bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and Theoretical Approaches Toward Anion‐Responsive Tripod–Lanthanide Complexes: Mixed‐Donor Ligand Effects on Lanthanide Complexation and Luminescence Sensing Profiles
Authors: Kataoka Yumiko , Paul Dharam , Miyake Hiroyuki , Yaita Tsuyoshi , Miyoshi Eisaku , Mori Hirotoshi , Tsukamoto Shinya , Tatewaki Hiroshi , Shinoda Satoshi , Tsukube Hiroshi
Published: April 2008

A new series of tripods were designed to form anion‐responsive, luminescent lanthanide complexes. These tripods contain pyridine, thiazole, pyrazine, or quinoline chromophores combined with amide carbonyl oxygen and tertiary nitrogen atoms. Crystallographic and EXAFS studies of the 10‐coordinated tripod–La(NO3)3 complexes revealed that each La3+ cation was cooperatively coordinated by one tetradentate tripod and three bidentate NO3− anions in the crystal and in CH3CN. Quantum chemical calculations indicated that the aromatic nitrogen plays a significant role in lanthanide complexation. The experimentally determined stability constants of complexes of the tripod with La(NO3)3, Eu(NO3)3, and Tb(NO3)3 were in good agreement with the theoretically calculated interaction energies. Complexation of each tripod with lanthanide triflate gave a mixture of several lanthanide complex species. Interestingly, the addition of a coordinative NO3− or Cl− anion to the mixture significantly influenced the lanthanide complexation profiles. The particular combination of tripod and a luminescent Eu3+ center gave anion‐selective luminescence enhancements. Pyridine‐containing tripods exhibited the highest NO3− anion‐selective luminescence and thus permit naked‐eye detection of the NO3− anion.
The Bound Conformation of Microtubule‐Stabilizing Agents: NMR Insights into the Bioactive 3D Structure of Discodermolide and Dictyostatin
Authors: Canales Angeles , Matesanz Ruth , Gardner Nicola M. , Andreu José Manuel , Paterson Ian , Díaz J. Fernando , Jiménez‐Barbero Jesús
Published: April 2008

A protocol based on a combination of NMR experimental data with molecular mechanics calculations and docking procedures has been employed to determine the microtubule‐bound conformation of two microtubule‐stabilizing agents, discodermolide (DDM) and dictyostatin (DCT). The data indicate that tubulin in assembled microtubules recognizes DDM through a conformational selection process, with minor changes in the molecular skeleton between the major conformer in water solution and that bound to assembled microtubules. For DCT, the deduced bound geometry presents some key conformation differences around certain torsion angles, with respect to the major conformer in solution, and still displays mobility even when bound. The bound conformer of DCT resembles that of DDM and provides very similar contacts with the receptor. Competition experiments indicate that both molecules compete with the taxane‐binding site. A model of the binding mode of DDM and DCT to tubulin is proposed.
Supramolecular Bidentate Ligands by Metal‐Directed in situ Formation of Antiparallel β‐Sheet Structures and Application in Asymmetric Catalysis
Authors: Laungani Andy C. , Slattery John M. , Krossing Ingo , Breit Bernhard
Published: April 2008

The principles of protein structure design, molecular recognition, and supramolecular and combinatorial chemistry have been applied to develop a convergent metal‐ion‐assisted self‐assembly approach that is a very simple and effective method for the de novo design and the construction of topologically predetermined antiparallel β‐sheet structures and self‐assembled catalysts. A new concept of in situ generation of bidentate P‐ligands for transition‐metal catalysis, in which two complementary, monodentate, peptide‐based ligands are brought together by employing peptide secondary structure motif as constructing tool to direct the self‐assembly process, is achieved through formation of stable β‐sheet motifs and subsequent control of selectivity. The supramolecular structures were studied by 1H, 31P, and 13C NMR spectroscopy, ESI mass spectrometry, X‐ray structure ana1ysis, and theoretical calculations. Our initial catalysis results confirm the close relationship between the self‐assembled sheet conformations and the catalytic activity of these metallopeptides in the asymmetric rhodium‐catalyzed hydroformylation. Good catalyst activity and moderate enantioselectivity were observed for the selected combination of catalyst and substrate, but most importantly the concept of this new methodology was successfully proven. This work presents a perspective interface between protein design and supramolecular catalysis for the design of β‐sheet mimetics and screening of libraries of self‐organizing supramolecular catalysts.
Polyacrylamide gel plugs enabling 2‐D microfluidic protein separations via isoelectric focusing and multiplexed sodium dodecyl sulfate gel electrophoresis
Authors: Liu Jikun , Yang Shuang , Lee Cheng S. , DeVoe Don L.
Published: April 2008

In situ photopolymerized polyacrylamide (PAAm) gel plugs are used as hydrodynamic flow control elements in a multidimensional microfluidic system combining IEF and parallel SDS gel electrophoresis for protein separations. The PAAm gel plugs offer a simple method to reduce undesirable bulk flow and limit reagent/sample crosstalk without placing unwanted constraints on the selection of separation media, and without hindering electrokinetic ion migration in the complex microchannel network. In addition to improving separation reproducibility, the discrete gel plugs integrated into critical regions of the chip enable the use of a simple pressure‐driven sample injection method which avoids electrokinetic injection bias. The gel plugs also serve to greatly simplify operation of the spatially multiplexed system by eliminating the need for complex external fluidic interfaces. Using an FITC‐labeled Escherichia coli cell lysate as a model system, the use of gel plugs is shown to significantly enhance separation reproducibility in a chip containing five parallel CGE channels, with an average variance in peak elution time of only 4.1%.
Detection of PEGylated proteins in polyacrylamide gels by reverse staining with zinc and imidazole salts
Authors: Hardy Eugenio , Ramón José , Saez Vivian , Báez Reynier , Tejeda Yosbel , Ruiz Amalia
Published: April 2008

