 may contribute to the pathophysiology of this disease. © 2016 by the Society for the Study of Reproduction, Inc.
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Iannacone, Michelle R; Gheit, Tarik; Pfister, Herbert; Giuliano, Anna R; Messina, Jane L; Fenske, Neil A; Cherpelis, Basil S; Sondak, Vernon K; Roetzheim, Richard G; Silling, Steffi; Pawlita, Michael; Tommasino, Massimo; Rollison, Dana E
2014-05-01
Cutaneous human papillomaviruses (HPV) have been reported in cutaneous squamous cell carcinoma (SCC). We conducted a clinic-based case-control study to investigate the association between genus-beta HPV DNA in eyebrow hairs (EBH) and SCC. EBH from 168 SCC cases and 290 controls were genotyped for genus-beta HPV DNA. SCC tumors from a subset of cases (n = 142) were also genotyped. Viral load was determined in a subset of specimens positive for a single HPV type. Associations with SCC were estimated by odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and sex using logistic regression. Statistical tests were two-sided. EBH DNA prevalence was greater in cases (87%) than controls (73%) (p genus-beta types tested, when accounting for DNA for the same HPV type in the tumor (ORs = 3.44-76.50). Compared to controls, the mean viral DNA load in EBH among the selected cases was greater for HPV5, HPV8 and HPV24, but lower for HPV38. SCC cases were more likely than controls to have HPV DNA+ EBH for single and multiple HPV types, providing additional support for the potential role of genus-beta HPV infections in SCC development. © 2013 UICC.
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International Nuclear Information System (INIS)
Rouyer-Fessard, P.; Garel, M.C.; Domenget, C.; Guetarni, D.; Bachir, D.; Colonna, P.; Beuzard, Y.
1989-01-01
The soluble pool of alpha hemoglobin chains present in blood or bone marrow cells was measured with a new affinity method using a specific probe, beta A hemoglobin chain labeled with [ 3 H]N-ethylmaleimide. This pool of soluble alpha chains was 0.067 ± 0.017% of hemoglobin in blood of normal adult, 0.11 ± 0.03% in heterozygous beta thalassemia and ranged from 0.26 to 1.30% in homozygous beta thalassemia intermedia. This elevated pool of soluble alpha chains observed in human beta thalassemia intermedia decreased 33-fold from a value of 10% of total hemoglobin in bone marrow cells to 0.3% in the most dense red blood cells. The amount of insoluble alpha chains was measured by using the polyacrylamide gel electrophoresis in urea and Triton X-100. In beta thalassemia intermedia the amount of insoluble alpha chains was correlated with the decreased spectrin content of red cell membrane and was associated with a decrease in ankyrin and with other abnormalities of the electrophoretic pattern of membrane proteins. The loss and topology of the reactive thiol groups of membrane proteins was determined by using [ 3 H]N-ethylmaleimide added to membrane ghosts prior to urea and Triton X-100 electrophoresis. Spectrin and ankyrin were the major proteins with the most important decrease of thiol groups
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Relation between the 2{nu}{beta}{beta} and 0{nu}{beta}{beta} nuclear matrix elements
Energy Technology Data Exchange (ETDEWEB)
Vogel, Petr [Kellogg Radiation Laboratory, Caltech, Pasadena, CA 91125 (United States); Simkovic, Fedor [Department of Nuclear Physics and Biophysics, Comenius University, Mlynska dolina F1, SK-84248 Bratislava (Slovakia)
2011-12-16
A formal relation between the GT part of the nuclear matrix elements M{sub GT}{sup 0{nu}} of 0{nu}{beta}{beta} decay and the closure matrix elements M{sub cl}{sup 2{nu}} of 2{nu}{beta}{beta} decay is established. This relation is based on the integral representation of these quantities in terms of their dependence on the distance r between the two nucleons undergoing transformation. We also discuss the difficulties in determining the correct values of the closure 2{nu}{beta}{beta} decay matrix elements.
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Poirel, Laurent; Cattoir, Vincent; Soares, Ana; Soussy, Claude-James; Nordmann, Patrice
2007-02-01
The plasmid-mediated quinolone resistance determinant QnrS1 was identified in non-clonally related Enterobacter cloacae isolates in association with a transferable narrow-spectrum beta-lactam resistance marker. Cloning experiments allowed the identification of a novel Ambler class A beta-lactamase, named LAP-1. It shares 62 and 61% amino acid identity with the most closely related beta-lactamases, TEM-1 and SHV-1, respectively. It has a narrow-spectrum hydrolysis of beta-lactams and is strongly inhibited by clavulanic acid and sulbactam and, to a lesser extent, by tazobactam. Association of the blaLAP-1 gene with the qnrS1 gene was identified in E. cloacae isolates from France and Vietnam. These genes were plasmid located and associated with similar insertion sequences but were not associated with sul1-type class 1 integrons, as opposed to the qnrA genes.
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Energy Technology Data Exchange (ETDEWEB)
Murata, Yoko
1995-12-31
Recombinant hTSH is now successfully being used in clinical studies of thyroid cancer. Because of its therapeutic potential, we have constructed a longer acting analog of hTSH by fusing the carboxy terminal extension peptide (CTEP) of hCG{beta} onto hTSH{beta}. When coexpressed either with {alpha}-subunit complementary DNA or {alpha}-minigene in African green monkey (Cos-7) and human embryonic kidney (293) cells, the chimera was fully bioactive in vitro and exhibited enhanced in vivo potency associated with a prolonged plasma half-life. The addition of 29 amino acids with 4 O-linked oligosaccharide chains did not affect the assembly and secretion of chimeric TSH. Wild type (WT) and chimeric hTSH secreted by Cos-7 and 293 cells displayed wide differences in their plasma half-lives, presumably due to the difference in the terminal sialic acid and sulfate of their oligosaccharide chains. Chimeric and WT hTSH secreted by both cell lines demonstrated similar bioactivity in cAMP production, with some differences in [{sup 3} H]-thymidine incorporation. Chimeric hTSH secreted by Cos-7 appears to be more active than that secreted by 293 cells, as judged by growth assay. Cos-7 produced chimeric hTSH showed the maximum increase in half-life, indicating the importance of sialic acid in prolonging half-life and in vivo potency. Sulfation of both subunits, predominantly {beta} and to a lesser extent {alpha}, appears to be responsible, at least in part, for the increased metabolic clearance of WT and chimeric TSH secreted by 293 cells. Apart from its therapeutic potential, chimeric TSH produced in various cell lines can be used as a tool to delineate the roles of sulfate and sialic acid in the in vivo clearance and, thereby in the in vivo bioactivity. (author). 104 refs., 23 figs., 3 tabs.
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Zannetti, Antonella; Del Vecchio, Silvana; Iommelli, Francesca; Del Gatto, Annarita; De Luca, Stefania; Zaccaro, Laura; Papaccioli, Angela; Sommella, Jvana; Panico, Mariarosaria; Speranza, Antonio; Grieco, Paolo; Novellino, Ettore; Saviano, Michele; Pedone, Carlo; Salvatore, Marco
2009-08-15
To test whether a novel bifunctional chimeric peptide comprising a cyclic Arg-Gly-Asp pentapeptide covalently bound to an echistatin domain can discriminate alpha(v)beta(3) from alpha(v)beta(5) integrin, thus allowing the in vivo selective visualization of alpha(v)beta(3) expression by single-photon and positron emission tomography (PET) imaging. The chimeric peptide was preliminarily tested for inhibition of alpha(v)beta(3)-dependent cell adhesion and competition of 125I-echistatin binding to membrane of stably transfected K562 cells expressing alpha(v)beta(3) (Kalpha(v)beta(3)) or alpha(v)beta(5) (Kalpha(v)beta(5)) integrin. The chimeric peptide was then conjugated with diethylenetriaminepentaacetic acid and labeled with 111In for single-photon imaging, whereas a one-step procedure was used for labeling the full-length peptide and a truncated derivative, lacking the last five C-terminal amino acids, with 18F for PET imaging. Nude mice bearing tumors from Kalpha(v)beta(3), Kalpha(v)beta(5), U87MG human glioblastoma, and A431 human epidermoid cells were subjected to single-photon and PET imaging. Adhesion and competitive binding assays showed that the novel chimeric peptide selectively binds to alpha(v)beta(3) integrin and does not cross-react with alpha(v)beta(5). In agreement with in vitro findings, single-photon and PET imaging studies showed that the radiolabeled chimeric peptide selectively localizes in tumor xenografts expressing alphavbeta3 and fails to accumulate in those expressing alpha(v)beta(5) integrin. When 18F-labeled truncated derivative was used for PET imaging, alphavbeta3- and alpha(v)beta(5)-expressing tumors were visualized, indicating that the five C-terminal amino acids are required to differentially bind the two integrins. Our findings indicate that the novel chimeric Arg-Gly-Asp peptide, having no cross-reaction with alphavbeta5 integrin, allows highly selective alphavbeta3 expression imaging and monitoring.
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Bolduc, Gilles R; Madoff, Lawrence C
2007-12-01
Group B Streptococcus (GBS) is the leading cause of bacterial pneumonia, sepsis and meningitis among neonates and a cause of morbidity among pregnant women and immunocompromised adults. GBS epithelial cell invasion is associated with expression of alpha C protein (ACP). Loss of ACP expression results in a decrease in GBS internalization and translocation across human cervical epithelial cells (ME180). Soluble ACP and its 170 amino acid N-terminal region (NtACP), but not the repeat protein RR', bind to ME180 cells and reduce internalization of wild-type GBS to levels obtained with an ACP-deficient isogenic mutant. In the current study, ACP colocalized with alpha(1)beta(1)-integrin, resulting in integrin clustering as determined by laser scanning confocal microscopy. NtACP contains two structural domains, D1 and D2. D1 is structurally similar to fibronectin's integrin-binding region (FnIII10). D1's (KT)D146 motif is structurally similar to the FnIII10 (RG)D1495 integrin-binding motif, suggesting that ACP binds alpha(1)beta(1)-integrin via the D1 domain. The (KT)D146A mutation within soluble NtACP reduced its ability to bind alpha(1)beta(1)-integrin and inhibit GBS internalization within ME180 cells. Thus ACP binding to human epithelial cell integrins appears to contribute to GBS internalization within epithelial cells.
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Primate beta oscillations and rhythmic behaviors.
Merchant, Hugo; Bartolo, Ramón
2018-03-01
The study of non-human primates in complex behaviors such as rhythm perception and entrainment is critical to understand the neurophysiological basis of human cognition. Next to reviewing the role of beta oscillations in human beat perception, here we discuss the role of primate putaminal oscillatory activity in the control of rhythmic movements that are guided by a sensory metronome or internally gated. The analysis of the local field potentials of the behaving macaques showed that gamma-oscillations reflect local computations associated with stimulus processing of the metronome, whereas beta-activity involves the entrainment of large putaminal circuits, probably in conjunction with other elements of cortico-basal ganglia-thalamo-cortical circuit, during internally driven rhythmic tapping. Thus, this review emphasizes the need of parametric neurophysiological observations in non-human primates that display a well-controlled behavior during high-level cognitive processes.
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Directory of Open Access Journals (Sweden)
Cunyou Zhao
Full Text Available BACKGROUND: Non-coding single nucleotide polymorphisms (SNPs in GABRB2, the gene for beta(2-subunit of gamma-aminobutyric acid type A (GABA(A receptor, have been associated with schizophrenia (SCZ and quantitatively correlated to mRNA expression and alternative splicing. METHODS AND FINDINGS: Expression of the Exon 10 region of GABRB2 from minigene constructs revealed this region to be an "alternative splicing hotspot" that readily gave rise to differently spliced isoforms depending on intron sequences. This led to a search in human brain cDNA libraries, and the discovery of two novel isoforms, beta(2S1 and beta(2S2, bearing variations in the neighborhood of Exon-10. Quantitative real-time PCR analysis of postmortem brain samples showed increased beta(2S1 expression and decreased beta(2S2 expression in both SCZ and bipolar disorder (BPD compared to controls. Disease-control differences were significantly correlated with SNP rs187269 in BPD males for both beta(2S1 and beta(2S2 expressions, and significantly correlated with SNPs rs2546620 and rs187269 in SCZ males for beta(2S2 expression. Moreover, site-directed mutagenesis indicated that Thr(365, a potential phosphorylation site in Exon-10, played a key role in determining the time profile of the ATP-dependent electrophysiological current run-down. CONCLUSION: This study therefore provided experimental evidence for the importance of non-coding sequences in the Exon-10 region in GABRB2 with respect to beta(2-subunit splicing diversity and the etiologies of SCZ and BPD.
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Directory of Open Access Journals (Sweden)
Zdeněk Kříž
Full Text Available Progressive cerebral deposition of amyloid beta occurs in Alzheimers disease and during the aging of certain mammals (human, monkey, dog, bear, cow, cat but not others (rat, mouse. It is possibly due to different amino acid sequences at positions 5, 10 and 13. To address this issue, we performed series of 100 ns long trajectories (each trajectory was run twice with different initial velocity distribution on amyloid beta (1-42 with the human and rat amino acid sequence in three different environments: water with only counter ions, water with NaCl at a concentration of 0.15 M as a model of intracellular Na(+ concentration at steady state, and water with NaCl at a concentration of 0.30 M as a model of intracellular Na(+ concentration under stimulated conditions. We analyzed secondary structure stability, internal hydrogen bonds, and residual fluctuation. It was observed that the change in ionic strength affects the stability of internal hydrogen bonds. Increasing the ionic strength increases atomic fluctuation in the hydrophobic core of the human amyloid, and decreases the atomic fluctuation in the case of rat amyloid. The secondary structure analyses show a stable α-helix part between residues 10 and 20. However, C-terminus of investigated amyloids is much more flexible showing no stable secondary structure elements. Increasing ionic strength of the solvent leads to decreasing stability of the secondary structural elements. The difference in conformational behavior of the three amino acids at position 5, 10 and 13 for human and rat amyloids significantly changes the conformational behavior of the whole peptide.
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International Nuclear Information System (INIS)
2013-01-01
The Ordinance Brazilian of Ministry of Health (MS 2914/2011) establishes the standards for quality of water intended for human consumption, being limits values of 5.0 Bq/L for gross alpha, and 1.0 Bq/L for gross beta radioactivity. The liquid scintillation spectrometry (LSC) technique has been presented as an alternative to conventional procedure using gas flow proportional counter. The present work shows a review of the methods for determination of gross alpha and gross beta in water by using LSC. Between the factors that influence the accuracy and repeatability of the analytical results we can highlight: thermal preconcentration, type of the acid and calibration standard. A procedure was established and carried out to samples of the National Program of Intercomparison of Radionuclides in Environmental Samples for evaluation of its performance. The gross alpha and gross beta analysis in samples of the public water supplies in the Metropolitan Region of Goiania, state of Goias was carried out. The results are consistent with the guideline values form the Ministry of Health concerning radioactivity. (author)
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International Nuclear Information System (INIS)
Turaihi, K.; Khokher, M.A.; Barradas, M.A.; Mikhailidis, D.P.; Dandona, P.
1989-01-01
Although active transport of potassium into human platelets has been demonstrated previously, there is hitherto no evidence that human platelets have an ouabain-inhibitable Na-K ATPase in their membrane. The present study demonstrates active rubidium (used as an index of potassium influx), 86 Rb(K), influx into platelets, inhibitable by ouabain, and also demonstrates the presence of specific [ 3 H]ouabain binding by the human platelet. This 86 Rb(K) influx was stimulated by adrenaline, isoprenaline, and salbutamol, but noradrenaline caused a mild inhibition. Active 86 Rb(K) influx by platelets was inhibited markedly by timolol, mildly by atenolol, but not by phentolamine. Therefore, active 86 Rb(K) influx in human platelets is enhanced by stimulation of beta adrenoceptors of the beta 2 subtype. The platelet may therefore replace the leukocyte in future studies of Na-K ATPase activity. This would be a considerable advantage in view of the ease and rapidity of preparation of platelets
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Jiang, Zhong; Li, Cuizhen; Fischer, Andrew; Dresser, Karen; Woda, Bruce A
2005-02-01
We assessed the usefulness of immunohistochemical analysis with a 3-antibody cocktail (alpha-methylacyl coenzyme A racemase [AMACR, or P504S], 34betaE12, p63) and a double-chromogen reaction for detection of limited prostate cancer in 138 needle biopsy specimens, including 82 with small foci of prostatic adenocarcinoma and 56 benign prostates. When carcinoma was present, red cytoplasmic granular staining (AMACR) in the malignant glands and cells and dark brown nuclear (p63) and cytoplasmic (34betaE12) staining in basal cells of adjacent nonmalignant glands were found. Of 82 cases of small foci of prostatic adenocarcinoma, 78 (95%) expressed AMACR; all malignant glands were negative for basal cell staining. All benign glands adjacent to malignant glands were recognized easily by basal cell marker positivity and little or no AMACR expression. No benign glands were simultaneously positive for AMACR and negative for basal cell markers (specificity, 100%). There were no differences in intensity and numbers of positive glands with double-chromogen staining compared with using 1-color staining. Our results indicate that immunohistochemistry with a 3-antibody cocktail and double chromogen is a simple and easy assay that can be used as a routine test, which overcomes the problems of studying small lesions in prostate needle biopsies with multiple immunohistochemical stains.
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Expression of human beta-N-acetylhexosaminidase B in yeast eases the search for selective inhibitors
Czech Academy of Sciences Publication Activity Database
Krejzová, Jana; Kulik, Natalia; Slámová, Kristýna; Křen, Vladimír
2016-01-01
Roč. 89, JUL (2016), s. 1-6 ISSN 0141-0229 R&D Projects: GA ČR(CZ) GC15-02578J Institutional support: RVO:61388971 Keywords : beta-N-acetylhexosaminidase * Hex B * enzyme inhibition Subject RIV: CE - Biochemistry Impact factor: 2.502, year: 2016
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Czech Academy of Sciences Publication Activity Database
Olejník, R.; Padělková, Z.; Horáček, Michal; Růžička, A.
2012-01-01
Roč. 35, 1-2 (2012), s. 13-27 ISSN 0334-7575 Institutional support: RVO:61388955 Keywords : beta-diketimines * beta-enaminones * lithium Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.207, year: 2011
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Kobayashi, S; Arai, S; Hayashi, S; Sakaguchi, T
1989-01-01
The effects of combinations of beta-lactams with two beta-lactamase inhibitors, sulbactam and clavulanic acid, were determined in vitro against 22 clinical isolates of methicillin-resistant Staphylococcus aureus. Combinations of cefpirome, cefotaxime, and cefazolin with sulbactam (10 micrograms/ml) showed synergistic effects against more than 70% of the strains. Combinations of methicillin and penicillin G with sulbactam also showed synergistic effects against 50 and 68% of the strains, respectively, while cefotiam, moxalactam, flomoxef, and cefmetazole in combination with sulbactam showed such effects against only 40% or fewer. Clavulanic acid was synergistic only when combined with penicillin G, the effect probably being due to the beta-lactamase inhibition by the inhibitor. Sulbactam did not improve the antimicrobial activities of the beta-lactams against methicillin-susceptible S. aureus strains. At 42 degrees C the MICs of cefotaxime, methicillin, and flomoxef alone were markedly decreased from the values at 35 degrees C, and no synergy between these beta-lactams and sulbactam appeared. The resistance to penicillin G was not inhibited by incubation at 42 degrees C, and combinations of penicillin G with sulbactam and clavulanic acid showed synergy. The amounts of beta-lactamase produced were not related to the decreases in the MICs of the beta-lactams, except for penicillin G combined with sulbactam. Clavulanic acid showed slightly stronger beta-lactamase-inhibiting activity than sulbactam did. These results suggest that the synergy between sulbactam and the beta-lactams, except for penicillin G, may not be due to beta-lactamase inhibition but to suppression of the methicillin-resistant S. aureus-specific resistance based on other factors. PMID:2786369
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Internal bremsstrahlung spectra of the allowed. beta. emitters /sup 32/P, /sup 35/S and /sup 45/Ca
Energy Technology Data Exchange (ETDEWEB)
Powar, M S; Singh, M [Punjabi Univ., Patiala (India). Dept. of Physics
1976-01-01
A study of Coulomb field effects in internal bremsstrahlung (IB) has been undertaken by measuring the IB spectra for the allowed beta emitters /sup 32/P, /sup 35/S and /sup 45/Ca in the photon energy intervals of 50 to 1600 keV, 25 to 150 keV and 30 to 240 keV respectively. The experimental results show increasing positive departures from the KUB and Coulomb-corrected theories of Lewis and Ford, and Nilsson, with decreasing beta end-point energy. In the case of /sup 35/S the experimental results are 40 % higher than the more exact theory of Struzynski and Pollock for this isotope.
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How Should Beta-Diversity Inform Biodiversity Conservation?
Socolar, Jacob B; Gilroy, James J; Kunin, William E; Edwards, David P
2016-01-01
To design robust protected area networks, accurately measure species losses, or understand the processes that maintain species diversity, conservation science must consider the organization of biodiversity in space. Central is beta-diversity--the component of regional diversity that accumulates from compositional differences between local species assemblages. We review how beta-diversity is impacted by human activities, including farming, selective logging, urbanization, species invasions, overhunting, and climate change. Beta-diversity increases, decreases, or remains unchanged by these impacts, depending on the balance of processes that cause species composition to become more different (biotic heterogenization) or more similar (biotic homogenization) between sites. While maintaining high beta-diversity is not always a desirable conservation outcome, understanding beta-diversity is essential for protecting regional diversity and can directly assist conservation planning. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Measurement of $sin2\\beta$ from $B^{0}_{d} \\rightarrow J/\\Psi K^{0}_{S}$ with the LHCb detector
Mangiafave, N; Calvi, M; Matteuzzi, C
2008-01-01
The LHCb experiment will study CP violation and rare B meson decays at the LHC accelerator, in the CERN laboratories of Geneva. The CP violation in the $b$ quark mesons was observed for the first time measuring the $\\sin2\\beta$ parameter. In the first year of data taking at LHCb the $\\sin2\\beta$ measurement will be performed in the channel $B_d ^0 \\rightarrow J/\\psi K_S ^0$ (called golden channel). The comparison with results obtained in previous experiments will show possible systematic errors. Once the systematic errors will be understood, the possible discrepancies with the expected results will be the sign of a new physics beyond the Standard Model. $\\sin2\\beta$ is extracted from the asymmetry in the decay $B_d ^0 \\rightarrow J/\\psi(\\mu^+\\mu^-) K_S ^0 (\\pi^+\\pi^-)$ and its CP conjugated $\\overline{B}_d ^0 \\rightarrow J/\\psi(\\mu^-\\mu^+) K_S ^0(\\pi^-\\pi^+)$. To distinguish between $B_d ^0$ and $\\overline{B}_d$ flavour tagging algorithms are used. These introduce an additional parameter: the wrong tag fracti...
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International Nuclear Information System (INIS)
Subhan, F.; Tahir, F.; Sultan, S.; Subhan, K.
2008-01-01
This study was designed to determine serum Alpha-fetoprotein (AFP) and beta-h Chornionic Gonodotropin hormone (beta-hCG) levels among adult Pakistani population, and to observe their correlation. Serum AFP and beta-hCG levels were evaluated, using Micro-particle Enzyme Immuno Assay (MEIA) technology of M/s Abbott Laboratories. Data were compared using students t-test and correlation was computed. In the patients advised serum AFP assessment, 52% had normal AFP levels. comprising 37% male and 63% female subjects. For patients having a non-pathological picture, AFP levels varied non-significantly (p>0.05) between the Genders however, age varied highly significantly (p 0.05) and highly significant (p 0.05). Comparison of the population in the same age groups of both genders revealed significant (p 0.05), due to a large standard error. Although the differences in beta-hCG levels were highly significant (p 0.05). Among the studied cases, 67% patients had normal and 33% patients had raised beta-hCG levels. Beta-hCG levels show a decreasing trend with increasing age and beta-hCG levels were statistically significant (p<0.05) when patients under 50 years of age were compared with patients above 50 years. The coefficient of correlation between serum AFP and beta- hCG levels was 0.996454, which indicated a very strong. Significant positive correlation between the two tumour markers. The study showed that both serum AFP and beta-hCG are useful tumour markers and had a very strong positive correlation. (author)
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Entrainment of prefrontal beta oscillations induces an endogenous echo and impairs memory formation.
Hanslmayr, Simon; Matuschek, Jonas; Fellner, Marie-Christin
2014-04-14
Brain oscillations across all frequency bands play a key role for memory formation. Specifically, desynchronization of local neuronal assemblies in the left inferior prefrontal cortex (PFC) in the beta frequency (∼18 Hz) has been shown to be central for encoding of verbal memories. However, it remains elusive whether prefrontal beta desynchronization is causally relevant for memory formation and whether these endogenous beta oscillations can be entrained by external stimulation. By using combined EEG-TMS (transcranial magnetic stimulation), we here address these fundamental questions in human participants performing a word-list learning task. Confirming our predictions, memory encoding was selectively impaired when the left inferior frontal gyrus (IFG) was driven at beta (18.7 Hz) compared to stimulation at other frequencies (6.8 Hz and 10.7 Hz) and to ineffective sham stimulation (18.7 Hz). Furthermore, a sustained oscillatory "echo" in the left IFG, which outlasted the stimulation period by approximately 1.5 s, was observed solely after beta stimulation. The strength of this beta echo was related to memory impairment on a between-subjects level. These results show endogenous oscillatory entrainment effects and behavioral impairment selectively in beta frequency for stimulation of the left IFG, demonstrating an intimate causal relationship between prefrontal beta desynchronization and memory formation. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Uzé, G; Lutfalla, G; Bandu, M T; Proudhon, D; Mogensen, K E
1992-05-15
A murine interferon (IFN) alpha/beta receptor was cloned from the IFN-sensitive L1210 cell line on the basis of its homology with the human receptor. A combination of methods that includes the screening of random-primed and oligo(dT)-primed cDNA libraries and polymerase chain reactions with a single-side specificity was used. At the amino acid level, the murine IFN-alpha/beta shows 46% identity with its human counterpart. Both human WISH cells presenting a low sensitivity to mouse IFN and a murine L1210 mutant subline that does not express the receptor have been stably transfected with the murine IFN-alpha/beta receptor. Whereas transfected human cells became sensitive to a limited number of mouse IFN-alpha/beta subtypes, the transfected murine L1210 mutant was found to be fully complemented and became sensitive to all mouse IFN-alpha/beta subtypes tested, including those that were not active on transfected human cells. These results strongly suggest that the receptor described here is implicated in the mediation of the activities of all murine IFN-alpha/beta subtypes.
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DEFF Research Database (Denmark)
Nissen, Mogens Holst; Plesner, T; Larsen, J K
1985-01-01
than 0.5, respectively) by day-to-day analysis of an untreated healthy control group. An increased expression of both HLA-ABC (mean 55%, P less than 0.0005) and beta 2m (mean 23%, P less than 0.01) was also observed prior to treatment in the lung cancer patients when compared to a group of age matched......The effect of cloned human interferon-alpha (IFN-alpha) on the expression of HLA-ABC antigens (HLA-ABC) and beta 2-microglobulin (beta 2m) on human peripheral lymphoid cells in vivo was studied by cytofluorometry using monoclonal antibodies and fluorescein-labelled rabbit anti-mouse immunoglobulin....... A significant increase in the mean fluorescence intensity of HLA-ABC (median 59%, P less than 0.001) and beta 2m (median 57%, P less than 0.001) on small lymphoid cells was observed 24 h after initiation of IFN-alpha treatment (50 X 10(6) units IFN-alpha/m2 three times a week). The enhanced expression...
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Qureshi, Hamid Yaqoob; Ricci, Gemma; Zafarullah, Muhammad
2008-09-01
Transforming growth factor beta (TGF-beta1) promotes cartilage matrix synthesis and induces tissue inhibitor of metalloproteinases-3 (TIMP-3), which inhibits matrix metalloproteinases, aggrecanases and TNF-alpha-converting enzyme implicated in articular cartilage degradation and joint inflammation. TGF-beta1 activates Akt, ERK and Smad2 pathways in chondrocytes. Here we investigated previously unexplored roles of specific Smads in TGF-beta1 induction of TIMP-3 gene by pharmacological and genetic knockdown approaches. TGF-beta1-induced Smad2 phosphorylation and TIMP-3 protein expression could be inhibited by the Smad2/3 phosphorylation inhibitors, PD169316 and SB203580 and by Smad2-specific siRNA. Specific inhibitor of Smad3 (SIS3) and Smad3 siRNA abolished TGF-beta induction of TIMP-3. Smad2/3 siRNAs also down regulated TIMP-3 promoter-driven luciferase activities, suggesting transcriptional regulation. SiRNA-driven co-Smad4 knockdown abrogated TIMP-3 augmentation by TGF-beta. TIMP-3 promoter deletion analysis revealed that -828 deletion retains the original promoter activity while -333 and -167 deletions display somewhat reduced activity suggesting that most of the TGF-beta-responsive, cis-acting elements are found in the -333 fragment. Chromatin Immunoprecipitation (ChIP) analysis confirmed binding of Smad2 and Smad4 with the -940 and -333 promoter sequences. These results suggest that receptor-activated Smad2 and Smad3 and co-Smad4 critically mediate TGF-beta-stimulated TIMP-3 expression in human chondrocytes and TIMP-3 gene is a target of Smad signaling pathway.
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Ectopic production of beta-HCG by a maxillary squamous cell carcinoma.
Scholl, P D; Jurco, S; Austin, J R
1997-12-01
Paraneoplastic syndromes of the head and neck are rare. Hypercalcemia and leukocytosis have been described. The literature was reviewed, and a case of a squamous cell carcinoma of the maxilla producing beta human chorionic gonadotropin (beta-HCG) is presented. A 47-year-old white man with a T4N1M0 squamous cell carcinoma of the left maxilla was treated with a maxillectomy and neck dissection for an N1 positive neck. After completing his planned radiotherapy, he developed distant metastases, which included an axillary node that stained positive for human beta-HCG. Retrospective review of the primary specimen showed beta-HCG positivity in an anaplastic component of the tumor along with vascular invasion. The first case in the literature of a paraneoplastic syndrome with beta-HCG production in association with squamous cell carcinoma of the maxilla is presented. This case history fits the aggressive nature of beta HCG producing tumors elsewhere in the body.
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Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki
2009-06-01
In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.
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Geng, Zhirong; Song, Xiaoli; Xing, Zhi; Geng, Jinlong; Zhang, Sichun; Zhang, Xinrong; Wang, Zhilin
2009-05-01
The effects of Se(IV) on the structure and function of recombinant human arsenic (+3 oxidation state) methyltransferase (AS3MT) purified from the cytoplasm of Escherichia coli were studied. The coding region of human AS3MT complementary DNA was amplified from total RNA extracted from HepG2 cell by reverse transcription PCR. Soluble and active human AS3MT was expressed in the E. coli with a Trx fusion tag under a lower induction temperature of 25 degrees C. Spectra (UV-vis, circular dichroism, and fluorescence) were first used to probe the interaction of Se(IV) and recombinant human AS3MT and the structure-function relationship of the enzyme. The recombinant human AS3MT had a secondary structure of 29.0% alpha-helix, 23.9% beta-pleated sheet, 17.9% beta-turn, and 29.2% random coil. When Se(IV) was added, the content of the alpha-helix did not change, but that of the beta-pleated sheet increased remarkably in the conformation of recombinant human AS3MT. Se(IV) inhibited the enzymatic methylation of inorganic As(III) in a concentration-dependent manner. The IC(50) value for Se(IV) was 2.38 muM. Double-reciprocal (1/V vs. 1/[inorganic As(III)]) plots showed Se(IV) to be a noncompetitive inhibitor of the methylation of inorganic As(III) by recombinant human AS3MT with a K (i) value of 2.61 muM. We hypothesized that Se(IV) interacts with the sulfhydryl group of cysteine(s) in the structural residues rather than the cysteines of the active site (Cys156 and Cys206). When Se(IV) was combined with cysteine(s) in the structural residues, the conformation of recombinant human AS3MT changed and the enzymatic activity decreased. Considering the quenching of tryptophan fluorescence, Cys72 and/or Cys226 are deduced to be primary targets for Se(IV).
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The structure of the human interferon alpha/beta receptor gene.
Lutfalla, G; Gardiner, K; Proudhon, D; Vielh, E; Uzé, G
1992-02-05
Using the cDNA coding for the human interferon alpha/beta receptor (IFNAR), the IFNAR gene has been physically mapped relative to the other loci of the chromosome 21q22.1 region. 32,906 base pairs covering the IFNAR gene have been cloned and sequenced. Primer extension and solution hybridization-ribonuclease protection have been used to determine that the transcription of the gene is initiated in a broad region of 20 base pairs. Some aspects of the polymorphism of the gene, including noncoding sequences, have been analyzed; some are allelic differences in the coding sequence that induce amino acid variations in the resulting protein. The exon structure of the IFNAR gene and of that of the available genes for the receptors of the cytokine/growth hormone/prolactin/interferon receptor family have been compared with the predictions for the secondary structure of those receptors. From this analysis, we postulate a common origin and propose an hypothesis for the divergence from the immunoglobulin superfamily.
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Structure of the T cell receptor in a Ti alpha V beta 2, alpha V beta 8-positive T cell line
DEFF Research Database (Denmark)
Hou, X; Dietrich, J; Kuhlmann, J
1994-01-01
not known; however, it has been suggested that each TcR contains two Ti dimers. To gain insight into the structure of the TcR we constructed a Ti alpha V beta 2, alpha V beta 8-positive T cell line which expressed the endogenous human TiV beta 8 and the transfected mouse TiV beta 2 both in association......The T cell receptor (TcR) is composed of at least six different polypeptide chains consisting of the clonotypic Ti heterodimer (Ti alpha beta or Ti gamma delta) and the noncovalently associated CD3 chains (CD3 gamma delta epsilon zeta). The exact number of subunits constituting the TcR is still...... with the endogenous Ti alpha and CD3 chains at the cell surface. Preclearing experiments with radioiodinated cell lysate prepared with digitonin lysis buffer demonstrated that depleting the lysate of Ti alpha V beta 8 by immunoprecipitation with anti V beta 8 monoclonal antibody (mAb) did not reduce the amount of Ti...
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Sheibani, Lili; Lechuga, Thomas J; Zhang, Honghai; Hameed, Afshan; Wing, Deborah A; Kumar, Sathish; Rosenfeld, Charles R; Chen, Dong-Bao
2017-03-01
Endogenous hydrogen sulfide (H2S) synthesized via metabolizing L-cysteine by cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) is a potent vasodilator and angiogenic factor. The objectives of this study were to determine if human uterine artery (UA) H2S production increases with augmented expression and/or activity of CBS and/or CSE during the menstrual cycle and pregnancy and whether exogenous H2S dilates UA. Uterine arteries from nonpregnant (NP) premenopausal proliferative (pPRM) and secretory (sPRM) phases of the menstrual cycle and pregnant (P) women were studied. H2S production was measured by the methylene blue assay. CBS and CSE mRNAs were assessed by quantitative real-time PCR, and proteins were assessed by immunoblotting and semiquantitative immunofluorescence microscopy. Effects of H2S on rat UA relaxation were determined by wire myography ex vivo. H2S production was greater in NP pPRM and P than NP sPRM UAs and inhibited by the specific CBS but not CSE inhibitor. CBS but not CSE mRNA and protein were greater in NP pPRM and P than NP sPRM UAs. CBS protein was localized to endothelium and smooth muscle and its levels were in a quantitative order of P >NP UAs of pPRM>sPRM. CSE protein was localized in UA endothelium and smooth muscle with no difference among groups. A H2S donor relaxed P > NP UAs but not mesentery artery. Thus, human UA H2S production is augmented with endothelium and smooth muscle CBS upregulation, contributing to UA vasodilation in the estrogen-dominant physiological states in the proliferative phase of the menstrual cycle and pregnancy. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Thymosin beta 4 and thymosin beta 10 expression in hepatocellular carcinoma
Directory of Open Access Journals (Sweden)
W. Theunissen
2014-03-01
Full Text Available Thymosin beta 4 (Tβ4 and thymosin beta 10 (Tβ10 are two members of the beta-thymosin family involved in many cellular processes such as cellular motility, angiogenesis, inflammation, cell survival and wound healing. Recently, a role for beta-thymosins has been proposed in the process of carcinogenesis as both peptides were detected in several types of cancer. The aim of the present study was to investigate the expression pattern of Tβ4 and Tβ10 in hepatocellular carcinoma (HCC. To this end, the expression pattern of both peptides was analyzed in liver samples obtained from 23 subjects diagnosed with HCC. Routinely formalin-fixed and paraffin-embedded liver samples were immunostained by indirect immunohistochemistry with polyclonal antibodies to Tβ4 and Tβ10. Immunoreactivity for Tβ4 and Tβ10 was detected in the liver parenchyma of the surrounding tumor area. Both peptides showed an increase in granular reactivity from the periportal to the periterminal hepatocytes. Regarding HCC, Tβ4 reactivity was detected in 7/23 cases (30% and Tβ10 reactivity in 22/23 (97% cases analyzed, adding HCC to human cancers that express these beta-thymosins. Intriguing finding was seen looking at the reactivity of both peptides in tumor cells infiltrating the surrounding liver. Where Tβ10 showed a strong homogeneous expression, was Tβ4 completely absent in cells undergoing stromal invasion. The current study shows expression of both beta-thymosins in HCC with marked differences in their degree of expression and frequency of immunoreactivity. The higher incidence of Tβ10 expression and its higher reactivity in tumor cells involved in stromal invasion indicate a possible major role for Tβ10 in HCC progression.
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Cooper, Nicholas R; Simpson, Andrew; Till, Amy; Simmons, Kelly; Puzzo, Ignazio
2013-01-01
The human mirror neuron system (hMNS) has been associated with various forms of social cognition and affective processing including vicarious experience. It has also been proposed that a faulty hMNS may underlie some of the deficits seen in the autism spectrum disorders (ASDs). In the present study we set out to investigate whether emotional facial expressions could modulate a putative EEG index of hMNS activation (mu suppression) and if so, would this differ according to the individual level of autistic traits [high versus low Autism Spectrum Quotient (AQ) score]. Participants were presented with 3 s films of actors opening and closing their hands (classic hMNS mu-suppression protocol) while simultaneously wearing happy, angry, or neutral expressions. Mu-suppression was measured in the alpha and low beta bands. The low AQ group displayed greater low beta event-related desynchronization (ERD) to both angry and neutral expressions. The high AQ group displayed greater low beta ERD to angry than to happy expressions. There was also significantly more low beta ERD to happy faces for the low than for the high AQ group. In conclusion, an interesting interaction between AQ group and emotional expression revealed that hMNS activation can be modulated by emotional facial expressions and that this is differentiated according to individual differences in the level of autistic traits. The EEG index of hMNS activation (mu suppression) seems to be a sensitive measure of the variability in facial processing in typically developing individuals with high and low self-reported traits of autism.
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Clements, J A; Funder, J W; Tracy, K; Morgan, F J; Campbell, D J; Lewis, P; Hearn, M T
1982-12-01
The expression of the proopiomelanocortin (POMC) gene by normal lung and thyroid was examined by measurement of the content of ACTH, beta-lipotropin (beta LPH), and beta-endorphin (beta EP) in porcine lung and thyroid tissue. Acid extracts of normal porcine lung and thyroid tissue each contained appreciable amounts of immunoreactive (ir) ACTH, ir-beta LPH, and ir-beta EP. The content of ir-beta LPH in both tissues exceeded by severalfold, on a molar basis, the content of ir-ACTH and ir-beta EP, suggesting that the common precursor POMC was processed predominantly to peptides other than ir-ACTH and ir-beta EP. A porcine thyroid extract (Calcitare, porcine calcitonin, Armour) showed equivalent levels of beta EP-like immunoreactivity and bioactivity, measured by opiate radioreceptor assay; in contrast, ACTH-like bioactivity, measured by rat zona fasciculata steroidogenesis, was only 4% of ACTH-like immunoreactivity. On reversed phase high performance liquid chromatography, Calcitare showed multiple peaks of ACTH-like immunoreactivity, one of which coeluted with porcine ACTH-(1-39), and two much smaller peaks of beta EP-like immunoreactivity, of which the smaller coeluted with porcine beta EP. These data suggest that both lung and thyroid gland synthesize POMC, which in normal tissue is usually predominantly processed to species other than ACTH and beta EP. Ectopic secretion of ACTH and beta EP by lung and thyroid neoplasms may thus represent the loss of a system(s) normally responsible for processing the precursor beyond ACTH and beta EP.
