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B1
Kinds of B1 Terms modified by B1 Selected AbstractsProposing magnetic nanoparticle hyperthermia in low-field MRICONCEPTS IN MAGNETIC RESONANCE, Issue 1 2010Pádraig Cantillon-Murphy Abstract This work examines feasibility, practical advantages, and disadvantages of a combined MRI/magnetic particle hyperthermia (MPH) system for cancerous tumor treatment in low perfusion tissue. Although combined MRI/hyperthermia systems have been proposed and constructed, the current proposal differs because the hyperthermia system would be specifically designed to interact with the magnetic nanoparticles injected at the tumor site. The proposal exploits the physical similarities between the magnetic nanoparticles currently employed for MPH and those used as superparamagnetic iron oxide (SPIO) contrast agents in MR imaging. The proposal involves the addition of a rotating magnetic field RF hyperthermia source perpendicular to the MRI B0 field which operates in a similar manner to the MRI RF excitation field, B1, but at significantly higher frequency and field strength such that the magnetic nanoparticles are forced to rotate in its presence. This rotation is the source of increases in temperature which are of therapeutic benefit in cancer therapy. For rotating magnetic fields with amplitudes much smaller than B0, the nanoparticles' suspension magnetization rapidly saturates with increasing B0. Therefore, the proposal is best suited to low-field MRI systems when magnetic saturation is incomplete. In addition, careful design of the RF hyperthermia source is required to ensure no physical or RF interference with the B1 field used for MRI excitation. Notwithstanding these caveats, the authors have shown that localized steady-state temperature rises in small spherical tumors of up to 10°C are conceivable with careful selection of the nanoparticle radius and concentration, RF hyperthermia field amplitude and frequency. © 2010 Wiley Periodicals, Inc. Concepts Magn Reson Part A 36A: 36,47, 2010. [source] The hydrogen atom, revisited: Parallel-field magnetic resonance,CONCEPTS IN MAGNETIC RESONANCE, Issue 5 2006John A. Weil Abstract Consideration of the magnetic resonance spectroscopy of the free hydrogen atom (1H0) reveals that, in addition to the well-known transitions (EPR and NMR) occurring between the four spin states when the excitation magnetic field B1 is perpendicular to the static external field B, there exists a combination line (simultaneous electronic and nuclear spin flips) when B1 , B, which becomes strong under some circumstances. The latter phenomenon is focused on and discussed herein, in some detail. © 2006 Wiley Periodicals, Inc. Concepts Magn Reson Part A 28A: 331,336, 2006 [source] Loop Diuretic Therapy, Thiamine Balance, and Heart FailureCONGESTIVE HEART FAILURE, Issue 4 2007Domenic A. Sica MD Thiamine, or vitamin B1, is a water-soluble B complex vitamin that was first discovered in 1910 in the process of exploring how rice bran cured patients of beriberi. Thiamine is not synthesized in humans, therefore its availability for necessary cellular processes hinges on its continual ingestion. The amount of thiamine one needs to ingest to maintain balance is disease state-dependent or medication-dependent. Severe chronic thiamine deficiency can have significant neurologic and cardiac effects, the latter is reflected in a particular type of heart failure called wet beriberi. This form of heart failure clearly benefits from thiamine supplementation. It is unclear, however, whether thiamine supplementation offers any benefit in other forms of heart failure. Despite this, it is not unreasonable for heart failure patients to routinely ingest a thiamine-containing multivitamin; patients using diuretics have an increased urinary excretion of thiamine and thus are at a higher risk for developing thiamine deficiency. The role of thiamine in heart failure, however, remains arguable. [source] From Red Lists to Species of Conservation ConcernCONSERVATION BIOLOGY, Issue 6 2004VERENA KELLER aves; conservación de especies; listas rojas; prioridades de conservación; Suiza Abstract:,National red lists of threatened animal and plant species prepared according to the criteria of the World Conservation Union (IUCN) adequately reflect the extinction risk of species within a country but cannot be used directly to set conservation priorities. In particular, the significance of national populations for the conservation of the species as a whole is not taken into account. We present a procedure that can be used to assess national responsibility based on the national red-list status of a species, the international importance of the national population, and the species' "historical rarity" status. We distinguished five responsibility classes for breeding birds: B1, threatened species with internationally important populations in Switzerland; B2, threatened species with internationally less important populations; B3, nonthreatened species with internationally important populations; B4, nonthreatened species with internationally less important populations; and B5, species that have never been common in Switzerland. Two responsibility classes were distinguished for birds occurring in Switzerland as visitors: G1, species with large concentrations in Switzerland and an unfavorable conservation status in Europe, and G2, species with large concentrations in Switzerland and a favorable conservation status in Europe. Two additional classes (G3 and G4) for visiting species occurring in internationally less important numbers are possible but were not analyzed in detail. Responsibility classes B1, B2, B3, G1, and G2 were defined as species of national conservation concern. We developed the method for birds in Switzerland, but it can be used in other countries and for other taxonomic groups as well. It is particularly suitable where national red lists are established according to IUCN guidelines. Resumen:,Las listas rojas nacionales de especies de animales y plantas amenazadas que siguen los criterios de la World Conservation Union (IUCN) reflejan adecuadamente el riesgo de extinción de especies en un país pero no pueden ser utilizadas directamente para