The reverse staining, with imidazole–SDS–zinc, of PEG‐linked proteins separated by SDS‐PAGE was studied. Using model conjugates (interferon‐α 2b (IFN‐α2b) reacted with either a branched‐chain (40 000) PEG (PEG2,40) or a linear monomethoxy PEG polymer (Mr of 12 000) and chromatographically purified monoPEG2,40‐IFN‐α2b), conventional small‐format analytical gels (<1 mm thick) showed typical detection patterns (i.e., transparent, colorless bands clearly discernible against a zinc imidazolate‐generated white gel background), in less than 20 min. Nonreacted (free) PEG was almost undetected, as expected. The reverse‐stained PEGylated IFN‐α2b patterns were qualitatively indistinguishable from those of parallel gels stained with iodine (I2). The LOD was estimated in the low nanogram range (e.g., at about 7 ng for mono‐ or bi‐PEG2,40 IFN‐α2b per lane on gradient (4–17%) gels). Also, this stain allowed the visualization of Coomassie blue‐undetected PEG‐IFN bands, and could be restained with I2. PEGylated species of lysozyme, a low‐molecular‐weight peptide, ovalbumin, and chymotrypsin were used to demonstrate the generality of this stain. We also show (i) how to counteract the adverse effect of some parameters (e.g., gel thickness above 1 mm, long gel length, low (e.g., 4–6%) acrylamide concentration) on the reverse staining process and (ii) that the properties of the reverse‐stained PEGylated proteins remain unchanged, as judged by analyzing both the ion exchange chromatography‐based positional isomer separation profile and enzyme‐linked immunosorbent response of PEG‐IFN recovered from gels. Consequently, this technique may be useful for the rapid analysis or the small‐scale preparation of PEGylated proteins.
Characterization of the genotoxicity of nitrilotriacetic acid
Authors: Nesslany Fabrice , Simar‐Meintières Sophie , Watzinger Malene , Talahari Ismail , Marzin Daniel
Published: April 2008

The chelating agent nitrilotriacetic acid (NTA), classified as an epigenetic rodent carcinogen, was assessed in the in vivo rodent Comet assay on isolated kidney cells. Unexpected potent increases in DNA damage were obtained in both the short (3–6 hr) and long‐term (22–26 hr) expression times after a single oral treatment at 1,000–2,000 mg/kg bw. NTA was assayed in the Ames test using TA1537, TA98, TA100, and TA102 tester strains, and in the in vitro micronucleus assay on L5178Y mouse lymphoma cells and on CTLL2 and CTLL2/Bcl2 cells coupled to the apoptosis measurement, both with and without metabolic activation by aroclor 1254‐induced liver or kidney rat S9‐mix. Whatever the S9 origin, neither genotoxicity nor apoptosis was detected, while a strong increase in the micronuclei formation was observed without S9 without any apoptosis induction. The direct genotoxicity of NTA was confirmed in the mouse lymphoma tk+/− gene mutation assay and in the chromosomal aberrations test on human lymphocytes. When tested in combination with an excess of Ca2+, NTA gave negative results on L5178Y mouse lymphoma cells in the in vitro Comet and micronucleus assays but still induced DNA damage on rat primary kidney cells. The higher sensitivity of renal cells to Ca2+ variations could explained the positive response observed in vivo. The carcinogenicity of NTA could be a consequence of the survival of kidney cells to intracellular variations of Ca2+, leading to a local and indirect genotoxicity. This suggests that threshold dose exists beyond which tumor‐generating events will be displayed. Environ. Mol. Mutagen., 2008. © 2008 Wiley‐Liss, Inc.
Testing for trends in the violation frequency of an environmental threshold in rivers
Authors: Clement Lieven , Thas Olivier
Published: April 2008

Nutrient pollution in rivers is a common problem. It can provoke algae blooms which are related to increased fish mortality. To restore the water status, the regulator recently has promulgated more restrictive regulations. In Flanders for instance, the government has introduced several manure decrees (MDs) to restrict nutrient pollution. Environmental regulations are commonly expressed in terms of threshold levels. This provides a binary response to the decision maker. To handle such data, we propose the use of marginalised generalised linear mixed models. They provide valid inference on trends in the exceedance frequency. The spatio‐temporal dependence of the river monitoring network is incorporated by the use of a latent variable. The temporal dependence is assumed to be AR(1) and the spatial dependence is derived from the river topology. The mean model contains a term for the trend and corrects for seasonal variation. The model formulation allows an assessment on the level of individual sampling locations and on a more regional scale. The methodology is applied to a case study on the river Yzer (Flanders). It assesses the impact of the MDs on the violation probability of the nitrate standard. A trend change is detected after the introduction of the second MD. Copyright © 2008 John Wiley & Sons, Ltd.
A linear benchmark for forecasting GDP growth and inflation?
Authors: Marcellino Massimiliano
Published: April 2008