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Energy Technology Data Exchange (ETDEWEB)
Forsberg, Anton; Andersson, Jan; Varnaes, Katarina; Halldin, Christer [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); Jureus, Anders; Swahn, Britt-Marie; Sandell, Johan; Julin, Per; Svensson, Samuel [AstraZeneca Research and Development, Neuroscience Research and Therapy Area, Soedertaelje (Sweden); Cselenyi, Zsolt; Schou, Magnus; Johnstroem, Peter; Farde, Lars [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); Karolinska Hospital, AstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden); Eriksdotter, Maria; Freund-Levi, Yvonne [Karolinska Institutet, Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Stockholm (Sweden); Karolinska University Hospital, Department of Geriatric Medicine, Stockholm (Sweden); Jeppsson, Fredrik [AstraZeneca Research and Development, Neuroscience Research and Therapy Area, Soedertaelje (Sweden); Karolinska Institutet, Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Stockholm (Sweden)
2013-04-15
The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-{beta} in Alzheimer's disease (AD). In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-{beta} PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [{sup 11}C]AZD2995 and [{sup 11}C]AZD2184 in three healthy control subjects and seven AD patients. AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-{beta}. [{sup 3}H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [{sup 11}C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [{sup 11}C]AZD2995 was greater in areas with lower amyloid-{beta} load, e.g. the hippocampus. Both AZD2995 and AZD2184 detect amyloid-{beta} with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [{sup 11}C]AZD2184 seems to be an amyloid-{beta} radioligand with higher uptake and better group separation when compared to [{sup 11}C]AZD2995. However, the very low nonspecific binding of [{sup 11}C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-{beta}. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy. (orig.)
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Khan, Ansar A.; Chow, Edwin C. Y.; Porte, Robert J.; Pang, K. Sandy; Groothuis, Geny M. M.
The regulation of the OST alpha and OST beta expression was studied in the rat jejunum, ileum, colon and liver and in human ileum and liver by ligands for the farnesoid X receptor (FXR), pregnane X receptor (PXR), vitamin D receptor (VDR) and glucocorticoid receptor (GR) using precision cut tissue
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Beta-secretase-cleaved amyloid precursor protein in Alzheimer brain: a morphologic study
DEFF Research Database (Denmark)
Sennvik, Kristina; Bogdanovic, N; Volkmann, Inga
2004-01-01
beta-amyloid (Abeta) is the main constituent of senile plaques seen in Alzheimer's disease. Abeta is derived from the amyloid precursor protein (APP) via proteolytic cleavage by proteases beta- and gamma-secretase. In this study, we examined content and localization of beta-secretase-cleaved APP...... the beta-sAPP immunostaining to be stronger and more extensive in gray matter in Alzheimer disease (AD) cases than controls. The axonal beta-sAPP staining was patchy and unevenly distributed for the AD cases, indicating impaired axonal transport. beta-sAPP was also found surrounding senile plaques...
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Directory of Open Access Journals (Sweden)
Gabriele Möller
Full Text Available Steroid-related cancers can be treated by inhibitors of steroid metabolism. In searching for new inhibitors of human 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD 1 for the treatment of breast cancer or endometriosis, novel substances based on 15-substituted estrone were validated. We checked the specificity for different 17beta-HSD types and species. Compounds were tested for specificity in vitro not only towards recombinant human 17beta-HSD types 1, 2, 4, 5 and 7 but also against 17beta-HSD 1 of several other species including marmoset, pig, mouse, and rat. The latter are used in the processes of pharmacophore screening. We present the quantification of inhibitor preferences between human and animal models. Profound differences in the susceptibility to inhibition of steroid conversion among all 17beta-HSDs analyzed were observed. Especially, the rodent 17beta-HSDs 1 were significantly less sensitive to inhibition compared to the human ortholog, while the most similar inhibition pattern to the human 17beta-HSD 1 was obtained with the marmoset enzyme. Molecular docking experiments predicted estrone as the most potent inhibitor. The best performing compound in enzymatic assays was also highly ranked by docking scoring for the human enzyme. However, species-specific prediction of inhibitor performance by molecular docking was not possible. We show that experiments with good candidate compounds would out-select them in the rodent model during preclinical optimization steps. Potentially active human-relevant drugs, therefore, would no longer be further developed. Activity and efficacy screens in heterologous species systems must be evaluated with caution.
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Beta-agonists and animal welfare
The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...
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International Nuclear Information System (INIS)
Borovikov, N.V.; Kosinov, G.A.; Fedorov, Yu.N.
1989-01-01
Portable transportable digital beta radiometer providing for measuring beta-decay radionuclide specific activity in the range from 5x10 -9 up to 10 -6 Cu/kg (Cu/l) with error of ±25% is designed and introduced into commercial production for determination of volume and specific water and food radioactivity. The device specifications are given. Experience in the BETA radiometer application under conditions of the Chernobyl' NPP 30-km zone has shown that it is convenient for measuring specific activity of the order of 10 -8 Cu/kg, and application of a set of different beta detectors gives an opportunity to use it for surface contamination measurement in wide range of the measured value
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International Nuclear Information System (INIS)
Kobayashi, M.; Shimada, K.; Ozawa, T.
1990-01-01
Cytokines are known to tip the balance of the coagulant-anticoagulant molecules on the endothelial cell surface toward intravascular coagulation. Their effects on endothelial cell surface-associated heparin-like compounds have not been examined yet. Incorporation of [35S]sulfate into heparan sulfate on cultured porcine aortic endothelial cells was suppressed by human recombinant interleukin-1 beta (rIL-1 beta) or tumor necrosis factor alpha (rTNF alpha) in a dose- and time-dependent manner with little effect on cell number, protein content, and [3H]leucine incorporation of cells. Maximal inhibition was achieved by incubation of cells with 100 ng/ml of rIL-1 beta or 5 ng/ml of rTNF alpha for 12-24 hours, resulting in a reduction of the synthesis of heparan sulfate on the cell surface by approximately 50%. The dose dependency was consistent with that seen in the stimulation of endothelial cell procoagulant activity by each cytokine. The suppression of heparan sulfate synthesis was sustained for at least 48 hours after pretreatment of cells with cytokines and was unchanged after the addition of indomethacin or polymyxin B. The rate of degradation of prelabeled 35S-heparan sulfate on the cell surface was not altered by cytokine treatments. Neither the size, the net negative charge, nor the proportion of the molecule with high affinity for antithrombin III of endothelial cell heparan sulfate was changed by cytokines. Furthermore, specific binding of 125I-labeled antithrombin III to the endothelial cell surface was reduced to 40-60% of control by cytokines. In parallel with reduction in binding, antithrombin III cofactor activity was partially diminished in cytokine-treated endothelial cells. Thus, cytokine-mediated suppression of heparin-like substance on endothelial cells appears to be another cytokine-inducible endothelial effects affecting coagulation
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Anjos, Liliana; Morgado, Isabel; Guerreiro, Marta; Cardoso, João C R; Melo, Eduardo P; Power, Deborah M
2017-02-01
Cartilage acidic protein1 (CRTAC1) is an extracellular matrix protein of chondrogenic tissue in humans and its presence in bacteria indicate it is of ancient origin. Structural modeling of piscine CRTAC1 reveals it belongs to the large family of beta-propeller proteins that in mammals have been associated with diseases, including amyloid diseases such as Alzheimer's. In order to characterize the structure/function evolution of this new member of the beta-propeller family we exploited the unique characteristics of piscine duplicate genes Crtac1a and Crtac1b and compared their structural and biochemical modifications with human recombinant CRTAC1. We demonstrate that CRTAC1 has a beta-propeller structure that has been conserved during evolution and easily forms high molecular weight thermo-stable aggregates. We reveal for the first time the propensity of CRTAC1 to form amyloid-like structures, and hypothesize that the aggregating property of CRTAC1 may be related to its disease-association. We further contribute to the general understating of CRTAC1's and beta-propeller family evolution and function. Proteins 2017; 85:242-255. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Energy Technology Data Exchange (ETDEWEB)
Chung, Eun Jee [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of); Chun, Ji Na; Jung, Sun-Ah [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of); Cho, Jin Won [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lee, Joon H., E-mail: joonhlee@konyang.ac.kr [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)
2011-11-18
Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information
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In-trap decay spectroscopy for {beta}{beta} decays
Energy Technology Data Exchange (ETDEWEB)
Brunner, Thomas
2011-01-18
The presented work describes the implementation of a new technique to measure electron-capture (EC) branching ratios (BRs) of intermediate nuclei in {beta}{beta} decays. This technique has been developed at TRIUMF in Vancouver, Canada. It facilitates one of TRIUMF's Ion Traps for Atomic and Nuclear science (TITAN), the Electron Beam Ion Trap (EBIT) that is used as a spectroscopy Penning trap. Radioactive ions, produced at the radioactive isotope facility ISAC, are injected and stored in the spectroscopy Penning trap while their decays are observed. A key feature of this technique is the use of a strong magnetic field, required for trapping. It radially confines electrons from {beta} decays along the trap axis while X-rays, following an EC, are emitted isotropically. This provides spatial separation of X-ray and {beta} detection with almost no {beta}-induced background at the X-ray detector, allowing weak EC branches to be measured. Furthermore, the combination of several traps allows one to isobarically clean the sample prior to the in-trap decay spectroscopy measurement. This technique has been developed to measure ECBRs of transition nuclei in {beta}{beta} decays. Detailed knowledge of these electron capture branches is crucial for a better understanding of the underlying nuclear physics in {beta}{beta} decays. These branches are typically of the order of 10{sup -5} and therefore difficult to measure. Conventional measurements suffer from isobaric contamination and a dominating {beta} background at theX-ray detector. Additionally, X-rays are attenuated by the material where the radioactive sample is implanted. To overcome these limitations, the technique of in-trap decay spectroscopy has been developed. In this work, the EBIT was connected to the TITAN beam line and has been commissioned. Using the developed beam diagnostics, ions were injected into the Penning trap and systematic studies on injection and storage optimization were performed. Furthermore, Ge
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Energy Technology Data Exchange (ETDEWEB)
Kang, Kyungsu; Lee, Kyung-Mi; Yoo, Ji-Hye; Lee, Hee Ju [Functional Food Center, Korea Institute of Science and Technology, Gangneung 210-340 (Korea, Republic of); Kim, Chul Young [Functional Food Center, Korea Institute of Science and Technology, Gangneung 210-340 (Korea, Republic of); College of Pharmacy, Hanyang University, Ansan 426-791 (Korea, Republic of); Nho, Chu Won, E-mail: cwnho@kist.re.kr [Functional Food Center, Korea Institute of Science and Technology, Gangneung 210-340 (Korea, Republic of)
2012-11-16
Graphical abstract: Schematic diagram of the possible molecular mechanism underlying the inhibition of the Wnt/{beta}-catenin signaling pathway and the induction of G0/G1-phase arrest by gomisins J and N, derived from the fruits of S. chinensis, in HCT116 human colon cancer cells. Highlights: Black-Right-Pointing-Pointer Gomisins J and N inhibited Wnt/{beta}-catenin signaling pathway in HCT116 cells. Black-Right-Pointing-Pointer Gomisins J and N disrupted the binding of {beta}-catenin to specific DNA sequences, TBE. Black-Right-Pointing-Pointer Gomisins J and N inhibited the HCT116 cell proliferation through G0/G1 phase arrest. Black-Right-Pointing-Pointer Gomisins J and N inhibited the expression of Cyc D1, a Wnt/{beta}-catenin target gene. -- Abstract: Here, we report that gomisin J and gomisin N, dibenzocyclooctadiene type lignans isolated from Schisandra chinensis, inhibit Wnt/{beta}-catenin signaling in HCT116 cells. Gomisins J and N appear to inhibit Wnt/{beta}-catenin signaling by disrupting the interaction between {beta}-catenin and its specific target DNA sequences (TCF binding elements, TBE) rather than by altering the expression of the {beta}-catenin protein. Gomisins J and N inhibit HCT116 cell proliferation by arresting the cell cycle at the G0/G1 phase. The G0/G1 phase arrest induced by gomisins J and N appears to be caused by a decrease in the expression of Cyclin D1, a representative target gene of the Wnt/{beta}-catenin signaling pathway, as well as Cdk2, Cdk4, and E2F-1. Therefore, gomisins J and N, the novel Wnt/{beta}-catenin inhibitors discovered in this study, may serve as potential agents for the prevention and treatment of human colorectal cancers.
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Transforming growth factor beta-1 expression in macrophages of human chronic periapical diseases.
Liang, Z-Z; Li, J; Huang, S-G
2017-03-30
The objective of this study was to observe the distribution of macrophages (MPs) expressing transforming growth factor beta-1 (TGF-β1) in tissue samples from patients with different human chronic periapical diseases. In this study, samples were collected from 75 volunteers, who were divided into three groups according to classified standards, namely, healthy control (N = 25), periapical granuloma (N = 25), and periapical cyst (N = 25). The samples were fixed in 10% buffered formalin for more than 48 h, dehydrated, embedded, and stained with hematoxylin and eosin for histopathology. Double immunofluorescence was conducted to analyze the expression of TGF-β-CD14 double-positive MPs in periapical tissues. The number of double-positive cells (cells/mm 2 ) were significantly higher in the chronic periapical disease tissues (P periapical cyst group than in the periapical granuloma group (P periapical diseases. The TGF-β1-CD14 double-positive cells might play an important role in the pathology of human chronic periapical diseases.
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Mangano, Carlo; Sinjari, Bruna; Shibli, Jamil A; Mangano, Francesco; Hamisch, Sabine; Piattelli, Adriano; Perrotti, Vittoria; Iezzi, Giovanna
2015-06-01
By mixing hydroxyapatite (HA) and tricalcium phosphate (TCP), biphasic calcium phosphate ceramics can be obtained, and by varying their ratio it is possible to tailor the characteristics of the biomaterial. The aim of the present human study was to evaluate the histological and radiographical aspects of bone formation in maxillary sinus augmentation using a 30/70 HA-beta-TCP with a reticular structure. A total of 12 patients, undergoing two-stage sinus augmentation procedure using HA-beta-TCP at a ratio of 30/70, were included in the present study. After a 6-month healing period, during implant insertion, radiographical analysis was performed, and then the bone core biopsies were harvested and processed for histology. At radiographic evaluation, the bone gain was on average 6.85 ± 0.60 mm. HA-beta-TCP 30/70 appeared to be lined by newly formed bone, with no gaps at the interface. The histomorphometric analysis revealed 26 ± 2% of residual grafted biomaterial, 29 ± 3% of newly formed bone, and 45 ± 2% of marrow spaces. The present results indicate histologically the high biocompatibility and osteoconductivity of HA-beta-TCP 30/70, and clinically its successful use for sinus augmentation procedures. © 2013 Wiley Periodicals, Inc.
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Structure modeling and mutational analysis of gap junction beta 2 ...
African Journals Online (AJOL)
Yomi
2012-04-03
Apr 3, 2012 ... Three dimensional (3 D) structure is very useful for understanding biological functions. Gap junction beta 2 (GJB2), human gene encoding for gap junction beta 2 protein is involved in ... Research in deafness became real.
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Fracture risk in perimenopausal women treated with beta-blockers
DEFF Research Database (Denmark)
Rejnmark, Lars; Vestergaard, Peter; Kassem, M.
2004-01-01
beta2-Adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with beta-adrenergic receptor antagonists (beta-blockers) on bone turnover, bone mineral density...... (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with beta-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study....... Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with beta-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with beta-blockers was associated with a threefold increased fracture...
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Irazoqui, Javier E; Ng, Aylwin; Xavier, Ramnik J; Ausubel, Frederick M
2008-11-11
We used the model nematode Caenorhabditis elegans infected with the human pathogen Staphylococcus aureus to identify components of epithelial immunity. Transcriptional profiling and reverse genetic analysis revealed that mutation of the C. elegans beta-catenin homolog bar-1 or the downstream homeobox gene egl-5 results in a defective response and hypersensitivity to S. aureus infection. Epistasis analysis showed that bar-1 and egl-5 function in parallel to previously described C. elegans immune-response pathways. Overexpression of human homologs of egl-5 modulated NF-kappaB-dependent TLR2 signaling in epithelial cells. These data suggest that beta-catenin and homeobox genes play an important and conserved role in innate immune defense.
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Zhang, Yuan; Shu, Yi Min; Wang, Shu Fang; Da, Bang Hong; Wang, Ze Hua; Li, Hua Bin
2010-02-23
PMS2 expression loss was reported in a variety of human. However, its importance has not been fully understood in cervical carcinoma. The aim of this study was to determine the expression of PMS2 in cervical carcinoma and evaluate the significance of mismatch repair gene PMS2 regulated by glycogen synthase kinase 3beta (GSK-3beta) in chemosensitivity. We examined PMS2 and phosphorylated GSK-3beta(s9) expression in cervical carcinoma tissues using immunohistochemical staining. Furthermore, we detected PMS2 expression in HeLa cells and evaluate the interaction with GSK-3beta after transfection with GSK-3beta by small interference RNA (siRNA), co-immunoprecipitation and immunoblotting. We also evaluated the effect of PMS2 transfection on HeLa cells' chemosensitivity to cisplatin treatment. We found significant downregulation of PMS2 in cervical carcinoma, which was negatively associated with phosphorylated GSK-3beta (s9). Furthermore, we demonstrated GSK-3beta transfection was able to interact with PMS2 and enhance PMS2 production in HeLa cells, and increased PMS2 production was responsible for enhanced chemosensitivity. Our results provide the evidence that stabilization of PMS2 production by GSK-3beta was important to improve chemosensitization, indicating the significance of GSK-3beta-related PMS2 downregulation in the development of cervical carcinoma and in developing a potential strategy for chemotherapy.
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Sato, W; Enzan, K; Masaki, Y; Kayaba, M; Suzuki, M
1995-07-01
The cytokines such as tumor necrosis factor and interleukin-1 secreted from macrophages/monocytes proved to play important roles in the pathogenesis of endotoxemia, severe pancreatitis and other surgical injuries. However, it is still unclear how inhalational anesthetic agents influence the secretion of these cytokines from macrophages/monocytes. We investigated the effects of isoflurane on TNF-alpha and IL-1 beta secretions from human peripheral blood monocytes stimulated by lipopolysaccharide. TNF-alpha and IL-1 beta secretions increased after LPS stimulation and this increase was inhibited by isoflurane in dose-dependent fashion. The inhibitory action of isoflurane disappeared between 1 and 3 hours after stopping isoflurane inhalation. We concluded that isoflurane could inhibit TNF-alpha and IL-1 beta secretions from peripheral blood monocytes stimulated by LPS in a dose-dependent fashion and that the inhibitory action of isoflurane was reversible.
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Energy Technology Data Exchange (ETDEWEB)
Turaihi, K.; Khokher, M.A.; Barradas, M.A.; Mikhailidis, D.P.; Dandona, P. (Royal Free Hospital and School of Medicine, London (England))
1989-08-01
Although active transport of potassium into human platelets has been demonstrated previously, there is hitherto no evidence that human platelets have an ouabain-inhibitable Na-K ATPase in their membrane. The present study demonstrates active rubidium (used as an index of potassium influx), {sup 86}Rb(K), influx into platelets, inhibitable by ouabain, and also demonstrates the presence of specific ({sup 3}H)ouabain binding by the human platelet. This {sup 86}Rb(K) influx was stimulated by adrenaline, isoprenaline, and salbutamol, but noradrenaline caused a mild inhibition. Active {sup 86}Rb(K) influx by platelets was inhibited markedly by timolol, mildly by atenolol, but not by phentolamine. Therefore, active {sup 86}Rb(K) influx in human platelets is enhanced by stimulation of beta adrenoceptors of the beta 2 subtype. The platelet may therefore replace the leukocyte in future studies of Na-K ATPase activity. This would be a considerable advantage in view of the ease and rapidity of preparation of platelets.
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Beta 2-adrenergic receptors on eosinophils. Binding and functional studies
International Nuclear Information System (INIS)
Yukawa, T.; Ukena, D.; Kroegel, C.; Chanez, P.; Dent, G.; Chung, K.F.; Barnes, P.J.
1990-01-01
We have studied the binding characteristics and functional effects of beta-adrenoceptors on human and guinea pig eosinophils. We determined the binding of the beta-antagonist radioligand [125I]pindolol (IPIN) to intact eosinophils obtained from the peritoneal cavity of guinea pigs and from blood of patients with eosinophilia. Specific binding was saturable, and Scatchard analysis showed a single binding site with a dissociation constant (Kd) of 24.6 pM and maximal number of binding sites (Bmax) of 7,166 per cell. ICI 118,551, a beta 2-selective antagonist, inhibited IPIN binding with a Ki value of 0.28 nM and was approximately 5,000-fold more effective than the beta 1-selective antagonist, atenolol. Isoproterenol increased cAMP levels about 5.5-fold above basal levels (EC50 = 25 microM); albuterol, a beta 2-agonist, behaved as a partial agonist with a maximal stimulation of 80%. Binding to human eosinophils gave similar results with a Kd of 25.3 pM and a Bmax corresponding to 4,333 sites per cell. Incubation of both human and guinea pig eosinophils with opsonized zymosan (2 mg/ml) or with phorbol myristate acetate (PMA) (10(-8) and 10(-6) M) resulted in superoxide anion generation and the release of eosinophil peroxidase; albuterol (10(-7) to 10(-5) M) had no inhibitory effect on the release of these products. Thus, eosinophils from patients with eosinophilia and from the peritoneal cavity of guinea pigs possess beta-receptors of the beta 2-subtype that are coupled to adenylate cyclase; however, these receptors do not modulate oxidative metabolism or degranulation. The possible therapeutic consequences of these observations to asthma are discussed
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Interactions between two beta-sheets. Energetics of beta/beta packing in proteins.
Chou, K C; Némethy, G; Rumsey, S; Tuttle, R W; Scheraga, H A
1986-04-20
The analysis of the interactions between regularly folded segments of the polypeptide chain contributes to an understanding of the energetics of protein folding. Conformational energy-minimization calculations have been carried out to determine the favorable ways of packing two right-twisted beta-sheets. The packing of two five-stranded beta-sheets was investigated, with the strands having the composition CH3CO-(L-Ile)6-NHCH3 in one beta-sheet and CH3CO-(L-Val)6-NHCH3 in the other. Two distinct classes of low-energy packing arrangements were found. In the class with lowest energies, the strands of the two beta-sheets are aligned nearly parallel (or antiparallel) with each other, with a preference for a negative orientation angle, because this arrangement corresponds to the best complementary packing of the two twisted saddle-shaped beta-sheets. In the second class, with higher interaction energies, the strands of the two beta-sheets are oriented nearly perpendicular to each other. While the surfaces of the two beta-sheets are not complementary in this arrangement, there is good packing between the corner of one beta-sheet and the interior part of the surface of the other, resulting in a favorable energy of packing. Both classes correspond to frequently observed orientations of beta-sheets in proteins. In proteins, the second class of packing is usually observed when the two beta-sheets are covalently linked, i.e. when a polypeptide strand passes from one beta-sheet to the other, but we have shown here that a large contribution to the stabilization of this packing arrangement arises from noncovalent interactions.
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Borcea, R; Aysto, J; Caurier, E; Dendooven, P; Doring, J; Gierlik, M; Gorska, M; Grawe, H; Hellstrom, M; Janas, Z; Jokinen, A; Karny, M; Kirchner, R; La Commara, M; Langanke, K; Martinez-Pinedo, G; Mayet, P; Nieminen, A; Nowacki, F; Penttila, H; Plochocki, A; Rejmund, M; Roeckl, E; Schlegel, C; Schmidt, K; Schwengner, R; Sawicka, M
2001-01-01
The proton-rich isotope Cu-56 was produced at the GSI On-Line Mass Separator by means of the Si-28(S-32, p3n) fusion-evaporation reaction. Its beta -decay properties were studied by detecting beta -delayed gamma rays and protons. A half-Life of 93 +/- 3 ms was determined for Cu-56. Compared to the
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Directory of Open Access Journals (Sweden)
Nathan C Rowland
2015-09-01
Full Text Available In Parkinson’s disease patients in the OFF medication state, basal ganglia local field potentials exhibit changes in beta and gamma oscillations that correlate with reduced voluntary movement, manifested as rigidity and akinesia. However, magnetoencephalography and low-resolution electrocorticography (ECoG studies in Parkinson’s patients suggest that changes in sensorimotor cortical oscillations differ from those of the basal ganglia. To more clearly define the role of sensorimotor cortex oscillatory activity in Parkinson’s, we performed intraoperative, high-resolution (4 mm spacing ECoG recordings in 10 Parkinson’s patients (2 females, ages 47-72 undergoing deep brain stimulation (DBS lead placement in the awake, OFF medication state. We analyzed ECoG potentials during a computer-controlled reaching task designed to separate movement preparation from movement execution and compared findings to similar invasive recordings in eight patients with essential tremor (3 females, ages 59-78, a condition not associated with rigidity or akinesia. We show that 1 cortical beta spectral power at rest does not differ between Parkinson’s and essential tremor patients (p = 0.85, 2 early motor preparation in Parkinson’s patients in the OFF medication state is associated with a larger beta desynchronization compared to patients with essential tremor (p = 0.0061, and 3 cortical broadband gamma power is elevated in Parkinson’s patients compared to essential tremor patients during both rest and task recordings (p = 0.004. Our findings suggest an oscillatory profile in sensorimotor cortex of Parkinson’s patients that, in contrast to the basal ganglia, may act to promote movement to oppose the anti-kinetic bias of the dopamine-depleted state.
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Directory of Open Access Journals (Sweden)
Everson Araújo Nunes
2008-04-01
Full Text Available O beta-hidroxi-beta-metilbutirato, metabólito do aminoácido leucina, vem sendo utilizado como suplemento alimentar, em situações específicas, com o intuito de aumentar ou manter a massa isenta de gordura. Os relatos dos efeitos do beta-hidroxi-beta-metilbutirato em estudos recentes fizeram crescer as expectativas sobre sua utilização em casos patológicos. Também foram demonstrados melhores resultados, quando da sua ingestão, no treinamento de força em indivíduos iniciantes e em idosos. Em humanos o beta-hidroxi-beta-metilbutirato tem sido usado como agente anti-catabólico, e em modelos animais foi demonstrado ser eficaz em inibir a atividade de vias proteolíticas em células musculares de indivíduos caquéticos in vitro e in vivo. Os mecanismos participantes desses processos envolvem: a inibição da atividade do sistema ubiquitina proteossoma ATP-dependente, a inibição de vias de sinalização com participação da proteína quinase C-alfa e a diminuição da concentração citoplasmática do fator nuclear - kappa B livre, eventos relacionados ao decréscimo da proteólise em células musculares.The leucine metabolite beta-hydroxy-beta-methylbutyrate has been used as a nutritional supplement in specific situations to prevent losing or to increase lean mass. Recent studies showed interesting results of beta-hydroxy-beta-methylbutyrate supplementation in certain disease states. Better results have also been demonstrated when it is taken by starters or old individuals doing strength training. In humans, beta-hydroxy-beta-methylbutyrate has been used as an anticatabolic agent and in animal models it has been demonstrated to be effective in inhibiting the activity of the proteolytic pathways in muscle cells of extremely weak individuals in vivo and in vitro. The mechanisms that participate in this process involve: inhibition of the ATP-ubiquitin-proteasome pathway, inhibition of the signalization pathways involving protein kinase C
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Role of growth factors in control of pancreatic beta cell mass: focus on betatrophin.
Levitsky, Lynne L; Ardestani, Goli; Rhoads, David B
2014-08-01
Betatrophin is a newly described hormone, which potently stimulates beta cell replication in mice. This discovery has engendered great hope that it could prove clinically important in the treatment of type 1 and type 2 diabetes. Betatrophin, a 198-amino acid protein secreted by liver and adipose tissue, stimulates growth of pancreatic beta cell mass in insulin-resistant mice. Betatrophin has previously been named RIFL, lipasin, and ANGPLT8, and its salutory effects on lipid metabolism have been described in mouse and human studies. Serum betatrophin levels in humans correlate with improved adipose tissue lipid storage and lower serum triglyceride levels in the fed state, but do not correlate with insulin resistance or carbohydrate tolerance in humans. Betatrophin has not yet been shown to have an effect on beta cell replication in human pancreatic islets. Many endocrine and paracrine factors, of which betatrophin is the newest described, increase beta cell mass in murine models. None of these factors, including betatrophin, have displayed the same activity in clinical studies. This may reflect a profound species difference in beta cell regeneration pathways in mice and humans.
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DEFF Research Database (Denmark)
Højlund, Kurt; Wrzesinski, Krzysztof; Larsen, Peter Mose
2003-01-01
quantitate a large number of proteins and their post-translational modifications simultaneously and is a powerful tool to study polygenic diseases like type 2 diabetes. Using this approach on human skeletal muscle biopsies, we have identified eight potential protein markers for type 2 diabetes in the fasting...... synthase beta-subunit phosphoisoform in diabetic muscle correlated inversely with fasting plasma glucose levels. These data suggest a role for phosphorylation of ATP synthase beta-subunit in the regulation of ATP synthesis and that alterations in the regulation of ATP synthesis and cellular stress proteins...
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Energy Technology Data Exchange (ETDEWEB)
Bidasee, K.R.; Besch, H.R. Jr.; Kwon, Sangyeol; Emmick, J.T.; Besch, K.T.; Gerzon, Koert; Humerickhouse, R.A. (Indiana Univ., Indianapolis, IN (United States). School of Medicine)
1994-01-01
A high affinity, photoactivatable, radio-iodinated ligand for the ryanodine binding site(s) of the sarcoplasmic reticulum calcium-release channel, C[sub 10]-O[sub e]-N-(4-azido-5-[sup 125]iodo salicyloyl)-[beta]-alanyl-[beta]-alanyl ryanodine (Az-[beta]AR), was synthesized at a specific activity of 1400mCi/mmol. (Author).
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LENUS (Irish Health Repository)
Wang, Jiang Huai
2012-02-03
Beta(1) integrins play a crucial role in supporting tumor cell attachment to and invasion into the extracellular matrix. Endotoxin\\/LPS introduced by surgery has been shown to enhance tumor metastasis in a murine model. Here we show the direct effect of LPS on tumor cell adhesion and invasion in extracellular matrix proteins through a beta(1) integrin-dependent pathway. The human colorectal tumor cell lines SW480 and SW620 constitutively expressed high levels of the beta(1) subunit, whereas various low levels of alpha(1), alpha(2), alpha(4), and alpha(6) expression were detected. SW480 and SW620 did not express membrane-bound CD14; however, LPS in the presence of soluble CD14 (sCD14) significantly up-regulated beta(1) integrin expression; enhanced tumor cell attachment to fibronectin, collagen I, and laminin; and strongly promoted tumor cell invasion through the Matrigel. Anti-beta(1) blocking mAbs (4B4 and 6S6) abrogated LPS- plus sCD14-induced tumor cell adhesion and invasion. Furthermore, LPS, when combined with sCD14, resulted in NF-kappaB activation in both SW480 and SW620 cells. Inhibition of the NF-kappaB pathway significantly attenuated LPS-induced up-regulation of beta(1) integrin expression and prevented tumor cell adhesion and invasion. These results provide direct evidence that although SW480 and SW620 cells do not express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-kappaB, up-regulate beta(1) integrin expression, and subsequently promote tumor cell adhesion and invasion. Moreover, LPS-induced tumor cell attachment to and invasion through extracellular matrix proteins is beta(1) subunit-dependent.
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Progress in molecular nuclear medicine imaging of pancreatic beta cells
International Nuclear Information System (INIS)
Wu Haifei; Yin Hongyan; Liu Shuai; Zhang Yifan
2010-01-01
Diabetes mellitus is a common and frequently occurring disease which seriously threaten the health of human beings. Type 1 and type 2 diabetes respectively results from being destroyed and insufficient beta-cell mass. The associated symptoms appear until 50%-60% decrease of beta-cell mass. Because pancreas is deeply located in the body, with few beta-cell mass, the current methods of clinical diagnosis are invasive and late. So diagnosis of metabolism disease of beta-cell early non-invasively becomes more and more popular, imaging diagnosis of diabetes mellitus becomes the focus of researches, but how to estimate the mass of beta-cell still an important subject in imaging technology. (authors)
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Directory of Open Access Journals (Sweden)
Thomas J Baumgarten
Full Text Available Neuronal oscillatory activity in the beta band (15-30 Hz is a prominent signal within the human sensorimotor cortex. Computational modeling and pharmacological modulation studies suggest an influence of GABAergic interneurons on the generation of beta band oscillations. Accordingly, studies in humans have demonstrated a correlation between GABA concentrations and power of beta band oscillations. It remains unclear, however, if GABA concentrations also influence beta peak frequencies and whether this influence is present in the sensorimotor cortex at rest and without pharmacological modulation. In the present study, we investigated the relation between endogenous GABA concentration (measured by magnetic resonance spectroscopy and beta oscillations (measured by magnetoencephalography at rest in humans. GABA concentrations and beta band oscillations were measured for left and right sensorimotor and occipital cortex areas. A significant positive linear correlation between GABA concentration and beta peak frequency was found for the left sensorimotor cortex, whereas no significant correlations were found for the right sensorimotor and the occipital cortex. The results show a novel connection between endogenous GABA concentration and beta peak frequency at rest. This finding supports previous results that demonstrated a connection between oscillatory beta activity and pharmacologically modulated GABA concentration in the sensorimotor cortex. Furthermore, the results demonstrate that for a predominantly right-handed sample, the correlation between beta band oscillations and endogenous GABA concentrations is evident only in the left sensorimotor cortex.
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Baumgarten, Thomas J.; Oeltzschner, Georg; Hoogenboom, Nienke; Wittsack, Hans-Jörg; Schnitzler, Alfons; Lange, Joachim
2016-01-01
Neuronal oscillatory activity in the beta band (15–30 Hz) is a prominent signal within the human sensorimotor cortex. Computational modeling and pharmacological modulation studies suggest an influence of GABAergic interneurons on the generation of beta band oscillations. Accordingly, studies in humans have demonstrated a correlation between GABA concentrations and power of beta band oscillations. It remains unclear, however, if GABA concentrations also influence beta peak frequencies and whether this influence is present in the sensorimotor cortex at rest and without pharmacological modulation. In the present study, we investigated the relation between endogenous GABA concentration (measured by magnetic resonance spectroscopy) and beta oscillations (measured by magnetoencephalography) at rest in humans. GABA concentrations and beta band oscillations were measured for left and right sensorimotor and occipital cortex areas. A significant positive linear correlation between GABA concentration and beta peak frequency was found for the left sensorimotor cortex, whereas no significant correlations were found for the right sensorimotor and the occipital cortex. The results show a novel connection between endogenous GABA concentration and beta peak frequency at rest. This finding supports previous results that demonstrated a connection between oscillatory beta activity and pharmacologically modulated GABA concentration in the sensorimotor cortex. Furthermore, the results demonstrate that for a predominantly right-handed sample, the correlation between beta band oscillations and endogenous GABA concentrations is evident only in the left sensorimotor cortex. PMID:27258089
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Lysosomal trafficking of {beta}-catenin induced by the tea polyphenol epigallocatechin-3-gallate
Energy Technology Data Exchange (ETDEWEB)
Dashwood, Wan-Mohaiza [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Carter, Orianna [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Al-Fageeh, Mohamed [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Li, Qingjie [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Dashwood, Roderick H. [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States)]. E-mail: Rod.Dashwood@oregonstate.edu
2005-12-11
{beta}-Catenin is a cadherin-binding protein involved in cell-cell adhesion, which also functions as a transcriptional activator when complexed in the nucleus with members of the T-cell factor (TCF)/lymphoid enhancer factor (LEF) family of proteins. There is considerable interest in mechanisms that down-regulate {beta}-catenin, since this provides an avenue for the prevention of colorectal and other cancers in which {beta}-catenin is frequently over-expressed. We show here that physiologically relevant concentrations of the tea polyphenol epigallocatechin-3-gallate (EGCG) inhibited {beta}-catenin/TCF-dependent reporter activity in human embryonic kidney 293 cells transfected with wild type or mutant {beta}-catenins, and there was a corresponding decrease in {beta}-catenin protein levels in the nuclear, cytosolic and membrane-associated fractions. However, {beta}-catenin accumulated as punctate aggregates in response to EGCG treatment, including in human colon cancer cells over-expressing {beta}-catenin endogenously. Confocal microscopy studies revealed that the aggregated {beta}-catenin in HEK293 cells was extra-nuclear and co-localized with lysosomes, suggesting that EGCG activated a pathway involving lysosomal trafficking of {beta}-catenin. Lysosomal inhibitors leupeptin and transepoxysuccinyl-L-leucylamido(4-guanido)butane produced an increase in {beta}-catenin protein in total cell lysates, without a concomitant increase in {beta}-catenin transcriptional activity. These data provide the first evidence that EGCG facilitates the trafficking of {beta}-catenin into lysosomes, presumably as a mechanism for sequestering {beta}-catenin and circumventing further nuclear transport and activation of {beta}-catenin/TCF/LEF signaling.
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Directory of Open Access Journals (Sweden)
Chong Seng Shueh
2012-10-01
Full Text Available The main objective of current study was to explore the function of chromosomal putative beta-lactamase gene (smlt 0115 in clinical Stenotrophomonas maltophilia. Antibiotic susceptibility test (AST screening for current antimicrobial drugs was done and Minimum Inhibitory Concentration (MIC level towards beta-lactams was determined by E-test. Putative beta-lactamase gene of S. maltophilia was amplified via PCR, with specific primers, then cloned into pET-15 expression plasmid and transformed into Escherichia coli BL21. The gene was sequenced and analyzed. The expressed protein was purified by affinity chromatography and the kinetic assay was performed. S. maltophilia ATCC 13637 was included in this experiment. Besides, a hospital strain which exhibited resistant to a series of beta-lactams including cefepime was identified via AST and MIC, hence it was named as S2 strain and was considered in this study. Sequencing result showed that putative beta-lactamase gene obtained from ATCC 13637 and S2 strains were predicted to have cephalosporinase activity by National Center for Biotechnology Information (NCBI blast program. Differences in the sequences of both ATCC 13637 and S2 strains were found via ClustalW alignment software. Kinetic assay proved a cephalosporinase characteristic produced by E. coli BL21 clone that overexpressed the putative beta-lactamase gene cloned under the control of an external promoter. Yet, expressed protein purified from S2 strain had high catalytic activity against beta-lactam antibiotics which was 14-fold higher than expressed protein purified from ATCC 13637 strain. This study represents the characterization analysis of putative beta-lactamase gene (smlt 0115 of S. maltophilia. The presence of the respective gene in the chromosome of S. maltophilia suggested that putative beta-lactamase gene (smlt 0115 of S. maltophilia plays a role in beta-lactamase resistance.
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A toxic approach to beta2-toxigenic Clostridium perfringens
Allaart, J.G.
2013-01-01
Clostridium perfringens is one of the most important causes of intestinal disease in animals and humans. Its virulence is attributed to the several toxins it can produce, including the beta2 toxin encoded by cpb2. In this thesis we studied the role of the beta2 toxin produced by C. perfringens in
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Energy Technology Data Exchange (ETDEWEB)
Khelia, C.; Ben Nasrallah, T.; Amlouk, M.; Belgacem, S. [Faculte des Sciences, Tunis (Tunisia). Lab. de Physique de la Matiere Condensee; Maiz, F. [Equipe de Photothermique de Nabeul, Inst. Preparatoire aux Etudes d' Ingenieur de Nabeul (Tunisia); Mnari, M. [Lab. de Chimie Analytique, Campus Univ., Tunis (Tunisia)
2000-03-01
Tin disulfide {beta}-SnS{sub 2} thin films have been prepared on pyrex substrates by the spray pyrolysis technique using tin tetrachloride and thiourea as starting materials. The depositions were carried out in the range of substrate temperatures from 240 to 400 C. Highly c-axis oriented {beta}-SnS{sub 2} films, having a strong (001) X-ray diffraction line are obtained at temperature 280 C and using concentration ratio in solution R = [S]/[Sn] = 2.5. Films surfaces were analyzed by contact atomic force microscopy (AFM) and by scanning electron microscopy (SEM) in order to understand the effect of the deposited temperature on the surface structure. On the other hand, from transmission and reflection spectra, the band gap energy determined is about 2.71 eV. Finally using the photodeflection spectroscopy technique, the thermal conductivity K{sub c} and diffusivity D{sub c} were obtained. Their values are 10 Wm{sup -1}K{sup -1} and 10{sup -5} m{sup 2}s{sup -1} respectively. (orig.)