definir prioridades de conservación. En particular, no se toma en cuenta el significado de poblaciones nacionales para la conservación de especies como tales. Presentamos un procedimiento que se puede utilizar para evaluar la responsabilidad nacional con base en el estatus de lista roja de una especie en un país, la importancia internacional de la población nacional y el estatus de "rareza histórica" de la especie. Distinguimos cinco clases de responsabilidad para aves residentes: B1, especies amenazadas con poblaciones internacionalmente importantes en Suiza; B2, especies amenazadas con poblaciones internacionalmente menos importantes; B3, especies no amenazadas con poblaciones internacionalmente importantes; B4, especies no amenazadas con poblaciones internacionalmente menos importantes; y B5, especies que nunca han sido comunes en Suiza. Se distinguieron dos clases de responsabilidad para aves que ocurren como visitantes en Suiza: G1, especies con grandes concentraciones en Suiza y un estatus de conservación desfavorable en Europa y G2, especies con grandes concentraciones en Suiza y un estatus de conservación favorable en Europa. Son posibles dos clases más, (G3 y G4) para especies visitantes que ocurren en números menos importantes internacionalmente, pero no fueron analizados en detalle. Las clases de responsabilidad B1, B2, B3, G1 y G2 fueron definidas como especies de interés nacional para la conservación. Desarrollamos el método para aves en Suiza, pero también se puede utilizar en otros países y con otros grupos taxonómicos, Es particularmente adecuado donde las listas rojas nacionales se establecen de acuerdo con lineamientos de IUCN. [source] Training response of mitochondrial transcription factors in human skeletal muscleACTA PHYSIOLOGICA, Issue 1 2010J. Norrbom Abstract Aim:, Mitochondrial function is essential for physical performance and health. Aerobic fitness is positively associated with mitochondrial (mt) biogenesis in muscle cells through partly unknown regulatory mechanisms. The present study aimed to investigate the influence of exercise and training status on key mt transcription factors in relation to oxidative capacity in human skeletal muscle. Methods:, The basal mRNA and protein levels of mitochondrial transcription factor A (TFAM), mitochondrial transcription factors B1 (TFB1M) or B2 (TFB2M), and mRNA levels of mitochondrial transcription termination factor (mTERF), were measured in a cross-sectional study with elite athletes (EA) and moderately active (MA) and the basal mRNA levels of these factors were measured during a 10-day endurance training programme with (R-leg) and without (NR-leg) restricted blood flow to the working leg. Results:, TFAM protein expression was significantly higher in the EA than in the MA, while protein levels of TFB1M and TFB2M were not different between the groups. There was no difference between EA and MA, or any effect with training on TFAM mRNA levels. However, the mRNA levels of TFB1M, TFB2M and mTERF were higher in EA compared with MA. For TFB1M and TFB2M, the mRNA expression was increased in the R-leg after 10 days of training, but not in the NR-leg. mTERF mRNA levels were higher in EA compared with MA. Conclusion:, This study further establishes that TFAM protein levels are higher in conditions with enhanced oxidative capacity. The mRNA levels of TFB1M and TFB2M are influenced by endurance training, possibly suggesting a role for these factors in the regulation of exercise-induced mitochondrial biogenesis. [source] Expression patterns and cell cycle profiles of PCNA, MCM6, cyclin D1, cyclin A2, cyclin B1, and phosphorylated histone H3 in the developing mouse retinaDEVELOPMENTAL DYNAMICS, Issue 3 2008Kirston M. Barton Abstract A challenge in studying organogenesis is the ability to identify progenitor cell populations. To address this problem, we characterized the expression patterns of cell cycle proteins during mouse retinal development and used flow cytometry to determine the expression profiles in the cell cycle. We found that MCM6 and PCNA are expressed in essentially all retinal progenitor cells throughout the proliferative period and these proteins are readily detectable in all cell cycle phases. Furthermore, their expression levels are downregulated as cells exit the cell cycle and differentiate. We also analyzed the expression of Cyclins D1, A2, and B1, and phosphorylated Histone H3 and found unexpected expression patterns and cell cycle profiles. The combined utilization of the markers tested and the use of flow cytometry should further facilitate the study of stem and progenitor cell behavior during development and in adult tissues. Developmental Dynamics 237:672,682, 2008. © 2008 Wiley-Liss, Inc. [source] Changes in gravitational force cause changes in gene expression in the lens of developing zebrafishDEVELOPMENTAL DYNAMICS, Issue 10 2006Naoko Shimada Abstract Gravity has been a constant physical factor during the evolution and development of life on Earth. We have been studying effects of simulated microgravity on gene expression in transgenic zebrafish embryos expressing gfp under the influence of gene-specific promoters. In this study, we assessed the effect of microgravity on the expression of the heat shock protein 70 (hsp70) gene in lens during development using transgenic zebrafish embryos expressing gfp under the control of hsp70 promoter/enhancer. Hsp70:gfp expression was up-regulated (45%) compared with controls during the developmental period that included the lens differentiation stage. This increase was lens specific, because the entire embryo showed only a 4% increase in gfp expression. Northern blot and in situ hybridization analysis indicated that the hsp70:gfp expression recapitulated endogenous hsp70 mRNA expression. Hypergravity exposure also increased hsp70 expression during the same period. In situ hybridization analysis for two lens-specific crystallin genes revealed that neither micro- nor hypergravity affected the expression level of ,B1 - crystallin, a non-hsp gene used as a marker for lens differentiation. However, hypergravity changed the expression level of ,A - crystallin, a member of the small hsp gene family. Terminal deoxynucleotidyl transferase,mediated