Predicting the future evolution of GDP growth and inflation is a central concern in economics. Forecasts are typically produced either from economic theory‐based models or from simple linear time series models. While a time series model can provide a reasonable benchmark to evaluate the value added of economic theory relative to the pure explanatory power of the past behavior of the variable, recent developments in time series analysis suggest that more sophisticated time series models could provide more serious benchmarks for economic models. In this paper we evaluate whether these complicated time series models can outperform standard linear models for forecasting GDP growth and inflation. We consider a large variety of models and evaluation criteria, using a bootstrap algorithm to evaluate the statistical significance of our results. Our main conclusion is that in general linear time series models can hardly be beaten if they are carefully specified. However, we also identify some important cases where the adoption of a more complicated benchmark can alter the conclusions of economic analyses about the driving forces of GDP growth and inflation. Copyright © 2008 John Wiley & Sons, Ltd.
The neuroglial population in the primary visual cortex of the aging rhesus monkey
Authors: Peters Alan , Verderosa Ameigh , Sethares Claire
Published: April 2008

The effects of age on neuroglial cells have been examined in the primary visual cortices of rhesus monkeys that had been behaviorally tested. The assessment of changes in the neuroglial populations was made on the basis of the frequency of occurrence of profiles of neuroglial cells in semithick sections of osmicated tissue stained with toluidine blue. No changes were found in the numbers of astrocytes and microglial cells with age, but the numbers of oligodendrocytes increased by about 50%. The myelinated nerve bundles at the level of layer 4 were also examined by electron microscopy to assess the effects of age on the nerve fibers. The numbers of nerve fiber profiles showing age‐related alterations in their myelin sheaths increase with age. There was also an age‐related increase in the frequency of profiles of nerve fibers sectioned through paranodes, indicating that shorter lengths of myelin are being produced by remyelination. These changes in sheaths both correlate significantly with the frequency of oligodendrocyte profiles, suggesting that with age additional oligodendrocytes are required to remyelinate nerve fibers whose sheaths have broken down, probably by death of the original parent oligodendroglial cell. Also the most cognitively impaired monkeys had the greatest numbers of oligodendrocytes, but this is probably a secondary correlation, reflecting the fact that altered myelin slows down the rate of conduction along nerve fibers, which leads to cognitive decline. © 2008 Wiley‐Liss, Inc.
Microglial phagocytosis is enhanced by monomeric α‐synuclein, not aggregated α‐synuclein: Implications for Parkinson's disease
Authors: Park Ji‐Young , Paik Seung R. , Jou Ilo , Park Sang Myun
Published: April 2008

Gathering evidence has associated activation of microglia with the pathogenesis of numerous neurodegenerative diseases of the central nervous system (CNS) such as Alzheimer's disease and Parkinson's disease. Microglia are the resident macrophages of the CNS whose functions include chemotaxis, phagocytosis, and secretion of a variety of cytokines and proteases. In this study, we examined the possibility that α‐synuclein (α‐syn), which is associated with the pathogenesis of Parkinson's disease, may affect the phagocytic function of microglia. We found that extracellular monomeric α‐syn enhanced microglial phagocytosis in both a dose‐ and time‐dependent manner, but β‐ and γ‐ syn did not. We also found that the N‐terminal and NAC region of α‐syn, especially the NAC region, might be responsible for the effect of α‐syn on microglial phagocytosis. In contrast to monomeric α‐syn, aggregated α‐syn actually inhibited microglial phagocytosis. The different effects of monomeric and aggregated α‐syn on phagocytosis might be related to their localization in cells. This study indicates that α‐syn can modulate the function of microglia and influence inflammatory changes such as those seen in neurodegenerative disorders. © 2008 Wiley‐Liss, Inc.
Expression of Notch‐1 receptor and its ligands Jagged‐1 and Delta‐1 in amoeboid microglia in postnatal rat brain and murine BV‐2 cells
Authors: Cao Qiong , Lu Jia , Kaur Charanjit , Sivakumar Viswanathan , Li Fan , Cheah Pike See , Dheen S. Thameem , Ling Eng‐Ang
Published: April 2008