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Wu, J H; Herp, A; Wu, A M
1993-03-01
To define carbohydrate specificity of Ricinus communis agglutinin (RCA1), the combining site of RCA1 was further characterized by quantitative precipitin (QPA) and precipitin-inhibition assays (QPIA). Among the oligosaccharides tested for QPIA, Gal beta 1-->4GlcNAc (II, human blood group type II precursor sequence) was found to be 7.1 times more active than Gal beta 1-->3GalNAc (T, Thomsen-Friedenreich sequence) and about 1.7 times more active than the other three disaccharides tested--Gal beta 1-->4Man, Gal beta 1-->3DAra and Gal beta 1-->6GalNAc. Gal alpha 1-->4Gal, the receptor of the uropathogenic E. coli ligand was 3.6 times less active than the II sequence. These results indicate that the beta 1-->4 linkage of the terminal Gal to subterminal GlcNAc is important as this beta 1-->4GlcNAc sequence is at least 1.6 times more active than other types of disaccharides. Among the glycoproteins examined for QPA, native and desialized bovine submandibular glycoproteins, native and desialized human plasma alpha 1-acid glycoproteins, as well as crude hog stomach mucin and its three mild acid hydrolyzed products reacted well with the lectin. These glycoproteins precipitated over 75% of the lectin nitrogen added indicating that RCA1 has the ability to recognize Gal beta 1-->4/3GlcNAc and/or the related residues at the non-reducing ends and at positions in the interior of the chains. However, Tn (GalNAc alpha 1-->Ser/Thr sequence) rich glycoproteins such as desialized ovine submandibular glycoprotein and desialized armadillo salivary glycoprotein, in which over 90% of the carbohydrate side chains are Tn determinants with none or only a trace of I/II or T determinants, precipitated poorly with RCA1. From the present and previous results obtained, the carbohydrate specificity of RCA1 can be constructed and summarized in decreasing order by lectin determinants as follows: II (Gal beta 1-->4GlcNAc) > I (Gal beta 1-->3GlcNAc) > E (Gal alpha 1-->4Gal) and B (Gal alpha 1-->3Gal
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Secondary structure determination of human. beta. -endorphin by /sup 1/H NMR spectroscopy
Energy Technology Data Exchange (ETDEWEB)
Lichtarge, O.; Jardetzky, O.; Li, C.H.
1987-09-08
The /sup 1/H NMR spectra of human ..beta..-endorphin indicate that the peptide exists in random-coil form in aqueous solution but becomes helical in mixed solvent. Thermal denaturation NMR experiments show that in water there is no transition between 24 and 75/sup 0/C, while a slow noncooperative thermal unfolding is observed in a 60% methanol-40% water mixed solvent in the same temperature range. These findings are consistent with circular dichroism studies by other workers concluding that ..beta..-endorphin is a random coil in water but that it forms 50% ..cap alpha..-helix or more in mixed solvents. The peptide in the mixed water-methanol solvent was further studied by correlated spectroscopy (COSY) and nuclear Overhauser effect spectroscopy (NOESY) experiments. These allow a complete set of assignments to be made and establish two distinct stretches over which the solvent induces formation of ..cap alpha..-helices: the first occurs between Tyr-1 and Thr-12 and the second between Leu-14 and extending to Lys-28. There is evidence that the latter is capped by a turn occurring between Lys-28 and Glu-31. These helices form at the enkephalin receptor binding site, which is at the amino terminus, and at the morphine receptor binding site, located at the carboxyl terminus. The findings suggest that these two receptors may specifically recognize ..cap alpha..-helices.
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Analyzing the evolution of beta-endorphin post-translational processing events: studies on reptiles.
Shoureshi, Pezhman; Baron, Andrea; Szynskie, Laura; Dores, Robert M
2007-01-01
In many cartilaginous fishes, most ray-finned fishes, lungfishes, and amphibians, the post-translational processing of POMC includes the monobasic cleavage of beta-endorphin to yield an opioid that is eight to ten amino acids in length. The amino acid motif within the beta-endorphin sequence required for a monobasic cleavage event is -E-R-(S/G)-Q-. Mammals and birds lack this motif and as a result beta-endorphin(1-8) is a not an end-product in either group. Since both mammals and birds were derived from ancestors with reptilian origins, an analysis of beta-endorphin sequences from extant groups of reptiles should provide insights into the manner in which beta-endorphin post-translational processing mechanisms have evolved in amniotes. To this end a POMC cDNA was cloned from the pituitary of the turtle, Chrysemys scripta. The beta-endorphin sequence in this species was compared to other reptile beta-endorphin sequences (i.e., Chinese soft shell turtle and gecko) and to known bird and mammal sequences. This analysis indicated that either the loss of the arginine residue at the cleavage site (the two turtle species, chick, and human) or a substitution at the glutamine position in the consensus sequence (gecko and ostrich) would account for the loss of the monobasic cleavage reaction in that species. Since amphibians are capable of performing the beta-endorphin monobasic reaction, it would appear that the amino acid substitutions that eliminated this post-translational process event in reptilian-related tetrapods must have occurred in the ancestral amniotes.
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De Muro, Pierina; Capobianco, Giampiero; Formato, Marilena; Lepedda, Antonio Junior; Cherchi, Gian Mario; Gordini, Laila; Dessole, Salvatore
2009-07-01
To evaluate transforming growth factor beta1 (TGF-beta1) and glycosaminoglycans (GAG) changes in human plasma and urine during the menstrual cycle, IVF-ET, and pregnancy. Prospective clinical study. University hospital. Thirteen women with apparently normal menstrual cycle (group 1); 18 women undergoing IVF-ET (group 2); and 14 low-risk pregnant women (group 3). We assayed plasma and urine concentrations of TGF-beta1, urine content, and distribution of GAG. Blood and urine samples were collected during days 2 to 3, 12 to 13, and 23 to 24 in group 1; in group 2, samples were obtained at menstrual phase, oocyte pick-up day, and 15 days after ET; in group 3, samples were obtained during gestational weeks 10-12, 22-24, and 30-32 and 1 month after delivery. Changes in TGF-beta1 and GAG content. The mean value of total urinary trypsin inhibitor/chondroitin sulfate (UTI/CS) showed a distinct peak at day 12 of the menstrual cycle in the fertile women in whom we monitored the ovulatory period. In the IVF-ET group, GAG distribution and TGF-beta1 levels showed significant differences during the cycle. We observed increased levels of plasma TGF-beta1 15 days after ET. A significant increase of total UTI/CS value with increasing gestation was detected. Transforming growth factor beta1 and GAG levels could represent an additional tool to monitor reproductive events and could be useful, noninvasive markers of ovulation and ongoing pregnancy.
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Alvarez, Vanessa; Rodríguez-Sáiz, Marta; de la Fuente, Juan Luis; Gudiña, Eduardo J; Godio, Ramiro P; Martín, Juan F; Barredo, José Luis
2006-04-01
The conversion of beta-carotene into xanthophylls is a subject of great scientific and industrial interest. We cloned the crtS gene involved in astaxanthin biosynthesis from two astaxanthin producing strains of Xanthophyllomyces dendrorhous: VKPM Y2410, an astaxanthin overproducing strain, and the wild type ATCC 24203. In both cases, the ORF has a length of 3166 bp, including 17 introns, and codes for a protein of 62.6 kDa with similarity to cytochrome-P450 hydroxylases. crtS gene sequences from strains VKPM Y2410, ATCC 24203, ATCC 96594, and ATCC 96815 show several nucleotide changes, but none of them causes any amino acid substitution, except a G2268 insertion in the 13th exon of ATCC 96815 which causes a change in the reading frame. A G1470 --> A change in the 5' splicing region of intron 8 was also found in ATCC 96815. Both point mutations explain astaxanthin idiotrophy and beta-carotene accumulation in ATCC 96815. Mutants accumulating precursors of the astaxanthin biosynthetic pathway were selected from the parental strain VKPM Y2410 (red) showing different colors depending on the compound accumulated. Two of them were blocked in the biosynthesis of astaxanthin, M6 (orange; 1% astaxanthin, 71 times more beta-carotene) and M7 (orange; 1% astaxanthin, 58 times more beta-carotene, 135% canthaxanthin), whereas the rest produced lower levels of astaxanthin (5-66%) than the parental strain. When the crtS gene was expressed in M7, canthaxanthin accumulation disappeared and astaxanthin production was partially restored. Moreover, astaxanthin biosynthesis was restored when X. dendrorhous ATCC 96815 was transformed with the crtS gene. The crtS gene was heterologously expressed in Mucor circinelloides conferring to this fungus an improved capacity to synthesize beta-cryptoxanthin and zeaxanthin, two hydroxylated compounds from beta-carotene. These results show that the crtS gene is involved in the conversion of beta-carotene into xanthophylls, being potentially useful to
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Energy Technology Data Exchange (ETDEWEB)
Toyama, Hiroshi [Fujita Health University, Department of Radiology, Aichi (Japan); National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Ye, Daniel; Cohen, Robert M. [National Institutes of Health, Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Ichise, Masanori; Liow, Jeih-San; Cai, Lisheng; Musachio, John L.; Hong, Jinsoo; Crescenzo, Mathew; Tipre, Dnyanesh; Lu, Jian-Qiang; Zoghbi, Sami; Vines, Douglass C.; Pike, Victor W.; Innis, Robert B. [National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Jacobowitz, David [USUHS, Department of Anatomy, Physiology, and Genetics, Bethesda, Maryland (United States); Seidel, Jurgen; Green, Michael V. [National Institutes of Health, Department of Nuclear Medicine, Warren Grant Magnuson Clinical Center, Bethesda, Maryland (United States); Katada, Kazuhiro [Fujita Health University, Department of Radiology, Aichi (Japan)
2005-04-01
The purpose of this study was to evaluate the capacity of [{sup 11}C]6-OH-BTA-1 and positron emission tomography (PET) to quantify {beta}-amyloid (A{beta}) plaques in the Tg2576 mouse model of Alzheimer's disease (AD). PET imaging was performed with the NIH ATLAS small animal scanner in six elderly transgenic mice (Tg2576; age 22.0{+-}1.8 months; 23.6{+-}2.6 g) overexpressing a mutated form of human {beta}-amyloid precursor protein (APP) known to result in the production of A{beta} plaques, and in six elderly wild-type litter mates (age 21.8{+-}1.6 months; 29.5{+-}4.7 g). Dynamic PET scans were performed for 30 min in each mouse under 1% isoflurane inhalation anesthesia after a bolus injection of 13-46 MBq of [{sup 11}C]6-OH-BTA-1. PET data were reconstructed with 3D OSEM. On the coronal PET image, irregular regions of interest (ROIs) were placed on frontal cortex (FR), parietal cortex (PA), striatum (ST), thalamus (TH), pons (PO), and cerebellum (CE), guided by a mouse stereotaxic atlas. Time-activity curves (TACs) (expressed as percent injected dose per gram normalized to body weight: % ID-kg/g) were obtained for FR, PA, ST, TH, PO, and CE. ROI-to-CE radioactivity ratios were also calculated. Following PET scans, sections of mouse brain prepared from anesthetized and fixative-perfused mice were stained with thioflavin-S. TACs for [{sup 11}C]6-OH-BTA-1 in all ROIs peaked early (at 30-55 s), with radioactivity washing out quickly thereafter in both transgenic and wild-type mice. Peak uptake in all regions was significantly lower in transgenic mice than in wild-type mice. During the later part of the washout phase (12-30 min), the mean FR/CE and PA/CE ratios were higher in transgenic than in wild-type mice (1.06{+-}0.04 vs 0.98{+-}0.07, p=0.04; 1.06{+-}0.09 vs 0.93{+-}0.08 p=0.02) while ST/CE, TH/CE, and PO/CE ratios were not. Ex vivo staining revealed widespread A{beta} plaques in cortex, but not in cerebellum of transgenic mice or in any brain regions of wild
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[Effect of sulfonation of polyethersulfone sheets on the adsorption of beta2-microglobulin].
Cheng, Liping; Sun, Shudong; Yue, Yilun; Huang, Jia; Mao, Huayi; Liang, Bo
2005-06-01
This study was performed to evaluate the adsorption of beta2-microglobulin(beta2 M) by blood dialysis membrane materials which are polyethersulfone (PES), sulfonated polyethersulfones, (PES-SO3Na-I and PES-SO3Na-I ) in vitro incubated in human serum and radiolabeled beta2M (125I-beta2 M) solution respectively. In these experiments, the materials were incubated in 125I-beta2 M solution and human serum at the appointed time ranging from 15 minutes to four hours at 37 degrees C, and then the amounts of 125I-beta2M and serum beta2M adsorbed by materials were measured by radioimmunoassay (RIA). In the 125I-beta2 M system, amounts of 125I-beta2M adsorbed by the materials decreased in sequence of PES-SO3 Na-II > PES-SO3Na-I > PES. In the serum system, amounts of beta2M adsorbed reached maximums at 30 minutes and the final adsorptions decreased in sequence of PES-SO3Na-II > PES-SO3Na-I > PES. Sulfonated PES removes beta2M more than PES does and the adsorption of beta2M increases with the increase in the degree of sulfonation. Its ability to remove significant amount of beta2M may result in less beta2M available for incorporation into amyloid. The use of PES-SO3Na membranes lessens the likelihood of dialysis-related amyloidosis (DRA) development, which remains a major source of morbidity for patients treated with long-term hemodialysis.
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Exotic nuclear beta transitions astrophysical examples
Takahashi, K
1981-01-01
A theoretical study of nuclear beta -transitions under various astrophysical circumstances is reviewed by illustrative examples: 1) continuum-state electron captures in a matter in the nuclear statistical equiplibrium, and ii) bound-state beta -decays in stars in connection with a cosmochronometer and with the s-process branchings. (45 refs).
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Energy Technology Data Exchange (ETDEWEB)
Gorgoseo, J. J.; Rojo, A.; Camara-Obregon, A.; Dieguez-Aranda, U.
2012-07-01
The purpose of this study was to compare the accuracy of the Weibull, Johnson's SB and beta distributions, fitted with some of the most usual methods and with different fixed values for the location parameters, for describing diameter distributions in even-aged stands of Pinus pinaster, Pinus radiata and Pinus sylvestris in northwest Spain. A total of 155 permanent plots in Pinus sylvestris stands throughout Galicia, 183 plots in Pinus pinaster stands throughout Galicia and Asturias and 325 plots in Pinus radiata stands in both regions were measured to describe the diameter distributions. Parameters of the Weibull function were estimated by Moments and Maximum Likelihood approaches, those of Johnson's SB function by Conditional Maximum Likelihood and by Knoebel and Burkhart's method, and those of the beta function with the method based on the moments of the distribution. The beta and the Johnson's SB functions were slightly superior to Weibull function for Pinus pinaster stands; the Johnson's SB and beta functions were more accurate in the best fits for Pinus radiata stands, and the best results of the Weibull and the Johnson's SB functions were slightly superior to beta function for Pinus sylvestris stands. However, the three functions are suitable for this stands with an appropriate value of the location parameter and estimation of parameters method. (Author) 44 refs.
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Protection from sunburn with beta-Carotene--a meta-analysis.
Köpcke, Wolfgang; Krutmann, Jean
2008-01-01
Nutritional protection against skin damage from sunlight is increasingly advocated to the general public, but its effectiveness is controversial. In this meta-analysis, we have systematically reviewed the existing literature on human supplementation studies on dietary protection against sunburn by beta-carotene. A review of literature until June 2007 was performed in PubMed, ISI Web of Science and EBM Cochrane library and identified a total of seven studies which evaluated the effectiveness of beta-carotene in protection against sunburn. Data were abstracted from these studies by means of a standardized data collection protocol. The subsequent meta-analysis showed that (1) beta-carotene supplementation protects against sunburn and (2) the study duration had a significant influence on the effected size. Regression plot analysis revealed that protection required a minimum of 10 weeks of supplementation with a mean increase of the protective effect of 0.5 standard deviations with every additional month of supplementation. Thus, dietary supplementation of humans with beta-carotene provides protection against sunburn in a time-dependent manner.
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Energy Technology Data Exchange (ETDEWEB)
Lundkvist, Camilla; Halldin, Christer; Ginovart, Nathalie; Swahn, Carl-Gunnar; Farde, Lars
1997-10-01
{beta}-CIT-FP [N-(3-fluoropropyl)-2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane] is a cocaine analogue with high affinity for the dopamine transporter. Positron emission tomography (PET) studies with [O-methyl-{sup 11}C]{beta}-CIT-FP ([{sup 11}C]{beta}-CIT-FP) has shown that equilibrium conditions were approached but, however, not reached at the end of measurement. Moreover, metabolite studies of [{sup 11}C]{beta}-CIT-FP in monkey plasma demonstrated a lipophilic-labelled metabolite that may enter the brain. We therefore labelled {beta}-CIT-FP with fluorine-18 in a position that may avoid the formation of labelled lipophilic metabolites. The more long-lived radionuclide ({sup 18}F) was used to allow for measurements over longer time. [N-fluoropropyl-{sup 18}F]{beta}-CIT-FP ([{sup 18}F]{beta}-CIT-FP) was prepared by N-alkylation of nor-{beta}-CIT with [{sup 18}F]fluoropropyl bromide. PET studies were performed in cynomolgus monkeys. [{sup 18}F]{beta}-CIT-FP entered the brain rapidly. There was a high concentration of radioactivity in the striatum and much lower in the thalamus, neocortex, and cerebellum. The striatum-to-cerebellum ratio was about 5 at time of transient equilibrium, which occurred after 60 to 100 min. After pretreatment with GBR 12909, radioactivity in the striatum was markedly reduced, thus indicating specific [{sup 18}F]{beta}-CIT-FP binding to the dopamine transporter. The fraction of unchanged [{sup 18}F]{beta}-CIT-FP determined by HPLC was 10-15% after 140 min. No lipophilic labelled metabolites were detected. The absence of measurable lipophilic labelled metabolites and the occurrence of transient equilibrium within the time of the PET measurement indicate that [{sup 18}F]{beta}-CIT-FP is superior to [{sup 11}C]{beta}-CIT-FP as a PET radioligand for quantification of the dopamine transporter in the human brain.
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A role for 12/15 lipoxygenase in the amyloid beta precursor protein metabolism.
Succol, Francesca; Praticò, Domenico
2007-10-01
12/15 Lipoxygenase (12/15LO) protein levels and activity are increased in pathologically affected regions of Alzheimer's disease (AD) brains, compared with controls. Its metabolic products are elevated in cerebrospinal fluid of patients with AD and individuals with mild cognitive impairment, suggesting that this enzyme may be involved early in AD pathogenesis. Herein, we investigate the effect of pharmacologic inhibition of 12/15LO on the amyloid beta precursor protein (APP) metabolism. To this end, we used CHO and N2A cells stably expressing human APP with the Swedish mutant, and two structurally distinct and selective 12/15LO inhibitors, PD146176 and CDC. Our results demonstrated that both drugs dose-dependently reduced Abeta formation without affecting total APP levels. Interestingly, in the same cells we observed a significant reduction in secreted (s)APPbeta and beta-secretase (BACE), but not sAPPalpha and ADAM10 protein levels. Together, these data show for the first time that this enzymatic pathway influences Abeta formation whereby modulating the BACE proteolytic cascade. We conclude that specific pharmacologic inhibition of 12/15LO could represent a novel therapeutic target for treating or preventing AD pathology in humans.
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Does selection for short sleep duration explain human vulnerability to Alzheimer’s disease?
Nesse, Randolph M; Finch, Caleb E; Nunn, Charles L
2017-01-01
Abstract Compared with other primates, humans sleep less and have a much higher prevalence of Alzheimer ’s disease (AD) pathology. This article reviews evidence relevant to the hypothesis that natural selection for shorter sleep time in humans has compromised the efficacy of physiological mechanisms that protect against AD during sleep. In particular, the glymphatic system drains interstitial fluid from the brain, removing extra-cellular amyloid beta (eAβ) twice as fast during sleep. In addition, melatonin—a peptide hormone that increases markedly during sleep—is an effective antioxidant that inhibits the polymerization of soluble eAβ into insoluble amyloid fibrils that are associated with AD. Sleep deprivation increases plaque formation and AD, which itself disrupts sleep, potentially creating a positive feedback cycle. These and other physiological benefits of sleep may be compromised by short sleep durations. Our hypothesis highlights possible long-term side effects of medications that reduce sleep, and may lead to potential new strategies for preventing and treating AD. PMID:28096295
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DEFF Research Database (Denmark)
Durkin, M E; Jäger, A C; Khurana, T S
1999-01-01
The laminin beta2 chain is an important constituent of certain kidney and muscle basement membranes. We have generated a detailed physical map of a 110-kb genomic DNA segment surrounding the human laminin beta2 chain gene (LAMB2) on chromosome 3p21.3-->p21.2, a region paralogous with the chromosome...... 7q22-->q31 region that contains the laminin beta1 chain gene locus (LAMB1). Several CpG islands and a novel polymorphic microsatellite marker (D3S4594) were identified. The 3' end of LAMB2 lies 16 kb from the 5' end of the glutaminyl tRNA synthetase gene (QARS). About 20 kb upstream of LAMB2 we...... found a gene encoding a transcribed, non-processed LAMB2-like pseudogene (LAMB2L). The sequence of 1.75 kb of genomic DNA at the 3' end of LAMB2L was similar to exons 8-12 of the laminin beta2 chain gene. The LAMB2L-LAMB2-QARS cluster lies telomeric to the gene encoding the laminin-binding protein...
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Energy Technology Data Exchange (ETDEWEB)
Cui Mengchao [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875 (China); Ono, Masahiro, E-mail: ono@pharm.kyoto-u.ac.j [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Kimura, Hiroyuki; Kawashima, Hidekazu [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Liu Boli [Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875 (China); Saji, Hideo, E-mail: hsaji@pharm.kyoto-u.ac.j [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)
2011-04-15
Five iodinated 2-phenyl-1H-benzo[d]imidazole derivatives were synthesized and evaluated as potential probes for {beta}-amyloid (A{beta}) plaques. One of the compounds, 4-(6-iodo-1H-benzo[d]imidazol-2-yl)-N,N-dimethylaniline (12), showed excellent affinity for A{beta}{sub 1-42} aggregates (K{sub i}=9.8 nM). Autoradiography with sections of postmortem Alzheimer's disease (AD) brain revealed that a radioiodinated probe [{sup 125}I]12, labeled A{beta} plaques selectively with low nonspecific binding. Biodistribution experiments with normal mice injected intravenously with [{sup 125}I]12 showed high uptake [4.14 percent injected dose per gram (% ID/g) at 2 min] into and rapid clearance (0.15% ID/g at 60 min) from the brain, which may bring about a good signal-to-noise ratio and therefore achieve highly sensitive detection of A{beta} plaques. In addition, [{sup 125}I]12 labeled amyloid plaques in vivo in an AD transgenic model. The preliminary results strongly suggest that [{sup 125}I]12 bears characteristics suitable for detecting amyloid plaques in vivo. When labeled with {sup 123}I, it may be a useful SPECT imaging agent for A{beta} plaques in the brain of living AD patients.
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Czech Academy of Sciences Publication Activity Database
Caracciolo, V.; D´Agostino, L.; Dráberová, Eduarda; Sládková, Vladimíra; Crozier-Fitzgerald, C.; Agamanolis, D.P.; De Chadarévian, J.P.; Legido, A.; Giordano, A.; Dráber, Pavel; Katsetos, C.D.
2010-01-01
Roč. 223, č. 2 (2010), s. 519-529 ISSN 0021-9541 R&D Projects: GA AV ČR KAN200520701 Institutional research plan: CEZ:AV0Z50520514 Keywords : gamma-tubulin * beta III-tubulin * meduloblastoma Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.986, year: 2010
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DEFF Research Database (Denmark)
Heegaard, Anne-Marie; Xie, Zhongjian; Young, Marian Frances
2004-01-01
. In this study, we have investigated the mechanism by which TGF-beta(1), TGF-beta(2) and TGF-beta(3) stimulate biglycan mRNA expression in the osteoblastic cell line MG-63. The cells were transfected with a series of deletional human biglycan promoter constructs and a region in the biglycan 5' DNA was found...... to respond to TGF-beta(1) with increased transcriptional activity in a dose-dependent manner. Also TGF-beta(2) and TGF-beta(3), two structurally highly related TGF-beta isoforms stimulated biglycan transcription. A TGF-beta responsive region was identified within the first 218 bp of the human biglycan...... was abrogated by mithramycin, an inhibitor of Sp1 binding to GC-rich DNA sequences. A mutation in the Sp1 site at -216 to -208 within the -218 biglycan promoter construct substantially diminished the transcriptional up-regulation by TGF-beta(1). Taken together this data shows for the first time that TGF-beta(1...
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International Nuclear Information System (INIS)
Gianoulakis, C.; Seidah, N.G.; Routhier, R.; Chretien, M.
1980-01-01
Rats pars intermedia cells were incubated for 3 h with the following amino-acids: a) 35 S-methionine and 3 H-phenylalamine; b) 3 H-valine; and c) 3 H-valine and 3 H-lysine. Radioactive gamma-lipotropin, beta-lipotropin and beta-endorphin were purified on carboxy- methyl-cellulose and characterized by polyacrylamide disc gel electrophoresis af pH 4.5, molecular weight estimation and microsequencing. Rat gamma-lipotropin was shown to differ slightly from ovine gamma-lipotropin in its NH 2 -terminal amino acid sequence, in containing no methionine and having phenylalanine at position 6, valine at positions 13 and 27, and lysine at position 20. The same variations were observed in the sequence of rat beta-lipotropin, while rat beta-endorphin was shown to be identical to the ovine beta-endorphin. Following a 3-h pulse of rat pars distalis, the cells were extracted with care to avoid beta-lipotropin degradation by proteolytic enzymes. A peptide was purified and identified to be rat beta-endorphin, thus demonstrating that beta-endorphin is biosynthesized in pars distalis and is not an extraction artifact. (author)
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Homaeigohar, S Sh; Shokrgozar, M A; Khavandi, A; Sadi, A Yari
2008-02-01
Beta-tricalcium phosphate reinforced high density polyethylene (beta-TCP/HDPE) was prepared to simulate bone composition and to study its capacity to act as bone tissue. This material was produced by replacing the mineral component and collagen soft tissue of the bone with beta-TCP and HDPE, respectively. The biocompatibility of the composite samples with different volume fractions of TCP (20, 30 and 40 vol %) was examined in vitro using two osteoblast cell lines G-292 and Saos-2, and also a type of fibroblast cell isolated from bone tissue, namely human bone fibroblast (HBF) by proliferation, and cell adhesion assays. Cell-material interaction with the surface of the composite samples was examined by scanning electron microscopy (SEM). The effect of beta-TCP/HDPE on the behavior of osteoblast and fibroblast cells was compared with those of composite and negative control samples; polyethylene (PE) and tissue culture polystyrene (TPS), respectively. In general, the results showed that the composite samples containing beta-TCP as reinforcement supported a higher rate of proliferation by various bone cells after 3, 7, and 14 days of incubation compared to the composite control sample. Furthermore, more osteoblast cells were attached to the surface of the composite samples when compared to the composite control samples after the above incubation periods (p HDPE composites are biocompatible, nontoxic, and act to stimulate proliferation and adhesion of the cells, whether osteoblast or fibroblast. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.
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Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis.
Halder, Sunil K; Beauchamp, R Daniel; Datta, Pran K
2005-07-01
Smad proteins play a key role in the intracellular signaling of the transforming growth factor beta (TGF-beta) superfamily of extracellular polypeptides that initiate signaling to regulate a wide variety of biological processes. The inhibitory Smad, Smad7, has been shown to function as intracellular antagonists of TGF-beta family signaling and is upregulated in several cancers. To determine the effect of Smad7-mediated blockade of TGF-beta signaling, we have stably expressed Smad7 in a TGF-beta-sensitive, well-differentiated, and non-tumorigenic cell line, FET, that was derived from human colon adenocarcinoma. Smad7 inhibits TGF-beta-induced transcriptional responses by blocking complex formation between Smad 2/3 and Smad4. While Smad7 has no effect on TGF-beta-induced activation of p38 MAPK and ERK, it blocks the phosphorylation of Akt by TGF-beta and enhances TGF-beta-induced phosphorylation of c-Jun. FET cells expressing Smad7 show anchorage-independent growth and enhance tumorigenicity in athymic nude mice. Smad7 blocks TGF-beta-induced growth inhibition by preventing TGF-beta-induced G1 arrest. Smad7 inhibits TGF-beta-mediated downregulation of c-Myc, CDK4, and Cyclin D1, and suppresses the expression of p21(Cip1). As a result, Smad7 inhibits TGF-beta-mediated downregulation of Rb phosphorylation. Furthermore, Smad7 inhibits the apoptosis of these cells. Together, Smad7 may increase the tumorigenicity of FET cells by blocking TGF-beta-induced growth inhibition and by inhibiting apoptosis. Thus, this study provides a mechanism by which a portion of human colorectal tumors may become refractory to tumor-suppressive actions of TGF-beta that might result in increased tumorigenicity.
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Wu, Shi-Biao; Ji, Yan-Ping; Zhu, Jing-Jing; Zhao, Yun; Xia, Gang; Hu, Ying-He; Hu, Jin-Feng
2009-09-01
Three new (1-3) and several known (4-6) steroids were isolated from the leaves of Chinese Melia azedarach. The structures of the new compounds were elucidated by means of spectroscopic methods including 2D NMR techniques and mass spectrometry to be (20S)-5,24(28)-ergostadiene-3beta,7alpha,16beta,20-tetrol (1), (20S)-5-ergostene-3beta,7alpha,16beta,20-tetrol (2), and 2alpha,3beta-dihydro-5-pregnen-16-one (3). The cytotoxicities of the isolated compounds against three human cancer cell lines (A549, H460, U251) were evaluated; only compounds 1, 2, and (20S)-5-stigmastene-3beta,7alpha,20-triol (4) were found to show significant cyctotoxic effects with IC(50)s from 12.0 to 30.1 microg/mL.
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A new alternative transcript encodes a 60 kDa truncated form of integrin beta 3.
Djaffar, I; Chen, Y P; Creminon, C; Maclouf, J; Cieutat, A M; Gayet, O; Rosa, J P
1994-05-15
A cDNA for integrin beta 3 isolated from a human erythroleukaemia (HEL) cell library contained a 340 bp insert at position 1281. This mRNA, termed beta 3c, results from the use of a cryptic AG donor splice site in intron 8 of the beta 3 gene, and is different from a previously described alternative beta 3 mRNA. The predicted open reading frame of beta 3C stops at a TAG stop codon 69 bp downstream from position 1281. It starts with the signal peptide and the 404 N-terminal extracellular residues of beta 3, encompassing the ligand binding sites, followed by 23 C-terminal intron-derived residues, corresponding to a truncated form of beta 3 lacking the cysteine-rich, transmembrane and cytoplasmic domains. Expression of beta 3C mRNA was demonstrated in human platelets, megakaryocytes, endothelial cells and HEL cells by reverse transcriptase/PCR. The beta 3C transcript was also demonstrated in the mouse, suggesting its conservation through evolution. Finally, a 60 kDa polypeptide corresponding to the beta 3C alternative transcript was demonstrated in platelets by Western blotting using a polyclonal antibody raised against a synthetic peptide designed from the beta 3C intronic sequence. Taken together, these results suggest a biological role for beta 3C, the first alternative transcript showing an altered extracellular domain of a beta integrin.
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MHC class I phenotype and function of human beta 2-microglobulin transgenic murine lymphocytes
DEFF Research Database (Denmark)
Bjerager, L; Pedersen, L O; Bregenholt, S
1996-01-01
. Based on data from cellular binding studies, Scatchard analyses and flow cytometry, it is concluded that exogenous h beta 2m does not bind to hybrid MHC class I (MHC-I) molecules composed of mouse heavy chain/h beta 2m molecules expressed on lymphocytes of transgenic mice. Immunoprecipitation and SDS......-PAGE analysis of metabolically labelled normal C57BL/6 lymph node cells showed binding of exogenous h beta 2m to MHC-I, in particular, to the H-2Db molecule through an exchange with endogenous mouse beta 2m. In contrast to normal H-2Db molecules, hybrid H-2Db expressed on the surface of transgenic lymphocytes...... binds radiolabelled peptide in the absence of exogenous added h beta 2m suggesting that a stable fraction of hybrid H-2Db molecules is empty or contain peptides with very low affinity. In a one-way allogenic mixed lymphocyte culture, transgenic splenocytes were found to be far less stimulatory than...
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Cabilla, Jimena P; Díaz, María del Carmen; Machiavelli, Leticia I; Poliandri, Ariel H; Quinteros, Fernanda A; Lasaga, Mercedes; Duvilanski, Beatriz H
2006-09-01
Previous studies showed that 17 beta-estradiol (17 beta-E2) regulates the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP pathway in many tissues. Evidence from our laboratory indicates that 17 beta-E2 disrupts the inhibitory effect of NO on prolactin release, decreasing sGC activity and affecting the cGMP pathway in anterior pituitary gland of adult ovariectomized and estrogenized rats. To ascertain the mechanisms by which 17 beta-E2 affects sGC activity, we investigated the in vivo and in vitro effects of 17 beta-E2 on sGC protein and mRNA expression in anterior pituitary gland from immature female rats. In the present work, we showed that 17 beta-E2 acute treatment exerted opposite effects on the two sGC subunits, increasing alpha1 and decreasing beta1 subunit protein and mRNA expression. This action on sGC protein expression was maximal 6-9 h after 17 beta-E2 administration. 17beta-E2 also caused the same effect on mRNA expression at earlier times. Concomitantly, 17 beta-E2 dramatically decreased sGC activity 6 and 9 h after injection. These effects were specific of 17 beta-E2, because they were not observed with the administration of other steroids such as progesterone and 17 alpha-estradiol. This inhibitory action of 17beta-E2 on sGC also required the activation of estrogen receptor (ER), because treatment with the pure ER antagonist ICI 182,780 completely blocked 17 beta-E2 action. 17 beta-E2 acute treatment caused the same effects on pituitary cells in culture. These results suggest that 17 beta-E2 exerts an acute inhibitory effect on sGC in anterior pituitary gland by down-regulating sGC beta 1 subunit and sGC activity in a specific, ER-dependent manner.
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Connolly, Allison T.; Muralidharan, Abirami; Hendrix, Claudia; Johnson, Luke; Gupta, Rahul; Stanslaski, Scott; Denison, Tim; Baker, Kenneth B.; Vitek, Jerrold L.; Johnson, Matthew D.
2015-12-01
Objective. Using the Medtronic Activa® PC + S system, this study investigated how passive joint manipulation, reaching behavior, and deep brain stimulation (DBS) modulate local field potential (LFP) activity in the subthalamic nucleus (STN) and globus pallidus (GP). Approach. Five non-human primates were implanted unilaterally with one or more DBS leads. LFPs were collected in montage recordings during resting state conditions and during motor tasks that facilitate the expression of parkinsonian motor signs. These recordings were made in the naïve state in one subject, in the parkinsonian state in two subjects, and in both naïve and parkinsonian states in two subjects. Main results. LFPs measured at rest were consistent over time for a given recording location and parkinsonian state in a given subject; however, LFPs were highly variable between subjects, between and within recording locations, and across parkinsonian states. LFPs in both naïve and parkinsonian states across all recorded nuclei contained a spectral peak in the beta band (10-30 Hz). Moreover, the spectral content of recorded LFPs was modulated by passive and active movement of the subjects’ limbs. LFPs recorded during a cued-reaching task displayed task-related beta desynchronization in STN and GP. The bidirectional capabilities of the Activa® PC + S also allowed for recording LFPs while delivering DBS. The therapeutic effect of STN DBS on parkinsonian rigidity outlasted stimulation for 30-60 s, but there was no correlation with beta band power. Significance. This study emphasizes (1) the variability in spontaneous LFPs amongst subjects and (2) the value of using the Activa® PC + S system to record neural data in the context of behavioral tasks that allow one to evaluate a subject’s symptomatology.
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Connolly, Allison T; Muralidharan, Abirami; Hendrix, Claudia; Johnson, Luke; Gupta, Rahul; Stanslaski, Scott; Denison, Tim; Baker, Kenneth B; Vitek, Jerrold L; Johnson, Matthew D
2016-01-01
Objective Using the Medtronic Activa® PC + S system, this study investigated how passive joint manipulation, reaching behavior, and deep brain stimulation (DBS) modulate local field potential (LFP) activity in the subthalamic nucleus (STN) and globus pallidus (GP). Approach Five non-human primates were implanted unilaterally with one or more DBS leads. LFPs were collected in montage recordings during resting state conditions and during motor tasks that facilitate the expression of parkinsonian motor signs. These recordings were made in the naïve state in one subject, in the parkinsonian state in two subjects, and in both naïve and parkinsonian states in two subjects. Main results LFPs measured at rest were consistent over time for a given recording location and parkinsonian state in a given subject; however, LFPs were highly variable between subjects, between and within recording locations, and across parkinsonian states. LFPs in both naïve and parkinsonian states across all recorded nuclei contained a spectral peak in the beta band (10–30 Hz). Moreover, the spectral content of recorded LFPs was modulated by passive and active movement of the subjects’ limbs. LFPs recorded during a cued-reaching task displayed task-related beta desynchronization in STN and GP. The bidirectional capabilities of the Activa® PC + S also allowed for recording LFPs while delivering DBS. The therapeutic effect of STN DBS on parkinsonian rigidity outlasted stimulation for 30–60 s, but there was no correlation with beta band power. Significance This study emphasizes (1) the variability in spontaneous LFPs amongst subjects and (2) the value of using the Activa® PC + S system to record neural data in the context of behavioral tasks that allow one to evaluate a subject’s symptomatology. PMID:26469737
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Beta-energy averaging and beta spectra
International Nuclear Information System (INIS)
Stamatelatos, M.G.; England, T.R.
1976-07-01
A simple yet highly accurate method for approximately calculating spectrum-averaged beta energies and beta spectra for radioactive nuclei is presented. This method should prove useful for users who wish to obtain accurate answers without complicated calculations of Fermi functions, complex gamma functions, and time-consuming numerical integrations as required by the more exact theoretical expressions. Therefore, this method should be a good time-saving alternative for investigators who need to make calculations involving large numbers of nuclei (e.g., fission products) as well as for occasional users interested in restricted number of nuclides. The average beta-energy values calculated by this method differ from those calculated by ''exact'' methods by no more than 1 percent for nuclides with atomic numbers in the 20 to 100 range and which emit betas of energies up to approximately 8 MeV. These include all fission products and the actinides. The beta-energy spectra calculated by the present method are also of the same quality
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Monitoring of gross alpha, gross beta and tritium activities in portuguese drinking waters
International Nuclear Information System (INIS)
Lopes, I.; Madruga, M.J.; Ferrador, G.O.; Sequeira, M.M.; Oliveira, E.J.; Gomes, A.R.; Rodrigues, F.D.; Carvalho, F.P.
2006-01-01
The gross beta and tritium activities in the forty Portuguese drinking waters analyzed using the ISO standard methods (Portuguese Guidelines) are below the guidance levels proposed in the Portuguese Drinking Water Quality Guidelines. In what concerns the gross alpha activity only 18% exceeded the recommended level. In general, it can be concluded that the ingestion of these drinking waters does not create a radiological hazard to the human consumption, however, more detailed analyses will be necessary mainly the determinations of the individual alpha emitters radionuclide concentrations. The minimum gross alpha and gross beta detectable activities by L.S.C. methodology are higher than for the proportional counting technique (ISO method). Higher concentration factors will be needed to reach lower required detection limits. (authors)
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Beta-endorphin and the immune system--possible role in autoimmune diseases
DEFF Research Database (Denmark)
Mørch, H; Pedersen, B K
1995-01-01
The immune system and the neuroendocrine system are closely interconnected having such means of bidirectional communication and regulation. In this review, a hypothesis is put forward regarding the possible role of beta-endorphins in the pathogenesis of autoimmune diseases: It is suggested...... that the increased cytokine production in immunoinflammatory disorders induces production of beta-endorphins from the pituitary and the lymphocytes; the enhanced level of beta-endorphin causes inhibition of human T helper cell function, which potentially down-regulate the antibody production. Also the beta......-endorphin-induced enhancement of the natural killer cell activity may suppress the B cell function. In addition, beta-endorphin also exerts a direct inhibitory effect on the antibody production. Thus, in autoimmune disorders the enhanced cytokine level may via stimulation of the production of beta-endorphins exert a negative...