deoxyuridinetriphosphate nick end-labeling (TUNEL) assay analysis showed that altered-gravity (,g) decreased apoptosis in lens during the same period and the decrease correlated with the up-regulation of hsp70 expression, suggesting that elimination of nuclei from differentiating lens fiber cells was suppressed probably through hsp70 up-regulation. These results support the idea that ,g influences hsp70 expression and differentiation in lens-specific and developmental period specific manners and that hsp family genes play a specific role in the response to ,g. Developmental Dynamics 235:2686,2694, 2006. © 2006 Wiley-Liss, Inc. [source] Effect of muscle activity and botulinum toxin dilution volume on muscle paralysisDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 3 2003Hyeon Sook Kim MD PhD The purpose of this study was to evaluate the effects of botulinum toxin A (BTX-A, Botox) dilution volume and post-injection exercise with electrical stimulation on muscle paralysis. We injected 10 units of BTX-A diluted with 0.1 ml (B1, n=8) or 0.5 ml (B5, n=8) normal saline into both gastrocnemius muscles of 16 New Zealand white rabbits; two controls received no BTX-A. After BTX-A injection, all rabbits received calf muscle stretching exercise and electrical stimulation for 2 hours on the left leg. The compound muscle action potential (CMAP) decrease was most pronounced at 1 week and progressive recovery was observed (i.e. recovery from paralysis, increase of CMAP). There was a significant decrease of CMAP amplitudes in the B5 group compared with the B1 group at week 1 and week 4 (p<0.001). Left limbs with stretching exercise and electrical stimulation showed lower CMAP amplitudes compared with control right limbs of all rabbits. To maximize the muscle paralysis effect of BTX-A, increasing dilution volume and performing post-injection stretching exercise with electrical stimulation may be a promising strategy for increasing the beneficial effect of BTX-A treatment. Future studies are needed to investigate the clinical application of this finding. [source] Induction of G2/M phase arrest and apoptosis by a novel indoloquinoline derivative, IQDMA, in K562 cellsDRUG DEVELOPMENT RESEARCH, Issue 9 2006Yi-Hsiung Lin Abstract The indoloquinoline, IQDMA (N,-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine), was identified as a novel antineoplastic agent with broad spectrum of antitumor activities against several human cancer cells. IQDMA-induced G2/M arrest was accompanied by up-regulation of the cyclin-dependent kinase inhibitors (CDKIs), p21 and p27, and down-regulation of Cdk1and Cdk2. IQDMA had no effect on the levels of cyclin A, cyclin B1, cyclin D3, or Cdc25C. IQDMA also increased apoptosis, as characterized by apoptotic body formation, increase of the sub G1 population and poly (ADP-ribose) polymerase (PARP) cleavage. Further mechanistic analysis demonstrated that IQDMA upregulated FasL protein expression, and kinetic studies showed the sequential activation of caspases-8, -3, and -9. Both caspase-8 and caspase-3 inhibitors, but not a caspase-9-specific inhibitor, suppressed IQDMA-induced cell death. These molecular alterations provide an insight into IQDMA-caused growth inhibition, G2/M arrest, and apoptotic death of K562 cells. Drug Dev. Res. 67:743,751, 2006. © 2006 Wiley-Liss, Inc. [source] Production of paramylon, a ,-1,3-glucan, by heterotrophic cultivation of Euglena gracilis on potato liquorENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 2 2010Bozidar, antek Abstract Euglena gracilis is shown to be able to grow on potato liquor as the main medium component leading to an interesting biotechnological product represented by paramylon , a ,-1,3-glucan , and, at the same time, revaluating an otherwise annoying waste stream of the potato-starch industry. Paramylon mass fractions of about 75% are obtained for biomass concentrations of 15,g/L during simple batch cultivation under heterotrophic conditions. Supplementation of the growth medium with glucose and the vitamins B1 and B12 are shown to improve growth rate as well as paramylon content. E. gracilis grows best at about 27.5°C without requiring pH control. [source] Assigning Escherichia coli strains to phylogenetic groups: multi-locus sequence typing versus the PCR triplex methodENVIRONMENTAL MICROBIOLOGY, Issue 10 2008David M. Gordon Summary It is well recognized that Escherichia coli consists of a number of distinct phylo-groups and that strains of the different phylo-groups vary in their ecological niches, life-history characteristics and propensity to cause disease. Consequently, much can be learnt by assigning a strain of E. coli to one of the recognized phylo-groups. A triplex PCR-based method that enables strains of E. coli to be assigned to a phylo-group using a dichotomous key approach based on the presence or absence of two genes (chuA and yjaA) and an anonymous DNA fragment (TSPE4.C2) has been developed. However, the accuracy with which this method assigns strains to their correct phylo-group has not been adequately evaluated. Consequently, 662 strains of E. coli were characterized using a multi-locus sequence typing approach. Unsupervised population assignment algorithms were used to assign strains to phylo-groups based on the multi-locus sequence typing data. The analyses revealed that 85,90% of E. coli strains can be assigned to a phylo-group and that 80,85% of the phylo-group memberships assigned using the Clermont method are correct. However, the accuracy with which strains are assigned to the correct phylo-group depends on their Clermont genotype. For example, strains yielding a Clermont genotype consistent with phylo-groups B1 and B2 are assigned correctly 95% of the time. Strains failing to yield any PCR products using the Clermont method are seldom members of phylo-group A and strains with such a genotype should not be assigned to a phylo-group. [source] CD34+ cells derived from fetal liver contained a high proportion of immature megakaryocytic progenitor cellsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2000Dong-Chu Ma Abstract: Endoreplication and maturation of the megakaryocyte (MK) may be retarded or delayed during ontogenesis. In this study, CD34+ cells were isolated from both human fetal liver and adult bone marrow and incubated with thrombopoietin (TPO). The cell number, morphological characteristics, platelet-associated antigen phenotype, maturation stage and DNA ploidy of CD41+cells were examined from day 0 to day 12 in culture. 