Notch‐1 receptor signaling pathway is involved in neuronal and glial differentiation. Its involvement in microglial functions, however, has remained elusive. This study reports the localization of Notch‐1 receptor immunoreactivity in the amoeboid microglial cells (AMC) in the postnatal rat brain. By immunofluorescence, Notch‐1 receptor was colocalized with its ligands, Jagged‐1 and Delta‐1, in the AMC in the corpus callosum and subventricular zone. Notch‐1 immunopositive cells were confirmed to be microglia labeled by OX42 and lectin. Immunoexpression of Notch‐1 receptor was progressively reduced with age. Western blot analysis showed that Notch‐1 protein level in the corpus callosum in which the AMC were heavily populated was concomitantly decreased. In postnatal rats challenged with lipopolysaccharide (LPS), Notch‐1 receptor immunofluorescence in AMC was noticeably enhanced. Furthermore, Notch‐1 protein level in the corpus callosum was increased as revealed by Western blotting analysis. In primary microglial culture treated with LPS, mRNA expression of Notch‐1 and its ligand Jagged‐1 was upregulated but that of Delta‐1 was reduced. The expression pattern of Notch‐1 and its ligands was confirmed in murine BV‐2 cells. Furthermore, Notch‐1 neutralization with its antibody reduced its protein expression. More importantly, neutralization of Notch‐1 concomitantly suppressed the mRNA expression of IL‐6, IL‐1, M‐CSF, and iNOS; TNF‐α, mRNA expression, however, was enhanced. Western blot confirmed the changes of protein level of the above except for IL‐6, which remained relatively unaltered. It is concluded that Notch‐1 signaling in the AMC and LPS‐activated microglia/BV‐2 cells modulates the expression of proinflammatory cytokines and nitric oxide. © 2008 Wiley‐Liss, Inc.
Variation in the prevalence of gastric cancer in Perú
Authors: Mendoza Daniel , Herrera Phabiola , Gilman Robert H. , Lanfranco Julio , Tapia Martín , Bussalleu Alejandro , Tenorio Jorge Huerta‐Mercado , Guillén‐Rodríguez Carlos Enrique , Arróspide Martín Tagle , Piscoya Alejandro , Rosas‐Aguirre Angel , Watanabe‐Yamamoto José , Ferrufino Juan Carlos , Scavino Yolanda , Ramírez‐Ramos Alberto
Published: April 2008

Most cases of gastric cancers occur in non‐industrialized countries but there is scarce information about the epidemiology of this illness in these countries. Our study examined whether there was a variation in the prevalence of gastric cancer in Lima, Perú over the last 2 decades. Subjects older than 29 years of age were included. They underwent an esophagogastroduedonoscopy at 3 socioeconomically different health facilities in Lima: a county hospital (7,168 subjects), a Peruvian‐Japanese Clinic (14,794 individuals) and a private hospital (4,893 individuals). Birth cohort prevalence of gastric cancer was used. Regression models were calculated to predict the future prevalence of gastric cancer. It was found that the birth cohort prevalence of gastric cancer decreased in Perú from 22.7 to 2% (p < 0.001), from 12 to 0.5% (p < 0.001), and from 6.5 to 0.1% (p < 0.001) in the low, middle and high socioeconomic group, respectively. The prevalence of intestinal metaplasia decreased from 44.3 to 12.5% (p < 0.001), from 28.4 to 5% (p < 0.001), and from 19.4 to 2.2% (p < 0.001) in the low, middle and high socioeconomic status, respectively. These trends will likely persist over the future decades. Nevertheless, the prevalence of gastric cancer remains high in subjects older than 59 years of age in the low socioeconomic status. It is concluded that the prevalence of gastric cancer is decreasing in Perú, similar to the current trend undergoing in industrialized nations. However, there are still specific groups with high prevalence that might benefit from screening for early detection and treatment. © 2008 Wiley‐Liss, Inc.
Novel human polyomaviruses—Re‐emergence of a well known virus family as possible human carcinogens
Authors: zur Hausen Harald
Published: April 2008

Polyomaviruses belong to a family of DNA tumorviruses that frequently cause cancer upon inoculation into heterologous hosts. The rhesus monkey virus SV40 and mouse polyomavirus have been studied in particular detail. Two members of the polyomavirus family, BK and JC viruses, were identified as human pathogens more than 30 years ago. Both are oncogenic when inoculated into newborn rodents. Their possible role in human cancers has been intensively investigated; conclusive results are, however, still missing. During the past year 3 new members of the polyomavirus family have been identified in humans, KI, WU, and MC‐Polyomavirus. Whereas the first 2 were only found in respiratory fluids of children with respiratory infections and in healthy individuals, the third virus was found to be specifically linked to Merkel tumors, a rare human cancer of neuroendocrine origin. The positive Merkel cells contain viral DNA in an integrated and clonal form, suggesting an involvement of this virus in the etiology of those tumors. This article will summarize the results of recent polyomavirus isolations from humans and animals and also address the potential role of members of this virus family in other human malignancies. It also makes reference to observations of polyomavirus‐like particles in other conditions, particularly in hair‐follicle cell‐related proliferations. © 2008 Wiley‐Liss, Inc.
Excessive Phosphorus Loading to Dal Lake, India: Implications for Managing Shallow Eutrophic Lakes in Urbanized Watersheds
Authors: Ul Solim Sabah , Wanganeo Ashwani
Published: April 2008

Extensive watershed development has resulted in excessive total phosphorus (TP) loads to Dal Lake, a high altitude Himalayan lake known for its tourism and economic potential. External and internal TP loads of 5 and ∼1 g m–2 yr–1, respectively, were estimated for the lake. These loading rates are high in relation to the lake's critical tolerance range of 0.1–0.2 g m–2 yr–1, and, over time, have resulted in severe eutrophication in view of extremely high macrophyte biomass (average = 3.2 kg m–2‐fresh weight) and bottom sediment enrichment (79 tons of TP reserves which contribute 88% of the annual TP budget). This study emphasizes the importance of external TP load reduction as a primary management objective to counteract internal TP loading and P storage within bottom sediments resulting from historic anthropogenic loads. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Environmental Heterogeneity and Morphological Variability in Pisidium subtruncatum (Sphaeriidae, Bivalvia)
Authors: Funk Andrea , Reckendorfer Walter
Published: April 2008