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Ferreira, Alexandre H P; Terra, Walter R; Ferreira, Clélia
2003-02-01
The midgut of the yellow mealworm, Tenebrio molitor L. (Coleoptera: Tenebrionidae) larvae has four beta-glycosidases. The properties of two of these enzymes (betaGly1 and betaGly2) have been described elsewhere. In this paper, the characterization of the other two glycosidases (betaGly3 and betaGly4) is described. BetaGly3 has one active site, hydrolyzes disaccharides, cellodextrins, synthetic substrates and beta-glucosides produced by plants. The enzyme is inhibited by amygdalin, cellotriose, cellotetraose and cellopentaose in high concentrations, probably due to transglycosylation. betaGly3 hydrolyzes beta 1,4-glycosidic linkages with a catalytic rate independent of the substrate polymerization degree (k(int)) of 11.9 s(-1). Its active site is formed by four subsites, where subsites +1 and -1 bind glucose residues with higher affinity than subsite +2. The main role of betaGly3 seems to be disaccharide hydrolysis. BetaGly4 is a beta-galactosidase, since it has highest activity against beta-galactosides. It can also hydrolyze fucosides, but not glucosides, and has Triton X-100 as a non-essential activator (K(a)=15 microM, pH 4.5). betaGly4 has two active sites that can hydrolyze p-nitrophenyl beta-galactoside (NPbetaGal). The one hydrolyzing NPbetaGal with more efficiency is also active against methylumbellipheryl beta-D-galactoside and lactose. The other active site hydrolyzes NPbetaFucoside and binds NPbetaGal weakly. BetaGly4 hydrolyzes hydrophobic substrates with high catalytical efficiency and is able to bind octyl-beta-thiogalactoside in its active site with high affinity. The betaGly4 physiological role is supposed to be the hydrolysis of galactolipids that are found in membranes from vegetal tissues. As the enzyme has a hydrophobic site where Triton X-100 can bind, it might be activated by membrane lipids, thus becoming fully active only at the surface of cell membranes.
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Fractional poisson--a simple dose-response model for human norovirus.
Messner, Michael J; Berger, Philip; Nappier, Sharon P
2014-10-01
This study utilizes old and new Norovirus (NoV) human challenge data to model the dose-response relationship for human NoV infection. The combined data set is used to update estimates from a previously published beta-Poisson dose-response model that includes parameters for virus aggregation and for a beta-distribution that describes variable susceptibility among hosts. The quality of the beta-Poisson model is examined and a simpler model is proposed. The new model (fractional Poisson) characterizes hosts as either perfectly susceptible or perfectly immune, requiring a single parameter (the fraction of perfectly susceptible hosts) in place of the two-parameter beta-distribution. A second parameter is included to account for virus aggregation in the same fashion as it is added to the beta-Poisson model. Infection probability is simply the product of the probability of nonzero exposure (at least one virus or aggregate is ingested) and the fraction of susceptible hosts. The model is computationally simple and appears to be well suited to the data from the NoV human challenge studies. The model's deviance is similar to that of the beta-Poisson, but with one parameter, rather than two. As a result, the Akaike information criterion favors the fractional Poisson over the beta-Poisson model. At low, environmentally relevant exposure levels (Poisson model; however, caution is advised because no subjects were challenged at such a low dose. New low-dose data would be of great value to further clarify the NoV dose-response relationship and to support improved risk assessment for environmentally relevant exposures. © 2014 Society for Risk Analysis Published 2014. This article is a U.S. Government work and is in the public domain for the U.S.A.
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Pessina, G P; Bocci, V; Nicoletti, C; Becherucci, C; Presentini, R; Parente, L; Villa, L; Tagliabue, A; Boraschi, D
1990-01-01
The pharmacokinetic parameters and distribution of the adjuvant synthetic nonapeptide VQGEESNDK, corresponding to the fragment in position 163-171 in human IL-1, were analyzed after administration to rabbit through different routes. The radiolabeled peptide did not bind to plasma proteins and, when inoculated i.v., it disappeared very rapidly from the circulation, with a t1/2 alpha of 1 min and a t 1/2 beta of 166 min. Upon administration through i.m., s.c. and oral route, the Cmax was reached between 30 and 90 min after inoculum and ranged between 7 and 4% of the administered dose. Organ distribution showed that most of the radioactivity was concentrated in kidneys and excreted in urine. From Sephadex G-10 chromatography, about 60% of the peptide recovered in the urine 4h after i.v. inoculum was intact, whereas it was more than 85% degraded when administered by other routes. The amount of intact peptide recovered in the urine correlated with the biological effectiveness through different routes, suggesting that the adjuvant effect in vivo is exerted by the intact peptide, rather than by its metabolites.
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Energy Technology Data Exchange (ETDEWEB)
Cameron, J F; Rhodes, J R [Physics Group, Isotope Research Division, (AERE), Wantage Research Laboratory, Wantage, Berks (United Kingdom)
1962-01-15
raison de leur longue periode, de leur bas prix, de leur facilite d'obtention et de leur activite specifique elevee. Pour la mise au point des sources excitees par les particules beta, on s'est efforce de realiser un compromis entre les exigences pratiques de la construction et celles du meilleur rendement theorique dans une zone energetique donnee. Dans le memoire presente, les auteurs explicitent par calcul le nombre de photons produits par particule beta et envisagent les corrections a apporter a ces calculs pour l'autoabsorption du rayonnement X produit. Ces calculs tiennent compte a la fois du rayonnement de freinage et du rayonnement caracteristique de {alpha}, l'emission maximum en rayonnement caracteristique se faisant pour des cibles de Z compris entre 40 et 60. Enfin ils constatent que dans la zone energetique souhaitee, on obtient le meilleur rendement en emission photonique avec des cibles
dont l'epaisseurmoitie correspond a 1 ou 2 parcours beta. Du point de vue de la fabrication, l'aluminium, l'argent et l'or conviennent pour le gainage des sources. On a aussi constate que ces metaux donnaient des resultats satisfaisants en ce qui concerne l'emission et la distribution du rayonnement de freinage et des rayons X pour diverses zones energetiques dans la gamme de 1 a 200 keV, lorsqu'on les combinait correctement avec les emetteurs beta susmentionnes. Les auteurs donnent plusieurs spectres d'energie, ainsi que certaines courbes d'absorption dans l'aluminium et le fer pour les meilleures combinaisons source-cible. Ils ont constate qu'il n'y avait que peu de difference entre les sources constituees par des emetteurs beta inseres entre les feuilles de la cible et celles qui sont intimement melangees a la cible. Le memoire contient des tableaux destines a servir de guide pour determiner la meilleure source a utiliser pour un absorbeur d'une gamme d'epaisseur determinee. (author) [Spanish] En este trabajo los autores describen fuentes de radiaciones -
Directory of Open Access Journals (Sweden)
Gentil Claudino de Galiza Neto
2005-10-01
Full Text Available No presente trabalho abordam-se vários aspectos relacionados à natureza molecular da anemia falciforme (AF, desordem hematológica de caráter hereditário. A descoberta do polimorfismo do DNA no grupamento do gene betaS, originando diferentes haplótipos da doença, permitiu ampliar o conhecimento em torno da heterogeneidade clínica observada nos pacientes falcêmicos nas mais diversas regiões do mundo. Analisaram-se os diferentes haplótipos e seus parâmetros hematológicos, presentes em um grupo de 22 pacientes naturais e procedentes do estado do Ceará. A distribuição das freqüências dos haplótipos encontrados foi de 55,9% para Benin; 41,2% para República Centro-Africana (CAR; e de 2,9% para o haplótipo Senegal. Esses dados, em comparação com os demais estudos realizados no Brasil, mostram associação entre os seus valores para um alfa de 5% (p The present work deals with numerous aspects related to the molecular nature of sickle cell anemia. The discovery of the DNA polymorphism in the betas-globin gene cluster, gave origin to different haplotypes of the disease, making possible to enlarge the knowledge about the clinical heterogenity observed on the patients with sickle cell disease, in the various regions of the world. The different haplotypes and its hematological parameters were analysed in a group of 22 patients born in the State of Ceará, northeast of Brazil. The distribution found in the haplotypes frequency was of 55.9% for the Benin, of 41.2% for the CAR, and of 2.9% for Senegal haplotype. The data, compared to the others works done in Brazil, show relations among their values to alpha of 5% (p < 0,05. The results make possible a full understanding of the pathophisiology of the illness and of its clinical complexity in our State, as well as it allows a better knowledge of the sickle cell disease in our country.
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Energy Technology Data Exchange (ETDEWEB)
Emond, P.; Farde, L.; Chalon, S.; Belzung, C.; Mauclaire, V.; Chiron, J. P.; Halldin, C.; Besnard, J.C.; Guilloteau, D
1998-05-01
The cocaine analog {beta}-CIT is one of the most used compounds for SPET examination of the dopamine transporter in drug abuse and Parkinson's disease. However, the toxicity of this agent has not yet been studied. We report here acute toxicity, mutagenicity, and effect on locomotor activity of {beta}-CIT. Acute toxicity experiments were performed in mice and rats. The LD50 values were about 20 mg and 5 mg for mice and rats, respectively. There was no sex difference. The mutagenicity was evaluated using the Ames' test. No mutagenic effect was observed for {beta}-CIT. Effects on locomotor activity were measured in mice using the open-field test. {beta}-CIT increased locomotion (+65%) when injected at a dose of 0.312 mg/kg; the maximal increase (+205%) was observed at a dose of 1.25 mg/kg; at higher doses, the effect was decreased slightly. These pharmacological findings are in agreement with an inhibitory effect of {beta}-CIT at the dopamine transporter. We conclude that with no mutagenic effects and LD50 more than 6 orders of magnitude higher than the routinely used doses in PET or SPET, it can be assumed that {beta}-CIT can be safely used as a radioligand in humans.
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Harrison Hong; David Sraer
2012-01-01
We provide a model for why high beta assets are more prone to speculative overpricing than low beta ones. When investors disagree about the common factor of cash-flows, high beta assets are more sensitive to this macro-disagreement and experience a greater divergence-of-opinion about their payoffs. Short-sales constraints for some investors such as retail mutual funds result in high beta assets being over-priced. When aggregate disagreement is low, expected return increases with beta due to r...
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Metalo-beta-lactamases Metallo-beta-lactamases
Directory of Open Access Journals (Sweden)
Rodrigo Elisandro Mendes
2006-04-01
the monobactam aztreonam, this class of enzyme virtually hydrolyze all the commercially available beta-lactams. Since 90s, several clinical important nosocomial microorganisms, including members of Enterobacteriaceae family, Pseudomonas spp. and Acinetobacter spp., have been found to produce MbetaLs enzymes. When these carbapenem non-susceptible strains are found, they may be submitted to phenotypic MbetaL detection test in the microbiology laboratory in order to help infection control practioners and prevent the MbetaL gene dissemination, once these genes are embedded in mobile genetic elements, which can spread rapidly to other Gram-negative species.
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Energy Technology Data Exchange (ETDEWEB)
Kamiguchi, Yujiroh; Tateno, Hiroyuki; Mikamo, Kazuya (Asahikawa Medical College (Japan). Department of Biological Sciences)
1990-02-01
THe effects of tritium (HTO) {beta}-rays on human sperm chromosomes were studied using our interspecific in vitro fertilization system between human spermatozoa and zona-free hamster oocytes. Semen samples were treated with media containing 1.53-24.3 mCi/ml HTO for about 80 min. 1290 spermatozoa from the controls and 1842 spermatozoa from the irradiated groups were karyotyped. The incidence of spermatozoa with structural chromosome aberrations increased linearly with increasing dosage. Breakage-type aberrations occurred far more frequently than exchange-type. Chromosome-type aberrations appeared far more frequently than chromatid-ype. All of these types of aberrations showed linear dose-dependent increases. The RBE valus of HTO {beta}-rays relative to X-rays were calculated for the above-mentioned 5 indices, respectively. Their RBE values franged from 1.89 to 3.00 when the absorbed dose was estimated to be the minimum, whereas the values ranged between 1.04 and 1.65 when the absorbed dose was estimated to be the maximum. (author). 15 refs.; 3 figs.; 4 tabs.
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Uptake of neutral alpha- and beta-amino acids by human proximal tubular cells
DEFF Research Database (Denmark)
Jessen, H; Røigaard, H; Jacobsen, Christian
1996-01-01
experiments revealed that all the neutral amino acids tested reduced the uptake of AIB, whereas there was no effect of taurine, L-aspartic acid, and L-arginine. By contrast, the influx of beta-alanine was only drastically reduced by beta-amino acids, whereas the inhibition by neutral alpha-amino acids...
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Babiloni, Claudio; Del Percio, Claudio; Vecchio, Fabrizio; Sebastiano, Fabio; Di Gennaro, Giancarlo; Quarato, Pier P; Morace, Roberta; Pavone, Luigi; Soricelli, Andrea; Noce, Giuseppe; Esposito, Vincenzo; Rossini, Paolo Maria; Gallese, Vittorio; Mirabella, Giovanni
2016-01-01
In the present study, we tested the hypothesis that both movement execution and observation induce parallel modulations of alpha, beta, and gamma electrocorticographic (ECoG) rhythms in primary somatosensory (Brodmann area 1-2, BA1-2), primary motor (BA4), ventral premotor (BA6), and prefrontal (BA44 and BA45, part of putative human mirror neuron system underlying the understanding of actions of other people) areas. ECoG activity was recorded in drug-resistant epileptic patients during the execution of actions to reach and grasp common objects according to their affordances, as well as during the observation of the same actions performed by an experimenter. Both action execution and observation induced a desynchronization of alpha and beta rhythms in BA1-2, BA4, BA6, BA44 and BA45, which was generally higher in amplitude during the former than the latter condition. Action execution also induced a major synchronization of gamma rhythms in BA4 and BA6, again more during the execution of an action than during its observation. Human primary sensorimotor, premotor, and prefrontal areas do generate alpha, beta, and gamma rhythms and differently modulate them during action execution and observation. Gamma rhythms of motor areas are especially involved in action execution. Oscillatory activity of neural populations in sensorimotor, premotor and prefrontal (part of human mirror neuron system) areas represents and distinguishes own actions from those of other people. This methodological approach might be used for a neurophysiological diagnostic imaging of social cognition in epileptic patients. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
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Differential beta-band event-related desynchronization during categorical action sequence planning.
Directory of Open Access Journals (Sweden)
Hame Park
Full Text Available A primate study reported the existence of neurons from the dorso-lateral prefrontal cortex which fired prior to executing categorical action sequences. The authors suggested these activities may represent abstract level information. Here, we aimed to find the neurophysiological representation of planning categorical action sequences at the population level in healthy humans. Previous human studies have shown beta-band event-related desynchronization (ERD during action planning in humans. Some of these studies showed different levels of ERD according to different types of action preparation. Especially, the literature suggests that variations in cognitive factors rather than physical factors (force, direction, etc modulate the level of beta-ERD. We hypothesized that the level of beta-band power will differ according to planning of different categorical sequences. We measured magnetoencephalography (MEG from 22 subjects performing 11 four-sequence actions--each consisting of one or two of three simple actions--in 3 categories; 'Paired (ooxx', 'Alternative (oxox' and 'Repetitive (oooo' ('o' and 'x' each denoting one of three simple actions. Time-frequency representations were calculated for each category during the planning period, and the corresponding beta-power time-courses were compared. We found beta-ERD during the planning period for all subjects, mostly in the contralateral fronto-parietal areas shortly after visual cue onset. Power increase (transient rebound followed ERD in 20 out of 22 subjects. Amplitudes differed among categories in 20 subjects for both ERD and transient rebound. In 18 out of 20 subjects 'Repetitive' category showed the largest ERD and rebound. The current result suggests that beta-ERD in the contralateral frontal/motor/parietal areas during planning is differentiated by the category of action sequences.
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Energy Technology Data Exchange (ETDEWEB)
NONE
2013-07-01
The Ordinance Brazilian of Ministry of Health (MS 2914/2011) establishes the standards for quality of water intended for human consumption, being limits values of 5.0 Bq/L for gross alpha, and 1.0 Bq/L for gross beta radioactivity. The liquid scintillation spectrometry (LSC) technique has been presented as an alternative to conventional procedure using gas flow proportional counter. The present work shows a review of the methods for determination of gross alpha and gross beta in water by using LSC. Between the factors that influence the accuracy and repeatability of the analytical results we can highlight: thermal preconcentration, type of the acid and calibration standard. A procedure was established and carried out to samples of the National Program of Intercomparison of Radionuclides in Environmental Samples for evaluation of its performance. The gross alpha and gross beta analysis in samples of the public water supplies in the Metropolitan Region of Goiania, state of Goias was carried out. The results are consistent with the guideline values form the Ministry of Health concerning radioactivity. (author)
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TGF-beta and 'adaptive' Foxp3(+) regulatory T cells.
Chen, Wanjun; Konkel, Joanne E
2010-02-01
In naïve T cells transforming growth factor-beta (TGF-beta) induces Foxp3, a transcription factor essential for programming and developing T regulatory cells (Treg cells). This finding reveals a physiological factor which can turn on the Foxp3 gene and establishes an experimental approach to induce antigen-specific Treg cells as a potential therapy for human diseases. While this role for TGF-beta is well confirmed, several critical questions remain largely unanswered and await further investigation. In this regard, it is imperative to understand the molecular pathways by which TGF-beta signaling initiates and regulates Foxp3 expression. It is also important to elucidate which factors and/or cytokines influence the TGF-beta-mediated conversion of naïve T cells and how to create an immunologically regulatory milieu to facilitate Treg cell generation in vivo. In this short article, we will highlight the key findings and recent progress in the field, discuss the molecular mechanisms underlying the TGF-beta-mediated induction of Foxp3, and attempt to outline the challenges ahead.
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Directory of Open Access Journals (Sweden)
Roger Hullin
2007-03-01
Full Text Available Increased activity of single ventricular L-type Ca(2+-channels (L-VDCC is a hallmark in human heart failure. Recent findings suggest differential modulation by several auxiliary beta-subunits as a possible explanation.By molecular and functional analyses of human and murine ventricles, we find that enhanced L-VDCC activity is accompanied by altered expression pattern of auxiliary L-VDCC beta-subunit gene products. In HEK293-cells we show differential modulation of single L-VDCC activity by coexpression of several human cardiac beta-subunits: Unlike beta(1 or beta(3 isoforms, beta(2a and beta(2b induce a high-activity channel behavior typical of failing myocytes. In accordance, beta(2-subunit mRNA and protein are up-regulated in failing human myocardium. In a model of heart failure we find that mice overexpressing the human cardiac Ca(V1.2 also reveal increased single-channel activity and sarcolemmal beta(2 expression when entering into the maladaptive stage of heart failure. Interestingly, these animals, when still young and non-failing ("Adaptive Phase", reveal the opposite phenotype, viz: reduced single-channel activity accompanied by lowered beta(2 expression. Additional evidence for the cause-effect relationship between beta(2-subunit expression and single L-VDCC activity is provided by newly engineered, double-transgenic mice bearing both constitutive Ca(V1.2 and inducible beta(2 cardiac overexpression. Here in non-failing hearts induction of beta(2-subunit overexpression mimicked the increase of single L-VDCC activity observed in murine and human chronic heart failure.Our study presents evidence of the pathobiochemical relevance of beta(2-subunits for the electrophysiological phenotype of cardiac L-VDCC and thus provides an explanation for the single L-VDCC gating observed in human and murine heart failure.
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International Nuclear Information System (INIS)
He Song; Huang Mei; Yan Qishu
2011-01-01
We study the holographic QCD model, which contains a quadratic term -σz 2 and a logarithmic term -c 0 log[(z IR -z)/z IR ] with an explicit infrared cutoff z IR in the deformed AdS 5 warp factor. We investigate the heavy-quark potential for three cases, i.e., with only a quadratic correction, with both quadratic and logarithmic corrections, and with only a logarithmic correction. We solve the dilaton field and dilation potential from the Einstein equation and investigate the corresponding beta function in the Guersoy-Kiritsis-Nitti framework. Our studies show that in the case with only a quadratic correction, a negative σ or the Andreev-Zakharov model is favored to fit the heavy-quark potential and to produce the QCD beta function at 2-loop level; however, the dilaton potential is unbounded in the infrared regime. One interesting observation for the case of positive σ is that the corresponding beta function exists in an infrared fixed point. In the case with only a logarithmic correction, the heavy-quark Cornell potential can be fitted very well, the corresponding beta function agrees with the QCD beta function at 2-loop level reasonably well, and the dilaton potential is bounded from below in the infrared. At the end, we propose a more compact model which has only a logarithmic correction in the deformed warp factor and has less free parameters.
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beta. -endorphin-like and. alpha. -MSH-like immunoreactivities in human milk
Energy Technology Data Exchange (ETDEWEB)
Ferrando, T.; Rainero, I.; De Gennaro, T.; Oggero, R.; Mostert, M.; Dattola, P.; Pinessi, L. (Univ. of Turin (Italy))
1990-01-01
We measured with radioimmunoassay the {beta}-endorphin-like and {alpha}-MSH-like immunoreactivities in milk and plasma of 8 lactating women. Mean {beta}-endorphin concentrations ({plus minus} SD) were 16.6 {plus minus} 6.7 fmol/ml in milk and 9.9 {plus minus} 4.1 fmol/ml in plasma. {alpha}-MSH concentrations were 39.4 {plus minus} 15.5 pg/ml in milk and 18.2 {plus minus} 8.4 pg/ml in plasma. The concentrations of both peptides in milk were significantly higher than in plasma. No significant correlation between milk and plasma concentrations of these peptides was found.
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Czech Academy of Sciences Publication Activity Database
Šíma, Petr; Vannucci, Luca; Větvička, V.
2017-01-01
Roč. 41, č. 4 (2017), s. 1799-1808 ISSN 1107-3756 Institutional support: RVO:61388971 Keywords : cholesterol * beta-glucans * diet Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.341, year: 2016
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Hypertrophic effect of inhaled beta -agonist with and without concurrent exercise training
DEFF Research Database (Denmark)
Jessen, Søren; Onslev, Johan; Lemminger, Anders
2018-01-01
INTRODUCTION: Due to a high prevalence of asthma and exercise-induced bronchoconstriction in elite athletes, there is a high use of beta2 -adrenoceptor agonists (beta2 -agonists) in the athletic population. While anabolic in rodents, no study has been able to detect hypertrophy in humans after...... chronic beta2 -agonist inhalation. METHODS: We investigated if inhaled beta2 -agonist, terbutaline, alters body composition and metabolic rate with and without concurrent exercise training in healthy young men. Sixty-seven participants completed a four-week intervention of daily terbutaline (8×0.5 mg...
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Chen, Xiaowen; Zhao, Luqian; Qin, Hongran; Zhao, Meijia; Zhou, Yirui; Yang, Shuqiang; Su, Xu; Xu, Xiaohua
2014-05-01
The aim of this work was to develop a method to provide rapid results for humans with internal radioactive contamination. The authors hypothesized that valuable information could be obtained from gas proportional counter techniques by screening urine samples from potentially exposed individuals rapidly. Recommended gross alpha and beta activity screening methods generally employ gas proportional counting techniques. Based on International Standards Organization (ISO) methods, improvements were made in the evaporation process to develop a method to provide rapid results, adequate sensitivity, and minimum sample preparation and operator intervention for humans with internal radioactive contamination. The method described by an American National Standards Institute publication was used to calibrate the gas proportional counter, and urine samples from patients with or without radionuclide treatment were measured to validate the method. By improving the evaporation process, the time required to perform the assay was reduced dramatically. Compared with the reference data, the results of the validation samples were very satisfactory with respect to gross-alpha and gross-beta activities. The gas flow proportional counting method described here has the potential for radioactivity monitoring in the body. This method was easy, efficient, and fast, and its application is of great utility in determining whether a sample should be analyzed by a more complicated method, for example radiochemical and/or γ-spectroscopy. In the future, it may be used commonly in medical examination and nuclear emergency treatment.Health Phys. 106(5):000-000; 2014.
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Directory of Open Access Journals (Sweden)
Kabeerdoss Jayakanthan
2011-12-01
Full Text Available Abstract Background Probiotics are used to provide health benefits. The present study tested the effect of a probiotic yoghurt on faecal output of beta-defensin and immunoglobulin A in a group of young healthy women eating a defined diet. Findings 26 women aged 18-21 (median 19 years residing in a hostel were given 200 ml normal yoghurt every day for a week, followed by probiotic yoghurt containing Bifidobacterium lactis Bb12® (109 in 200 ml for three weeks, followed again by normal yoghurt for four weeks. Stool samples were collected at 0, 4 and 8 weeks and assayed for immunoglobulin A and human beta-defensin-2 by ELISA. All participants tolerated both normal and probiotic yoghurt well. Human beta-defensin-2 levels in faeces were not altered during the course of the study. On the other hand, compared to the basal sample, faecal IgA increased during probiotic feeding (P = 0.0184 and returned to normal after cessation of probiotic yoghurt intake. Conclusions Bifidobacterium lactis Bb12® increased secretory IgA output in faeces. This property may explain the ability of probiotics to prevent gastrointestinal and lower respiratory tract infections.
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beta. and. gamma. -comparative dose estimates on Enewetak Atoll
Energy Technology Data Exchange (ETDEWEB)
Crase, K.W.; Gudiksen, P.H.; Robison, W.L. (California Univ., Livermore (USA). Lawrence Livermore National Lab.)
1982-05-01
Enewetak Atoll in the Pacific is used for atmospheric testing of U.S. nuclear weapons. Beta dose and ..gamma..-ray exposure measurements were made on two islands of the Enewetak Atoll during July-August 1976 to determine the ..beta.. and low energy ..gamma..-contribution to the total external radiation doses to the returning Marshallese. Measurements were made at numerous locations with thermoluminescent dosimeters (TLD), pressurized ionization chambers, portable NaI detectors, and thin-window pancake GM probes. Results of the TLD measurements with and without a ..beta..-attenuator indicate that approx. 29% of the total dose rate at 1 m in air is due to ..beta..- or low energy ..gamma..-contribution. The contribution at any particular site, however, is reduced by vegetation. Integral 30-yr external shallow dose estimates for future inhabitants were made and compared with external dose estimates of a previous large scale radiological survey. Integral 30-yr shallow external dose estimates are 25-50% higher than whole body estimates. Due to the low penetrating ability of the ..beta..'s or low energy ..gamma..'s, however, several remedial actions can be taken to reduce the shallow dose contribution to the total external dose.
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Directory of Open Access Journals (Sweden)
Vijendra K. SINGH
2008-06-01
Full Text Available Amyloid beta-protein1-40 (AP40 is a low molecular weight peptide produced throughout life during normal cell metabolism and neurodegenerative diseases. Owing to its neurotrophic and neurotoxic effects, the present study was conducted to evaluate serum levels of AP40 in healthy subjects, autistic children and Alzheimer’s disease patients. Serum AP40 was measured by enzyme-linked immunosorbent assay (ELISA. AP40 was significantly higher in normal children compared to normal older controls, in normal children compared to autistic children, and in autistic children compared to Alzheimer’s patients (p value was less than 0.05 for all groups. This finding suggests an age-related decline of serum AP40 in normal aging, as well as in autism and Alzheimer’s disease. This decline may result from abnormal processing of amyloid beta-protein precursor (APP during normal aging and age-related diseases such as autism in children and Alzheimer’s disease in elderly. Possible explanations for this decline may include age-related increased interactions of AP40 with cytoskeletal proteins for brain tissue deposition, increased serine proteases for APP metabolism or hyperimmune reaction (antibodies to AP40 for removal of circulating AP40. To conclude, the AP40 metabolism declines with normal aging and in addition to its role in Alzheimer’s disease this protein might also be a contributing factor in autism.
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Liou, Saou-Hsing; Yang, Gordon C C; Wang, Chih-Lung; Chiu, Yu-Han
2014-07-30
This 5-month study contains two parts: (1) to monitor the concentrations of 11 phthalate esters metabolites (PAEMs) and two beta-agonists in human urine samples collected from a small group of consented participants including 16 females and five males; and (2) to analyze the residues of phthalate esters (PAEs) and beta-agonists in various categories of drinking water consumed by the same group of subjects. Each category of human urine and drinking water had 183 samples of its own. The analytical results showed that nine PAEMs were detected in human urine and eight PAEs were detected in drinking water samples. It was found that average concentrations of PAEMs increased as the age increased, but no significant difference between sexes. Further, using the principal component analysis, the loadings of age effect were found to be two times greater than that of gender effect in terms of four DEHP metabolites. Regarding beta-agonists of concern (i.e., ractopamine and salbutamol), they were neither detected in human urine nor drinking water samples in this study. Copyright © 2014 Elsevier B.V. All rights reserved.
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Microstructural stability and thermomechanical processing of boron modified beta titanium alloys
Cherukuri, Balakrishna
One of the main objectives during primary processing of titanium alloys is to reduce the prior beta grain size. Producing an ingot with smaller prior beta grain size could potentially eliminate some primary processing steps and thus reduce processing cost. Trace additions of boron have been shown to decrease the as-cast grain size in alpha + beta titanium alloys. The primary focus of this dissertation is to investigate the effect of boron on microstructural stability and thermomechanical processing in beta titanium alloys. Two metastable beta titanium alloys: Ti-15Mo-2.6Nb-3Al-0.2Si (Beta21S) and Ti-5Al-5V-5Mo-3Cr (Ti5553) with 0.1 wt% B and without boron additions were used in this investigation. Significant grain refinement of the as-cast microstructure and precipitation of TiB whiskers along the grain boundaries was observed with boron additions. Beta21S and Beta21S-0.1B alloys were annealed above the beta transus temperature for different times to investigate the effect of boron on grain size stability. The TiB precipitates were very effective in restricting the beta grain boundary mobility by Zener pinning. A model has been developed to predict the maximum grain size as a function of TiB size, orientation, and volume fraction. Good agreement was obtained between model predictions and experimental results. Beta21S alloys were solution treated and aged for different times at several temperatures below the beta transus to study the kinetics of alpha precipitation. Though the TiB phase did not provide any additional nucleation sites for alpha precipitation, the grain refinement obtained by boron additions resulted in accelerated aging. An investigation of the thermomechanical processing behavior showed different deformation mechanisms above the beta transus temperature. The non-boron containing alloys showed a non-uniform and fine recrystallized necklace structure at grain boundaries whereas uniform intragranular recrystallization was observed in boron containing
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Bacillus subtilis generates a major specific deletion in pAM beta 1.
van der Lelie, D; Venema, G
1987-01-01
pAM beta 1, a 26.5-kilobase plasmid originally isolated from Streptococcus faecalis, was conjugally transferred from Streptococcus lactis to Bacillus subtilis. No conjugal transfer of pAM beta 1 from B. subtilis to S. lactis was observed. In addition, pAM beta 1 which had been reintroduced in S. lactis after cycling through B. subtilis had lost its conjugal transferability to Streptococcus cremoris, although under the same conditions noncycled pAM beta 1 was transferred at high efficiency. Re...
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International Nuclear Information System (INIS)
Kratochwil, C.; Giesel, F.L.; Mier, W.; Haberkorn, U.; Bruchertseifer, F.; Apostolidis, C.; Morgenstern, A.; Boll, R.; Murphy, K.
2014-01-01
Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as 90 Y/ 177 Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with 213 Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with 90 Y/ 177 Lu-DOTATOC were treated with an intraarterial infusion of 213 Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of 213 Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and 68 Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. The biodistribution of 213 Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses. (orig.)
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de Bruin, Daphne; de Jong, Igle J.; Arts, Eugene G. J. M.; Nuver, Janine; Dullaart, Robin P. F.; Sluiter, Willem J.; Hoekstra, Harald J.; Sleijfer, Dirk T.; Gietema, Jourik A.
Objective: To compare the semen quality and hormonal status between patients with testicular cancer and normal versus increased serum levels of beta-hCG. Design: Retrospective study. Setting: Academic research environment. Patient(s): All 203 patients with testicular cancer who required chemotherapy
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International Nuclear Information System (INIS)
Kao, K.J.
1988-01-01
To determine whether chloroquine can specifically elute HLA antigens and beta 2-microglobulin (beta 2-M) from the platelet surface, quantitative immunofluorescence flow cytometry and monoclonal antibodies were used to show that HLA antigens and beta 2-M were proportionally eluted from the platelet surface without affecting the membrane glycoproteins IIb and IIIa. Second, an autoradiogram of electrophoresed I-125-labeled platelets showed that only beta 2-M but not other I-125-labeled membrane proteins could be eluted. Although HLA antigens were poorly labeled by I-125 and could not be detected on the autoradiogram, the eluted HLA antigens could be detected by anti-HLA monoclonal antibody and immunoblotting techniques. No loss of plasma membrane integrity was observed by transmission electron microscopy after chloroquine treatment of platelets. The results indicate that chloroquine selectively elutes HLA antigens and their noncovalently associated beta 2-M without affecting other integral platelet membrane proteins
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DEFF Research Database (Denmark)
Meggio, F; Boldyreff, B; Marin, O
1992-01-01
Recombinant human alpha subunit from casein kinase-2 (CK-2) was subjected, either alone or in combination with recombinant human beta subunit, to high temperature, tryptic digestion and urea treatment. In all three cases, it was shown that the presence of the beta subunit could drastically reduce...... the autophosphorylation site. It is suggested that the acidic domain of the beta subunit, encompassing residues 55-71, plays a role in the interactions between the beta and alpha subunits....
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Axin-mediated CKI phosphorylation of beta-catenin at Ser 45
DEFF Research Database (Denmark)
Amit, Sharon; Hatzubai, Ada; Birman, Yaara
2002-01-01
The Wnt pathway controls numerous developmental processes via the beta-catenin-TCF/LEF transcription complex. Deregulation of the pathway results in the aberrant accumulation of beta-catenin in the nucleus, often leading to cancer. Normally, cytoplasmic beta-catenin associates with APC and axin...... and is continuously phosphorylated by GSK-3beta, marking it for proteasomal degradation. Wnt signaling is considered to prevent GSK-3beta from phosphorylating beta-catenin, thus causing its stabilization. However, the Wnt mechanism of action has not been resolved. Here we study the regulation of beta......-catenin phosphorylation and degradation by the Wnt pathway. Using mass spectrometry and phosphopeptide-specific antibodies, we show that a complex of axin and casein kinase I (CKI) induces beta-catenin phosphorylation at a single site: serine 45 (S45). Immunopurified axin and recombinant CKI phosphorylate beta...
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Characterization of beta-adrenergic receptors through the replicative life span of IMR-90 cells
International Nuclear Information System (INIS)
Scarpace, P.J.
1987-01-01
Beta-adrenergic receptor number and receptor affinity for isoproterenol were assessed at various in vitro ages of the human diploid fibroblast cell line IMR-90. From population doubling level (PDL) 33 to 44, there was a positive correlation between beta-adrenergic receptor density and PDL. Beta-adrenergic receptors, assessed by Scatchard analysis of [ 125 I]-iodocyanopindolol (ICYP) binding, increased from 15 fmol/mg protein at PDL 33 to 36 fmol/mg protein at PDL 44. In contrast, from PDL 44 to 59, there was a negative correlation between beta-adrenergic receptor density and PDL. Receptor density declined to 12 fmol/mg protein at PDL 59. When the density of beta-adrenergic receptors was expressed as receptor per cell, the findings were similar. Receptor agonist affinity for isoproterenol was determined from Hill plots of [ 125 I]-ICYP competition with isoproterenol. There was no change in the dissociation constant for isoproterenol with in vitro age. In humans, serum norepinephrine concentrations increase with age. This increase in serum norepinephrine may be partially responsible for the decreased beta-adrenergic receptor-agonist affinity observed with age in human lymphocytes and rat heart and lung. The present findings are consistent with the hypothesis that the decreases in receptor agonist affinity in rat and man with age are secondary to increases in catecholamine concentrations
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DEFF Research Database (Denmark)
Boldyreff, B; Meggio, F; Pinna, L A
1993-01-01
Twenty-one mutants of the noncatalytic beta-subunit of human casein kinase-2 have been created, expressed in Escherichia coli, and purified to homogeneity. They are either modified at the autophosphorylation site (mutants beta delta 1-4 and beta A 5,6) or bear variable deletions in their C...
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Cerebral oxygenation decreases during exercise in humans with beta-adrenergic blockade
DEFF Research Database (Denmark)
Seifert, T.; Rasmussen, P.; Secher, Niels H.
2009-01-01
AIM: Beta-blockers reduce exercise capacity by attenuated increase in cardiac output, but it remains unknown whether performance also relates to attenuated cerebral oxygenation. METHODS: Acting as their own controls, eight healthy subjects performed a continuous incremental cycle test to exhaustion...... attenuated the increase in cardiac output of consequence for cerebral perfusion and oxygenation. We suggest that a decrease in cerebral oxygenation limits exercise capacity Udgivelsesdato: 2009/7...... with or without administration of the non-selective beta-blocker propranolol. Changes in cerebral blood flow velocity were measured with transcranial Doppler ultrasound and those in cerebral oxygenation were evaluated using near-infrared spectroscopy and the calculated cerebral mitochondrial oxygen tension...
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Czech Academy of Sciences Publication Activity Database
Krištofíková, Z.; Řípová, D.; Bartoš, A.; Bocková, Markéta; Hegnerová, Kateřina; Říčný, J.; Čechová, L.; Vrajová, M.; Homola, Jiří
2013-01-01
Roč. 10, č. 2 (2013), s. 165-173 ISSN 1567-2050 R&D Projects: GA MZd(CZ) NT11225 Institutional support: RVO:67985882 Keywords : Amyloid beta * mitochondrial enzyme * Alzheimer 's disease Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 3.796, year: 2013
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Directory of Open Access Journals (Sweden)
Julio E. Enders
1995-02-01
Full Text Available Experimental Chagas' disease (45 to 90 days post-infection showed serious cardiac alterations in the contractility and in the pharmacological response to beta adrenergic receptors in normal and T. cruzi infected mice (post-acute phase. Chagasic infection did not change the beta receptors density (78.591 ± 3.125 fmol/mg protein and 73.647 ± 2.194 fmol/mg protein for controls but their affinity was significantly diminished (Kd = 7.299 ± 0.426 nM and Kd = 3.759 ± 0.212 nM for the control p Estudaram-se os receptores beta cardíacos de camundongos infectados pelo Trypanosoma cruzi na fase pós-aguda da doença de Chagas para estabelecer em que medida os mesmos contribuem a gerar respostas anômalas às catecolaminas observadas nestes miocardios. Utilizara-se 3-H/DHA para a marcação dos receptores beta cardíacos dos camundongos normais e dos infectados na fase pós-aguda (45 a 90 dias pós-infecção. O número dos sítios de fixação foi similar nos dois grupos, 78.591 ± 3.125 fmol/mg. Proteína nos chagásicos e 73.647 ± 2.194 fmol/mg. Proteína no grupo controle. Em vez disso, a afinidade verificou-se significativamente diminuida no grupo chagásico (Kd = 7.299 ± 0.426 nM respeito do controle (Kd = 3.759 ± 0.212 nM p < 0.001. Os resultados obtidos demonstram que as modificações observadas na estimulação adrenérgica do miocárdio chagásico se correlacionam com a menor afinidade dos receptores beta cardíacos e que estas alterações exerceriam uma parte determinante para as consequências funcionais que são detectadas na fase crônica.