1) TPO stimulated the proliferation of fetal liver (FL)-derived CD34+ cells with a mean 73.14-fold increase of CD41+ cells after 12 d in culture. Adult BM-derived CD34+ cells increased only slightly, with a mean 8.18-fold increase of CD41+ cells. 2) Although the membrane phenotype of both FL CD34+ -derived MKs and BM CD34+ -derived MKs analyzed with CD41a, CD42a, CD61 and CD34 were similar, all FL CD34+ -derived MKs were in maturation stage I and II and in low ploidy (<4N) class. By comparison, BM CD34+ MKs possessed 15% MKs in maturation stage III and IV and with 23% MKs in high ploidy class (>4N). 3) Most of cultured FL-derived CD34+ cells did not have a well developed demarcation system (DM) and numerous ,-granules after 12 d incubation. von Willebrand factor (vWF) appeared earlier on the cultured BM-derived CD34+ cells than on FL-derived CD34+ cells. 4) The expression of both cyclin E and cyclin B1 progressively increased in FL CD34+cells induced by TPO during 12 d in culture. 5) The expression of cyclin D1 gradually decreased in FL CD34+cells induced by TPO over 12 d incubation. 6) Immunocytochemical analysis showed that cyclin D3 was detected only in cytoplasm of cultured FL-derived CD34+ cells, whereas in both cytoplasm and nuclei of cultured BM-derived CD34+ cells. These data suggest that FL-derived CD34+ cells contain a high proportion of immature megakaryocytic progenitor cells. It further suggests that TPO can push these progenitor cells into proliferation by upregulating the expression of cyclins B1 and E, and drive a high proportion of cells into megakaryocytic lineage. [source] c-Rel phenocopies PKC, but not Bcl-10 in regulating CD8+ T-cell activation versus tolerance,EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2010Elissa K. Deenick Abstract Elucidating the signaling events that promote T-cell tolerance versus activation provides important insights for manipulating immunity in vivo. Previous studies have suggested that the absence of PKC, results in the induction of anergy and that the balance between the induction of the transcription factors NFAT, AP1 and NF-,B plays a key role in determining whether T-cell anergy or activation is induced. Here, we examine whether Bcl-10 and specific family members of NF-,B act downstream of PKC, to alter CD8+ T-cell activation and/or anergy. We showed that T cells from mice deficient in c-Rel but not NF-,B1 (p50) have increased susceptibility to the induction of anergy, similar to T cells from PKC,-deficient mice. Surprisingly T cells from Bcl-10-deficient mice showed a strikingly different phenotype to the PKC,-deficient T cells, with a severe block in TCR-mediated activation. Furthermore, we have also shown that survival signals downstream of NF-,B, are uncoupled from signals that mediate T-cell anergy. These results suggest that c-Rel plays a critical role downstream of PKC, in controlling CD8+ T-cell anergy induction. [source] Systemic IFN-, drives kidney nephritis in B6.Sle123 miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Anna-Marie Fairhurst Abstract The impact of IFN-, secretion on disease progression was assessed by comparing phenotypic changes in the lupus-prone B6.Sle1Sle2Sle3 (B6.Sle123) strain and the parental C57BL/6 (B6) congenic partner using an adenovirus (ADV) expression vector containing a recombinant IFN-, gene cassette (IFN-ADV). A comprehensive comparison of cell lineage composition and activation in young B6 and B6.Sle123 mice revealed a variety of cellular alterations in the presence and absence of systemic IFN-,. Most IFN-,-induced phenotypes were similar in B6 and B6.Sle123 mice; however, B6.Sle123 mice uniquely exhibited increased B1 and plasma cells after IFN-, exposure, although both strains had an overall loss of mature B cells in the bone marrow, spleen and periphery. Although most of the cellular effects of IFN-, were identical in both strains, severe glomerulonephritis occurred only in B6.Sle123 mice. Mice injected with IFN-ADV showed an increase in immune complex deposition in the kidney, together with an unexpected decrease in serum anti-nuclear antibody levels. In summary, the predominant impact of systemic IFN-, in this murine model is an exacerbation of mechanisms mediating end organ damage. [source] Immune modulation of HLA-G dimer in maternal-fetal interfaceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007Kimiko Kuroki Abstract HLA-G is a non-classical human MHC class I molecule, which has several characteristics distinct from classical MHC, such as low polymorphism and restricted tissue distribution. HLA-G is expressed on placenta, thymus and some tumors. At the maternal-fetal interface, trophoblasts do not express major classical MHC class I molecules (MHCI), HLA-A and -B, to prevent normal T cell responses. Instead, HLA-G is expressed and can suppress a wide range of immune responses by binding to inhibitory immune cell surface receptors, such as leukocyte Ig-like receptor (LILR) B1 and LILRB2. HLA-G exists in various forms, including ,2m-associated or -free disulfide-linked dimers that can be expressed either at the cell surface or in soluble form. However, until recently the physiological role of these different molecular forms has been unclear. In this issue of the European Journal of Immunology, one article demonstrates that the disulfide-linked homodimer of ,2m-associated HLA-G is the major fraction expressed by trophoblast cells. The HLA-G dimer modulates the function of LILRB1-expressing antigen-presenting cells by principally binding to LILRB1. On the other hand, another recent report showed that ,2m-free disulfide-linked HLA-G dimers are produced by villous cytotrophoblast cells. Taken together, these results provide strong evidence in support of the hypothesis that HLA-G dimers play a role in immune suppression at the maternal-fetal interface. Further in-depth investigation will help to clarify the precise mechanism of HLA-G receptor recognition and