On the example of P. subtruncatum, a widely distributed bivalve, we studied the relationship between environmental and morphological variability. The main questions addressed were: (1) are there differences in shell morphology between different populations, (2) are they dependent on sediment composition, hydrology or water chemistry, (3) are there differences in morphological variability between stable and unstable environments. Measurements of specimen from nine sampling sites showed high variability in shell shape and size. Length‐height relation, symmetry, width and dry weight of the shell all varied significantly. Shell shape was significantly correlated with sediment composition and dependent on hydrological connectivity, with higher, asymmetric shells occurring in sandy sediments and lower, rounded shells in muddy sediments. Analysis of intrapopulation morphometric variation showed that variability is higher in habitats with high temporal and spatial environmental variability and lower in habitats with low or reduced environmental heterogeneity. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fluctuations of Testate Amoebae Populations (Rhizopoda) in Plankton from Different Environments on the Upper Paraná River Floodplain, Brazil
Authors: Mucio Alves Geziele , Amodêo Lansac‐Tôha Fábio , Mayumi Takahashi Érica , Machado Velho Luiz Felipe
Published: April 2008

Fluctuations in temporal and spatial abundance are remarkable features of all animal populations. Regional synchrony of local population dynamics has been verified in several studies. This study investigated the existence of coherent patterns in temporal fluctuations of the principal testate amoebae population abundance in plankton from the upper Paraná river floodplain in Brazil. Testate amoebae sampling was carried out every three months, from February 2000 to November 2002, and twice in 2003. Sampling occurred in 12 environments associated with three different rivers. Samples were obtained at the subsurface of the pelagic region, using a motorized pump and a 68 μm mesh plankton net. Ninety–three testate amoebae species from eight families were identified. The families Difflugiidae, Arcellidae, and Centropyxidae had the greatest number of species. Arcella conica, A. discoides, A. vulgaris, Centropyxis aculeata, C. ecornis, Difflugia gramen, D. pseudogramen and Cucurbitella dentata were the most abundant species, and they were chosen for spatial synchrony analysis. No coherent pattern of abundance fluctuation was found, in any of the floodplain environments studied. Nevertheless, when analyzing only the channels, spatial synchrony was observed to Centropyxis ecornis. Mantel tests showed that the synchrony level, as identified by Spearman and Pearson correlations, was not correlated to geographic distance between environments. We conclude that regional factors in the Upper Paraná River floodplain are not the main determinants of the population dynamics of testate amoebae. The high floodplain heterogeneity seems determine a great relevance of local factors. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Abundance, Species Composition and Spatial Distribution of Planktonic Rotifers and Crustaceans in Lake Ziway (Rift Valley, Ethiopia)
Authors: Dagne Adamneh , Herzig Alois , Jersabek Christian D. , Tadesse Zenebe
Published: April 2008

Species composition, abundance, and spatial distribution of rotifer and crustacean zooplankton were studied in Lake Ziway from late April to early July 2004. A total of 49 rotifer species was recorded, with Anuraeopsis fissa, Brachionus angularis, Filinia novaezealandiae, and Trichocerca ruttneri being numerically dominant. Variation in abundance was extremely high, ranging from 2 to 1000+ individuals per litre. There was no significant difference in the distribution of rotifer species between inshore and offshore regions. Crustacean species richness was low, with only five cladoceran and three copepod species occurring in the open water. Moina micrura and Diaphanosoma excisum dominated the cladoceran community, whereas Thermocyclops decipiens was the dominant copepod. Although numerically dominant (75%), rotifers accounted for less than 30% of mean total zooplankton biomass. Peak abundance of crustaceans was observed in May and June, following the onset of the rainy season and increased phytoplankton production. Variation in the spatial distribution of crustacean species was neither observed horizontally between inshore and offshore areas nor vertically in the highly turbid and wind exposed deeper part of the lake. On the other hand, Moina micrura varied significantly in size between inshore and offshore areas. Adult M. micrura dominated offshore, whereas juveniles were more abundant inshore, suggesting a predominantly littoral selective predation on large and adult crustaceans by fish. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Alumina ceramic particles, in comparison with titanium particles, hardly affect the expression of RANK‐, TNF‐α‐, and OPG‐mRNA in the THP‐1 human monocytic cell line
Authors: Bylski David , Wedemeyer Christian , Xu Jie , Sterner Thomas , Löer Franz , von Knoch Marius
Published: April 2008

Particle‐induced osteolysis is the most frequent cause of aseptic loosening after total joint replacement. We performed a study to illuminate the effect of ceramic particles with different diameters and concentrations on the mRNA expression of certain key regulators in particle‐induced aseptic osteolysis (RANK, RANKL, OPG, and TNF‐α) in THP‐1 macrophage‐like cells. Titanium particles were used as a positive control. RNA was analyzed by quantitative RTPCR. Our results demonstrate that alumina ceramic particles, regardless of particle size, caused only slight upregulations of RANK, TNF‐α, and OPG mRNA, whose levels were significantly lower in comparison with those of titanium particles (p < 0.05). The continuous increasing tendency to time and particle‐dependent mRNA expression of all the parameters stimulated by titanium particles was not found after stimulation with ceramic materials. Even after the concentration of ceramic particles was increased, only a mild upregulation of mRNA expression was found. Furthermore, we observed that the bioinert properties of ceramic particles did not change much in diameters ranging from 0.5 to 1.5 μm. At most of the measuring time points, there was no significant difference between the reactions of the large and small particles in this range. Our results support the theory about the relative bioinert properties of alumina ceramic particles. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
A multi center study of granulocyte and monocyte adsorption apheresis therapy for ulcerative colitis—Clinical efficacy and production of interleukin‐1 receptor antagonist
Authors: Takeda Hiroaki , Suzuki Yasukuni , Takeda Yuji , Nishise Shoichi , Fukui Tadahisa , Fujishima Shoichiro , Orii Tomohiko , Otake Sayaka , Sato Takeshi , Suzuki Koji , Nakamuara Yukiko , Kawata Sumio
Published: April 2008