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THE NEW METALL-BETA-LACTAMASE’S INHIBITOR EFFICACY IN A MODEL SYSTEM IN VITRO
Directory of Open Access Journals (Sweden)
A. G. Afinogenova
2016-01-01
Full Text Available The Enterobacteriaceae antibiotics resistance depends on a combination of several mechanisms, such as the beta-lactamases overproduction, the microbial cell reduction outer membrane permeability (usually associated with loss of protein porin, the presence of efflux systems. Particularly noteworthy are the metallo-beta-lactamases (MBL whose presence causes resistance of gram-negative microorganisms to all beta-lactam antibiotics (in some cases except aztreonam. Currently there are no MBL inhibitors permitted for use in the clinic. The effective inhibitors search for carbapenem-resistant bacteria’ MBL authorized for use in the clinic and reinforcing effects of carbapenems, served as the basis for the present study. The work was carried out in three stages: 1 creating a model system using a standard enzyme reagent metallo-beta-lactamase P. aeruginosa recombinant expressed in E. coli, to evaluate the increasing of minimal inhibitory concentrations (MIC of carbapenems against previously sensitive Gram-negative microorganisms strains in vitro; 2 evaluation of MBL promising inhibitors in the presence of the same standard enzyme reagent; 3 evaluation of the ability of the identified inhibitors increase the carbapenems effects against clinical isolates of Gram-negative microorganisms producing MBL, in terms of the their MIC and fractional inhibitory concentration index (FIC index. The checkerboard array was modified to evaluate the combined use of carbapenems and potential MBL inhibitor — a drug from the group of bisphosphonates — etidronic acid. Using a standard enzyme reagent metallo-beta-lactamase P. aeruginosa recombinant expressed in E. coli, we created a model system that allows to assess the prospects of new inhibitors MBL gram-negative microorganisms. A dose-dependent effect of increasing the meropenem level MIC from reagent MBL quantity in a model system against previously antibiotic sensitive reference strains of microorganisms was
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International Nuclear Information System (INIS)
Gupta, Anil; Lenka, P.; Sahoo, S.K.; Patra, A.C.; Jha, S.K.; Tripathi, R.M.
2018-01-01
Quality of water is important in environmental studies because of its daily use for human consumption and an important route of intake for various elements and radionuclides. Therefore radiological quality of drinking water must be ensured. The screening parameter to evaluate the radiological safety of potable water is by estimating gross alpha and gross beta activities with a limit of 0.5 Bq/l and 1 Bq/l respectively. These have been traditionally being done by radiochemical co-precipitation of alpha and beta emitters followed by counting by ZnS(Ag) counter for alpha and gas flow proportional counter for beta. Gross alpha estimation in water samples with high TDS by ZnS(Ag) is difficult and often leads to underestimation of result due to self-absorption of alpha within the residue. This study was carried out to standardize a method to provide rapid results by simultaneously estimating both gross alpha and gross beta activity in the presence of TDS with adequate sensitivity, minimum sample processing
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Impact of amyloid imaging on drug development in Alzheimer's disease
Energy Technology Data Exchange (ETDEWEB)
Mathis, Chester A. [Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States)], E-mail: mathisca@upmc.edu; Lopresti, Brian J. [Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Klunk, William E. [Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States)
2007-10-15
Imaging agents capable of assessing amyloid-beta (A{beta}) content in vivo in the brains of Alzheimer's disease (AD) subjects likely will be important as diagnostic agents to detect A{beta} plaques in the brain as well as to help test the amyloid cascade hypothesis of AD and as an aid to assess the efficacy of anti-amyloid therapeutics currently under development and in clinical trials. Positron emission tomography (PET) imaging studies of amyloid deposition in human subjects with several A{beta} imaging agents are currently underway. We reported the first PET studies of the carbon 11-labeled thioflavin-T derivative Pittsburgh Compound B in 2004, and this work has subsequently been extended to include a variety of subject groups, including AD patients, mild cognitive impairment patients and healthy controls. The ability to quantify regional A{beta} plaque load in the brains of living human subjects has provided a means to begin to apply this technology as a diagnostic agent to detect regional concentrations of A{beta} plaques and as a surrogate marker of therapeutic efficacy in anti-amyloid drug trials.
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International Nuclear Information System (INIS)
Okada, Tomoya; Fujita, Masahiro; Shimada, Shoichi; Sato, Kohji; Schloss, Patrick; Watanabe, Yoshiyuki; Itoh, Yasushi; Tohyama, Masaya; Nishimura, Tsunehiko
1998-01-01
We investigated the effects of three cocaine analogs, beta-CIT (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane), beta-CIT-FE (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(2-fluoroethyl)-nortropane), and beta-CIT-FP (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane), on the uptake of [ 3 H]dopamine(DA), serotonin(5-HT), and 1-norepinephrine (NE) using cell lines permanently expressing DA, 5-HT, and NE transporters, respectively, to determine their affinities for these three transporters. We generated cell lines stably expressing DA, 5-HT, and NE transporters, respectively, by the Chen-Okayama method, and then tested the abilities of (-)cocaine, beta-CIT, beta-CIT-FE, beta-CIT-FP, and clomipramine to inhibit the uptake of [ 3 H]DA, 5-HT, and 1-NE. Ki values of beta-CIT, beta-CIT-FE, and beta-CIT-FP for [ 3 H]DA, 5-HT, 1-NE uptake were 6, 29, and 33 nM, 91, 133, and 130 nM, and 28, 113 and 70 nM, respectively, whereas those of cocaine and clomipramine were 316, 581, and 176 nM and > 10,000, 437, and 851 nM, respectively. Beta-CIT, beta-CIT-FE, and beta-CIT-FP were shown to be potent DA, 5-HT, and NE uptake inhibitors. Beta-CIT and beta-CIT-FP were highly potent and selective dopamine uptake inhibitors, and therefore might be useful for imaging of DA transporter with single photon emission computed tomography (SPECT) or positron emission tomography (PET)
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Energy Technology Data Exchange (ETDEWEB)
Kumar, Divya P.; Rajagopal, Senthilkumar; Mahavadi, Sunila [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Mirshahi, Faridoddin [Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Grider, John R. [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Murthy, Karnam S., E-mail: skarnam@vcu.edu [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Sanyal, Arun J., E-mail: asanyal@mcvh-vcu.edu [Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA (United States)
2012-10-26
Highlights: Black-Right-Pointing-Pointer G protein coupled receptor TGR5 is expressed in mouse and human islets. Black-Right-Pointing-Pointer TGR5 is coupled to activation of Gs and Ca{sup 2+} release via cAMP/Epac/PLC-{epsilon} pathway. Black-Right-Pointing-Pointer Activation of TGR5 by bile salts and selective ligands causes insulin secretion. Black-Right-Pointing-Pointer TGR5 could be a potential therapeutic target to treat diabetes. -- Abstract: Bile acids act as signaling molecules and stimulate the G protein coupled receptor, TGR5, in addition to nuclear farnesoid X receptor to regulate lipid, glucose and energy metabolism. Bile acid induced activation of TGR5 in the enteroendocrine cells promotes glucagon like peptide-1 (GLP-1) release, which has insulinotropic effect in the pancreatic {beta} cells. In the present study, we have identified the expression of TGR5 in pancreatic {beta} cell line MIN6 and also in mouse and human pancreatic islets. TGR5 selective ligands, oleanolic acid (OA) and INT-777 selectively activated G{alpha}{sub s} and caused an increase in intracellular cAMP and Ca{sup 2+}. OA and INT-777 also increased phosphoinositide (PI) hydrolysis and the increase was blocked by NF449 (a selective G{alpha}{sub s} inhibitor) or (U73122) (PI hydrolysis inhibitor). OA, INT-777 and lithocholic acid increased insulin release in MIN6 and human islets and the increase was inhibited by treatment with NF449, (U73122) or BAPTA-AM (chelator of calcium), but not with myristoylated PKI (PKA inhibitor), suggesting that the release is dependent on G{sub s}/cAMP/Ca{sup 2+} pathway. 8-pCPT-2 Prime -O-Me-cAMP, a cAMP analog, which activates Epac, but not PKA also stimulated PI hydrolysis. In conclusion, our study demonstrates that the TGR5 expressed in the pancreatic {beta} cells regulates insulin secretion and highlights the importance of ongoing therapeutic strategies targeting TGR5 in the control of glucose homeostasis.
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Tweedie, David; Brossi, Arnold; Chen, DeMoa; Ge, Yuan-Wen; Bailey, Jason; Yu, Qian-Sheng; Kamal, Mohammad A; Sambamurti, Kumar; Lahiri, Debomoy K; Greig, Nigel H
2006-09-01
Classical hallmarks of Alzheimer's disease (AD) are a synaptic loss, cholinergic neuron death, and abnormal protein deposition, particularly of toxic amyloid-beta peptide (Abeta) that is derived from amyloid-beta protein precursor (AbetaPP) by the action of beta- and gamma-secretases. The trigger(s) initiating the biochemical cascades that underpin these hallmarks have yet to be fully elucidated. The typical forebrain cholinergic cell demise associated with AD brain results in a loss of presynaptic cholinergic markers and acetylcholine (ACh). Neurine (vinyl-trimethyl-ammonium hydroxide) is a breakdown product of ACh, consequent to autolysis and is an organic poison found in cadavre brain. The time- and concentration-dependent actions of neurine were assessed in human neuroblastoma (NB, SK-N-SH) cells in culture by quantifying cell viability by lactate dehydrogenase (LDH) and MTS assay, and AbetaPP and Abeta levels by Western blot and ELISA. NB cells displayed evidence of toxicity to neurine at > or = 3 mg/ml, as demonstrated by elevated LDH levels in the culture media and a reduced cell viability shown by the MTS assay. Using subtoxic concentrations of neurine, elevations in AbetaPP and Abeta1-40 peptide levels were detected in conditioned media samples.
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Rijks, L. J.; Boer, G. J.; Endert, E.; de Bruin, K.; Janssen, A. G.; van Royen, E. A.
1997-01-01
The potential of both stereoisomers of 11 beta-methoxy-17 alpha-[123I] iodovinylestradiol (E- and Z-[123I]MIVE) as suitable radioligands for imaging of estrogen receptor (ER)-positive human breast tumours was studied. The 17 alpha-[123I]iodovinylestradiol derivatives were prepared stereospecifically
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Association of. beta. -glucosidase with intact cells of thermoactinomyces
Energy Technology Data Exchange (ETDEWEB)
Haegerdal, B; Harris, H; Pye, E K
1979-03-01
The location of the ..beta..-glucosidase activity in a whole culture broth of the thermophilic organism Thermoactinomyces has been studied. Little ..beta..-glucosidase activity was found in the culture filtrate, while the culture solids contained the major part of the activity of the whole culture broth. The activity does not appear to be adsorbed to the culture solids; rather there is evidence that it is an intracellular soluble enzyme(s). The pH and temperature optima for a crude ..beta..-glucosidase preparation were determined to be pH 6.5 and 50 to 55/sup 0/C. Enzyme activity studies indicate that the same enzyme(s) accounts for the ..beta..-glucosidase and the cellobiase activities. The validity of using the filter paper activity of culture filtrates from Thermoactinomyces to predict the total saccharification of cellulosic materials to glucose is discussed.
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Isolation of beta-glucan from the cell wall of Saccharomyces cerevisiae.
Shokri, Hojjatollah; Asadi, Farzad; Khosravi, Ali Reza
2008-03-20
Beta-glucan, one of the major cell wall components of Saccharomyces cerevisiae (S. cerevisiae), has been found to enhance immune functions. At present study, we developed an optimal procedure to extract and purify beta-glucan. At first, yeast cells were grown in sabouraud dextrose agar and then cultured in yeast extract-peptone-glucose (YPG) broth. After incubation, cells were harvested, washed and disrupted by means of sonication method. The obtained cell walls were used to prepare alkali-soluble beta-glucan (glucan-S1). In this regard, 2% sodium hydroxide (NaOH) and 3% acetic acid were used in alkaline-acid extraction, respectively. This preparation contained 2.4% protein. In the next step, DEAE sephacel chromatography was used to remove remaining proteins (glucan-S2). Subsequently this preparation was applied into concanavalin-A sepharose column to remove manann. Finally, beta-glucan free of mannoprotein complexes was prepared (glucan-S3).
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Astrocytic expression of the Alzheimer's disease beta-secretase (BACE1) is stimulus-dependent
DEFF Research Database (Denmark)
Hartlage-Rübsamen, Maike; Zeitschel, Ulrike; Apelt, Jenny
2003-01-01
The beta-site APP-cleaving enzyme (BACE1) is a prerequisite for the generation of beta-amyloid peptides, which give rise to cerebrovascular and parenchymal beta-amyloid deposits in the brain of Alzheimer's disease patients. BACE1 is neuronally expressed in the brains of humans and experimental...... paradigms studied. In contrast, BACE1 expression by reactive astrocytes was evident in chronic but not in acute models of gliosis. Additionally, we observed BACE1-immunoreactive astrocytes in proximity to beta-amyloid plaques in the brains of aged Tg2576 mice and Alzheimer's disease patients....
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Obertreis, B; Ruttkowski, T; Teucher, T; Behnke, B; Schmitz, H
1996-04-01
An extract of Urtica dioica folium (IDS 23, Rheuma-Hek), monographed positively for adjuvant therapy of rheumatic diseases and with known effects in partial inhibition of prostaglandin and leukotriene synthesis in vitro, was investigated with respect to effects of the extract on the lipopolysaccharide (LPS) stimulated secretion of proinflammatory cytokines in human whole blood of healthy volunteers. In the assay system used, LPS stimulated human whole blood showed a straight increase of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion reaching maximum concentrations within 24 h following a plateau and slight decrease up to 65 h, respectively. The concentrations of these cytokines was strongly positively correlated with the number of monocytes/macrophages of each volunteer. TNF-alpha and IL-1 beta concentration after LPS stimulation was significantly reduced by simultaneously given IDS 23 in a strictly dose dependent manner. At time 24 h these cytokine concentrations were reduced by 50.8% and 99.7%, respectively, using the highest test IDS 23 assay concentration of 5 mg/ml (p flavonoides such as caffeic malic acid, caffeic acid, chlorogenic acid, quercetin and rutin did not influence LPS stimulated TNF-alpha, IL-1 beta and IL-6 secretion in tested concentrations up to 5 x 10(-5) mol/l. These further findings on the pharmacological mechanism of action of Urticae dioica folia may explain the positive effects of this extract in the treatment of rheumatic diseases.
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Extrasynaptic location of laminin beta 2 chain in developing and adult human skeletal muscle
DEFF Research Database (Denmark)
Wewer, U M; Thornell, L E; Loechel, F
1997-01-01
and Becker muscular dystrophy. Immunoaffinity chromatography of muscle extracts with a monoclonal antibody to the laminin alpha 2 chain followed by immunoblotting with various antibodies to the beta 2 chain demonstrated the presence of the laminin-4 (alpha 2-beta 2-gamma 1) isoform. Together the present...
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Effects of ultrasound on Transforming Growth Factor-beta genes in bone cells
Directory of Open Access Journals (Sweden)
J Harle
2005-12-01
Full Text Available Therapeutic ultrasound (US is a widely used form of biophysical stimulation that is increasingly applied to promote fracture healing. Transforming growth factor-beta (TGF-beta, which is encoded by three related but different genes, is known to play a major part in bone growth and repair. However, the effects of US on the expression of the TGF-beta genes and the physical acoustic mechanisms involved in initiating changes in gene expression in vitro, are not yet known. The present study demonstrates that US had a differential effect on these TGF-beta isoforms in a human osteoblast cell line, with the highest dose eliciting the most pronounced up-regulation of both TGF-beta1 and TGF-beta3 at 1 hour after treatment and thereafter declining. In contrast, US had no effect on TGF-beta2 expression. Fluid streaming rather than thermal effects or cavitation was found to be the most likely explanation for the gene responses observed in vitro.
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International Nuclear Information System (INIS)
Liotta, A.S.; Yamaguchi, H.; Krieger, D.T.
1981-01-01
Continuous labeling and pulse-chase techniques were employed to study the synthesis and secretion of multiple forms of immunoreactive beta-endorphin by cultured dispersed rat anterior lobe cells and intact neurointermediate pituitary lobe. Intact neurointermediate lobes incorporated radiolabeled amino acids into four to six forms of immunoreactive beta-endorphin. Four of these forms were physicochemically similar to authentic beta-endorphin, N-acetylated beta-endorphin, beta-endorphin-(1-27), and N-acetylated beta-endorphin-(1-27). Pulse-chase studies indicated that a beta-lipotropin-like molecule served as a metabolic intermediate for a beta-endorphin-like molecule. As beta-endorphin-like material accumulated in the cell, some of it was N-acetylated (approximately 18% at 2 hr chase and approximately 65% at 18 hr chase). At later chase times, beta-endorphin-(1-27)- and N-acetylated beta-endorphin-(1-27)-like peptides were the predominant molecular species detected. All endorphin forms were detected in unlabeled tissue maintained in culture or tissue continuously labeled for 72 hr and were released into the medium under basal, stimulatory (10(-8) M norepinephrine), or inhibitory (10(-7) M dopamine) incubation conditions. In all cases, beta-endorphin-(1-27)-like species were the predominant forms (more than 70% of total) present in the cells and released into the medium. In contrast, approximately 90% of radiolabeled immunoreactive beta-endorphin extracted from anterior lobe cells and medium similarly incubated appeared to represent the authentic beta-endorphin molecule. Continuous labeling (72 hr) revealed the beta-lipotropin/beta-endorphin molar ratio to be approximately 4. We conclude that, in anterior lobe, most of the beta-endorphin is not processed further and is released intact, while in neurointermediate lobe, it serves as a biosynthetic intermediate
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Energy Technology Data Exchange (ETDEWEB)
Kratochwil, C.; Giesel, F.L.; Mier, W.; Haberkorn, U. [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Bruchertseifer, F.; Apostolidis, C.; Morgenstern, A. [European Commission, Institute for Transuranium Elements, Karlsruhe (Germany); Boll, R.; Murphy, K. [Oak Ridge National Laboratory, Oak Ridge, TN (United States)
2014-11-15
Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as {sup 90}Y/{sup 177}Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with {sup 213}Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with {sup 90}Y/{sup 177}Lu-DOTATOC were treated with an intraarterial infusion of {sup 213}Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of {sup 213}Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and {sup 68}Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. The biodistribution of {sup 213}Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses. (orig.)
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Geylis, Valeria; Steinitz, Michael
2006-01-01
The deposition of amyloid beta (Abeta) protein is a key pathological feature in Alzheimer's disease (AD). In murine models of AD, both active and passive immunization against Abeta induce a marked reduction in amyloid brain burden and an improvement in cognitive functions. Preliminary results of a prematurely terminated clinical trial where AD patients were actively vaccinated with aggregated Abeta bear resemblance to those documented in murine models. Passive immunization of AD patients with anti-Abeta antibodies, in particular human antibodies, is a strategy that provides a more cautious management and control of any undesired side effects. Sera of all healthy adults contain anti-Abeta IgG autoimmune antibodies. Hence antigen-committed human B-cells are easily immortalized by Epstein-Barr virus (EBV) into anti-Abeta secreting cell lines. Two anti-Abeta human monoclonal antibodies which we recently prepared bind to the N-terminus of Abeta peptide and were shown to stain amyloid plaques in non-fixed brain sections from an AD patient. It is anticipated that specifically selected anti-Abeta human monoclonal antibodies could reduce and inhibit deposits of amyloid in brain while avoiding the cognitive decline that characterizes AD. In the future, this type of antibody may prove to be a promising immune therapy for the disease.
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Music genre preference and tempo alter alpha and beta waves in human non-musicians
Directory of Open Access Journals (Sweden)
Hunter Gentry
2013-10-01
Full Text Available This study examined the effects of music genre and tempo on brain activation patterns in 10 nonmusicians.Two genres (rock and jazz and three tempos (slowed, medium/normal, andquickened were examined using EEG recording and analyzed through Fast Fourier Transform(FFT analysis. When participants listened to their preferred genre, an increase in alpha waveamplitude was observed. Alpha waves were not significantly affected by tempo. Beta waveamplitude increased significantly as the tempo increased. Genre had no effect on beta waves. Thefindings of this study indicate that genre preference and artificially modified tempo do affectalpha and beta wave activation in non-musicians listening to preselected songs.
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Wright, M O; Nishida, K; Bavington, C; Godolphin, J L; Dunne, E; Walmsley, S; Jobanputra, P; Nuki, G; Salter, D M
1997-09-01
Mechanical stimuli influence chondrocyte metabolism, inducing changes in intracellular cyclic adenosine monophosphate and proteoglycan production. We have previously demonstrated that primary monolayer cultures of human chondrocytes have an electrophysiological response after intermittent pressure-induced strain characterised by a membrane hyperpolarisation of approximately 40%. The mechanisms responsible for these changes are not fully understood but potentially involve signalling molecules such as integrins that link extracellular matrix with cytoplasmic components. The results reported in this paper demonstrate that the transduction pathways involved in the hyperpolarisation response of human articular chondrocytes in vitro after cyclical pressure-induced strain involve alpha 5 beta 1 integrin. We have demonstrated, using pharmacological inhibitors of a variety of intracellular signalling pathways, that the actin cytoskeleton, the phospholipase C calmodulin pathway, and both tyrosine protein kinase and protein kinase C activities are important in the transduction of the electrophysiological response. These results suggest that alpha 5 beta 1 is an important chondrocyte mechanoreceptor and a potential regulator of chondrocyte function.
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Kleinschmidt, Martin; Marian, Christel M; Waletzke, Mirko; Grimme, Stefan
2009-01-28
We present a parallelized version of a direct selecting multireference configuration interaction (MRCI) code [S. Grimme and M. Waletzke, J. Chem. Phys. 111, 5645 (1999)]. The program can be run either in ab initio mode or as semiempirical procedure combined with density functional theory (DFT/MRCI). We have investigated the efficiency of the parallelization in case studies on carotenoids and porphyrins. The performance is found to depend heavily on the cluster architecture. While the speed-up on the older Intel Netburst technology is close to linear for up to 12-16 processes, our results indicate that it is not favorable to use all cores of modern Intel Dual Core or Quad Core processors simultaneously for memory intensive tasks. Due to saturation of the memory bandwidth, we recommend to run less demanding tasks on the latter architectures in parallel to two (Dual Core) or four (Quad Core) MRCI processes per node. The DFT/MRCI branch has been employed to study the low-lying singlet and triplet states of mini-n-beta-carotenes (n=3, 5, 7, 9) and beta-carotene (n=11) at the geometries of the ground state, the first excited triplet state, and the optically bright singlet state. The order of states depends heavily on the conjugation length and the nuclear geometry. The (1)B(u) (+) state constitutes the S(1) state in the vertical absorption spectrum of mini-3-beta-carotene but switches order with the 2 (1)A(g) (-) state upon excited state relaxation. In the longer carotenes, near degeneracy or even root flipping between the (1)B(u) (+) and (1)B(u) (-) states is observed whereas the 3 (1)A(g) (-) state is found to remain energetically above the optically bright (1)B(u) (+) state at all nuclear geometries investigated here. The DFT/MRCI method is seen to underestimate the absolute excitation energies of the longer mini-beta-carotenes but the energy gaps between the excited states are reproduced well. In addition to singlet data, triplet-triplet absorption energies are
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Energy Technology Data Exchange (ETDEWEB)
Keren, O.; Gioannini, T.L.; Hiller, J.M.; Simon, E.J.
1986-01-01
Affinity crosslinking of human /sup 125/I-beta-Endorphin to cell lines possessing either mu or delta binding sites was carried out. Autoradiography of SDS-PAGE gels from these crosslinked cell lines revealed that these two sites contain major peptide subunits that differ in molecular size. This confirms our earlier finding in mammalian brain which demonstrated separate and distinct subunits for mu and delta opioid receptors.
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A new alternative transcript encodes a 60 kDa truncated form of integrin beta 3.
Djaffar, I; Chen, Y P; Creminon, C; Maclouf, J; Cieutat, A M; Gayet, O; Rosa, J P
1994-01-01
A cDNA for integrin beta 3 isolated from a human erythroleukaemia (HEL) cell library contained a 340 bp insert at position 1281. This mRNA, termed beta 3c, results from the use of a cryptic AG donor splice site in intron 8 of the beta 3 gene, and is different from a previously described alternative beta 3 mRNA. The predicted open reading frame of beta 3C stops at a TAG stop codon 69 bp downstream from position 1281. It starts with the signal peptide and the 404 N-terminal extracellular residu...
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Tubulin Beta-3 Chain as a New Candidate Protein Biomarker of Human Skin Aging: A Preliminary Study
Directory of Open Access Journals (Sweden)
Sylvia G. Lehmann
2017-01-01
Full Text Available Skin aging is a complex process, and a lot of efforts have been made to identify new and specific targets that could help to diagnose, prevent, and treat skin aging. Several studies concerning skin aging have analyzed the changes in gene expression, and very few investigations have been performed at the protein level. Moreover, none of these proteomic studies has used a global quantitative labeled proteomic offgel approach that allows a more accurate description of aging phenotype. We applied such an approach on human primary keratinocytes obtained from sun-nonexposed skin biopsies of young and elderly women. A total of 517 unique proteins were identified, and 58 proteins were significantly differentially expressed with 40 that were downregulated and 18 upregulated with aging. Gene ontology and pathway analysis performed on these 58 putative biomarkers of skin aging evidenced that these dysregulated proteins were mostly involved in metabolism and cellular processes such as cell cycle and signaling pathways. Change of expression of tubulin beta-3 chain was confirmed by western blot on samples originated from several donors. Thus, this study suggested the tubulin beta-3 chain has a promising biomarker in skin aging.
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BETASCAN: probable beta-amyloids identified by pairwise probabilistic analysis.
Directory of Open Access Journals (Sweden)
Allen W Bryan
2009-03-01
Full Text Available Amyloids and prion proteins are clinically and biologically important beta-structures, whose supersecondary structures are difficult to determine by standard experimental or computational means. In addition, significant conformational heterogeneity is known or suspected to exist in many amyloid fibrils. Recent work has indicated the utility of pairwise probabilistic statistics in beta-structure prediction. We develop here a new strategy for beta-structure prediction, emphasizing the determination of beta-strands and pairs of beta-strands as fundamental units of beta-structure. Our program, BETASCAN, calculates likelihood scores for potential beta-strands and strand-pairs based on correlations observed in parallel beta-sheets. The program then determines the strands and pairs with the greatest local likelihood for all of the sequence's potential beta-structures. BETASCAN suggests multiple alternate folding patterns and assigns relative a priori probabilities based solely on amino acid sequence, probability tables, and pre-chosen parameters. The algorithm compares favorably with the results of previous algorithms (BETAPRO, PASTA, SALSA, TANGO, and Zyggregator in beta-structure prediction and amyloid propensity prediction. Accurate prediction is demonstrated for experimentally determined amyloid beta-structures, for a set of known beta-aggregates, and for the parallel beta-strands of beta-helices, amyloid-like globular proteins. BETASCAN is able both to detect beta-strands with higher sensitivity and to detect the edges of beta-strands in a richly beta-like sequence. For two proteins (Abeta and Het-s, there exist multiple sets of experimental data implying contradictory structures; BETASCAN is able to detect each competing structure as a potential structure variant. The ability to correlate multiple alternate beta-structures to experiment opens the possibility of computational investigation of prion strains and structural heterogeneity of amyloid
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Liao, Chien-Wei; Fan, Chia-Kwung; Kao, Ting-Chang; Ji, Dar-Der; Su, Kua-Eyre; Lin, Yun-Ho; Cho, Wen-Long
2008-06-24
Because the outcomes and sequelae after different types of brain injury (BI) are variable and difficult to predict, investigations on whether enhanced expressions of BI-associated biomarkers (BIABs), including transforming growth factor beta1 (TGF-beta1), S100B, glial fibrillary acidic protein (GFAP), neurofilament light chain (NF-L), tissue transglutaminases (tTGs), beta-amyloid precursor proteins (AbetaPP), and tau are present as well as whether impairment of the ubiquitin-proteasome system (UPS) is present have been widely used to help delineate pathophysiological mechanisms in various BIs. Larvae of Toxocara canis can invade the brain and cause BI in humans and mice, leading to cerebral toxocariasis (CT). Because the parasitic burden is light in CT, it may be too cryptic to be detected in humans, making it difficult to clearly understand the pathogenesis of subtle BI in CT. Since the pathogenesis of murine toxocariasis is very similar to that in humans, it appears appropriate to use a murine model to investigate the pathogenesis of CT. BIAB expressions and UPS function in the brains of mice inoculated with a single dose of 250 T. canis embryonated eggs was investigated from 3 days (dpi) to 8 weeks post-infection (wpi) by Western blotting and RT-PCR. Results revealed that at 4 and 8 wpi, T. canis larvae were found to have invaded areas around the choroid plexus but without eliciting leukocyte infiltration in brains of infected mice; nevertheless, astrogliosis, an indicator of BI, with 78.9~142.0-fold increases in GFAP expression was present. Meanwhile, markedly increased levels of other BIAB proteins including TGF-beta1, S100B, NF-L, tTG, AbetaPP, and tau, with increases ranging 2.0~12.0-fold were found, although their corresponding mRNA expressions were not found to be present at 8 wpi. Concomitantly, UPS impairment was evidenced by the overexpression of conjugated ubiquitin and ubiquitin in the brain. Further studies are needed to determine whether there is an
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Directory of Open Access Journals (Sweden)
Andreas Bayer
2017-01-01
Full Text Available Platelet-released growth factors (PRGF and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF® contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3 is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR. In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds.
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Lammel, Justus; Tohidnezhad, Mersedeh; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Cremer, Jochen; Jahr, Holger; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen
2017-01-01
Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF®)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR). In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds. PMID:28811680
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Fibronectin regulates the activation of THP-1 cells by TGF-beta1.
Wang, A C; Fu, L
2001-03-01
To determine how fibronectin regulates the immunomodulatory effects of transforming growth factor (TGF)-beta on THP-1 cells. THP-1 monocytic cell line. THP-1 cells were primed for 48 h in the presence or absence of 250 pM TGF-beta1. Assays or assessments carried out, together with statistical test applied. We found that adherence to fibronectin dramatically modulates the effects of TGF-beta1 on the human monocytic cell line THP-1. TGF-beta did not significantly affect constitutive interleukin (IL)-8 secretion or IL-1beta-induced IL-8 secretion from suspended cells. In contrast, TGF-beta stimulated IL-8 secretion as well as augmented IL-1beta-induced IL-8 secretion from adherent cells. The differential effects of TGF-beta1 on IL-8 secretion from suspended and adherent cells could not be explained by differences in IL-1 receptor antagonist production. The effects of fibronectin on TGF-beta1 induced IL-8 secretion from THP-1 cells were mimicked by adhesion to immobilized anti-a4beta1 integrin antibody and to a fibronectin fragment containing the CS-1 domain. These results indicate that alpha4beta1-mediated adhesion to fibronectin may play a key role during inflammation by profoundly influencing the effects of TGF-beta1 on monocytes.
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Purification of beta-acetylglucosaminase and beta-galactosidase from ram testis.
Caygill, J C; Roston, C P; Jevons, F R
1966-02-01
1. The presence of beta-galactosidase (EC 3.2.1.23) in an acetic acid extract of ram testis is reported. Some properties of the crude enzyme preparation were studied. 2. The purification of beta-acetylglucosaminase (EC 3.2.1.30) and of beta-galactosidase from the ram-testis extract by ammonium sulphate precipitation and chromatography on a CM-cellulose column is described. 3. The final purifications of the separated enzymes achieved were for the beta-acetylglucosaminase 35 times and for the beta-galactosidase 99 times. 4. The possibility of using DEAE-cellulose and Sephadex G-200 to purify the enzymes was investigated.
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beta- and gamma-Comparative dose estimates on Eniwetok Atoll
Energy Technology Data Exchange (ETDEWEB)
Crase, K.W.; Gudiksen, P.H.; Robison, W.L.
1982-05-01
Eniwetok Atoll is one of the Pacific atolls used for atmospheric testing of U.S. nuclear weapons. Beta dose and gamma-ray exposure measurements were made on two islands of the Eniwetok Atoll during July-August 1976 to determine the beta and low energy gamma-contribution to the total external radiation doses to the returning Marshallese. Measurements were made at numerous locations with thermoluminescent dosimeters (TLD), pressurized ionization chambers, portable NaI detectors, and thin-window pancake GM probes. Results of the TLD measurements with and without a beta-attenuator indicate that approx. 29% of the total dose rate at 1 m in air is due to beta- or low energy gamma-contribution. The contribution at any particular site, however, is somewhat dependent on ground cover, since a minimal amount of vegetation will reduce it significantly from that over bare soil, but thick stands of vegetation have little effect on any further reductions. Integral 30-yr external shallow dose estimates for future inhabitants were made and compared with external dose estimates of a previous large scale radiological survey (En73). Integral 30-yr shallow external dose estimates are 25-50% higher than whole body estimates. Due to the low penetrating ability of the beta's or low energy gamma's, however, several remedial actions can be taken to reduce the shallow dose contribution to the total external dose.
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Beta-amyloid and cholinergic neurons
Czech Academy of Sciences Publication Activity Database
Doležal, Vladimír; Kašparová, Jana
2003-01-01
Roč. 28, 3-4 (2003), s. 499-506 ISSN 0364-3190 R&D Projects: GA ČR GA305/01/0283; GA AV ČR IAA5011206 Institutional research plan: CEZ:AV0Z5011922 Keywords : cholinergic neurons * AlzheimerŽs disease * beta-amyloid Subject RIV: FH - Neurology Impact factor: 1.511, year: 2003
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State of the Art in Beta Titanium Alloys for Airframe Applications
Cotton, James D.; Briggs, Robert D.; Boyer, Rodney R.; Tamirisakandala, Sesh; Russo, Patrick; Shchetnikov, Nikolay; Fanning, John C.
2015-06-01
Beta titanium alloys were recognized as a distinct materials class in the 1950s, and following the introduction of Ti-13V-11Cr-3Al in the early 1960s, intensive research occurred for decades thereafter. By the 1980s, dozens of compositions had been explored and sufficient work had been accomplished to warrant the first major conference in 1983. Metallurgists of the time recognized beta alloys as highly versatile and capable of remarkable property development at much lower component weights than steels, coupled with excellent corrosion resistance. Although alloys such as Ti-15V-3Al-3Sn-3Cr, Ti-10V-2Fe-3Al and Ti-3AI-8V-6Cr-4Mo-4Zr (Beta C) were commercialized into well-known airframe systems by the 1980s, Ti-13V-11Cr-3Al was largely discarded following extensive employment on the SR-71 Blackbird. The 1990s saw the implementation of specialty beta alloys such as Beta 21S and Alloy C, in large part for their chemical and oxidation resistance. It was also predicted that by the 1990s, cost would be the major limitation on expansion into new applications. This turned out to be true and is part of the reason for some stagnation in commercialization of new such compositions over the past two decades, despite a good understanding of the relationships among chemistry, processing, and performance and some very attractive offerings. Since then, only a single additional metastable beta alloy, Ti-5Al-5V-5Mo-3Cr-0.5Fe, has been commercialized in aerospace, although low volumes of other chemistries have found a place in the biomedical implant market. This article examines the evolution of this important class of materials and the current status in airframe applications. It speculates on challenges for expanding their use.
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Energy Technology Data Exchange (ETDEWEB)
Riche, R [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires
1965-09-01
The kinetic and perturbation equations are derived from the time-dependent transport equation. Kinetic equations depend only on the ratios a = {rho}-bar/{beta}-bar and b = {beta}-bar/{lambda}, which are definite, while the reactivity {rho}-bar, the delayed neutron fraction ({beta}-bar and the generation time {lambda} are expressed in terms of an arbitrary function I. The 'static' definitions of these parameters, which reduce kinetic problems to a set of purely term dependent equations, introduce the effective fraction {beta}-bar. One way of determining experimentally the ratio b is presented; it consists in analysing the power transient after a rapid variation of the reactivity, caused by the implosion of an empty glass-bull. A simple interpretation is proposed. The apparatus can be transformed easily into a reactimeter. The value of the effective delayed neutron fraction {beta}-bar has been determined by averaging the reactivity effects of a copper sheet through out the reactor core. Experimental results: b = {beta}-bar/{lambda} = 129 s{sup -1} and {beta}-bar 795.10{sup -5}, have been determined on a light-water moderated, enriched-uranium fuelled reactor. The calculated values of the effectiveness of delayed neutrons {gamma} {beta}-bar/{beta} 1.23 and the generation time {lambda} 59.10{sup -6}s agrees fairly well with the experimental results. (author) [French] Les equations de la cinetique et de la perturbation sont deduites de la theorie du transport, par l'intermediaire de la 'notion' d'importance des neutrons. La cinetique ne depend que des rapports a = {rho}-bar/{beta}-bar et b = {beta}-bar/{lambda}, qui sont parfaitement definis; par contre, la reactivite {rho}-bar, la proportion de neutrons retardes {beta}-bar et le temps de generation des neutrons prompts {lambda} s'expriment a l'aide d'une meme fonction arbitraire I. Les definitions 'statiques' de ces parametres, qui permettent de rendre compte de la cinetique par des equations dependant purement du
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Double beta decays and related subjects for particle and nuclear physics
International Nuclear Information System (INIS)
Ejiri, Hiroyasu
1991-01-01
Present status and some perspectives in 1990's are briefly given on double beta decays and related subjects. Subjects discussed are as follows I) Double beta decays without neutrinos, which require lepton number non-conservations and finite neutrino mass. II) Double beta decays followed by two neutrinos. III) Double weak processes with strangeness change ΔS = 2, leading to the H particle with 6 quarks of ss uu dd. IV) Charge non-conservation and electron decays. These are very rare nuclear processes studied by Ultra RAre-process NUclear Spectroscopy (URANUS). It is shown that URANUS is an important detector frontier of non-accelerator nuclear physics in 1990's. (orig.)
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de Wit, R.; Bakker, P. J.; Reiss, P.; Hoek, F. J.; Lange, J. M.; Goudsmit, J.; Veenhof, K. H.
1990-01-01
Beta 2-microglobulin (beta 2-M) levels were determined in the serum of 24 patients treated with high-dose human recombinant interferon-alpha (IFN alpha) for AIDS-associated Kaposi's sarcoma. There was a significant increase in serum beta 2-M levels, irrespective of the response to treatment.
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Michel, M. C.; Galal, O.; Stoermer, J.; Bock, K. D.; Brodde, O. E.
1989-01-01
To study whether changes in alpha- and beta-adrenoceptors in human essential hypertension (EHT) might be genetically determined, we assessed platelet alpha 2- and lymphocyte beta 2-adrenoceptor density in 48 normotensive children of normotensive parents (NT) and in 41 normotensive children with one
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Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K
1993-01-01
The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene d...
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Energy Technology Data Exchange (ETDEWEB)
Kozlov, Guennadi [McGill University, Department of Biochemistry (Canada); Ekiel, Irena [National Research Council of Canada, Biomolecular NMR Group, Sector of Pharmaceutical Biotechnology, Biotechnology Research Institute (Canada); Beglova, Natalia [McGill University, Department of Biochemistry (Canada); Yee, Adelinda; Dharamsi, Akil; Engel, Asaph [University of Toronto, Department of Medical Biophysics (Canada); Siddiqui, Nadeem; Nong, Andrew; Gehring, Kalle [McGill University, Department of Biochemistry (Canada)
2000-07-15
The tertiary fold of the elongation factor, aEF-1{beta}, from Methanobacterium thermoautotrophicum was determined in a high-throughput fashion using a minimal set of NMR experiments. NMR secondary structure prediction, deuterium exchange experiments and the analysis of chemical shift perturbations were combined to identify the protein fold as an alpha-beta sandwich typical of many RNA binding proteins including EF-G. Following resolution of the tertiary fold, a high resolution structure of aEF-1{beta} was determined using heteronuclear and homonuclear NMR experiments and a semi-automated NOESY assignment strategy. Analysis of the aEF-1{beta} structure revealed close similarity to its human analogue, eEF-1{beta}. In agreement with studies on EF-Ts and human EF-1{beta}, a functional mechanism for nucleotide exchange is proposed wherein Phe46 on an exposed loop acts as a lever to eject GDP from the associated elongation factor G-protein, aEF-1{alpha}. aEF-1{beta} was also found to bind calcium in the groove between helix {alpha}2 and strand {beta}4. This novel feature was not observed previously and may serve a structural function related to protein stability or may play a functional role in archaeal protein translation.
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DEFF Research Database (Denmark)
Kristensen, Stine Gry; Andersen, Kasper; Clement, Christian Alexandro
2014-01-01
In mammals, members of the transforming growth factor-beta (TGF-β) superfamily are known to have key roles in the regulation of follicular growth and development. The aim of the study was to evaluate the expression of TGF-β superfamily growth factors, their receptors, downstream SMAD signalling m...... growth. Moreover, the presence of multiple TGF-β/BMP antagonists imply that certain growth factors are subjected to local regulation on different levels which address another important level of intraovarian regulation of follicle development in humans.......In mammals, members of the transforming growth factor-beta (TGF-β) superfamily are known to have key roles in the regulation of follicular growth and development. The aim of the study was to evaluate the expression of TGF-β superfamily growth factors, their receptors, downstream SMAD signalling...... molecules and TGF- β/BMP antagonists during early human folliculogenesis.Human preantral follicles were enzymatically isolated from surplus ovarian tissue obtained from women having ovarian cortical tissue frozen for fertility preservation. A total of 348 human preantral follicles, ranging from 40 to 200 µm...