signaling in vivo and the role of these interactions in successful reproduction. See accompanying article: http://dx.doi.org/10.1002/eji.200737089 [source] Toll-like receptor stimulation induces airway hyper-responsiveness to bradykinin, an effect mediated by JNK and NF-,B signaling pathwaysEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2004Ofir Bachar Abstract Airway infections induce hyper-responsiveness in asthmatic patients. Toll-like receptors (TLR) mediate inflammatory responses to microbes. Occurrence and effects of TLR2, TLR3 and TLR4 were examined in a mouse organ culture model of asthma focusing on the smooth muscle responses to bradykinin. TLR2, TLR3 and TLR4 mRNA, and TLR2 and TLR4 immunoreactivity were detected in the tracheal muscle layer. Tracheal organ culture for 1 or 4,days with lipopolysaccharide (LPS; TLR2/4 agonist) or polyinosinic polycytidylic acid (poly-I-C; TLR3 agonist) enhanced bradykinin- and [des-Arg9]-bradykinin-induced contractions. Simultaneous LPS and poly-I-C treatment resulted in synergistic enhancement of bradykinin-induced contraction. In carbachol-pre-contracted segments TLR stimulationinduced less potent relaxations to bradykinin and [des-Arg9]-bradykinin. The LPS and poly-I-C enhancement of bradykinin-induced contraction was inhibited by the transcriptional inhibitor actinomycin-D, dexamethasone, the proteasome inhibitor MG-132 and the c-Jun N-terminal kinase (JNK) inhibitor SP600125. LPS and poly-I-C induced translocation of NF-,B p65 to the nucleus and up-regulation of kinin B1 and B2 receptor mRNA. In summary, TLR2, TLR3 and TLR4 are expressed in the mouse tracheal smooth muscle. Costimulation of these receptors results in NF-,B- and JNK-mediated transcription of B1 and B2 receptor, inducing hyper-responsiveness to bradykinin. [source] Combinations of Acidic and Basic Monodentate Binaphtholic Phosphites as Supramolecular Bidentate Ligands for Enantioselective Rh-Catalyzed HydrogenationsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2009Luca Pignataro Abstract A small library of chiral BINOL-derived monodentate phosphites containing either a carboxylic acid (-COOH, A1,A3) or a tertiary amine (-NMe2, B1,B4) was synthesized. The ligand combinations were screened in the enantioselective rhodium-catalyzed hydrogenation of methyl 2-acetamidoacrylate. The heterocombinations of the amine-derived phosphite (R)- B2 and of a carboxylic-phosphite [(R)- A1, (R)- A2, (R)- A3] displayed a slightly higher level of enantioselectivity compared to the corresponding homocombinations [up to 90,% ee using (R)- A1/(R)- B2]. The nature and extent of the interaction between the acidic and basic ligands in the rhodium complexes were studied by IR and 31P-NMR spectroscopy. The formation of an intramolecular salt in the Rh-heterocomplex, between the carboxylic acid and the tertiary amine, was suggested by the IR spectra. The selective formation of the Rh-heterocomplex was quantitatively assessed by 31P-NMR spectroscopy, using a modified acidic ligand (R)- A1-Me. In this way, a moderate (ca. 70:30) heterocomplex/homocomplexes ratio was determined.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] An Improved Synthesis of Procyanidin Dimers: Regio- and Stereocontrol of the Interflavan BondEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 23 2006Isabelle Tarascou Abstract A direct and general synthesis of procyanidin dimers B1, B2, B3 and B4 (10a,d) is presented. The approach is based on the stoichiometric coupling of two protected monomeric units (the nucleophilic 2a,b and electrophilic 4a,b partners) and deals with the regio- and stereocontrol of the C4,C8 interflavan bond as well as the control of the degree of oligomerization. The synthesis involves a five-step pathway starting from the native catechin (1a) or epicatechin (1b) to the fully deprotected dimers 10a,d. Furthermore, the process appears to be iterative as the coupling intermediates 9a,d themselves can be readily used in further selective syntheses of trimers or higher oligomers. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Cyrmenins, Novel Antifungal Peptides Containing a Nitrogen-Linked ,-Methoxyacrylate Pharmacophore: Isolation and Structural ElucidationEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 2 2004Thomas Leibold Abstract The novel antifungal metabolites cyrmenin A, B1, and B2 (1,3) were isolated from Archangium gephyra and Cystobacter armeniaca strains (myxobacteria). The cyrmenins are modified N -acyldipeptide esters containing a didehydroalanine, a 3- O -methyl-didehydroserine and a (2E,4Z)-undecadienoic or -dodecadienoic acid residue. These compounds represent the first bacterial counterparts of strobilurins that are characterized by an ,-substituted ,-methoxyacrylate pharmacophore. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Terrein inhibits keratinocyte proliferation via ERK inactivation and G2/Mcell cycle arrestEXPERIMENTAL DERMATOLOGY, Issue 4 2008Dong-Seok Kim Abstract:, Terrein, a fungal metabolite, has been recently shown to have a strong antiproliferative effect on skin equivalents. In the present study, we further investigated the effects of terrein on the possible signalling pathways involved in the growth inhibition of human epidermal keratinocytes by examining the regulations of extracellular signal-regulated protein kinase (ERK) and of the Akt pathway by terrein. It was observed that ERK was inactivated by terrein and that keratinocyte proliferation was inhibited, whereas Akt was unaffected. The inhibition of the ERK pathway by U0126 (a specific ERK inhibitor) also had a dose-dependent antiproliferative effect on human keratinocytes. These results indicate that ERK inhibition is involved in keratinocyte growth inhibition by terrein. Moreover, flow cytometric analysis showed that terrein inhibits DNA synthesis, as evidenced by a reduction in the S phase and an increase in the G2/M phase of the cell cycle. Thus, we next examined changes in the expressions of G2/M cell cycle-related proteins. Terrein was found to downregulate cyclin B1 and Cdc2 without Cdc2 phosphorylation, but upregulated p27KIP1 (p27), a known inhibitor of cyclin-dependent kinase. These results suggest that terrein reduces human keratinocyte proliferation by inhibiting ERK and by decreasing the expressions of cyclin B1 and Cdc2 complex. [source] The effect of thiamine supplementation on tumour proliferationFEBS JOURNAL, Issue 15 2001A metabolic control analysis study Thiamine deficiency frequently occurs in patients with advanced cancer and therefore thiamine supplementation is used as nutritional support. Thiamine (vitamin B1) is metabolized to thiamine pyrophosphate, the cofactor of transketolase, which is involved in ribose synthesis, necessary for cell replication. Thus, it is important to determine whether the benefits of thiamine supplementation outweigh the risks of tumor proliferation. Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour. Thus, transketolase enzyme and thiamine clearly determine cell proliferation in the Ehrlich's ascites tumour model. This high control coefficient allows us to predict that in advanced tumours, which are commonly thiamine deficient, supplementation of thiamine could significantly increase tumour growth through transketolase activation. The effect of thiamine supplementation on tumour proliferation was demonstrated by in vivo experiments in mice with the ascites tumour. Thiamine supplementation in doses between 12.5 and 250 times the recommended dietary allowance (RDA) for mice were administered starting on day four of tumour inoculation. We observed a high stimulatory effect on tumour growth of 164% compared to controls at a thiamine dose of 25 times the RDA. This growth stimulatory effect was predicted on the basis of correction of the pre-existing level of thiamine deficiency (42%), as assayed by the cofactor/enzyme ratio. Interestingly, at very high overdoses of thiamine, ,,2500 times the RDA, thiamine supplementation had the opposite effect and caused 10% inhibition of tumour growth. This effect was heightened, resulting in a 36% decrease, when thiamine supplementation was administered from the 7th day prior to tumour inoculation. Our results show that thiamine supplementation sufficient to correct existing thiamine deficiency stimulates tumour proliferation as predicted by MCA. The tumour inhibitory effect at high doses of thiamine is unexplained and merits further study. [source] Visualization of the interaction between archaeal DNA polymerase and uracil-containing DNA by atomic force microscopyGENES TO CELLS, Issue 1 2006Yasuo Asami Deamination of cytosine to uracil is a hydrolytic reaction that is greatly accelerated at high temperatures. The resulting uracil pairs with adenine during DNA replication, thereby inducing G:C to A:T transitions in the progeny. Interestingly, B-family DNA polymerases from hyperthermophilic Archaea recognize the presence of uracil in DNA and stall DNA synthesis. To better understand the recognition mechanism, the binding modes of DNA polymerase B1 of Sulfolobus solfataricus (Pol B1) to uracil-containing DNA were examined by gel mobility shift assays and atomic force microscopy. Although PolB1 per se specifically binds to uracil-containing single-stranded DNA, the binding efficiency was substantially enhanced by the initiation of DNA synthesis. Analysis by the atomic force microscopy showed a number of double-stranded DNA (dsDNA) in the products of DNA synthesis. The generation of ds DNA was significantly inhibited, however, by the presence of template uracil, and intermediates where monomeric forms of Pol B1 appeared to bind to uracil-containing DNA were observed. These results suggest that Pol B1 more efficiently recognizes uracil in DNA during DNA synthesis rather than during random diffusion in solution, and that single molecules of Pol B1 bind to template uracil and stall DNA synthesis. [source] Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1GENES TO CELLS, Issue 7 2005Takashi Sasayama Aurora-A is a centrosomal serine-threonine kinase that regulates mitosis. Over-expression of Aurora-A has been found in a wide range of tumors and has been implicated in oncogenic transformation. However, how Aurora-A over-expression contributes to promotion of carcinogenesis remains elusive. Immunohistochemical analysis of breast tumors revealed that over-expressed Aurora-A is not restricted to the centrosomes but is also found in the cytoplasm. This over-expressed Aurora-A appeared to be phosphorylated on Thr288, which is known to be required for its enzymatic activation. In analogy to Aurora-A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over-expressed Aurora-A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h-CPEB. In vitro experiments revealed that Aurora-A binds directly to, and phosphorylates, h-CPEB. We found that polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically stimulated when Aurora-A and h-CPEB were over-expressed, and they were further promoted in the presence of an Aurora-A activator Ajuba. Our results suggest a function of ectopically over-expressed Aurora-A that might be relevant for carcinogenesis. [source] Replication of Theiler's virus requires NF-,B-activation: Higher viral replication and spreading in astrocytes from susceptible miceGLIA, Issue 9 2008Min Hyung Kang Abstract To investigate viral replication and cell,cell spreading in astrocytes, recombinant Theiler's murine encephalomyelitis virus (TMEV) expressing green fluorescent protein (GFP) during the replication was generated. GFP and TMEV proteins were processed correctly in infected cells and production of viral proteins could be tracked by fluorescent microscopy. Viral replication of both wild-type TMEV and GFP-TMEV was dependent on the activation of NF-,B and partially MAP kinase, based on chemical inhibition studies. Viral replication was significantly reduced in primary astrocytes from NF-,B1 (p105)-deficient mice compared with that from wild-type control mice, whereas cytokine production was enhanced. These results suggest an association of canonical NF-,B subunits in viral replication, but not cytokine production. Viral replication was also suppressed in both IKK, and IKK,-deficient mouse embryonic fibroblasts (MEFs), compared with that in wild-type MEF. However, the inhibition was significantly greater in IKK,-deficient MEF, suggesting that IKK, plays a stronger role in supporting viral replication. Interestingly, viral