Granulocyte and monocyte adsorption apheresis (GCAP) is a useful strategy for intractable ulcerative colitis, but its mechanisms of therapy is not fully explained. Previously, depleting activated granulocytes and monocytes (GMs) and modifying product of proinflammatory cytokines had been proposed. In addition, activated GMs are releasing anti‐inflammatory cytokines, interleukin‐1 receptor antagonist (IL‐1ra) that may contribute to the clinical efficacy of GCAP therapy. Hence, to investigate contribution of IL‐1ra as well as to confirm clinical efficacy of this therapy based on clinical activity index (CAI), we performed a multicenter study. Twenty‐five of 38 (65.8%) patients achieved remission state (CAI ≤ 4) and two of 38 (5.3%) revealed clinical improvement. Almost effective cases significantly decreased CAI even at 3rd session of GCAP. Plasma level of IL‐1ra from outflow of the GCAP column at 30 min was significantly increased rather than inflow. Median exact elevated level of IL‐1ra was 221 pg/ml and median of increasing ratio was 1.6 times. Furthermore, the responsive patients, who well released the IL‐1ra at outflow more than 100 pg/ml compared with inflow, tended to show clinical effectiveness. While, the increased ratio of IL‐1ra in effective cases did not differ from ineffective cases, and there were no significant relationship with improvement of CAI score. These conflict results suggest that the increase of IL‐1ra at outflow is not a direct factor to the clinical improvement, but the induction of clinical improvement is accompanied by the release of IL‐1ra. The IL‐1ra may be involved in the multiple steps for the improvement induced by GCAP. J. Clin. Apheresis, 2008. © 2008 Wiley‐Liss, Inc.
Sympathectomy alters bone architecture in adult growing rats
Authors: Pagani F. , Sibilia V. , Cavani F. , Ferretti M. , Bertoni L. , Palumbo C. , Lattuada N. , De Luca E. , Rubinacci A. , Guidobono F.
Published: April 2008

Sympathetic nervous system (SNS) fibres and α‐ and β‐receptors are present in bone, indicating that the SNS may participate in bone metabolism. The importance of these observations is controversial because stimulation or inhibition of the SNS has had various effects upon both anabolic and catabolic activity in this tissue. In this study we evaluated the effects of pharmacological sympathectomy, using chronic treatment of maturing male rats with 40 mg of guanethidine/kg i.p., upon various parameters in bone. Double labelling with tetracycline injection was also performed 20 and 2 days before sacrifice. Bone mass, mineral content, density and histomorphometric characteristics in different skeletal regions were determined. Bone metabolic markers included urinary deoxypyridinoline and serum osteocalcin measurements. Guanethidine significantly reduced the accretion of lumbar vertebral bone and of mineral content and density, compared to controls. Femoral bone mineral content and density were also significantly reduced, compared to controls. Histomorphometric analyses indicated these effects were related to a reduction of cortical bone and mineral apposition rate at femoral diaphysials level. Both markers of bone metabolism were reduced in controls as they approached maturity. Guanethidine significantly decreased serum osteocalcin compared to controls, while urinary deoxypyridinoline was unchanged. These data indicate that guanethidine‐induced sympathectomy caused a negative balance of bone metabolism, leading to decreased mass by regulating deposition rather than resorption during modeling and remodeling of bone. J. Cell. Biochem. 104: 2155–2164, 2008. © 2008 Wiley‐Liss, Inc.
Comparing the transcriptional profile of mesenchymal cells to cardiac and skeletal muscle cells
Authors: Akavia Uri David , Veinblat Olga , Benayahu Dafna
Published: April 2008

Marrow‐derived stroma cells (MSCs) can differentiate into multiple lineages including myogenic cells. However, the molecular mechanisms that direct MSCs to each differentiation pathway are poorly understood. Our study was designed to gain insights into the potential regulatory pathways that may assist in defining MSC commitment and differentiation properties. This will delineate the similarities or differences in the expression of genes between several cell types of mesenchymal origin. In this study, we established in vitro models, which allow following the discrete stages of differentiation of cardio‐ and myogenic‐cells compared with MSC. Gene expression of each cell type at several stages of their differentiation path was evaluated by means of Affymetrix Gene Chips. Bioinformatic clustering of genes confirmed that with time in culture the myogenic cells ceased proliferating and commenced with differentiation. The expression profile analysis revealed the similarity and differences between myogenic cells and MSCs. This research compared at the molecular levels snapshots of gene expression patterns and elaborated on the overlap or differences between the analyzed cellular systems. Our results shed light on gene profiles of cells throughout their differentiation pathways. Establishing the gene signature of the differentiation process of cells that belong to several mesenchymal lineages may contribute to the understanding of molecular pathways that underlay mesenchymal tissue remodeling. J. Cell. Physiol. 216: 663–672, 2008, © 2008 Wiley‐Liss, Inc.
Genetic upregulation of matriptase‐2 reduces the aggressiveness of prostate cancer cells in vitro and in vivo and affects FAK and paxillin localisation
Authors: Sanders Andrew J. , Parr Christian , Martin Tracey A. , Lane Jane , Mason Malcolm D. , Jiang Wen G.
Published: April 2008