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Do post-translational beta cell protein modifications trigger type 1 diabetes?
DEFF Research Database (Denmark)
Størling, Joachim; Overgaard, Anne Julie; Brorsson, Caroline Anna
2013-01-01
beta cell-specific neo-epitopes. We suggest that the current paradigm of type 1 diabetes as a classical autoimmune disease should be reconsidered since the immune response may not be directed against native beta cell proteins. A modified model for the pathogenetic events taking place in islets leading...... diabetes exists in the published literature. Furthermore, we report that cytokines change the expression levels of several genes encoding proteins involved in PTM processes in human islets, and that there are type 1 diabetes-associated polymorphisms in a number of these. In conclusion, data from...... the literature and presented experimental data support the notion that PTM of beta cell proteins may be involved in triggering beta cell destruction in type 1 diabetes. If the beta cell antigens recognised by the immune system foremost come from modified proteins rather than native ones, the concept of type 1...
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Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy
DEFF Research Database (Denmark)
Nalla, Amarnadh; Ringholm, Lene; Søstrup, Birgitte
2014-01-01
is able to stimulate proliferation of rat beta cells. We have identified several circulating factors that may contribute to beta cell adaptation to pregnancy. Further studies are needed to elucidate their possible role in glucose homeostasis in the mother and her offspring.......OBJECTIVE: Several studies have shown an increase in beta cell mass during pregnancy. Somatolactogenic hormones are known to stimulate the proliferation of existing beta cells in rodents whereas the mechanism in humans is still unclear. We hypothesize that in addition to somatolactogenic hormones...... there are other circulating factors involved in beta cell adaptation to pregnancy. This study aimed at screening for potential pregnancy-associated circulating beta cell growth factors. SAMPLES: Serum samples from nonpregnant and pregnant women. METHODS: The effect of serum from pregnant women...
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International Nuclear Information System (INIS)
Hubert, F.; Dufour, J.P.; Moral, R. del; Fleury, A.; Jean, D.; Pravikoff, M.S.; Delagrange, H.; Geissel, H.; Schmidt, K.H.; Hanelt, E.
1989-01-01
The beta-gamma spectroscopic study of 22 O is presented. This nucleus, produced as a projectile-like fragment from the interaction of a 60 MeV/n 40 Ar beam with a Be target, has been separated by the LISE spectrometer. Several gamma rays from 22 O decay have been observed, from which a half-life of (2.25±0.15) s has been determined. Accurate excitation energies have been deduced for several states in 22 F. A partial beta decay scheme of 22 O has been established. Experimental results have been compared with shell model calculations. (orig.)
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Beta-N-Acetylhexosaminidase: What's in a name…?
Czech Academy of Sciences Publication Activity Database
Slámová, Kristýna; Bojarová, Pavla; Petrásková, Lucie; Křen, Vladimír
2010-01-01
Roč. 28, č. 6 (2010), s. 682-693 ISSN 0734-9750 R&D Projects: GA ČR GD305/09/H008; GA ČR GP203/09/P024; GA MŠk(CZ) LC06010; GA MŠk OC09045 Institutional research plan: CEZ:AV0Z50200510 Keywords : beta-N-Acetylhexosaminidase * O-GlcNAcase * beta-N-Acetylglucosaminidase Subject RIV: CE - Biochemistry Impact factor: 7.600, year: 2010
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[Effect of IL-1beta on growth properties of vaginal microsymbionts].
Kremleva, E A; Bukharin, O V
2013-01-01
Study the effect of IL-1beta in concentrations that are characteristic for vaginal normo- and pathocenosis on growth properties of vaginal microsymbionts. Concentration of IL-1beta in vaginal contents of women during bacterial vaginosis and normocenosis was determined by using enzume immunoassay. Changes of growth characteristics and biofilm formation ability of Staphylococcus aureus, Escherichia coli, Lactobacilus spp., Corynebacterium spp. under the effect of various IL-1beta concentrations by method of O'Toole G.A. (1999) were studied. IL-1beta in concentrations characteristic for normocenosis was shown to be able to cause stimulating effect on growth properties of lactobacilli and corynebacteria and suppress growth of S. aureus and E. coli in both plankton and biofilm cultures. IL-1beta concentrations characteristic for vaginal dysbiosis on the contrary result in suppression of growth of lactobacilli biomass against the background of stimulation of growth properties and biofilm formation ability of S. aureus and E. coli. Differential dose-dependent effect of IL-1beta on biomass growth and biofilm formation ability of vaginal microsymbionts is a mechanism of regulation of vaginal microbiocenosis.
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Fuller, Geraldine A; Bicer, Sabahattin; Hamlin, Robert L; Yamaguchi, Mamoru; Reiser, Peter J
2007-10-01
Dilated cardiomyopathy is a naturally occurring disease in humans and dogs. Human studies have shown increased levels of myosin heavy chain (MHC)-beta in failing ventricles and the left atria (LA) and of ventricular light chain (VLC)-2 in the right atria in dilated cardiomyopathy. This study evaluates the levels of MHC-beta in all heart chambers in prolonged canine right ventricular pacing. In addition, we determined whether levels of VLC2 were altered in these hearts. Failing hearts demonstrated significantly increased levels of MHC-beta in the right atria, right atrial appendage, LA, left atrial appendage (LAA), and right ventricle compared with controls. Significant levels of VLC2 were detected in the right atria of paced hearts. Differences in MHC-beta expression were observed between the LA and the LAA of paced and control dogs. MHC-beta expression was significantly greater in the LA of paced and control dogs compared with their respective LAA. The cardiac myosin isoform shifts in this study were similar to those observed in end-stage human heart failure and more severe than those reported in less prolonged pacing models, supporting the use of this model for further study of end-stage human heart failure. The observation of consistent differences between sampling sites, especially LA versus LAA, indicates the need for rigorous sampling consistency in future studies.
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Space environment durability of beta cloth in LDEF thermal blankets
Linton, Roger C.; Whitaker, Ann F.; Finckenor, Miria M.
1993-01-01
Beta cloth performance for use on long-term space vehicles such as Space Station Freedom (S.S. Freedom) requires resistance to the degrading effects of the space environment. The major issues are retention of thermal insulating properties through maintaining optical properties, preserving mechanical integrity, and generating minimal particulates for contamination-sensitive spacecraft surfaces and payloads. The longest in-flight test of beta cloth's durability was on the Long Duration Exposure Facility (LDEF), where it was exposed to the space environment for 68 months. The LDEF contained 57 experiments which further defined the space environment and its effects on spacecraft materials. It was deployed into low-Earth orbit (LEO) in Apr. 1984 and retrieved Jan. 1990 by the space shuttle. Among the 10,000 plus material constituents and samples onboard were thermal control blankets of multilayer insulation with a beta cloth outer cover and Velcro attachments. These blankets were exposed to hard vacuum, thermal cycling, charged particles, meteoroid/debris impacts, ultraviolet (UV) radiation, and atomic oxygen (AO). Of these space environmental exposure elements, AO appears to have had the greatest effect on the beta cloth. The beta cloth analyzed in this report came from the MSFC Experiment S1005 (Transverse Flat-Plate Heat Pipe) tray oriented approximately 22 deg from the leading edge vector of the LDEF satellite. The location of the tray on LDEF and the placement of the beta cloth thermal blankets are shown. The specific space environment exposure conditions for this material are listed.
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DEFF Research Database (Denmark)
Christoffersen, Peter; Jacobs, Kris; Vainberg, Gregory
Few issues are more important for finance practice than the computation of market betas. Existing approaches compute market betas using historical data. While these approaches differ in terms of statistical sophistication and the modeling of the time-variation in the betas, they are all backward......-looking. This paper introduces a radically different approach to estimating market betas. Using the tools in Bakshi and Madan (2000) and Bakshi, Kapadia and Madan (2003) we employ the information embedded in the prices of individual stock options and index options to compute our forward-looking market beta...
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Lafeber, F. P.; Vander Kraan, P. M.; Huber-Bruning, O.; Vanden Berg, W. B.; Bijlsma, J. W.
1993-01-01
Osteoarthritis is a degenerative joint disease, characterized by the destruction of the articular cartilage. One of the first changes in the osteoarthritic articular cartilage is a reduction in proteoglycan content. In this study we demonstrate that transforming growth factor beta (TGF beta), a
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Mechanisms of pancreatic beta-cell growth and regeneration
DEFF Research Database (Denmark)
Nielsen, Jens Høiriis
1989-01-01
Information about the mechanism of beta-cell growth and regeneration may be obtained by studies of insulinoma cells. In the present study the growth and function of the rat insulinoma cell lines RINm5F and 5AH were evaluated by addition of serum, hormones, and growth factors. It was found...... of insulin mRNA content showed that the insulinoma cells only contained about 2% of that of normal rat beta-cells. These results are discussed in relation to the role of growth factors, oncogenes, and differentiation in the growth and regeneration of beta-cells....... that transferrin is the only obligatory factor whereas growth hormone, epidermal growth factor, fibroblast growth factor, and TRH had modulating effects. A heat-labile heparin binding serum factor which stimulated thymidine incorporation but not cell proliferation was demonstrated in human serum. Measurements...
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Beta decay of twelve light neutron-rich isotopes from 17C to 40S
International Nuclear Information System (INIS)
Dufour, J.P.; Del Moral, R.; Fleury, A.; Hubert, F.; Jean, D.; Pravikoff, M.S.; Geissel, H.; Schmidt, K.H.
1986-07-01
The results reported here have been obtained with an 40 Argon beam on a Be target. The separated nuclei were implanted in a catcher foil placed in between a thin scintillator detecting the betas and a high volume Ge detector; only gammas in coincidence with betas were recorded. Results for the gamma energies and the half-lives of the observed isotopes are given
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Energy Technology Data Exchange (ETDEWEB)
Moraes, Carolina Morales; Abrami, Priscila; Goncalves, Marcos Moises; Andreo Filho, Newton [Universidade de Sorocaba, SP (Brazil); Fernandes, Sergio Antonio; Paula, Eneida de [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Biologia. Dept. de Bioquimica; Fraceto, Leonardo Fernandes [UNESP, Sorocaba, SP (Brazil). Dept. de Engenharia Ambiental]. E-mail: leonardo@sorocaba.unesp.br
2007-07-15
S(-) Bupivacaine (S(-)BVC) and Lidocaine (LDC) are widely used local anesthetics (LA). Hydroxypropyl {beta}-cyclodextrin (HP-{beta}-CD) is used as a drug-carrier system. The aim of this work was to characterize inclusion complexes between LA and HP-{beta}-CD. The affinity constants determined at different pHs show favourable complexation. The release kinetics experiments showed that S(-)BVC and LDC changed the released profiles in the presence of HP-{beta}-CD. Nuclear magnetic resonance experiments gave information about the interaction between LA and the cyclodextrin cavity. This study focused on the physicochemical characterization of drug-delivery formulations that come out as potentially new therapeutic options for pain treatment. (author)
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Elumalai, Suma; Karunakaran, Udayakumar; Lee, In Kyu; Moon, Jun Sung; Won, Kyu Chang
2017-04-01
We recently reported that cluster determinant 36 (CD36), a fatty acid transporter, plays a pivotal role in glucotoxicity-induced β-cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression. Emerging evidence suggests that the small GTPase Rac1 is involved in the pathogenesis of beta cell dysfunction in type 2 diabetes (T2D). The primary objective of the current study was to determine the role of Rac1 in CD36 activation and its impact on β-cell dysfunction in diabetes mellitus. To address this question, we subjected INS-1 cells and human beta cells (1.1B4) to high glucose conditions (30mM) in the presence or absence of Rac1 inhibition either by NSC23766 (Rac1 GTPase inhibitor) or small interfering RNA. High glucose exposure in INS-1 and human beta cells (1.1b4) resulted in the activation of Rac1 and induced cell apoptosis. Rac1 activation mediates NADPH oxidase (NOX) activation leading to elevated ROS production in both cells. Activation of the Rac1-NOX complex by high glucose levels enhanced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. The inhibition of Rac1 by NSC23766 inhibited NADPH oxidase activity and ROS generation induced by high glucose concentrations in INS-1 & human 1.1b4 beta cells. Inhibition of Rac1-NOX complex activation by NSC23766 significantly reduced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. In addition, Rac1 inhibition by NSC23766 significantly reduced high glucose-induced mitochondrial dysfunction. Furthermore, NADPH oxidase inhibition by VAS2870 also attenuated high glucose-induced ROS generation and cell apoptosis. These results suggest that Rac1-NADPH oxidase dependent CD36 expression contributes to high glucose-induced beta cell dysfunction and cell death. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
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von Bueren, A O; Schlumpf, M; Lichtensteiger, W
2008-01-01
Delta(9)-tetrahydrocannabinol (THC) exerts palliative effects in cancer patients, but produces adverse effects on the endocrine and reproductive systems. Experimental evidence concerning such effects is controversial. Whether THC exhibits estrogenic or androgenic activity in vitro was investigated. Estrogenic effects of THC were analyzed in vitro by measuring the proliferation of estrogen-sensitive MCF7 cells. Androgenic activity was investigated by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1. In contrast to 17beta-estradiol, included as positive control with an EC50 value (concentration required for 50% of maximal 17beta-estradiol-induced proliferation) of 1.00 x 10(-12) M, THC failed to induce cell proliferation in the MCF7 cell line at concentrations between 10(-13) and 10(-4) M. THC inhibited 17beta-estradiol-induced proliferation in wild-type MCF7 and MCF7-AR1 cells, with an IC50 value of 2.6 x 10(-5) M and 9 x 10(-6) M, respectively. THC failed to act as an estrogen, but antagonized 17beta-estradiol-induced proliferation. This effect was independent of the AR expression level.
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Regand, Alejandra; Tosh, Susan M; Wolever, Thomas M S; Wood, Peter J
2009-10-14
To assess the effect of food processing on the capacity of oat beta-glucan to attenuate postprandial glycemia, isocaloric crisp bread, granola, porridge, and pasta containing 4 g of beta-glucan as well as control products with low beta-glucan content were prepared. The physicochemical properties (viscosity, peak molecular weight (M(p)), and concentration (C)) of beta-glucan in in-vitro-digestion extracts were evaluated, and fasting and postprandial blood glucose concentrations were measured in human subjects. Porridge and granola had the highest efficacy in attenuating the peak blood glucose response (PBGR) because of their high M(p) and viscosity. beta-Glucan depolymerization in bread and pasta reduced beta-glucan bioactivity. Pastas, known to have low glycemic responses, showed the lowest PBGR. The analyses of these products with previously reported data indicated that 73% of the bioactivity in reducing PBGR can be explained by M(p) x C. Characterizing the physicochemical properties of beta-glucan in bioactive foods aids functional food development.
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Directory of Open Access Journals (Sweden)
Andrea Díaz-Villaseñor
Full Text Available The incidence of type 2 diabetes mellitus (T2DM is increasing worldwide and diverse environmental and genetic risk factors are well recognized. Single nucleotide polymorphisms (SNPs in the calpain-10 gene (CAPN-10, which encodes a protein involved in the secretion and action of insulin, and chronic exposure to inorganic arsenic (iAs through drinking water have been independently associated with an increase in the risk for T2DM. In the present work we evaluated if CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin secretion (beta-cell function and insulin sensitivity were evaluated indirectly through validated indexes (HOMA2 in subjects with and without T2DM who have been exposed to a gradient of iAs in their drinking water in northern Mexico. The results were analyzed taking into account the presence of the risk factor SNPs SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell function and insulin sensitivity. An inverse association was found between beta-cell function and iAs exposure, the association being more pronounced in subjects with T2DM. Subjects without T2DM who were carriers of the at-risk genotype SNP-43 or -44, also had significantly lower beta-cell function. The association of SNP-43 with beta-cell function was dependent on iAs exposure, age, gender and BMI, whereas the association with SNP-44 was independent of all of these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in humans through the reduction of beta-cell function, with an enhanced effect seen in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 SNP-44 have also shown reduced beta-cell function.
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Yen, Ching-Yu; Chiu, Chien-Chih; Chang, Fang-Rong; Chen, Jeff Yi-Fu; Hwang, Chi-Ching; Hseu, You-Cheng; Yang, Hsin-Ling; Lee, Alan Yueh-Luen; Tsai, Ming-Tz; Guo, Zong-Lun; Cheng, Yu-Shan; Liu, Yin-Chang; Lan, Yu-Hsuan; Chang, Yu-Ching; Ko, Ying-Chin; Chang, Hsueh-Wei; Wu, Yang-Chang
2010-02-18
The crude extract of the fruit bearing plant, Physalis peruviana (golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown. Herein, we isolated the main pure compound, 4beta-Hydroxywithanolide (4betaHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug. It was shown that DNA damage was significantly induced by 1, 5, and 10 microg/mL 4betaHWE for 2 h in a dose-dependent manner (p < 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4betaHWE in both dose- and time-dependent manners (p < 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC50) of 4betaHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 microg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4betaHWE produced cell cycle perturbation in the form of sub-G1 accumulation and slight arrest at the G2/M phase with 1 microg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 microg/mL for 24 h. In this study, we demonstrated that golden berry-derived 4betaHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.
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Czech Academy of Sciences Publication Activity Database
Šmahel, M.; Poláková, I.; Pokorná, D.; Ludvíková, V.; Dušková, M.; Vlasák, Josef
2008-01-01
Roč. 16, - (2008), S60 ISSN 0022-1732. [HPV in Human Pathology :International Conference. 01.05.2008-03.05.2008, Prague] R&D Projects: GA ČR GA521/05/2092; GA MZd NR9246 Institutional research plan: CEZ:AV0Z50510513 Keywords : oncology * beta-glucuronidase * T cell Subject RIV: FD - Oncology ; Hematology
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Enantioselective synthesis of alpha,beta-disubstituted-beta-amino acids.
Sibi, Mukund P; Prabagaran, Narayanasamy; Ghorpade, Sandeep G; Jasperse, Craig P
2003-10-01
Highly diastereoselective and enantioselective addition of N-benzylhydroxylamine to imides 17 and 20-30 produces alpha,beta-trans-disubstituted N-benzylisoxazolidinones 19 and 31-41. These reactions proceed in 60-96% ee with 93-99% de's using 5 mol % of Mg(NTf2)2 and ligand 18. The product isoxazolidinones can be hydrogenolyzed directly to provide alpha,beta-disubstituted-beta-amino acids.
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Role for transforming growth factor-beta1 in alport renal disease progression.
Sayers, R; Kalluri, R; Rodgers, K D; Shield, C F; Meehan, D T; Cosgrove, D
1999-11-01
Alport syndrome results from mutations in either the alpha3(IV), alpha4(IV), or alpha5(IV) collagen genes. The disease is characterized by a progressive glomerulonephritis usually associated with a high-frequency sensorineural hearing loss. A mouse model for an autosomal form of Alport syndrome [collagen alpha3(IV) knockout] was produced and characterized. In this study, the model was exploited to demonstrate a potential role for transforming growth factor-beta1 (TGF-beta1) in Alport renal disease pathogenesis. Kidneys from normal and Alport mice, taken at different stages during the course of renal disease progression, were analyzed by Northern blot, in situ hybridization, and immunohistology for expression of TGF-beta1 and components of the extracellular matrix. Normal and Alport human kidney was examined for TGF-beta1 expression using RNase protection. The mRNAs encoding TGF-beta1 (in both mouse and human), entactin, fibronectin, and the collagen alpha1(IV) and alpha2(IV) chains were significantly induced in total kidney as a function of Alport renal disease progression. The induction of these specific mRNAs was observed in the glomerular podocytes of animals with advanced disease. Type IV collagen, laminin-1, and fibronectin were markedly elevated in the tubulointerstitium at 10 weeks, but not at 6 weeks, suggesting that elevated expression of specific mRNAs on Northern blots reflects events associated with tubulointerstitial fibrosis. The concomitant accumulation of mRNAs encoding TGF-beta1 and extracellular matrix components in the podocytes of diseased kidneys may reflect key events in Alport renal disease progression. These data suggest a role for TGF-beta1 in both glomerular and tubulointerstitial damage associated with Alport syndrome.
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Demonstration of synthesis of beta-trace protein in different tissues of squirrel monkey
Energy Technology Data Exchange (ETDEWEB)
Olsson, J E; Sandberg, M [Department of Neurology, University Hospital, S-221 85 Lund, Sweden
1975-01-01
The sites of synthesis of the low molwculat weight beta-trace protein, present in a seven times higher concentration in normal human CSF than in normal human serum, have been studied by means of a radioactive immunoprecipitation method. Adult squirrel monkey tissue were cultured in Eagle's minium essential medium in the presence of /sup 14/C-labelled valine, threonine and leucine for 24 hours. Synthesis could be demonstrated in cultures of white CNS matter, whereas cultures of grey CNS matter, peripheral nerve, skeletal muscle, kidney and ovary did not show any signs of synthesis. Some cultures of spinal cord, basal ganglia, genital organs except ovary, and liver showed a probable synthesis of beta-trace protein. By means of autoradiography, the synthesis of beta-trace protein in white CNS matter could be confirmed.
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Demonstration of synthesis of beta-trace protein in different tissues of squirrel monkey
International Nuclear Information System (INIS)
Olsson, J.-E.; Sandberg, M.
1975-01-01
The sites of synthesis of the low molwculat weight beta-trace protein, present in a seven times higher concentration in normal human CSF than in normal human serum, have been studied by means of a radioactive immunoprecipitation method. Adult squirrel monkey tissue were cultured in Eagle's minium essential medium in the presence of 14 C-labelled valine, threonine and leucine for 24 hours. Synthesis could be demonstrated in cultures of white CNS matter, whereas cultures of grey CNS matter, peripheral nerve, skeletal muscle, kidney and ovary did not show any signs of synthesis. Some cultures of spinal cord, basal ganglia, genital organs except ovary, and liver showed a probable synthesis of beta-trace protein. By means of autoradiography, the synthesis of beta-trace protein in white CNS matter could be confirmed. (author)
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Energy Technology Data Exchange (ETDEWEB)
Garzon, J.; Sanchez-Blazquez, P. (Cajal Institute, Madrid (Spain))
1991-01-01
{sup {alpha}}N-acetyl human {beta}-endorphin(1-31) injected icv to mice antagonized the analgesic activity of {beta}-endorphin-(1-31) and morphine whereas the analgesia evoked by DADLE and DAGO was enhanced by this treatment. The modulatory activity of {sup {alpha}}N-acetyl {beta}-endorphin-(1-31) was exhibited at remarkable low doses (fmols) reaching a maximum that persisted even though the dose was increased 100,000 times. The regulatory effect of a single dose of the acetylated neuropeptide lasted for 24h. The activity of {sup {alpha}}N-acetyl human {beta}-endorphin(1-31) was partially retained by the shorter peptide {sup {alpha}}N-acetyl human {beta}-endorphin-(1-27) and to a lesser extent by {beta}-endorphin-(1-27), {beta}-endorphin-(1-31) lacked this regulatory activity on opioid analgesia. Acetylated {beta}-endorphin-(1-31) displayed a biphasic curve when competing with 5 pM ({sup 125}I)-Tyr{sup 27} human {beta}-endorphin-(1-31) specific binding, the first step was abolished with an apparent IC{sub 50} of 0.35 nM, and the rest with an IC{sub 50} of 200 nM. It is suggested that {sup {alpha}}N-acetyl {beta}-endorphin-(1-31) changed the efficiency of the opioid analgesics by acting upon a specific substrate that is functionally coupled to the opioid receptor, presumably the guanine nucleotide binding regulatory proteins G{sub i}/G{sub 0}.
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Nuclear topography of beta-like globin gene cluster in IL-3-stimulated human leukemic K-562 cells
Czech Academy of Sciences Publication Activity Database
Galiová-Šustáčková, Gabriela; Bártová, Eva; Kozubek, Stanislav
2004-01-01
Roč. 33, č. 1 (2004), s. 4-14 ISSN 1079-9796 R&D Projects: GA ČR GA301/01/0186; GA AV ČR KSK5052113; GA AV ČR IAA5004306; GA ČR GA202/04/0907; GA MŠk ME 565 Institutional research plan: CEZ:AV0Z5004920 Keywords : beta-like globin gene cluster * K-562 cells * nuclear topography Subject RIV: BO - Biophysics Impact factor: 2.549, year: 2004
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Palozza, Paola; Bellovino, Diana; Simone, Rossella; Boninsegna, Alma; Cellini, Francesco; Monastra, Giovanni; Gaetani, Sancia
2009-07-01
Lycopene beta-cyclase (tlcy-b) tomatoes, obtained by modulating carotenogenesis via genetic engineering, contain a large amount of beta-carotene, as clearly visible by their intense orange colour. In the present study we have subjected tlcy-b tomatoes to an in vitro simulated digestion and analysed the effects of digestate on cell proliferation. To this aim we used HT-29 human colon adenocarcinoma cells, grown in monolayers, as a model. Digested tomatoes were diluted (20 ml, 50 ml and 100 ml/l) in culture medium and added to the cells for different incubation times (24 h, 48 h and 72 h). Inhibition of cell growth by tomato digestate was dose-dependent and resulted from an arrest of cell cycle progression at the G0/G1 and G2/M phase and by apoptosis induction. A down-regulation of cyclin D1, Bcl-2 and Bcl-xl expression was observed. We also found that heat treatment of samples before digestion enhanced beta-carotene release and therefore cell growth inhibition. To induce with purified beta-carotene solubilised in tetrahydrofuran the same cell growth inhibition obtained with the tomato digestate, a higher amount of the carotenoid was necessary, suggesting that beta-carotene micellarised during digestion is utilised more efficiently by the cells, but also that other tomato molecules, reasonably made available during digestion, may be present and cooperate with beta-carotene in promoting cell growth arrest.
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Bace1 activity impairs neuronal glucose metabolism: rescue by beta-hydroxybutyrate and lipoic acid
Directory of Open Access Journals (Sweden)
John A Findlay
2015-10-01
Full Text Available Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer’s disease (AD pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP cleaving enzyme 1 (BACE1, responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.
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21 CFR 522.84 - Beta-aminopropionitrile fumarate.
2010-04-01
... use in breeding animals since the effects on fertility, pregnancy, or fetal health have not been... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Beta-aminopropionitrile fumarate. 522.84 Section 522.84 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...
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Law, Marilyn P; Wagner, Stefan; Kopka, Klaus; Renner, Christiane; Pike, Victor W; Schober, Otmar; Schäfers, Michael
2010-05-01
Radioligand binding studies indicate a down-regulation of myocardial beta(1)-adrenoceptors (beta(1)-AR) in cardiac disease which may or may not be associated with a decrease in beta(2)-ARs. We have chosen ICI 89,406, a beta(1)-selective AR antagonist, as the lead structure to develop new beta(1)-AR radioligands for PET and have synthesised a fluoro-ethoxy derivative (F-ICI). (S)-N-[2-[3-(2-Cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]-N'-[4-(2-[(18)F]fluoro-ethoxy)-phenyl]-urea ((S)-[(18)F]F-ICI) was synthesised. Myocardial uptake of radioactivity after intravenous injection of (S)-[(18)F]F-ICI into adult CD(1) mice or Wistar rats was assessed with positron emission tomography (PET) and postmortem dissection. Metabolism was assessed by high-performance liquid chromatography analysis of plasma and urine. The heart was visualised with PET after injection of (S)-[(18)F]F-ICI but neither unlabelled F-ICI nor propranolol (non-selective beta-AR antagonist) injected 15 min after (S)-[(18)F]F-ICI affected myocardial radioactivity. Ex vivo dissection demonstrated that predosing with propranolol or CGP 20712 (beta(1)-selective AR-antagonist) did not affect myocardial radioactivity. Radiometabolites rapidly appeared in plasma and both (S)-[(18)F]F-ICI and radiometabolites accumulated in urine. Myocardial uptake of (S)-[(18)F]F-ICI after intravenous injection was mainly at sites unrelated to beta(1)-ARs. (S)-[(18)F]F-ICI is not a suitable beta(1)-selective-AR radioligand for PET. (c) 2010 Elsevier Inc. All rights reserved.
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The T-cell receptor beta chain CDR3 region of BV8S1/BJ1S5 transcripts in type 1 diabetes.
Naserke, H E; Durinovic-Bellò, I; Seidel, D; Ziegler, A G
1996-01-01
We recently described the T-cell receptor (TCR) beta chain CDR3 motif S-SDRLG-NQPQH (BV8S1-BJ1S5) in an islet-specific T-cell clone (K2.12) from a type 1 diabetic patient (AS). A similar motif (RLGNQ) was also reported in a T-cell clone of non-obese diabetic (NOD) mice by others. In order to determine the frequency of our motif in selected and unselected T-cell populations, we cloned and sequenced the CDR3 region of BV8S1-BJ1S5 transcripts. These transcripts were derived from unstimulated peripheral blood T lymphocytes from two type 1 diabetic patients (AS and FS) and their non-diabetic sibling (WS), as well as from an islet-specific T-cell line of one of the patients. In addition, we compared the structure and composition of the CDR3 region in BV8S1-BJ1S5 transcripts from peripheral blood T cells between the patients and their non-diabetic sibling (>50 sequences each). We found that 30% of the islet-specific T-cell line cDNA clones expressed the entire sequence-motif, whereas it was absent in the clones of unstimulated peripheral blood T cells from both patients and their non-diabetic sibling. The average length of the CDR3 region was shorter in the patients (mean AS 9.9, FS 9.9, versus WS 10.7, p = 0.0037) and the number of inserted nucleotides in N nucleotide addition at the DJ-junction lower (mean AS 3.5, FS 3. 2, versus WS 5.2, P = diabetic sibling. Moreover, the pattern of amino acid usage in the CDR3 region was dissimilar at positions 5 and 6, where polar amino acids predominated in both diabetic siblings. In contrast, basic amino acids are preferentially used at position 5 in the clones of the non-diabetic sibling. These data provide information on the general structure of the TCR(BV8S1-BJ1S5) CDR3 region in type 1 diabetes and may indicate differences in the amino and nucleic acid composition of the TCR beta chain CDR3 region between two type 1 diabetic patients and their non-diabetic sibling.
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Walla, P J; Linden, Patricia A; Ohta, Kaoru
2002-01-01
The excited-state dynamics of the carotenoids (Car) in light- harvesting complex II (LHC II) of Chlamydomonas reinhardtii were studied by transient absorption measurements. The decay of the Car S //1 population ranges from similar to 200 fs to over 7 ps, depending on the excitation and detection wavelengths. In contrast, a 200 fs Car S//1 yields Chlorophyll (Chl) energy transfer component was the dominant time constant for our earlier two-photon fluorescence up- conversion measurements (Walla, P.J. ; et al. J. Phys. Chem. B 2000, 104, 4799-4806). We also present the two-photon excitation (TPE) spectra of lutein and beta-carotene in solution and compare them with the TPE spectrum of LHC II. The TPE-spectrum of LHC II has an onset much further to the blue and a width that is narrower than expected from comparison to the S//1 fluorescence of lutein and beta-carotene in solution. Different environments may affect the shape of the S//1 spectrum significantly. To explain the blue shift of the TPE spectrum and the d...
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BetaTPred: prediction of beta-TURNS in a protein using statistical algorithms.
Kaur, Harpreet; Raghava, G P S
2002-03-01
beta-turns play an important role from a structural and functional point of view. beta-turns are the most common type of non-repetitive structures in proteins and comprise on average, 25% of the residues. In the past numerous methods have been developed to predict beta-turns in a protein. Most of these prediction methods are based on statistical approaches. In order to utilize the full potential of these methods, there is a need to develop a web server. This paper describes a web server called BetaTPred, developed for predicting beta-TURNS in a protein from its amino acid sequence. BetaTPred allows the user to predict turns in a protein using existing statistical algorithms. It also allows to predict different types of beta-TURNS e.g. type I, I', II, II', VI, VIII and non-specific. This server assists the users in predicting the consensus beta-TURNS in a protein. The server is accessible from http://imtech.res.in/raghava/betatpred/
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Refining Our Understanding of Beta through Quantile Regressions
Directory of Open Access Journals (Sweden)
Allen B. Atkins
2014-05-01
Full Text Available The Capital Asset Pricing Model (CAPM has been a key theory in financial economics since the 1960s. One of its main contributions is to attempt to identify how the risk of a particular stock is related to the risk of the overall stock market using the risk measure Beta. If the relationship between an individual stock’s returns and the returns of the market exhibit heteroskedasticity, then the estimates of Beta for different quantiles of the relationship can be quite different. The behavioral ideas first proposed by Kahneman and Tversky (1979, which they called prospect theory, postulate that: (i people exhibit “loss-aversion” in a gain frame; and (ii people exhibit “risk-seeking” in a loss frame. If this is true, people could prefer lower Beta stocks after they have experienced a gain and higher Beta stocks after they have experienced a loss. Stocks that exhibit converging heteroskedasticity (22.2% of our sample should be preferred by investors, and stocks that exhibit diverging heteroskedasticity (12.6% of our sample should not be preferred. Investors may be able to benefit by choosing portfolios that are more closely aligned with their preferences.
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Directory of Open Access Journals (Sweden)
Coralie Di Scala
2016-03-01
Full Text Available The data here consists of calcium imaging of human neuroblastoma SH-SY5Y cells treated with the calcium-sensitive dye Fluo-4AM and then incubated with nanomolar concentrations of either human or rat Alzheimer’s β-amyloid peptide Aβ1-42. These data are both of a qualitative (fluorescence micrographs and semi-quantitative nature (estimation of intracellular calcium concentrations of cells probed by Aβ1-42 peptides vs. control untreated cells. Since rat Aβ1-42 differs from its human counterpart at only three amino acid positions, this comparative study is a good assessment of the specificity of the amyloid pore forming assay. The interpretation of this dataset is presented in the accompanying study “Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides” [1].
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DEFF Research Database (Denmark)
Bollerslev, Tim; Li, Sophia Zhengzi; Todorov, Viktor
-section. An investment strategy that goes long stocks with high jump betas and short stocks with low jump betas produces significant average excess returns. These higher risk premiums for the discontinuous and overnight market betas remain significant after controlling for a long list of other firm characteristics......Motivated by the implications from a stylized equilibrium pricing framework, we investigate empirically how individual equity prices respond to continuous, or \\smooth," and jumpy, or \\rough," market price moves, and how these different market price risks, or betas, are priced in the cross......-section of expected returns. Based on a novel highfrequency dataset of almost one-thousand individual stocks over two decades, we find that the two rough betas associated with intraday discontinuous and overnight returns entail significant risk premiums, while the intraday continuous beta is not priced in the cross...
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Oxidative stress and the amyloid beta peptide in Alzheimerâs disease
Directory of Open Access Journals (Sweden)
C. Cheignon
2018-04-01
Full Text Available Oxidative stress is known to play an important role in the pathogenesis of a number of diseases. In particular, it is linked to the etiology of Alzheimerâs disease (AD, an age-related neurodegenerative disease and the most common cause of dementia in the elderly. Histopathological hallmarks of AD are intracellular neurofibrillary tangles and extracellular formation of senile plaques composed of the amyloid-beta peptide (Aβ in aggregated form along with metal-ions such as copper, iron or zinc. Redox active metal ions, as for example copper, can catalyze the production of Reactive Oxygen Species (ROS when bound to the amyloid-β (Aβ. The ROS thus produced, in particular the hydroxyl radical which is the most reactive one, may contribute to oxidative damage on both the Aβ peptide itself and on surrounding molecule (proteins, lipids, â¦. This review highlights the existing link between oxidative stress and AD, and the consequences towards the Aβ peptide and surrounding molecules in terms of oxidative damage. In addition, the implication of metal ions in AD, their interaction with the Aβ peptide and redox properties leading to ROS production are discussed, along with both in vitro and in vivo oxidation of the Aβ peptide, at the molecular level. Keywords: Oxidative stress, Amyloid beta peptide, Metal-ions, Reactive oxygen species, Oxidative damages
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Energy Technology Data Exchange (ETDEWEB)
Tang, T; Zhang, G; PY Lau, Carol; Zheng, L Z; Xie, X H; Wang, X L; Patrick, Y; Qin, L; Kumta, Shekhar M [Department of Orthopaedics and Traumatology, Chinese University of Hong Kong (Hong Kong); Wang, X H; He, K, E-mail: kumta@cuhk.edu.hk [Department of Mechanical Engineering, Institute of Bio-manufacturing Engineering, Tsinghua University, Beijing (China)
2011-02-15
Water-soluble phosphorylated chitosan (P-chitosan) and disodium (1 {yields} 4)-2-deoxy-2-sulfoamino-{beta}-D-glucopyranuronan (S-chitosan) are two chemically modified chitosans. In this study, we found that P-chitosan significantly promotes cell proliferation of both human primary osteoblasts (OBs) and the OB like stromal cell component of the giant cell tumor of bone (GCTB) cells at the concentration from 125 to 1000 {mu}g ml{sup -1} at all time points of 1, 3, 5 and 7 days after treatment. Further investigation of the osteogenic effect of the P-chitosan suggested that it regulates the levels of osteoclastogenic factors, receptor activator of nuclear factor kappa B ligand and osteoprotegerin expression. An interesting finding is that S-chitosan at lower concentration (100 {mu}g ml{sup -1}) stimulates cell proliferation while a higher dose (1000 {mu}g ml{sup -1}) of S-chitosan inhibits it. The inhibitory effect of S-chitosan on human primary GCT stromal cells was greater than that of OBs (p < 0.05). Taken together, our findings elucidated the osteogenic effect of P-chitosan and the varying effects of S-chitosan on the proliferation of human primary OBs and GCT stromal cells and provided us the rationale for the construction of novel bone repair biomaterials with the dual properties of bone induction and bone tumor inhibition.
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New Insights in the Amyloid-Beta Interaction with Mitochondria
Directory of Open Access Journals (Sweden)
Carlos Spuch
2012-01-01
Full Text Available Biochemical and morphological alterations of mitochondria may play an important role in the pathogenesis of Alzheimer’s disease (AD. Particularly, mitochondrial dysfunction is a hallmark of amyloid-beta-induced neuronal toxicity in Alzheimer’s disease. The recent emphasis on the intracellular biology of amyloid-beta and its precursor protein (APP has led researchers to consider the possibility that mitochondria-associated and mitochondrial amyloid-beta may directly cause neurotoxicity. Both proteins are known to localize to mitochondrial membranes, block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins, disrupt the electron transport chain, increase reactive oxygen species production, cause mitochondrial damage, and prevent neurons from functioning normally. In this paper, we will outline current knowledge of the intracellular localization of amyloid-beta. Moreover, we summarize evidence from AD postmortem brain as well as animal AD models showing that amyloid-beta triggers mitochondrial dysfunction through a number of pathways such as impairment of oxidative phosphorylation, elevation of reactive oxygen species production, alteration of mitochondrial dynamics, and interaction with mitochondrial proteins. Thus, this paper supports the Alzheimer cascade mitochondrial hypothesis such as the most important early events in this disease, and probably one of the future strategies on the therapy of this neurodegenerative disease.
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Metabolism of dehydroepiandrosterone sulfate and estrone-sulfate by human platelets.
Garrido, A; Munoz, Y; Sierralta, W; Valladares, L
2012-01-01
The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [(3)H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [(3)H]-DHEAS to [(3)H]-androstenedione, [(3)H]-testosterone, [(3)H]-estrone and [(3)H]-17beta-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E(1)S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [(3)H]-estrone to [(3)H]-17beta-estradiol. This is the first demonstration that human platelets are able to import DHEAS and E(1)S using the OATP family and to convert DHEAS to active DHEA, and to transform E(1)S to 17beta-estradiol.