replication and spreading in primary astrocytes from susceptible SJL/J mice were several-fold higher than those in astrocytes from resistant C57BL/6 mice, suggesting that higher viral replication levels in astrocytes may also contribute to the viral persistence in the central nervous system (CNS) of susceptible SJL/J mice. A relatively higher level of activated NF-,B was found in the nuclei of virus-infected SJL astrocytes compared with C57BL/6 astrocytes suggest that the NF-,B activation level affects on viral replication. © 2008 Wiley-Liss, Inc. [source] Projected changes in the organic carbon stocks of cropland mineral soils of European Russia and the Ukraine, 1990,2070GLOBAL CHANGE BIOLOGY, Issue 2 2007JO SMITH Abstract In this paper, we use the Rothamsted Carbon Model to estimate how cropland mineral soil carbon stocks are likely to change under future climate, and how agricultural management might influence these stocks in the future. The model was run for croplands occurring on mineral soils in European Russia and the Ukraine, representing 74 Mha of cropland in Russia and 31 Mha in the Ukraine. The model used climate data (1990,2070) from the HadCM3 climate model, forced by four Intergovernmental Panel on Climate Change (IPCC) emission scenarios representing various degrees of globalization and emphasis on economic vs. environmental considerations. Three land use scenarios were examined, business as usual (BAU) management, optimal management (OPT) to maximize profit, and soil sustainability (SUS) in which profit was maximized within the constraint that soil carbon must either remain stable or increase. Our findings suggest that soil organic carbon (SOC) will be lost under all climate scenarios, but less is lost under the climate scenarios where environmental considerations are placed higher than purely economic considerations (IPCC B1 and B2 scenarios) compared with the climate associated with emissions resulting from the global free market scenario (IPCC A1FI scenario). More SOC is lost towards the end of the study period. Optimal management is able to reduce this loss of SOC, by up to 44% compared with business as usual management. The soil sustainability scenario could be run only for a limited area, but in that area was shown to increase SOC stocks under three climate scenarios, compared with a loss of SOC under business as usual management in the same area. Improved agricultural soil management will have a significant role to play in the adaptation to, and mitigation of, climate change in this region. Further, our results suggest that this adaptation could be realized without damaging profitability for the farmers, a key criteria affecting whether optimal management can be achieved in reality. [source] Projecting future N2O emissions from agricultural soils in BelgiumGLOBAL CHANGE BIOLOGY, Issue 1 2007CAROLINE ROELANDT Abstract This study analyses the spatial and temporal variability of N2O emissions from the agricultural soils of Belgium. Annual N2O emission rates are estimated with two statistical models, MCROPS and MGRASS, which take account of the impact of changes in land use, climate, and nitrogen-fertilization rate. The models are used to simulate the temporal trend of N2O emissions between 1990 and 2050 for a 10, latitude and longitude grid. The results are also aggregated to the regional and national scale to facilitate comparison with other studies and national inventories. Changes in climate and land use are derived from the quantitative scenarios developed by the ATEAM project based on the Intergovernmental Panel on Climate Change-Special Report on Emissions Scenarios (IPCC-SRES) storylines. The average N2O flux for Belgium was estimated to be 8.6 × 106 kg N2O-N yr,1 (STD = 2.1 × 106 kg N2O-N yr,1) for the period 1990,2000. Fluxes estimated for a single year (1996) give a reasonable agreement with published results at the national and regional scales for the same year. The scenario-based simulations of future N2O emissions show the strong influence of land-use change. The scenarios A1FI, B1 and B2 produce similar results between 2001 and 2050 with a national emission rate in 2050 of 11.9 × 106 kg N2O-N yr,1. The A2 scenario, however, is very sensitive to the reduction in agricultural land areas (,14% compared with the 1990 baseline), which results in a reduced emission rate in 2050 of 8.3 × 106 kg N2O-N yr,1. Neither the climatic change scenarios nor the reduction in nitrogen fertilization rate could explain these results leading to the conclusion that N2O emissions from Belgian agricultural soils will be more markedly affected by changes in agricultural land areas. [source] Inhibition of hepatitis C virus infection by anti-claudin-1 antibodies is mediated by neutralization of E2,CD81,Claudin-1 associations,HEPATOLOGY, Issue 4 2010Sophie E. Krieger The tight junction protein claudin-1 (CLDN1) has been shown to be essential for hepatitis C virus (HCV) entry,the first step of viral infection. Due to the lack of neutralizing anti-CLDN1 antibodies, the role of CLDN1 in the viral entry process is poorly understood. In this study, we produced antibodies directed against the human CLDN1 extracellular loops by genetic immunization and used these antibodies to investigate the mechanistic role of CLDN1 for HCV entry in an infectious HCV cell culture system and human hepatocytes. Antibodies specific for cell surface,expressed CLDN1 specifically inhibit HCV infection in a dose-dependent manner. Antibodies specific for CLDN1, scavenger receptor B1, and CD81 show an additive neutralizing capacity compared with either agent used alone. Kinetic studies with anti-CLDN1 and anti-CD81 antibodies demonstrate that HCV interactions with both entry factors occur at a similar time in the internalization process. Anti-CLDN1 antibodies inhibit the binding of envelope glycoprotein E2 to HCV permissive cell lines in the absence of detectable CLDN1-E2 interaction. Using fluorescent-labeled entry factors and fluorescence resonance energy transfer methodology, we demonstrate that anti-CLDN1 antibodies inhibit CD81-CLDN1 association. In contrast, CLDN1-CLDN1 and CD81-CD81 associations were not modulated. Taken together, our results demonstrate that antibodies targeting