The cellular function and the role of matriptase‐2 in cancer progression are poorly understood. This study assesses the importance of this protease in prostate cancer cell lines. Two prostate cancer cell lines, PC‐3 and DU‐145, previously displaying minimal expression of matriptase‐2, were forced to over‐express matriptase‐2 using a human mammalian expression construct. Over‐expression of matriptase‐2 significantly reduced the invasive capacity and significantly slowed the migration rates of PC‐3 and DU‐145 cells in vitro. Similarly, PC‐3 cells containing the matriptase‐2 expression plasmid were dramatically less able to survive, grow and develop into noticeable tumours, compared to control PC‐3 cells containing an empty plasmid alone, following subcutaneous inoculation into CD1 nude mice. This trend was observed throughout the experiment, becoming apparent after the initial reading on day 7 (P = 0.0002) and continuing to the experimental end point at day 27 (P = 0.0002). Enhanced matriptase‐2 levels were also seen to correlate with increased fluorescent staining of the paxillin and FAK adhesion molecules, where a greater extent of these molecules were localised to the focal adhesion complexes. This data suggests a suppressive role for matriptase‐2 in the invasion and migration of prostate cancer cells in vitro and also in their development and growth in vivo, highlighting the potential of this molecule to interfere with key stages of metastasis. Furthermore, the data presented implies a possible connection between matriptase‐2 and the paxillin and FAK adhesion molecules which may ultimately contribute to the reduced migration rates seen in this study. J. Cell. Physiol. 216: 780–789, 2008, © 2008 Wiley‐Liss, Inc.
Heparin inhibits BMP‐2 osteogenic bioactivity by binding to both BMP‐2 and BMP receptor
Authors: Kanzaki Shin , Takahashi Tetsu , Kanno Takahiro , Ariyoshi Wataru , Shinmyouzu Kouhei , Tujisawa Toshiyuki , Nishihara Tatsuji
Published: April 2008

Heparin demonstrates several kinds of biological activities by binding to various extracellular molecules and plays pivotal roles in bone metabolism. However, the role of heparin in the biological activity of bone morphogenetic protein (BMP) remains unclear. In the present study, we examined whether heparin has the effects on osteoblast differentiation induced by BMP‐2 in vitro and also elucidated the precise mechanism by which heparin regulates bone metabolism induced by this molecule. Our results showed that heparin inhibited alkaline phosphatase (ALP) activity and mineralization in osteoblastic cells cultured with BMP‐2. Heparin was found to suppress the mRNA expressions of osterix, Runx2, ALP and osteocalcin, as well as phosphorylation of Smad1/5/8 and p38 MAPK. Further, heparin bound to both BMP‐2 and BMP receptor (BMPR). These results suggest that heparin suppresses BMP‐2‐BMPR binding, and inhibits BMP‐2 osteogenic activity in vitro. J. Cell. Physiol. 216: 844–850, 2008, © 2008 Wiley‐Liss, Inc.
Nucleic acid sensor for insecticide detection
Authors: Solanki Pratima R. , Prabhakar Nirmal , Pandey M. K. , Malhotra B. D.
Published: April 2008

Nucleic acid sensor based on polyaniline (PANI) has been fabricated by covalently immobilizing double stranded calf thymus (dsCT) DNA onto perchlorate (ClO−4)‐doped PANI film deposited onto indium‐tin‐oxide (ITO) glass plate using 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide hydrochloride (EDC)/N‐hydroxysuccinimide (NHS) chemistry. These dsCT‐DNA‐PANI‐ClO4/ITO and PANI‐ClO4/ITO electrodes have been characterized using square wave voltammetry, electrochemical impedance, scanning electron microscopy (SEM) and Fourier‐transform‐infrared (FTIR) measurements. This disposable dsCT‐DNA‐PANI‐ClO4/ITO bioelectrode, stable for about 4 months, can be used to detect cypermethrin (0.005 ppm) and trichlorfon (0.01 ppm) in 30 and 60 s, respectively. Copyright © 2008 John Wiley & Sons, Ltd.
Modeling an active conformation for linear peptides and design of a competitive inhibitor for HMG‐CoA reductase
Authors: Pak Valeriy V. , Koo Minseon , Kim Min Jung , Yang Hye Jeong , Yun Lyubov , Kwon Dae Young
Published: April 2008