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Energy Technology Data Exchange (ETDEWEB)
Riche, R. [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires
1965-09-01
The kinetic and perturbation equations are derived from the time-dependent transport equation. Kinetic equations depend only on the ratios a = {rho}-bar/{beta}-bar and b = {beta}-bar/{lambda}, which are definite, while the reactivity {rho}-bar, the delayed neutron fraction ({beta}-bar and the generation time {lambda} are expressed in terms of an arbitrary function I. The 'static' definitions of these parameters, which reduce kinetic problems to a set of purely term dependent equations, introduce the effective fraction {beta}-bar. One way of determining experimentally the ratio b is presented; it consists in analysing the power transient after a rapid variation of the reactivity, caused by the implosion of an empty glass-bull. A simple interpretation is proposed. The apparatus can be transformed easily into a reactimeter. The value of the effective delayed neutron fraction {beta}-bar has been determined by averaging the reactivity effects of a copper sheet through out the reactor core. Experimental results: b = {beta}-bar/{lambda} = 129 s{sup -1} and {beta}-bar 795.10{sup -5}, have been determined on a light-water moderated, enriched-uranium fuelled reactor. The calculated values of the effectiveness of delayed neutrons {gamma} {beta}-bar/{beta} 1.23 and the generation time {lambda} 59.10{sup -6}s agrees fairly well with the experimental results. (author) [French] Les equations de la cinetique et de la perturbation sont deduites de la theorie du transport, par l'intermediaire de la 'notion' d'importance des neutrons. La cinetique ne depend que des rapports a = {rho}-bar/{beta}-bar et b = {beta}-bar/{lambda}, qui sont parfaitement definis; par contre, la reactivite {rho}-bar, la proportion de neutrons retardes {beta}-bar et le temps de generation des neutrons prompts {lambda} s'expriment a l'aide d'une meme fonction arbitraire I. Les definitions 'statiques' de ces parametres, qui permettent de rendre compte de la
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Minocycline does not affect amyloid beta phagocytosis by human microglial cells
Familian, Atoosa; Eikelenboom, Piet; Veerhuis, Robert
2007-01-01
Activated microglia accumulate in amyloid beta (Abeta) plaques containing amyloid associated factors SAP and C1q in Alzheimer's disease (AD) brain. Microglia are involved in AD pathogenesis by promoting Abeta plaque formation and production of pro-inflammatory cytokines. On the other hand,
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ADAM12 and alpha9beta1 integrin are instrumental in human myogenic cell differentiation
DEFF Research Database (Denmark)
Lafuste, Peggy; Sonnet, Corinne; Chazaud, Bénédicte
2005-01-01
of alpha9 parallels that of ADAM12 and culminates at time of fusion. alpha9 and ADAM12 coimmunoprecipitate and participate to mpc adhesion. Inhibition of ADAM12/alpha9beta1 integrin interplay, by either ADAM12 antisense oligonucleotides or blocking antibody to alpha9beta1, inhibited overall mpc fusion...
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Amour, Julien; Loyer, Xavier; Michelet, Pierre; Birenbaum, Aurélie; Riou, Bruno; Heymes, Christophe
2008-10-01
In diabetic cardiomyopathy, diastolic dysfunction results in part from sarcoplasmic reticulum abnormalities affecting both phospholamban and sarcoplasmic reticulum Ca2+ uptake (SERCA2a). Consequently, the positive lusitropic effect of beta-adrenoceptors stimulation could be altered, and beta3-adrenoceptor over-expression may play a role, as previously demonstrated with an altered positive inotropic effect. In this study, we tested the hypothesis that the beta-adrenergic positive lusitropic effect is altered in diabetic cardiomyopathy, and that beta3-adrenoceptor over-expression is involved. beta-adrenergic responses were investigated in vivo (dobutamine-echocardiography) and in vitro (papillary muscle preparation) in healthy and diabetic rats killed 4 (4W) and 12 (12W) wk after IV streptozotocin injection. The effect of beta3-adrenoceptor pathway inhibition by S-cyanopindolol (selective beta3-adrenoceptor antagonist) or by NG-nitro-L-arginine-methyl-ester (nonselective nitric oxide synthase inhibitor) on the lusitropic response to isoproterenol (nonselective beta-adrenoceptors agonist) was studied in vitro. Western blots were performed to quantify the protein expressions of beta1- and beta3-adrenoceptors, phospholamban, and SERCA2a. Data are presented as mean percentages of baseline+/-sd. Despite the increased phospholamban/SERCA2a protein ratio and documented diastolic dysfunction, the positive lusitropic effect of beta-adrenoceptors stimulation was preserved in vivo (dobutamine) and in vitro (isoproterenol) in 4W and 12W diabetic, compared with healthy, rats. The beta3-adrenoceptor was up-regulated whereas beta1-adrenoceptor was down-regulated in 4W and 12W diabetic, compared with healthy, rats. Nevertheless, S-cyanopindolol or NG-nitro-L-arginine-methyl-ester had no lusitropic effect. The positive lusitropic effect of beta-adrenoceptor stimulation was preserved in diabetic cardiomyopathy. beta3-adrenoceptor over-expression does not seem to affect this process.
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Directory of Open Access Journals (Sweden)
Ivan L. Angulo
2009-01-01
Full Text Available A hemoglobina C (Hb C é originária do oeste da África e é detectada por migração lenta na eletroforese alcalina em acetato de celulose. Consiste na mutação do gene da globina beta no códon 6 (GAG-AAG, resultando na substituição do sexto aminoácido da cadeia beta da hemoglobina humana, o ácido glutâmico, pelo aminoácido lisina. A cromatografia de alto desempenho (HPLC separa completamente as frações C e A2, permitindo caracterizar a presença da interação com talassemia beta. Esta entidade (Hb CC, em homozigoze é considerada benigna em relação à doença falciforme, já que a falcização não faz parte de sua fisiopatologia. A raridade do diagnóstico C homozigoto e C talassemia beta nos pacientes portadores de hemoglobinopatias nos alertou para a necessidade de se conhecer melhor e estudar aspectos clínicos e hematológicos dos casos dessa mutação em homozigose e na interação com a talassemia beta no ambulatório de anemias do Centro Regional de Hematologia e Hemoterapia de Ribeirão Preto, SP, Brasil.Hemoglobin C (Hb C originated in the west of Africa and is detected by alkaline electrophoresis by slow migration in cellulose acetate. It consists of a mutation of the beta globin gene in codon 6 (GAG-AAG, resulting in a substitution of glutamic acid, the sixth amino acid of the beta string of the human hemoglobin, for lysine. High performance chromatography (HPLC separates the C and A2 fractions completely, allowing the characterization of the presence of interactions with thalassemia beta. This entity (Hb CC is considered benign in respect to sickle cell disease, as sickle cells are not part of its physiopathology. The rarity of the diagnosis of homozygous C and beta thalassemia in patients with hemoglobinopathies showed the necessity of studying clinical and hematologic aspects of the cases of this mutation in homozygosis carriers and the interaction with beta thalassemia in the anemias clinic of the Regional Blood
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Chemical rescue of cleft palate and midline defects in conditional GSK-3beta mice.
Liu, Karen J; Arron, Joseph R; Stankunas, Kryn; Crabtree, Gerald R; Longaker, Michael T
2007-03-01
Glycogen synthase kinase-3beta (GSK-3beta) has integral roles in a variety of biological processes, including development, diabetes, and the progression of Alzheimer's disease. As such, a thorough understanding of GSK-3beta function will have a broad impact on human biology and therapeutics. Because GSK-3beta interacts with many different pathways, its specific developmental roles remain unclear. We have discovered a genetic requirement for GSK-3beta in midline development. Homozygous null mice display cleft palate, incomplete fusion of the ribs at the midline and bifid sternum as well as delayed sternal ossification. Using a chemically regulated allele of GSK-3beta (ref. 6), we have defined requirements for GSK-3beta activity during discrete temporal windows in palatogenesis and skeletogenesis. The rapamycin-dependent allele of GSK-3beta produces GSK-3beta fused to a tag, FRB* (FKBP/rapamycin binding), resulting in a rapidly destabilized chimaeric protein. In the absence of drug, GSK-3beta(FRB)*(/FRB)* mutants appear phenotypically identical to GSK-3beta-/- mutants. In the presence of drug, GSK-3betaFRB* is rapidly stabilized, restoring protein levels and activity. Using this system, mutant phenotypes were rescued by restoring endogenous GSK-3beta activity during two distinct periods in gestation. This technology provides a powerful tool for defining windows of protein function during development.
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On Fuzzy {beta}-I-open sets and Fuzzy {beta}-I-continuous functions
Energy Technology Data Exchange (ETDEWEB)
Keskin, Aynur [Department of Mathematics, Faculty of Science and Arts, Selcuk University, Campus, 42075 Konya (Turkey)], E-mail: akeskin@selcuk.edu.tr
2009-11-15
In this paper, first of all we obtain some properties and characterizations of fuzzy {beta}-I-open sets. After that, we also define the notion of {beta}-I-closed sets and obtain some properties. Lastly, we introduce the notions of fuzzy {beta}-I-continuity with the help of fuzzy {beta}-I-open sets to obtain decomposition of fuzzy continuity.
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Beta blockers and their combinations in the management of ...
African Journals Online (AJOL)
Review Article: Beta blockers and their combinations in the management of hypertension. 409. Vol 54 No 5. S Afr Fam Pract 2012. Introduction. Beta blockers have been prescribed for the treatment of primary hypertension for a very long time. Currently, it is doubtful whether this is still a good idea. In fact, many are of the ...
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Beta-decay studies at the N=28 shell closure
Czech Academy of Sciences Publication Activity Database
Grévy, S.; Mrázek, Jaromír; Angelique, J. C.; Baumann, P.; Borcea, C.; Buta, A.; Canchel, G.; Cargord, W.; Courtin, S.; Daugas, J. M.; de Oliveira Santos, F.; Dlouhý, Zdeněk; Knipper, A.; Kratz, K. L.; Lecouey, J. L.; Lecolley, F. R.; Lehrsenneau, G.; Lewitowicz, M.; Lienard, E.; Lukianov, S.; Marechal, F.; Miehe, C.; Negoita, F.; Orr, NA.; Pantelica, D.; Penionzhkevich, Y. E.; Peter, J.; Pfeiffer, B.; Pietri, S.; Poirier, E.; Sorlin, O.; Stanoiu, M.; Stodel, C.; Timis, C.
2003-01-01
Roč. 722, - (2003), s. 424C-428C ISSN 0375-9474 R&D Projects: GA AV ČR IAA1048605; GA AV ČR KSK1048102 Institutional research plan: CEZ:AV0Z1048901 Keywords : beta-decay spectroscopy * beta half-lives Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 1.761, year: 2003
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Sibi; Liu
2000-10-19
Chiral Lewis acid catalyzed N-benzylhydroxylamine addition to pyrrolidinone-derived enoates afforded beta-aryl-beta-amino acid derivatives in high enantiomeric purity with moderate to very good chemical efficiency.
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Proteomic profiling of bone marrow mesenchymal stem cells upon TGF-beta stimulation
Energy Technology Data Exchange (ETDEWEB)
Wang, Daojing; Park, Jennifer S.; Chu, Julia S.F.; Ari, Krakowski; Luo, Kunxin; Chen, David J.; Li, Song
2004-08-08
Bone marrow mesenchymal stem cells (MSCs) can differentiate into different types of cells, and have tremendous potential for cell therapy and tissue engineering. Transforming growth factor {beta}1 (TGF-{beta}) plays an important role in cell differentiation and vascular remodeling. We showed that TGF-{beta} induced cell morphology change and an increase in actin fibers in MSCs. To determine the global effects of TGF-{beta} on MSCs, we employed a proteomic strategy to analyze the effect of TGF-{beta} on the human MSC proteome. By using two-dimensional gel electrophoresis and electrospray ionization coupled to Quadrupole/time-of-flight tandem mass spectrometers, we have generated a proteome reference map of MSCs, and identified {approx}30 proteins with an increase or decrease in expression or phosphorylation in response to TGF-{beta}. The proteins regulated by TGF-{beta} included cytoskeletal proteins, matrix synthesis proteins, membrane proteins, metabolic enzymes, etc. TGF-{beta} increased the expression of smooth muscle (SM) {alpha}-actin and decreased the expression of gelsolin. Over-expression of gelsolin inhibited TGF-{beta}-induced assembly of SM {alpha}-actin; on the other hand, knocking down gelsolin expression enhanced the assembly of {alpha}-actin and actin filaments without significantly affecting {alpha}-actin expression. These results suggest that TGF-{beta} coordinates the increase of {alpha}-actin and the decrease of gelsolin to promote MSC differentiation. This study demonstrates that proteomic tools are valuable in studying stem cell differentiation and elucidating the underlying molecular mechanisms.
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Boltz, Kathryn W; Frasch, Wayne D
2006-09-19
F(1)-ATPase mutations in Escherichia coli that changed the strength of hydrogen bonds between the alpha and beta subunits in a location that links the catalytic site to the interface between the beta catch loop and the gamma subunit were examined. Loss of the ability to form the hydrogen bonds involving alphaS337, betaD301, and alphaD335 lowered the k(cat) of ATPase and decreased its susceptibility to Mg(2+)-ADP-AlF(n) inhibition, while mutations that maintain or strengthen these bonds increased the susceptibility to Mg(2+)-ADP-AlF(n) inhibition and lowered the k(cat) of ATPase. These data suggest that hydrogen bonds connecting alphaS337 to betaD301 and betaR323 and connecting alphaD335 to alphaS337 are important to transition state stabilization and catalytic function that may result from the proper alignment of catalytic site residues betaR182 and alphaR376 through the VISIT sequence (alpha344-348). Mutations betaD301E, betaR323K, and alphaR282Q changed the rate-limiting step of the reaction as determined by an isokinetic plot. Hydrophobic mutations of betaR323 decreased the susceptibility to Mg(2+)-ADP-AlF(n)() inhibition and lowered the number of interactions required in the rate-limiting step yet did not affect the k(cat) of ATPase, suggesting that betaR323 is important to transition state formation. The decreased rate of ATP synthase-dependent growth and decreased level of lactate-dependent quenching observed with alphaD335, betaD301, and alphaE283 mutations suggest that these residues may be important to the formation of an alternative set of hydrogen bonds at the interface of the alpha and beta subunits that permits the release of intersubunit bonds upon the binding of ATP, allowing gamma rotation in the escapement mechanism.
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High LET Radiation Can Enhance TGF(Beta) Induced EMT and Cross-Talk with ATM Pathways
Wang, Minli; Hada, Megumi; Huff, Janice; Pluth, Janice M.; Anderson, Janniffer; ONeill, Peter; Cucinotta, Francis A.
2010-01-01
The TGF(Beta) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation in mammary epithelial cells. We investigated possible interactions between the TGF(Beta) and ATM pathways following simulated space radiation using hTERT immortalized human esophageal epithelial cells (EPC-hTERT), mink lung epithelial cells (Mv1lu), and several human fibroblast cell lines. TGF(Beta) is a key modulator of the Epithelial-Mesenchymal Transition (EMT), important in cancer progression and metastasis. The implication of EMT by radiation also has several lines of developing evidence, however is poorly understood. The identification of TGF(Beta) induced EMT can be shown in changes to morphology, related gene over expression or down regulation, which can be detected by RT-PCR, and immunostaining and western blotting. In this study, we have observed morphologic and molecular alternations consistent with EMT after Mv1lu cells were treated with TGF(Beta) High LET radiation enhanced TGF(Beta) mediated EMT with a dose as low as 0.1Gy. In order to consider the TGF(Beta) interaction with ATM we used a potent ATM inhibitor Ku55933 and investigated gene expression changes and Smad signaling kinetics. Ku559933 was observed to reverse TGF(Beta) induced EMT, while this was not observed in dual treated cells (radiation+TGF(Beta)). In EPC-hTERT cells, TGF(Beta) alone was not able to induce EMT after 3 days of application. A combined treatment with high LET, however, significantly caused the alteration of EMT markers. To study the function of p53 in the process of EMT, we knocked down P53 through RNA interference. Morphology changes associated with EMT were observed in epithelial cells with silenced p53. Our study indicates: high LET radiation can enhance TGF(Beta) induced EMT; while ATM is triggering the process of TGF(Beta)-induced EMT, p53 might be an essential repressor for EMT phenotypes.
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Moon, Dong-Oh; Kim, Mun-Ok; Choi, Yung Hyun; Park, Yung-Min; Kim, Gi-Young
2010-05-01
Curcumin, a major component of turmeric, has been shown to exhibit anti-oxidant and anti-inflammatory activities. The present study was performed to determine whether curcumin is efficacious against both collagen-induced arthritis (CIA) in mice and IL-1beta-induced activation in fibroblast-like synoviocytes (FLSs). DBA/1 mice were immunized with bovine type II collagen (CII) and treated with curcumin every other day for 2weeks after the initial immunization. For arthritis, we evaluated the incidence of disease and used an arthritis index based on paw thickness. In vitro proliferation of CII- or concanavalin A-induced splenic T cells was examined using IFN-gamma production. Pro-inflammatory cytokines TNF-alpha and IL-1beta were examined in the mouse ankle joint and serum IgG1 and IgG2a isotypes were analyzed. The expression levels of prostaglandin E(2) (PGE(2)), cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs) in human FLSs were also determined. The results showed that compared with untreated CIA mice, curcumin-treated mice downregulated clinical arthritis score, the proliferation of splenic T cells, expression levels of TNF-alpha and IL-1beta in the ankle joint, and expression levels of IgG2a in serum. Additionally, by altering nuclear factor (NF)-kappaB transcription activity in FLSs, curcumin inhibited PGE(2) production, COX-2 expression, and MMP secretion. These results suggest that curcumin can effectively suppress inflammatory response by inhibiting pro-inflammatory mediators and regulating humoral and cellular immune responses. Copyright 2010 Elsevier B.V. All rights reserved.
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Beta Emission and Bremsstrahlung
Energy Technology Data Exchange (ETDEWEB)
Karpius, Peter Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
2017-11-13
Bremsstrahlung is continuous radiation produced by beta particles decelerating in matter; different beta emitters have different endpoint energies; high-energy betas interacting with high-Z materials will more likely produce bremsstrahlung; depending on the data, sometimes all you can say is that a beta emitter is present.
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Gross alpha and beta activities in Tunisian mineral water
International Nuclear Information System (INIS)
Hamrouni Benbelgacem, Samar
2011-01-01
The quality of natural mineral water is a universal health problem seeing its vital importance. This problem is related to the presence of the radionuclides since this water is coming from underground, during their circulation it dissolves and conveys the radionuclides which are present in the earth's crust. This problem which leads to the contamination of the mineral water urged the World Health Organization to set standards and to recommend the respect of the median values of the activities alpha and beta within the framework of the man protection against this internal exhibition. Concerning the radiological quality of Tunisian mineral water studied in this project, we showed, by using the gross alpha and beta activities counting, that this water is specific to human consumption since their gross alpha and beta activities do not forward any risk on health.
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Energy Technology Data Exchange (ETDEWEB)
Welsh, N.; Nilsson, T.; Hallberg, A.; Arkhammar, P.; Berggren, P.-O.; Sandler, S.
1989-01-01
Isolated islets from adult rats or obese hyperglycemic (ob/ob) mice were incubated with human recombinant interleukin 1{beta} in order to study whether the acute effects of the cytokine on islet insulin release are associated with changes in islet phospholipase C activity, Ca{sup 2+} handling or protein phosphorylation. The cytokine stimulated insulin release both at low and high glucose concentrations during one hour incubations. In shortterm incubations (<1 min) interleukin 1{beta} did not affect the production of inositoltrisphosphate. Addition of interleukin 1{beta} affected neither the cytoplasmic free Ca{sup 2+} concentration at rest nor that observed subsequent to stimulation with a high concentration of glucose. Furthermore, the endogenous protein kinase C activity, as visualized by immunoprecipitation of a {sup 32}P-labelled substrate for this enzyme, was not altered by interleukin 1{beta}. Separation of {sup 32}P-labelled proteins by means of 2-dimensional gel electrophoresis failed to reveal any specific effects of the cytokine on the total protein phosphorylation activity. These results suggest that the stimulatory effects on insulin release exerted by interleukin 1{beta} are not caused by acute activation of phospholipase C and protein kinase C or by an alternation of islet Ca{sup 2+} handling of the B-cells. (author).
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Directory of Open Access Journals (Sweden)
Alexandre H. Fujita
2003-08-01
Full Text Available Foi utilizado o método enzimático recomendado pela AOAC para determinação de beta-glucanas em cereais e alimentos que os contém. O método, utiliza liquenase (EC 3.2.1.73 e beta-glucosidase (EC 3.2.1.21 para hidrólise debeta-glucanas, é rápido, fácil de executar e específico para beta-glucanas com ligações beta(1->3 e beta(1->4. As sementes analisadas foram subministradas pelo Instituto Agronômico de Campinas (IAC e os alimentos adquiridos nos supermercados. Aveia e cevada são os grãos com maior conteúdo de beta-glucanas. Na aveia os teores determinados foram 6,48 e 5,94%. Nos 10 cultivares de cevada os teores de beta-glucanas oscilaram entre 2,04 e 9,68%. Trigo e triticale apresentaram teores de b-glucanas menores que 1%. Nos produtos comerciais o teor de beta-glucanas estava relacionado ao tipo de cereal da fórmula. O produto comercial de maior conteúdo de beta-glucanas é o farelo de aveia. As beta-glucanas são ingredientes funcionais em potencial e a conveniência ou não de estimular sua incorporação em alimentos deve ser mais estudada. Quanto à composição centesimal dos grãos de cereais, o teor de proteínas foi o que apresentou a maior variação e isso se reflete na composição dos produtos comerciais.The method employed was the enzymatic one recommended by de AOAC for the determination of beta-glucans in cereals and in foodstuffs containing cereals in their formulation. The method, using lichenase (EC 3.2.1.73 and beta-glucosidase (EC 3.2.1.21 for the hydrolysis of beta-glucans, is quick and easy to execute, but is specific for beta-glucans with beta(1->3 and beta(1->4 bonds. The Agronomic Institute of Campinas (IAC supplied the seeds analyzed, and the foodstuffs were acquired in supermarkets. Oat and barley are the grains with the highest content of beta-glucans. In the oats, the determined values were 6.48 and 5.94%. In the 10 cultivars of barley, the content of beta-glucans varied between 2.04 and 9
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New additions to the National Plant Germplasm System's Beta collection: Southern Morocco collection
The USDA Agricultural Research Service’s National Plant Germplasm System’s (NPGS) Beta collection is comprised of 2,541 accessions from 14 species. The largest number of accessions is from Beta vulgaris ssp. vulgaris, (domesticated beet crops – table, leaf (Swiss chard), fodder and, primarily, sugar...
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DEFF Research Database (Denmark)
Hougaard, S; Nørgaard, P; Abrahamsen, N
1999-01-01
Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung...
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Rapid model building of beta-sheets in electron-density maps.
Terwilliger, Thomas C
2010-03-01
A method for rapidly building beta-sheets into electron-density maps is presented. beta-Strands are identified as tubes of high density adjacent to and nearly parallel to other tubes of density. The alignment and direction of each strand are identified from the pattern of high density corresponding to carbonyl and C(beta) atoms along the strand averaged over all repeats present in the strand. The beta-strands obtained are then assembled into a single atomic model of the beta-sheet regions. The method was tested on a set of 42 experimental electron-density maps at resolutions ranging from 1.5 to 3.8 A. The beta-sheet regions were nearly completely built in all but two cases, the exceptions being one structure at 2.5 A resolution in which a third of the residues in beta-sheets were built and a structure at 3.8 A in which under 10% were built. The overall average r.m.s.d. of main-chain atoms in the residues built using this method compared with refined models of the structures was 1.5 A.
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The Determination of Gross Alpha And Beta Activity of Drinking Water in Turkey
International Nuclear Information System (INIS)
Dilaver, A.T.; Cifter, C.; Altay, T.
2002-01-01
Man and his environment must be protected from the adverse effects of pesticides, radiation, noise and other forms of pollutions. Radioactive materials occur naturally in the environment (for example uranium, thorium and potassium). Same radioactive compounds arise from human activities (for example from medical or industrial uses of radioactivity). Drinking water should be safe to use and aesthetically pleasing. World Health Organisation (WHO) and Turkish Standards (TSE) have established maximum contaminant levels for gross alpha and gross beta. The purpose of these study is to determine the level of gross alpha and gross beta activities of samples collected from the different Regional Directories of The State Hydraulic Works (DSI)). After that compare the results versus permissible values of World Health Organisation and Turkish Standards. Collected samples from 14 Regional Directories of The State Hydraulic Works (DSI), have completed. All the analyses results suitable for WHO and TSE. We will give all the research our final report after completed the other Regional Directories' s analyses
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Nuclear Matrix Elements for the $\\beta\\beta$ Decay of the $^{76}$Ge
Brown, B A; Horoi, M
2015-01-01
The nuclear matrix elements for two-neutrino double-beta (2 n$\\beta\\beta$ ) and zero-neutrino double-beta (0 n$\\beta\\beta$) decay of 76 Ge are evaluated in terms of the configuration interaction (CI), quasiparticle random phase approximation (QRPA) and interacting boson model (IBM) methods. We show that the decomposition of the matrix elements in terms of interemediate states in 74 Ge is dominated by ground state of this nucleus. We consider corrections to the CI results that arise from configurations admixtures involving orbitals out-side of the CI configuration space by using results from QRPA, many-body-perturbation theory, and the connections to related observables. The CI two-neutrino matrix element is reduced due to the inclusion of spin-orbit partners, and to many-body correlations connected with Gamow-Teller beta decay. The CI zero-neutrino matrix element for the heavy neutrino is enhanced due to particle-particle correlations that are connected with the odd-even oscillations in the nuclear masse...
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Hosotani, Keisuke; Kitagawa, Masahiro
2003-07-05
Among the many simultaneous determination methods for carotenoid and retinoid, there are only a few reports including the saponification process. However, the yields of beta-carotene and retinol were higher when using this process. In this study, the analytical conditions, including saponification, were investigated. The extraction solvent was n-hexane and the sample solvent was HPLC mobile phase in the beta-carotene and retinol analysis. BHT as an antioxidant was added at concentrations of 0.125 and 0.025%, respectively, to ethanol and n-hexane phase in the extraction process for serum. The recovery rates were 99.7, 93.7 and 98.3% for beta-carotene, retinol and retinyl palmitate in serum, respectively, and 107.1, 92.8 and 98.8% for beta-carotene, retinol and retinyl palmitate in liver, respectively. The within-day coefficients of variation (C.V.) were 6.0% for serum and 4.7% for liver in the case of beta-carotene, 7.1% for serum, and 5.1% for liver in the case of retinol. The between-day coefficients of variation were 2.7% for serum and 2.7% for liver in the case of beta-carotene, and for retinol, 6.4% for serum and 2.7% for liver.
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LENUS (Irish Health Repository)
Mitchell, Jacqueline C
2009-12-01
Increased production and deposition of amyloid beta-protein (Abeta) are believed to be key pathogenic events in Alzheimer\\'s disease. As such, routes for lowering cerebral Abeta levels represent potential therapeutic targets for Alzheimer\\'s disease. X11beta is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11beta inhibits Abeta production in a number of experimental systems. However, whether these changes to APP processing and Abeta production induced by X11beta overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11beta-mediated reduction in cerebral Abeta is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer\\'s disease. Overexpression of X11beta itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11beta function represents a therapeutic target for Abeta-mediated neuronal dysfunction in Alzheimer\\'s disease.
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Chen, Hao; Kshirsagar, Sarika; Jensen, Ingvill; Lau, Kevin; Simonson, Caitlin; Schluter, Samuel F
2010-02-01
Beta 2 microglobulin (beta2m) is an essential subunit of major histocompatibility complex (MHC) type I molecules. In this report, beta2m cDNAs were identified and sequenced from sandbar shark spleen cDNA library. Sandbar shark beta2m gene encodes one amino acid less than most teleost beta2m genes, and 3 amino acids less than mammal beta2m genes. Although sandbar shark beta2m protein contains one beta sheet less than that of human in the predicted protein structure, the overall structure of beta2m proteins is conserved during evolution. Germline gene for the beta2m in sandbar and nurse shark is present as a single locus. It contains three exons and two introns. CpG sites are evenly distributed in the shark beta2m loci. Several DNA repeat elements were also identified in the shark beta2m loci. Sequence analysis suggests that the beta2m locus is not linked to the MHC I loci in the shark genome.
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Tsonkova, Violeta Georgieva; Sand, Fredrik Wolfhagen; Wolf, Xenia Asbæk; Grunnet, Lars Groth; Kirstine Ringgaard, Anna; Ingvorsen, Camilla; Winkel, Louise; Kalisz, Mark; Dalgaard, Kevin; Bruun, Christine; Fels, Johannes Josef; Helgstrand, Charlotte; Hastrup, Sven; Öberg, Fredrik Kryh; Vernet, Erik; Sandrini, Michael Paolo Bastner; Shaw, Allan Christian; Jessen, Carsten; Grønborg, Mads; Hald, Jacob; Willenbrock, Hanni; Madsen, Dennis; Wernersson, Rasmus; Hansson, Lena; Jensen, Jan Nygaard; Plesner, Annette; Alanentalo, Tomas; Petersen, Maja Borup Kjær; Grapin-Botton, Anne; Honoré, Christian; Ahnfelt-Rønne, Jonas; Hecksher-Sørensen, Jacob; Ravassard, Philippe; Madsen, Ole D; Rescan, Claude; Frogne, Thomas
2018-02-01
To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates. EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, and ER stress responses were assessed. Beta cell relevant mRNA and protein expression were investigated by qPCR and antibody staining. Hundreds of proteins or peptides were tested for their effect on insulin secretion and proliferation. Transplantation of EndoC-βH1 cells restored normoglycemia in streptozotocin induced diabetic mice. Both in vitro and in vivo, we observed a clear insulin response to glucose, and, in vitro, we found a significant increase in insulin secretion from EndoC-βH1 pseudoislets compared to monolayer cultures for both glucose and incretins. Apoptosis and ER stress were inducible in the cells and caspase 3/7 activity was elevated in response to cytokines, but not affected by the saturated fatty acid palmitate. By screening of various proteins and peptides, we found Bombesin (BB) receptor agonists and Pituitary Adenylate Cyclase-Activating Polypeptides (PACAP) to significantly induce insulin secretion and the proteins SerpinA6, STC1, and APOH to significantly stimulate proliferation. ER stress was readily induced by Tunicamycin and resulted in a reduction of insulin mRNA. Somatostatin (SST) was found to be expressed by 1% of the cells and manipulation of the SST receptors was found to significantly affect insulin secretion. Overall, the EndoC-βH1 cells strongly resemble human islet beta cells in terms of glucose and incretin stimulated insulin secretion capabilities. The cell line has an active
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Energy Technology Data Exchange (ETDEWEB)
Koutmos, Markos; Kabil, Omer; Smith, Janet L.; Banerjee, Ruma (Michigan-Med)
2011-08-17
The catalytic potential for H{sub 2}S biogenesis and homocysteine clearance converge at the active site of cystathionine {beta}-synthase (CBS), a pyridoxal phosphate-dependent enzyme. CBS catalyzes {beta}-replacement reactions of either serine or cysteine by homocysteine to give cystathionine and water or H{sub 2}S, respectively. In this study, high-resolution structures of the full-length enzyme from Drosophila in which a carbanion (1.70 {angstrom}) and an aminoacrylate intermediate (1.55 {angstrom}) have been captured are reported. Electrostatic stabilization of the zwitterionic carbanion intermediate is afforded by the close positioning of an active site lysine residue that is initially used for Schiff base formation in the internal aldimine and later as a general base. Additional stabilizing interactions between active site residues and the catalytic intermediates are observed. Furthermore, the structure of the regulatory 'energy-sensing' CBS domains, named after this protein, suggests a mechanism for allosteric activation by S-adenosylmethionine.
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Constraining the Mass Loss Geometry of Beta Lyrae
Directory of Open Access Journals (Sweden)
Jamie R. Lomax
2012-03-01
Full Text Available Massive binary stars lose mass by two mechanisms: jet-driven mass loss during periods of active mass transfer and by wind-driven mass loss. Beta Lyrae is an eclipsing, semi-detached binary whose state of active mass transfer provides a unique opportunity to study how the evolution of binary systems is affected by jet-driven mass loss. Roche lobe overflow from the primary star feeds the thick accretion disk which almost completely obscures the mass-gaining star. A hot spot predicted to be on the edge of the accretion disk may be the source of beta Lyrae’s bipolar outflows. I present results from spectropolarimetric data taken with the University of Wisconsin’s Half-Wave Spectropolarimeter and the Flower and Cook Observatory’s photoelastic modulating polarimeter instrument which have implications for our current understanding of the system’s disk geometry. Using broadband polarimetric analysis, I derive new information about the structure of the disk and the presence and location of a hot spot. These results place constraints on the geometrical distribution of material in beta Lyrae and can help quantify the amount of mass lost from massive interacting binary systems during phases of mass transfer and jet-driven mass loss.
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Monitoring gross alpha and beta activity in liquids by using ZnS(Ag) scintillation detectors
Energy Technology Data Exchange (ETDEWEB)
Stevanato, L.; Cester, D.; Filippi, D.; Lunardon, M.; Mistura, G.; Moretto, S.; Viesti, G. [Department of Physics and Astronomy ' Galileo Galilei' , University of Padova, (Italy); Badocco, D.; Pastore, P.; Romanini, F. [Department of Chemical Sciences, University of Padova, (Italy)
2015-07-01
In this work the possibility of monitoring gross alpha and beta activity in liquids using EJ-444 was investigated. Specific tests were carried out to determine the change of the detector properties in water tests. Possible protecting coating is also proposed and tested. Alpha/beta real-time monitoring in liquids is a goal of the EU project TAWARA{sub R}TM. (authors)
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Energy Technology Data Exchange (ETDEWEB)
Tierney, L.A.; Bloomfield, C.; Johnson, N.F. [and others
1995-12-01
Tumors arising from epithelial cells, including lung cancers are frequently resistant to factors that regulate growth and differentiation in normal in normal cells. Once such factor is transforming growth factor-{Beta} (TGF-{Beta}). Escape from the growth-inhibitory effects of TGF-{Beta} is thought to be a key step in the transformation of airway epithelial cells. most lung cancer cell lines require serum for growth. In contrast, normal human bronchial epithelial (NHBE) cells are exquisitely sensitive to growth-inhibitory and differentiating effects of TGF-{Beta}. The recent identification of a novel cyclin-dependent kinase inhibitor, p15{sup INK4B}, which is regulated by TGF-{Beta}, suggests a mechanism by which TGF-{Beta} mediates growth arrest in NHBE cells. The purpose of this study was two-fold: (1) to determine if p15{sup INK4B} is induced by TGF-{Beta} in NHBE cells or immortalized bronchial epithelial (R.1) cells and if that induction corresponds to a G1/S cell-cycle arrest; (2) to determine the temporal relationship between p15{sup INK4B} induction, cell-cycle arrest, and the phosphorylation state of the pRB because it is thought that p15{sup INK4B} acts indirectly by preventing phosphorylation of the RB gene product. In this study, expression of p15{sup INK4B} was examined in NHBE cells and R.1 cells at different time intervals following TGF-{Beta} treatment. The expression of this kinase inhibitor and its relationship to the cell and the pRb phosphorylation state were examined in cells that were both sensitive (NHBE) and resistant (R.1) to the effects of TGF-{Beta}. These results suggest that the cyclin-dependent kinase inhibitor, p15{sup INK4B}, is involved in airway epithelial cell differentiation and that loss or reduction of expression plays a role in the resistance of transformed or neoplastic cells to the growth-inhibitory effects of TGF-{Beta}.
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Energy Technology Data Exchange (ETDEWEB)
Silverman, Joseph [Radiation Applications Incorporated (United States)
1960-07-15
test the validity of the calculations. 4. An engineering cost analysis indicates that fission product beta power can be competitive with alternative sources of radiation. (author) [French] Si les emetteurs beta ne sont pas entres en ligne de compte en tant que sources de rayonnement de grandes dimensions, c'est que dans le passe les procedes sous irradiation presentant un interet pour l'industrie etaient bases sur l'utilisation de particules a grand pouvoir de penetration; de la l'importance considerable que l'on accordait aux rayons gamma et aux electrons artificiellement acceleres. Il y a environ quatre ans, il devint evident que de vastes perspectives s'ouvraient aux applications pratiques des rayonnements beta dans le domaine du traitement par irradiation superficielle, par exemple, la modification par copolymerisation greffee de la surface des moulages en matiere plastique et la pasteurisation superficielle des aliments. En effet, l'irradiation en profondeur occasionne dans ces cas des pertes et peut meme presenter des dangers. D'autre part, il y a deux autres domaines dans lesquels l'utilisation des electrons artificiellement acceleres ne semble pas indiquee; ce sont les syntheses chimiques amorcees par irradiation dans des cuves sous pression et certaines categories de reactions en chaine provoquees par des radicaux libres pour lesquels le taux de production par kilowatt decroit en fonction de la racine carree de l'intensite d'irradiation. Dans tous ces domaines, les sources beta de grandes dimensions presentent des avantages potentiels evidents; puisque la fission nucleaire permet d'en obtenir en quantites importantes, elles meritent que leurs- possibilites d'utilisation fassent l'objet d'un examen approfondi. Compte tenu de ces considerations, on a procede - sous l'egide de la Commission de l'energie atomique - a une etude des applications'et de la technologie des sources beta de fission. Cette etude a permis d'aboutir aux conclusions suivantes: 1. Des
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Energy Technology Data Exchange (ETDEWEB)
Yoichiro Kusunoki; Seishi Kyoizumi; Yuko Hirai; Shoichiro Fujita; Mitoshi Akiyama [Radiation Effects Research Foundation, Hiroshima (Japan)
1994-07-01
A rare T-cell subpopulation, CD4{sup -z}8{sup -}{alpha}{beta} cells, may be differentiated through a pathway (or pathways) different from the pathway(s) of conventional CD4+ or CD8+ cells. In the present study, the frequencies of CD4{sup -}8{sup -} T cells in peripheral-blood {alpha}{beta} T cells in 409 atomic bomb survivors were determined to investigate late effects of radiation on the composition of human T-cell subpopulations. The frequency of CD4{sup -}8{sup -}{alpha}{beta} T-cell decreased significantly with the subject`s age and was higher in females than males. A significant increase in the frequency was found in the survivors exposed to more than 1.5Gy, suggesting that the previous radiation exposure altered differentiation and development of T cells. 25 refs., 4 figs., 3 tabs.
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Baqui, A A; Meiller, T F; Chon, J J; Turng, B F; Falkler, W A
1998-05-01
Cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF), are used to assist in bone marrow recovery during cancer chemotherapy. Interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) play important roles in inflammatory processes, including exacerbation of periodontal diseases, one of the most common complications in patients who undergo this therapy. A human monocyte cell line (THP-1) was utilized to investigate IL-1beta and TNF-alpha production following GM-CSF supplementation with lipopolysaccharide (LPS) from two oral microorganisms, Porphyromonas gingivalis and Fusobacterium nucleatum. LPS of P. gingivalis or F. nucleatum was prepared by a phenol-water extraction method and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and determination of total protein and endotoxin contents. Resting THP-1 cells were treated with LPS of P. gingivalis or F. nucleatum and/or GM-CSF (50 IU/ml) by using different concentrations for various time periods. Production of IL-1beta and TNF-alpha in THP-1 cells was measured by solid-phase enzyme-linked immunosorbent assay. Reverse transcription (RT)-PCR was used to evaluate the gene expression of resting and treated THP-1 cells. IL-1beta was not detected in untreated THP-1 cells. IL-1beta production was, however, stimulated sharply at 4 h. GM-CSF amplified IL-1beta production in THP-1 cells treated with LPS from both oral anaerobes. No IL-1beta-specific mRNA transcript was detected in untreated THP-1 cells. However, IL-1beta mRNA was detected by RT-PCR 2 h after stimulation of THP-1 cells with LPS from both organisms. GM-CSF did not shorten the IL-1beta transcriptional activation time. GM-CSF plus F. nucleatum or P. gingivalis LPS activated THP-1 cells to produce a 1.6-fold increase in TNF-alpha production at 4 h over LPS stimulation alone. These investigations with the in vitro THP-1 model indicate that there may be an increase in the cellular immune response to oral
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Wanten, G J; Geijtenbeek, T B; Raymakers, R A; van Kooyk, Y; Roos, D; Jansen, J B; Naber, A H
2000-01-01
To test the hypothesis that lipid emulsions with different triglyceride structures have distinct immunomodulatory properties, we analyzed human neutrophil adhesion and degranulation after lipid incubation. Neutrophils, isolated from the blood of 10 healthy volunteers, were incubated in medium or physiologic (2.5 mmol/L) emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, or structured (SL) triglycerides. Expression of adhesion molecules and degranulation markers was evaluated by flow cytometry. Also, functional adhesion was investigated by means of a flow cytometric assay using fluorescent beads coated with the integrin ligand intercellular adhesion molecule (ICAM)-1. Although LCT and SL had no effect, LCT/MCT significantly increased expression of the beta2 integrins lymphocyte-function-associated antigen 1 (+18%), macrophage antigen 1 (+387%), p150,95 (+82%), and (alphaDbeta2 (+230%). Degranulation marker expression for azurophilic (CD63, +210%) and specific granules (CD66b, +370%) also significantly increased, whereas L-selectin (CD62L, -70%) decreased. The effects of LCT/MCT were mimicked by the MCT emulsion. ICAM-1 adhesion (% beads bound) was increased by LCT/MCT (34% +/- 4%), whereas LCT (19% +/-3%) and SL (20% +/- 2%) had no effect compared with medium (17% +/- 3%). LCT/MCT and MCT, contrary to LCT and SL emulsions, increased neutrophil beta2 integrin expression, adhesion, and degranulation. Apart from other emulsion constituents, triglyceride chain length might therefore be a key feature in the interaction of lipid emulsions and the phagocyte immune system.