CLDN1 neutralize HCV infectivity by reducing E2 association with the cell surface and disrupting CD81-CLDN1 interactions. Conclusion: These results further define the function of CLDN1 in the HCV entry process and highlight new antiviral strategies targeting E2-CD81-CLDN1 interactions. (HEPATOLOGY 2010.) [source] Cyclin-dependent kinase 1 plays a critical role in DNA replication control during rat liver regeneration,HEPATOLOGY, Issue 6 2009Delphine Garnier Liver regeneration is a unique process to restore hepatic homeostasis through rapid and synchronous proliferation of differentiated hepatocytes. Previous studies have shown that hepatocyte proliferation is characterized by high expression levels of the "mitotic" cyclin-dependent kinase 1 (Cdk1) during S-phase compared to other mammalian cells. In the light of findings showing that Cdk1 compensates for the loss of Cdk2 and drives S-phase in Cdk2-deficient cells derived from Cdk2 knockout mice, we took advantage of the models of liver regeneration following partial hepatectomy and primary cultures of normal rat hepatocytes to further examine the involvement of Cdk1 during DNA replication in hepatocytes and to dissect specific cell cycle regulation in hepatocytes compared to control human foreskin fibroblasts. In hepatocytes, Cdk1 exhibited a biphasic activation pattern correlating S-phase and G2/M transition, bound to cyclin A or B1 and localized to the nucleus during DNA replication. Importantly, small interfering RNA (siRNA)-mediated silencing of Cdk1 led to a strong decrease in DNA synthesis without affecting centrosome duplication. Furthermore, in hepatocytes arrested by the iron chelator O-Trensox in early S-phase prior to DNA replication, Cdk1/cyclin complexes were active, while replication initiation components such as the minichromosome maintenance 7 (Mcm7) protein were loaded onto DNA. Moreover, Mcm7 expression and loading onto DNA were not modified by Cdk1 silencing. Conversely, in fibroblasts, Cdk1 expression and activation were low in S-phase and its silencing did not reduce DNA synthesis. Conclusion: Cdk1 is essential for DNA replication downstream formation of replication initiation complexes in hepatocytes but not in fibroblasts and, as such, our data exemplify crucial differences in the cell cycle regulation between various mammalian cell types. (HEPATOLOGY 2009.) [source] Aging does not reduce the hepatocyte proliferative response of mice to the primary mitogen TCPOBOPHEPATOLOGY, Issue 4 2004Giovanna M. Ledda-Columbano It has been shown that the magnitude of DNA synthesis and the time at which maximal DNA synthesis occurs after two-thirds partial hepatectomy (PH) is greatly reduced in the liver of aged rodents compared to young animals. This reduction could represent an intrinsic defect in proliferation or a more specialized change in the response to PH. We therefore evaluated the proliferative capacity of hepatocytes in aged animals, following treatment with primary liver mitogens. We show that treatment of 12-month-old CD-1 mice with the hepatomitogen 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) caused an increase in hepatocyte proliferation similar to that seen in young (8-week-old) mice. The labeling index was 82% in the livers of aged mice versus 76% in young animals. Histological observation demonstrated that the number of hepatocytes entering mitoses was similar in both groups; the mitotic indices were 2.5 per thousand and 2.7 per thousand, respectively. Additional experiments showed that the timing of DNA synthesis and M phase were nearly identical in both aged and young mice. Stimulation of hepatocyte DNA synthesis was associated with increased expression of several cell cycle-associated proteins (cyclin D1, cyclin A, cyclin B1, E2F, pRb, and p107); all were comparable in aged mice and young mice. TCPOBOP treatment also increased expression of the Forkhead Box transcription factor m1b (Foxm 1b) to a similar degree in both groups. In conclusion, hepatocytes retain their proliferative capacity in old age despite impaired liver regeneration. These findings suggest that therapeutic use of mitogens would alleviate the reduction in hepatocyte proliferation observed in the elderly. (Hepatology 2000;40:981,988). [source] Growth hormone stimulates proliferation of old-aged regenerating liver through forkhead box m1bHEPATOLOGY, Issue 6 2003Katherine Krupczak-Hollis The Forkhead Box (Fox) proteins are an extensive family of transcription factors that shares homology in the winged helix DNA-binding domain and the members of which play essential roles in cellular proliferation, differentiation, and longevity. Reduced cellular proliferation during aging is associated with a progressive decline in both growth hormone (GH) secretion and Foxm1b expression. Liver regeneration studies with 12-month-old (old-aged) transgenic mice indicated that increased hepatocyte expression of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver. GH therapy in older people has been shown to cause an increase in cellular proliferation, but the transcription factors that mediated this stimulation in proliferation remain uncharacterized. In this study, we showed that human GH administration to old-aged Balb/c mice dramatically increased both expression of Foxm1b and regenerating hepatocyte proliferation. This increase in old-aged regenerating hepatocyte proliferation was associated with elevated protein expression of Cdc25A, Cdc25B, and cyclin B1, with reduced protein levels of cyclin-dependent kinase inhibitor p27Kip1 (p27). GH treatment also was found to stimulate hepatocyte proliferation and expression of Foxm1b protein without partial hepatectomy (PHx). Furthermore, GH treatment of young Foxm1b ,/, mice failed to restore regenerating hepatocyte DNA replication and mitosis caused by Foxm1b deficiency. These genetic studies provided strong evidence that the presence of Foxm1b is essential for GH to stimulate regenerating hepatocyte proliferation. In conclusion, our old-aged liver regeneration studies show that increased Foxm1b levels are essential for GH to stimulate hepatocyte proliferation, thus providing a mechanism for GH action in the elderly. [source] | |||||||||||||||||||||||||||||||||||||||||||