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DEFF Research Database (Denmark)
Wainø, M.; Ingvorsen, K.
2003-01-01
-xylosidase stabilities, approximately 55% and 83% of the initial beta-xylanase and beta-xylosidase activities, respectively, remained after 24 h incubation at 20% NaCl. The enzymes were also shown to be slightly thermophilic: P-xylanase activity exhibiting two optima at 55degrees and 70degreesC, while beta......The extremely halophilic archaeon, Halorhabdus utahensis, isolated from the Great Salt Lake, Utah, produced beta-xylanase and beta-xylosidase activities. Both enzymes were active over a broad NaCl range from near zero to 30% NaCl when tested with culture broth. A broad NaCl optimum was observed...... for beta-xylanase activity between 5% and 15% NaCl, while beta-xylosidase activity was highest at 5% NaCl. Almost half of the maximum activities remained at 27%-30% NaCl for both enzyme activities. When dialyzed culture supernatant and culture broth were employed for determination of beta-xylanase and beta...
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Gibbs, Marie E; Hutchinson, Dana S; Summers, Roger J
2008-09-01
Noradrenaline, acting via beta(2)- and beta(3)-adrenoceptors (AR), enhances memory formation in single trial-discriminated avoidance learning in day-old chicks by mechanisms involving changes in metabolism of glucose and/or glycogen. Earlier studies of memory consolidation in chicks implicated beta(3)- rather than beta(2)-ARs in enhancement of memory consolidation by glucose, but did not elucidate whether stimulation of glucose uptake or of glycolysis was responsible. This study examines the role of glucose transport in memory formation using central injection of the nonselective facilitative glucose transporter (GLUT) inhibitor cytochalasin B, the endothelial/astrocytic GLUT-1 inhibitor phloretin and the Na(+)/energy-dependent endothelial glucose transporter (SGLT) inhibitor phlorizin. Cytochalasin B inhibited memory when injected into the mesopallium (avian cortex) either close to or between 25 and 45 min after training, whereas phloretin and phlorizin only inhibited memory at 30 min. This suggested that astrocytic/endothelial (GLUT-1) transport is critical at the time of consolidation, whereas a different transporter, probably the neuronal glucose transporter (GLUT-3), is important at the time of training. Inhibition of glucose transport by cytochalasin B, phloretin, or phlorizin also interfered with beta(3)-AR-mediated memory enhancement 20 min posttraining, whereas inhibition of glycogenolysis interfered with beta(2)-AR agonist enhancement of memory. We conclude that in astrocytes (1) activities of both GLUT-1 and SGLT are essential for memory consolidation 30 min posttraining; (2) neuronal GLUT-3 is essential at the time of training; and (3) beta(2)- and beta(3)-ARs consolidate memory by different mechanisms; beta(3)-ARs stimulate central glucose transport, whereas beta(2)-ARs stimulate central glycogenolysis.
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Low-beta investment strategies
Korn, Olaf; Kuntz, Laura-Chloé
2015-01-01
This paper investigates investment strategies that exploit the low-beta anomaly. Although the notion of buying low-beta stocks and selling high-beta stocks is natural, a choice is necessary with respect to the relative weighting of high-beta stocks and low-beta stocks in the investment portfolio. Our empirical results for US large-cap stocks show that this choice is very important for the risk-return characteristics of the resulting portfolios and their sensitivities to common risk factors. W...
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Shen, H; Ranganathan, S; Kuzmich, S; Tew, K D
1995-10-12
Ethacrynic acid (EA) is a plant phenolic acid that is both an inhibitor and an inducer of glutathione S-transferase (GST) activity. To determine contributory factors in the increased GST activity caused by EA treatment, human colon carcinoma HT29 cells were compared with a cloned EA-resistant population (HT6-8) maintained in medium containing 72 microM EA. Several factors are involved in the increased expression of GST pi in HT6-8. For example, nuclear run-on experiments showed an approximately 2-fold increase in the rate of transcription of GST pi. In addition, the half-life of GST pi transcript was increased from 4.1 (wild type, HT29, HT4-1) to 8.4 hr. The half-life of GST pi protein was 1-2 hr in HT4-1 cells versus 8-9 hr in HT6-8 cells. When either human ovarian carcinoma cells (SKOV3) or human prostatic carcinoma cells (DU145) were treated with EA, the half-life of the GST pi transcript was also increased. The transcript half-lives of another thiol-metabolism enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), and a phase II detoxification enzyme, dihydrodiol dehydrogenase (DDH), were also increased in HT6-8, SKOV3 and DU145 cells treated with EA. However, the half-lives of transcripts from "housekeeping genes," such as glyceraldehyde 3-phosphate dehydrogenase (G3PDH), beta-actin and beta-tubulin, were not changed in these cell lines following EA. Apparently, a number of coordinated factors are involved in EA-enhanced expression of GST pi and other detoxification enzymes.
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Effect of beta-alanine, with and without sodium bicarbonate, on 2000-m rowing performance.
Hobson, Ruth M; Harris, Roger C; Martin, Dan; Smith, Perry; Macklin, Ben; Gualano, Bruno; Sale, Craig
2013-10-01
To examine the effect of beta-alanine only and beta-alanine with sodium bicarbonate supplementation on 2,000-m rowing performance. Twenty well-trained rowers (age 23 ± 4 y; height 1.85 ± 0.08 m; body mass 82.5 ± 8.9 kg) were assigned to either a placebo or beta-alanine (6.4 g · d(-1) for 4 weeks) group. A 2,000-m rowing time trial (TT) was performed before supplementation (Baseline) and after 28 and 30 days of supplementation. The post supplementation trials involved supplementation with either maltodextrin or sodium bicarbonate in a double-blind, crossover design, creating four study conditions (placebo with maltodextrin; placebo with sodium bicarbonate; beta-alanine with maltodextrin; beta-alanine with sodium bicarbonate). Blood lactate, pH, bicarbonate, and base excess were measured pre-TT, immediately post-TT and at TT+5 min. Performance data were analyzed using magnitude based inferences. Beta-alanine supplementation was very likely to be beneficial to 2,000-m rowing performance (6.4 ± 8.1 s effect compared with placebo), with the effect of sodium bicarbonate having a likely benefit (3.2 ± 8.8 s). There was a small (1.1 ± 5.6 s) but possibly beneficial additional effect when combining chronic beta-alanine supplementation with acute sodium bicarbonate supplementation compared with chronic beta-alanine supplementation alone. Sodium bicarbonate ingestion led to increases in plasma pH, base excess, bicarbonate, and lactate concentrations. Both chronic beta-alanine and acute sodium bicarbonate supplementation alone had positive effects on 2,000-m rowing performance. The addition of acute sodium bicarbonate to chronic beta-alanine supplementation may further enhance rowing performance.
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Clearance from cerebrospinal fluid of intrathecally administered beta-endorphin in monkeys
International Nuclear Information System (INIS)
Lee, V.C.; Burns, R.S.; Dubois, M.; Cohen, M.R.
1984-01-01
Five adult male monkeys (Macaca mulatta) weighing 7.1-9.9 kg were given synthetic human beta-endorphin (800 micrograms) and [ 14 C]methoxy-inulin (50 microCi) in 400 microliters of normal saline intrathecally. Serial samples of cerebrospinal fluid were drawn through a previously positioned indwelling spinal catheter and were assayed for concentrations of beta-endorphin (determined by radioimmunoassay) and inulin (determined by liquid scintillation counter). Spinal fluid concentrations of beta-endorphin and inulin peaked and declined in a parallel manner. The clearance ratio (calculated from the reciprocal of the ratio of the areas under the respective curves of elimination of the two species) remained remarkably similar from animal to animal, giving a mean value of 1.060 +/- 0.090 (SEM). This ratio, being near unity, suggests that beta-endorphin is eliminated from spinal fluid in a fashion similar to that of inulin, which is removed exclusively by bulk absorption
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Energy Technology Data Exchange (ETDEWEB)
Ham, J.S.; Jeong, S.G.; Lee, S.G.; Han, G.S.; Chae, H.S.; Yoo, Y.M.; Kim, D.H. [Animal Food Processing Division, National Institute of Animal Science, Suwon 441-706 (Korea, Republic of); Lee, W.K. [College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Jo, C. [Department of Animal Science and Biotechnology, Chungnam National University, Daejeon 305-764 (Korea, Republic of)], E-mail: cheorun@cnu.ac.kr
2009-02-15
Milk and Queso Blanco cheese were exposed to irradiation with doses of 1, 2, 3, 5, and 10 kGy to investigate the irradiation effect on {alpha}- and {beta}-casein using a capillary electrophoresis. {alpha}{sub S1}-Casein to total protein ratio in raw milk was decreased from 19.63% to 8.64% by 10 kGy of gamma irradiation. The ratio of {alpha}{sub S1}- to {alpha}{sub S0}-casein was also decreased from 1.38 to 0.53, which showed {alpha}{sub S1}-casein is more susceptible to gamma irradiation than {alpha}{sub S0}-casein. Similarly, {alpha}{sub S1}-casein to total protein ratio in Queso Blanco cheese was decreased from 17.48% to 7.82% and the ratio of {alpha}{sub S1}- to {alpha}{sub S0}-casein was decreased from 1.16 to 0.43 by 10 kGy of gamma irradiation. Dose-dependent reduction of {beta}{sub A1}-casein was also found. {beta}{sub A1}-Casein to total protein ratios in raw milk and Queso Blanco cheese were decreased from 22.00% to 14.16% and from 21.96% to 13.89% after 10 kGy, respectively. The ratios of {beta}{sub A1}- to {beta}{sub A2}-casein were from 1.10 to 0.64 and 0.93 to 0.57 in milk and Queso Blanco cheese, respectively. However, {alpha}{sub S0}-, {beta}{sub B}-, and {beta}{sub A3}-casein increased by irradiation at 10 kGy. The results suggest that {alpha}{sub S1}-casein and {beta}{sub A1}-casein were more susceptible to gamma irradiation, and may be related to the reduction of milk allergenicity caused by gamma irradiation.
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Canciani, Elena; Dellavia, Claudia; Ferreira, Lorena Maria; Giannasi, Chiara; Carmagnola, Daniela; Carrassi, Antonio; Brini, Anna Teresa
2016-05-01
In the study, we assess a rapid prototyped scaffold composed of 30/70 hydroxyapatite (HA) and beta-tricalcium-phosphate (β-TCP) loaded with human adipose-derived stem cells (hASCs) to determine cell proliferation, differentiation toward osteogenic lineage, adhesion and penetration on/into the scaffold.In this in vitro study, hASCs isolated from fat tissue discarded after plastic surgery were expanded, characterized, and then loaded onto the scaffold. Cells were tested for: viability assay (Alamar Blue at days 3, 7 and Live/Dead at day 32), differentiation index (alkaline phosphatase activity at day 14), scaffold adhesion (standard error of the mean analysis at days 5 and 18), and penetration (ground sections at day 32).All the hASC populations displayed stemness markers and the ability to differentiate toward adipogenic and osteogenic lineages.Cellular vitality increased between 3 and 7 days, and no inhibitory effect by HA/β-TCP was observed. Under osteogenic stimuli, scaffold increased alkaline phosphatase activity of +243% compared with undifferentiated samples. Human adipose-derived stem cells adhered on HA/β-TCP surface through citoplasmatic extensions that occupied the macropores and built networks among them. Human adipose derived stem cells were observed in the core of HA/β-TCP. The current combination of hASCs and HA/β-TCP scaffold provided encouraging results. If authors' data will be confirmed in preclinical models, the present engineering approach could represent an interesting tool in treating large bone defects.
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Zhang, Can; Browne, Andrew; Child, Daniel; Divito, Jason R; Stevenson, Jesse A; Tanzi, Rudolph E
2010-03-19
Alzheimer disease (AD) is a devastating neurodegenerative disease with complex and strong genetic inheritance. Four genes have been established to either cause familial early onset AD (APP, PSEN1, and PSEN2) or to increase susceptibility for late onset AD (APOE). To date approximately 80% of the late onset AD genetic variance remains elusive. Recently our genome-wide association screen identified four novel late onset AD candidate genes. Ataxin 1 (ATXN1) is one of these four AD candidate genes and has been indicated to be the disease gene for spinocerebellar ataxia type 1, which is also a neurodegenerative disease. Mounting evidence suggests that the excessive accumulation of Abeta, the proteolytic product of beta-amyloid precursor protein (APP), is the primary AD pathological event. In this study, we ask whether ATXN1 may lead to AD pathogenesis by affecting Abeta and APP processing utilizing RNA interference in a human neuronal cell model and mouse primary cortical neurons. We show that knock-down of ATXN1 significantly increases the levels of both Abeta40 and Abeta42. This effect could be rescued with concurrent overexpression of ATXN1. Moreover, overexpression of ATXN1 decreased Abeta levels. Regarding the underlying molecular mechanism, we show that the effect of ATXN1 expression on Abeta levels is modulated via beta-secretase cleavage of APP. Taken together, ATXN1 functions as a genetic risk modifier that contributes to AD pathogenesis through a loss-of-function mechanism by regulating beta-secretase cleavage of APP and Abeta levels.
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Rapid synthesis of beta zeolites
Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng
2015-08-18
The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.
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Mega, T; Nishijima, T; Ikenaka, T
1990-04-01
beta-D-Galactopyranosylmethyl-p-nitrophenyltriazene (beta-GalMNT), a specific inhibitor of beta-galactosidase, was isolated as crystals by HPLC and its chemical and physicochemical characteristics were examined. Aspergillus oryzae beta-galactosidase was inactivated by the compound. We studied the inhibition mechanism in detail. The inhibitor was hydrolyzed by the enzyme to p-nitroaniline and an active intermediate (beta-galactopyranosylmethyl carbonium or beta-galactopyranosylmethyldiazonium), which inactivated the enzyme. The efficiency of inactivation of the enzyme (the ratio of moles of inactivated enzyme to moles of beta-GalMNT hydrolyzed by the enzyme) was 3%; the efficiency of Escherichia coli beta-galactosidase was 49%. In spite of the low efficiency, the rate of inactivation of A. oryzae enzyme was not very different from that of the E. coli enzyme, because the former hydrolyzed beta-GalMNT faster than the latter did. A. oryzae beta-galactosidase was also inactivated by p-chlorophenyl, p-tolyl, and m-nitrophenyl derivatives of beta-galactopyranosylmethyltriazene. However, E. coli beta-galactosidase was not inactivated by these triazene derivatives. The results showed that the inactivation of A. oryzae and E. coli beta-galactosidases by beta-GalMNT was an enzyme-activated and active-site-directed irreversible inactivation. The possibility of inactivation by intermediates produced nonenzymatically was ruled out for E. coli, but not for the A. oryzae enzyme.
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Browning, A J; Butt, W R; Lynch, S S; Shakespear, R A
1983-12-01
Plasma beta-LPH, beta-EP and gamma-LPH concentrations were measured by radioimmunoassay in 10 pregnant women from 12 weeks gestation until term and in nine women in the early follicular phase of the cycle. There was a progressive and significant rise in the concentration of all three peptides throughout pregnancy and by 32 weeks the concentrations of beta-LPH and beta-EP were greater than the corresponding concentrations in the follicular phase: gamma-LPH was greater than in the follicular phase by the end of pregnancy in those women who were delivered after 40 weeks. The ratio of beta-LPH to gamma-LPH did not change significantly throughout pregnancy, but there was a progressive fall in the beta-LPH/beta-EP ratio. The possible presence of a 'big LPH' to explain this finding is discussed.
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LENUS (Irish Health Repository)
White, Mary
2012-02-01
INTRODUCTION: The occurrence of severe sepsis may be associated with deficient pro-inflammatory cytokine production. Transforming growth factor beta-1 (TGFbeta-1) predominantly inhibits inflammation and may simultaneously promote IL-17 production. Interleukin-17 (IL-17) is a recently described pro-inflammatory cytokine, which may be important in auto-immunity and infection. We investigated the hypothesis that the onset of sepsis is related to differential TGFbeta-1 and IL-17 gene expression. METHODS: A prospective observational study in a mixed intensive care unit (ICU) and hospital wards in a university hospital. Patients (59) with severe sepsis; 15 patients with gram-negative bacteraemia but without critical illness and 10 healthy controls were assayed for TGFbeta-1, IL-17a, IL-17f, IL-6 and IL-1beta mRNA in peripheral blood mononuclear cells (PBMC) by quantitative real-time PCR and serum protein levels by ELISA. RESULTS: TGFbeta-1 mRNA levels are reduced in patients with bacteraemia and sepsis compared with controls (p=0.02). IL-6 mRNA levels were reduced in bacteraemic patients compared with septic patients and controls (p=0.008). IL-1beta mRNA levels were similar in all groups, IL-17a and IL-17f mRNA levels are not detectable in peripheral blood mononuclear cells. IL-6 protein levels were greater in patients with sepsis than bacteraemic and control patients (p<0.0001). Activated TGFbeta-1 and IL-17 protein levels were similar in all groups. IL-1beta protein was not detectable in the majority of patients. CONCLUSIONS: Down regulation of TGFbeta-1 gene transcription was related to the occurrence of infection but not the onset of sepsis. Interleukin-17 production in PBMC may not be significant in the human host response to infection.
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Low level GAMMA0 spectrometry by beta-gamma coincidence
International Nuclear Information System (INIS)
Grigorescu, E.L.; Luca, A.; Razdolescu, A.C.; Ivan, C.
1999-01-01
Low level gamma spectrometry has a wide application, especially in environmental monitoring. Two variants, based on a beta-gamma coincidence technique, were studied. The equipment was composed of a beta detector and a Ge(Li) gamma detector (6% - relative efficiency), with the associated electronics. The gamma rays are recorded by the multichannel analyzer (4096 channels) only if the associated beta particles, which precede the gamma transitions, are registered in coincidence. Two types of beta detectors were used: plastic and liquid scintillators. In both cases, an external lead shield of 5 cm thick was used. The integral gamma background (50-1700 KeV) was reduced about 85 and 50 times, respectively. The corresponding MDA (Minimum Detectable Activity) values decreased about 1.5 and (3-7) times, respectively. The 2π sr plastic beta detector was placed on top the Ge(Li). The sample was inserted between the two detectors. The measurement time was 10 4 s. A 4π sr detector, built of the same material, was also studied, but it proved to be less advantageous because the background was reduced only 16 times; for a MDA reduction similar with that of the 2π sr variant, a longer measurement was needed (3.10 4 s). The other type of beta detector used, was a liquid scintillator. The dissolving of the samples in scintillator ensures a 4π sr measurement geometry. The vials with scintillator (10 ml volume) were placed on top the Ge(Li) and visualised by the photocathode of a phototube. This setup was surrounded by an enclosure which prevent the light penetration. The measurement time was 10 4 s. The only difficulty encountered in this low level measurement method is the accurate determination of the beta efficiency. A limitation is the possibility to measure only small mass samples. These variants are more simple and cheaper than others, previously studied. The advantage of the method is obvious when, instead of low MDA values, shorter measurement times are preferred. The
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Search for B^0 meson decays to \\pi^0 K^0_S K^0_S, \\eta K^0_S K^0_S, and \\eta^{\\prime}K^0_S K^0_S
Energy Technology Data Exchange (ETDEWEB)
Aubert, B.
2009-05-08
We describe searches for B{sup 0} meson decays to the charmless final states {pi}{sup 0}K{sub S}{sup 0}K{sub S}{sup 0}, {eta}K{sub S}{sup 0}K{sub S}{sup 0}, and {eta}{prime}K{sub S}{sup 0}K{sub S}{sup 0}. The data sample corresponds to 467 x 10{sup 6} B{bar B} pairs produced in e{sup +}e{sup -} annihilation and collected with the BABAR detector at the SLAC National Accelerator Laboratory. We find no significant signals and determine the 90% confidence level upper limits on the branching fractions, in units of 10{sup -7}, {Beta}(B{sup 0} {yields} {pi}{sup 0}K{sub S}{sup 0}K{sub S}{sup 0}) < 12, {Beta}(B{sup 0} {yields} {eta}K{sub S}{sup 0}K{sub S}{sup 0}) < 10, and {Beta}(B{sup 0} {yields} {eta}{prime}K{sub S}{sup 0}K{sub S}{sup 0}) < 20.
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Beta-Delayed Neutron Spectroscopy of 72Co with VANDLE
Keeler, Andrew; Grzywacz, Robert; King, Thomas; Taylor, Steven; Paulauskas, Stanley; Zachary, Christopher; Vandle Collaboration
2017-09-01
Measurements of simple, closed-shell isotopes far from stability provide important benchmarks for nuclear models and are a key constraint in r-process calculations. In particular, r-process models are sensitive to beta decay lifetimes and branching ratios of these neutron-rich isotopes. In this experiment, the Versatile Array of Neutron Detectors at Low Energy (VANDLE) was used to observe decays of nuclei produced by the fragmentation of 82Se at the National Superconducting Cyclotron Laboratory (NSCL). The neutron and gamma emissions of 72Co were measured to map the beta strength distribution (S_beta) above the neutron separation energy and infer the size of the Z = 28 shell gap in the 78Ni region. An implantation detector made of a radiation-hardened, inorganic scintillator was used to correlate implanted ions with beta decays as well as provide a start signal for the neutron Time of Flight measurement. Funded by the National Nuclear Security Administration under the Stewardship Science Academic Alliances program through DOE Award No. DE-NA0002132 and by the Office of Nuclear Physics, U.S. Department of Energy under Awards No. DE-FG02-96ER40983 (UTK).
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Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis
Directory of Open Access Journals (Sweden)
Burgess Juliana
2005-12-01
Full Text Available Abstract Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2 is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF, and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.
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Power output and efficiency of beta-emitting microspheres
International Nuclear Information System (INIS)
Cheneler, David; Ward, Michael
2015-01-01
Current standard methods to calculate the dose of radiation emitted during medical applications by beta-minus emitting microspheres rely on an over-simplistic formalism. This formalism is a function of the average activity of the radioisotope used and the physiological dimensions of the patient only. It neglects the variation in energy of the emitted beta particle due to self-attenuation, or self-absorption, effects related to the finite size of the sphere. Here it is assumed the sphere is comprised of a pure radioisotope with beta particles being emitted isotropically throughout the material. The full initial possible kinetic energy distribution of a beta particle is taken into account as well as the energy losses due to scattering by other atoms in the microsphere and bremsstrahlung radiation. By combining Longmire’s theory of the mean forward range of charged particles and the Rayleigh distribution to take into account the statistical nature of scattering and energy straggling, the linear attenuation, or self-absorption, coefficient for beta-emitting radioisotopes has been deduced. By analogy with gamma radiation transport in spheres, this result was used to calculate the rate of energy emitted by a beta-emitting microsphere and its efficiency. Comparisons to standard point dose kernel formulations generated using Monte Carlo data show the efficacy of the proposed method. Yttrium-90 is used as a specific example throughout, as a medically significant radioisotope, frequently used in radiation therapy for treating cancer. - Highlights: • Range-energy relationship for the beta particles in yttrium-90 is calculated. • Formalism for the semi-analytical calculation of self-absorption coefficients. • Energy-dependent self-absorption coefficient calculated for yttrium-90. • Flux rate of beta particles from a self-attenuating radioactive sphere is shown. • The efficiency of beta particle emitting radioactive microspheres is calculated
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Method of fission product beta spectra measurements for predicting reactor anti-neutrino emission
Energy Technology Data Exchange (ETDEWEB)
Asner, D.M.; Burns, K.; Campbell, L.W.; Greenfield, B.; Kos, M.S., E-mail: markskos@gmail.com; Orrell, J.L.; Schram, M.; VanDevender, B.; Wood, L.S.; Wootan, D.W.
2015-03-11
The nuclear fission process that occurs in the core of nuclear reactors results in unstable, neutron-rich fission products that subsequently beta decay and emit electron antineutrinos. These reactor neutrinos have served neutrino physics research from the initial discovery of the neutrino to today's precision measurements of neutrino mixing angles. The prediction of the absolute flux and energy spectrum of the emitted reactor neutrinos hinges upon a series of seminal papers based on measurements performed in the 1970s and 1980s. The steadily improving reactor neutrino measurement techniques and recent reconsiderations of the agreement between the predicted and observed reactor neutrino flux motivates revisiting the underlying beta spectra measurements. A method is proposed to use an accelerator proton beam delivered to an engineered target to yield a neutron field tailored to reproduce the neutron energy spectrum present in the core of an operating nuclear reactor. Foils of the primary reactor fissionable isotopes placed in this tailored neutron flux will ultimately emit beta particles from the resultant fission products. Measurement of these beta particles in a time projection chamber with a perpendicular magnetic field provides a distinctive set of systematic considerations for comparison to the original seminal beta spectra measurements. Ancillary measurements such as gamma-ray emission and post-irradiation radiochemical analysis will further constrain the absolute normalization of beta emissions per fission. The requirements for unfolding the beta spectra measured with this method into a predicted reactor neutrino spectrum are explored.
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International Nuclear Information System (INIS)
Aiyer, R.A.; Aggarwal, B.B.
1990-01-01
High affinity receptors for recombinant human tumor necrosis factor-alpha (rhTNF-alpha) were identified on membranes prepared from full term human placenta. Highly purified rhTNF-alpha iodinated by the iodogen method was found to bind placental membranes in a displaceable manner with an approximate dissociation constant (KD) of 1.9 nM. The membrane bound TNF-alpha receptor could be solubilized by several detergents with optimum extraction being obtained with 1% Triton X-100. The binding of 125I-rhTNF-alpha to the solubilized receptor was found to be time and temperature dependent, yielding maximum binding within 1 h, 24 h and 48 h at 37 degrees C, 24 degrees C and 4 degrees C, respectively. However, the maximum binding obtainable at 4 degrees C was only 40% of that at 37 degrees C. The binding 125I-rhTNF-alpha to solubilized placental membrane extracts was displaceable by unlabeled rhTNF-alpha, but not by a related protein recombinant human tumor necrosis factor-beta (rhTNF-beta; previously called lymphotoxin). This is similar to the behavior of TNF-alpha receptors derived from detergent-solubilized cell extracts, although on intact cells, both rhTNF-alpha and rhTNF-beta bind with equal affinity to TNF receptors. The Scatchard analysis of the binding data of the solubilized receptor revealed high affinity binding sites with a KD of approximately 0.5 nM and a receptor concentration of about 1 pmole/mg protein. Gel filtration of the solubilized receptor-ligand complexes on Sephacryl S-300 revealed two different peaks of radioactivity at approximate molecular masses of 50,000 Da and 400,000 Da. The 400,000 dalton peak corresponded to the receptor-ligand complex. Overall, our results suggest that high affinity receptors for TNF-alpha are present on human placental membranes and provide evidence that these receptors may be different from that of rhTNF-beta
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Preventive immunization of aged and juvenile non-human primates to beta-amyloid
Directory of Open Access Journals (Sweden)
Kofler Julia
2012-05-01
Full Text Available Abstract Background Immunization against beta-amyloid (Aβ is a promising approach for the treatment of Alzheimer’s disease, but the optimal timing for the vaccination remains to be determined. Preventive immunization approaches may be more efficacious and associated with fewer side-effects; however, there is only limited information available from primate models about the effects of preclinical vaccination on brain amyloid composition and the neuroinflammatory milieu. Methods Ten non-human primates (NHP of advanced age (18–26 years and eight 2-year-old juvenile NHPs were immunized at 0, 2, 6, 10 and 14 weeks with aggregated Aβ42 admixed with monophosphoryl lipid A as adjuvant, and monitored for up to 6 months. Anti-Aβ antibody levels and immune activation markers were assessed in plasma and cerebrospinal fluid samples before and at several time-points after immunization. Microglial activity was determined by [11C]PK11195 PET scans acquired before and after immunization, and by post-mortem immunohistochemical and real-time PCR evaluation. Aβ oligomer composition was assessed by immunoblot analysis in the frontal cortex of aged immunized and non-immunized control animals. Results All juvenile animals developed a strong and sustained serum anti-Aβ IgG antibody response, whereas only 80 % of aged animals developed detectable antibodies. The immune response in aged monkeys was more delayed and significantly weaker, and was also more variable between animals. Pre- and post-immunization [11C]PK11195 PET scans showed no evidence of vaccine-related microglial activation. Post-mortem brain tissue analysis indicated a low overall amyloid burden, but revealed a significant shift in oligomer size with an increase in the dimer:pentamer ratio in aged immunized animals compared with non-immunized controls (P Conclusions Our results indicate that preventive Aβ immunization is a safe therapeutic approach lacking adverse CNS immune system
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On Marx’s human significance, Harvey’s right to the city, and Nussbaum’s capability approach
Basta, C.
2017-01-01
In this article, I juxtapose David Harvey’s idea of the ‘right to the city’ and Martha Nussbaum’s central human capability of ‘control over one’s environment’, and I approach them from the perspective of their mutual convergence on Marx’s conception of human significance. In particular,
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Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.
Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko
2017-07-17
Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.
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Pype, Stefan; Moechars, Dieder; Dillen, Lieve; Mercken, Marc
2003-02-01
Alzheimer's disease (AD) is marked by the presence of neurofibrillary tangles and amyloid plaques in the brain of patients. To study plaque formation, we report on further quantitative and qualitative analysis of human and mouse amyloid beta peptides (Abeta) from brain extracts of transgenic mice overexpressing the London mutant of human amyloid precursor protein (APP). Using enzyme-linked immunosorbant assays (ELISAs) specific for either human or rodent Abeta, we found that the peptides from both species aggregated to form plaques. The ratios of deposited Abeta1-42/1-40 were in the order of 2-3 for human and 8-9 for mouse peptides, indicating preferential deposition of Abeta42. We also determined the identity and relative levels of other Abeta variants present in protein extracts from soluble and insoluble brain fractions. This was done by combined immunoprecipitation and mass spectrometry (IP/MS). The most prominent peptides truncated either at the carboxyl- or the amino-terminus were Abeta1-38 and Abeta11-42, respectively, and the latter was strongly enriched in the extracts of deposited peptides. Taken together, our data indicate that plaques of APP-London transgenic mice consist of aggregates of multiple human and mouse Abeta variants, and the human variants that we identified were previously detected in brain extracts of AD patients.
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International Nuclear Information System (INIS)
Dryak, P.; Zderadicka, J.; Plch, J.; Kokta, L.; Novotna, P.
1977-01-01
For the purpose of beta spectrometry, a semiconductor spectrometer with one Si(Li) detector cooled with liquid nitrogen was designed. Geometrical detection efficiency is about 10% 4 sr. The achieved resolution for 624 keV conversion electrons of sup(137m)Ba is 2.6 keV (FWHM). A program was written in the FORTRAN language for the correction of the deformation of the measured spectra by backscattering in the analysis of continuous beta spectra. The method permits the determination of the maximum energy of the beta spectrum with an accuracy of +-5 keV. (author)
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Energy Technology Data Exchange (ETDEWEB)
Bergstroem, K.A. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden)]|[Kuopio University Hospital, Clinical Physiology, FIN-70210 Kuopio (Finland); Halldin, C. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Hall, H. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Lundkvist, C. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Ginovart, N. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Swahn, C.G. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Farde, L. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden)
1997-06-10
Radiolabelled 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane ({beta}-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2{beta}-Carbomethoxy-3{beta}-(4-iodophenyl)nortropane (nor-{beta}-CIT) is a des-methyl analogue of {beta}-CIT, which in vitro has tenfold higher affinity (IC{sub 50}=0.36 nM) to the serotonin transporter than {beta}-CIT (IC{sub 50}=4.2 nM). Nor-{beta}-CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor-{beta}-CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [{sup 125}I]nor-{beta}-CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 {mu}M) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [{sup 11}C]nor-{beta}-CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [{sup 11}C]nor-{beta}-CIT were 20%-40% higher than those previously obtained with [{sup 11}C]{beta}-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor-{beta}-CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain. (orig.). With 4 figs.
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Directory of Open Access Journals (Sweden)
Sierra O
2012-06-01
Full Text Available El 29 de octubre de 2005 el huracán Beta, de categoría 1 pasó a 15 km norte de la isla de Providencia, Caribe colombiano. Con el propósito de determinar eventuales cambios estructurales de las praderas de fanerógamas marinas, se monitorearon cuatro praderas de Thalassia testudinum Banks ex König alrededor de la isla, uno y dos años después del paso del huracán. Se seleccionaron dos sitios no afectados y dos afectados por el paso del huracán. Se observó que las praderas de pastos marinos en la isla de Providencia parecen sanas y sin signos de alteraciones significativas ocasionadas por el huracán Beta. La única posible alteración de tipo estructural, fue devolver a un estado sucesional más temprano a este ecosistema en las zonas afectadas, alteración que actualmente parece haberse superado.
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Hwang, Jae-Ho; Parton, Angela; Czechanski, Anne; Ballatori, Nazzareno; Barnes, David
2008-01-01
The organic solute and steroid transporter (OST/Ost) is a unique membrane transport protein heterodimer composed of subunits designated alpha and beta, that transports conjugated steroids and prostaglandin E2 across the plasma membrane. Ost was first identified in the liver of the cartilaginous fish Leucoraja erinacea, the little skate, and subsequently was found in many other species, including humans and rodents. The present study describes the isolation of a new cell line, LEE-1, derived from an early embryo of L. erinacea, and characterizes the expression of Ost in these cells. The mRNA size and amino acid sequence of Ost-beta in LEE-1 was identical to that previously reported for Ost-beta from skate liver, and the primary structure was identical to that of the spiny dogfish shark (Squalus acanthias) with the exception of a single amino acid. Ost-beta was found both on the plasma membrane and intracellularly in LEE-1 cells, consistent with its localization in other cell types. Interestingly, arachidonic acid, the precursor to eiconsanoids, strongly induced Ost-beta expression in LEE-1 cells and a lipid mixture containing arachidonic acid also induced Ost-alpha. Overall, the present study describes the isolation of a novel marine cell line, and shows that this cell line expresses relatively high levels of Ost when cultured in the presence of arachidonic acid. Although the function of this transport protein in embryo-derived cells is unknown, it may play a role in the disposition of eicosanoids or steroid-derived molecules. PMID:18407792
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Saitoh, Morihisa; Kunitomo, Jun; Kimura, Eiji; Yamano, Toru; Itoh, Fumio; Kori, Masakuni
2010-09-01
Glycogen synthase kinase 3beta (GSK-3beta) inhibitors are expected to be attractive therapeutic agents for the treatment of Alzheimer's disease (AD). Recently we discovered sulfoxides (S)-1 as a novel GSK-3beta inhibitor having in vivo efficacy. We investigated practical asymmetric preparation methods for the scale-up synthesis of (S)-1. The highly enantioselective synthesis of (S)-1 (94% ee) was achieved by titanium-mediated oxidation with D-(-)-diethyl tartrate on gram scale.
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Identification of active anti-inflammatory principles of beta- beta ...
African Journals Online (AJOL)
chromatography. Components of the extracts were identified by thin layer chromatography (TLC) scanner and UV-visible spectroscopy, using scopoletin as standard. Results: ... basic coumarin skeleton ring structure reduce ... Figure 2: Thin-layer chromatogram: (1) Ethanol extract; (2) Dichloromethane fraction; (3) Beta-beta.
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Possible Depolarization Mechanism due to Low Beta Squeeze
International Nuclear Information System (INIS)
Ranjbar, V.; Luccio, A.; Bai, M.
2008-01-01
Simulations reveal a potential depolarization mechanism during low beta squeeze. This depolarization appears to be driven by a spin tune modulation caused by spin precession through the strong low beta quads due to the vertical fields. The modulation of the spin tune introduces an additional snake resonance condition at ν s0 ± nν x - ν z l = integer which while the same numerology as the well known sextupole resonance, can operate in the absence of sextupole elements
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Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis
DEFF Research Database (Denmark)
Aszodi, Attila; Hunziker, Ernst B; Brakebusch, Cord
2003-01-01
Beta1 integrins are highly expressed on chondrocytes, where they mediate adhesion to cartilage matrix proteins. To assess the functions of beta1 integrin during skeletogenesis, we inactivated the beta1 integrin gene in chondrocytes. We show here that these mutant mice develop a chondrodysplasia...... of various severity. beta1-deficient chondrocytes had an abnormal shape and failed to arrange into columns in the growth plate. This is caused by a lack of motility, which is in turn caused by a loss of adhesion to collagen type II, reduced binding to and impaired spreading on fibronectin, and an abnormal F......-actin organization. In addition, mutant chondrocytes show decreased proliferation caused by a defect in G1/S transition and cytokinesis. The G1/S defect is, at least partially, caused by overexpression of Fgfr3, nuclear translocation of Stat1/Stat5a, and up-regulation of the cell cycle inhibitors p16 and p21...
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Lutters, B. C.; Meijers, J. C.; Derksen, R. H.; Arnout, J.; de Groot, P. G.
2001-01-01
Anti-beta(2)-glycoprotein I antibodies are thought to cause lupus anticoagulant activity by forming bivalent complexes with beta(2)-glycoprotein I (beta(2)GPI). To test this hypothesis, chimeric fusion proteins were constructed of the dimerization domain (apple 4) of factor XI and beta(2)GPI. Both a
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Exercise- and cold-induced changes in plasma beta-endorphin and beta-lipotropin in men and women.
Viswanathan, M; Van Dijk, J P; Graham, T E; Bonen, A; George, J C
1987-02-01
The plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) response of men, eumenorrheic women, and amenorrheic women (n = 6) to 1 h of rest or to a bicycle ergometer test [20 min at 30% maximum O2 uptake (VO2max), 20 min at 60% VO2max, and at 90% VO2max to exhaustion] was studied in both normal (22 degrees C) and cold (5 degrees C) environments. beta-EP and beta-LPH was measured by radioimmunoassay in venous samples collected every 20 min during rest or after each exercise bout. Exhaustive exercise at ambient temperature (Ta) 22 degrees C induced significant increases in plasma beta-EP and beta-LPH in all subjects as did work at 60% VO2max in amenorrheic and eumenorrheic women. During work at Ta 5 degrees C, the relative increase in beta-EP and beta-LPH was suppressed in eumenorrheic women and completely prevented in amenorrheic women. Although significant lowering of beta-EP and beta-LPH was observed in men and eumenorrheic women during rest at 5 degrees C, amenorrheic women maintained precold exposure levels. These findings suggest that plasma beta-EP and beta-LPH may reflect a thermoregulatory response to heat load. There appears to be a sexual dimorphism in exercise- and cold-induced release of beta-EP and beta-LPH and amenorrhea may be accompanied by alterations in these responses.
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Clearance from cerebrospinal fluid of intrathecally administered beta-endorphin in monkeys
Energy Technology Data Exchange (ETDEWEB)
Lee, V.C.; Burns, R.S.; Dubois, M.; Cohen, M.R.
1984-05-01
Five adult male monkeys (Macaca mulatta) weighing 7.1-9.9 kg were given synthetic human beta-endorphin (800 micrograms) and (/sup 14/C)methoxy-inulin (50 microCi) in 400 microliters of normal saline intrathecally. Serial samples of cerebrospinal fluid were drawn through a previously positioned indwelling spinal catheter and were assayed for concentrations of beta-endorphin (determined by radioimmunoassay) and inulin (determined by liquid scintillation counter). Spinal fluid concentrations of beta-endorphin and inulin peaked and declined in a parallel manner. The clearance ratio (calculated from the reciprocal of the ratio of the areas under the respective curves of elimination of the two species) remained remarkably similar from animal to animal, giving a mean value of 1.060 +/- 0.090 (SEM). This ratio, being near unity, suggests that beta-endorphin is eliminated from spinal fluid in a fashion similar to that of inulin, which is removed exclusively by bulk absorption.