This study presents an approach that can be used to search for lead peptide candidates, including unconstrained structures in a recognized sequence. This approach was performed using the design of a competitive inhibitor for 3‐hydroxy‐3‐methylglutaryl CoA reductase (HMGR). In a previous design for constrained peptides, a head‐to‐tail cyclic structure of peptide was used as a model of linear analog in searches for lead peptides with a structure close to an active conformation. Analysis of the conformational space occupied by the peptides suggests that an analogical approach can be applied for finding a lead peptide with an unconstrained structure in a recognized sequence via modeling a cycle using fixed residues of the peptide backbone. Using the space obtained by an analysis of the bioactive conformations of statins, eight cyclic peptides were selected for a peptide library based on the YVAE sequence as a recognized motif. For each cycle, the four models were assessed according to the design criterion (“V” parameter) applied for constrained peptides. Three cyclic peptides (FGYVAE, FPYVAE, and FFYVAE) were selected as lead cycles from the library. The linear FGYVAE peptide (IC50 = 0.4 µM) showed a 1200‐fold increase the inhibitory activity compared to the first isolated LPYP peptide (IC50 = 484 µM) from soybean. Experimental analysis of the modeled peptide structures confirms the appropriateness of the proposed approach for the modeling of active conformations of peptides. Copyright © 2008 John Wiley & Sons, Ltd.
Formation of [b3 − 1 + cat]+ ions from metal‐cationized tetrapeptides containing β‐alanine, γ‐aminobutyric acid or ε‐aminocaproic acid residues
Authors: Osburn Sandra M. , Ochola Sila O. , Talaty Erach R. , Van Stipdonk Michael J.
Published: April 2008

The presence and position of a single β‐alanine (βA), γ‐aminobutyric acid (γABu) or ε‐aminocaproic acid (Cap) residue has been shown to have a significant influence on the formation of bn+ and yn+ product ions from a series of model, protonated peptides. In this study, we examined the effect of the same residues on the formation of analogous [b3 − 1 + cat]+ products from metal(Li+, Na+ and Ag+)‐cationized peptides. The larger amino acids suppress formation of b3+ from protonated peptides with general sequence AAXG (where X = β‐alanine, γ‐aminobutyric acid or ε‐aminocaproic acid), presumably because of the prohibitive effect of larger cyclic intermediates in the ‘oxazolone’ pathway. However, abundant [b3 − 1 + cat]+ products are generated from metal‐cationized versions of AAXG. Using a group of deuterium‐labeled and exchanged peptides, we found that formation of [b3 − 1 + cat]+ involves transfer of either amide or α‐carbon position H atoms, and the tendency to transfer the atom from the α‐carbon position increases with the size of the amino acid in position X. To account for the transfer of the H atom, a mechanism involving formation of a ketene product as [b3 − 1 + cat]+ is proposed. Copyright © 2008 John Wiley & Sons, Ltd.
Transcription factor Sp1 dysregulation in Alzheimer's disease
Authors: Citron Bruce A. , Dennis John S. , Zeitlin Ross S. , Echeverria Valentina
Published: April 2008

Altered gene expression occurs in central nervous system disorders, including Alzheimer's disease (AD). Transcription factor Sp1 may be involved insofar as it can regulate the expression of several AD‐related proteins, including amyloid precursor protein (APP) and tau. Sp1 could itself be regulated by inflammatory and other factors associated with AD, such as interleukin‐1β. We measured an almost threefold elevation in the number of mRNA molecules of this cytokine in the AD frontal cortex. Sp1 mRNA was found to be up‐regulated in these AD brains (along with Sp1‐regulated COX‐2), and the Sp1 increase was also seen at the protein level by Western immunoblotting. To determine whether this would also occur in transgenic mice developing AD pathology, we examined the expression of Sp1 in the cortex and hippocampus and observed higher levels of Sp1 mRNA and protein. These results indicate that elements of regulatory pathways involving transcription factor Sp1 may be useful targets for therapeutic intervention to prevent or reverse AD. © 2008 Wiley‐Liss, Inc.
Global atmospheric energetics from NCEP–Reanalysis 2 and ECMWF–ERA40 Reanalysis
Authors: Marques Carlos A. F. , Rocha Alfredo , Corte‐Real João , Castanheira José M. , Ferreira Juan , Melo‐Gonçalves Paulo
Published: April 2008

The global atmospheric energy cycle is estimated on an annual basis using Reanalysis 2 data from the National Centers for Environmental Prediction and National Center for Atmospheric Research (NCEP/NCAR), and ERA 40 Reanalyses from the European Centre for Medium‐Range Weather Forecasts (ECMWF) for the period 1979–2001. A formalism to avoid belowground data on pressure levels intercepted by topography is adopted. No appreciable differences were found between the two datasets from the energetics point of view. The so‐called ωα and v·grad z formulations were both used for the conversions from zonal available potential energy into zonal kinetic energy (CZ) and from eddy available potential energy into eddy kinetic energy (CE). Results with both formulations are comparable only when using the formalism preventing belowground data to enter into the computations.

Atmospheric energetics are also computed using ECMWF Reanalyses for the period 1958–1978. A significant increase was found in the eddy kinetic and eddy available potential energies from the early period to the later period, likely related to the assimilation in the reanalyses of satellite data after 1979. The conversion rate, CZ, was found to change its sign throughout the years.

The atmospheric energy cycle using the ECMWF Reanalyses data is compared with five previous estimates. Differences in the direction of the conversion rate, CZ, between the various estimates may be explained by the different time periods chosen for averaging. Owing to the omission of belowground data, the conversion from zonal available potential energy into eddy available potential energy (CA) was somewhat smaller in ECMWF Reanalyses than in the previous estimates. Despite those differences, an overall agreement may be found between the various estimates for the atmospheric energy cycle. Copyright © 2008 Royal Meteorological Society
A prospective study of surgical margin status in oral squamous cell carcinoma: A preliminary report
Authors: Yahalom Ran , Dobriyan Alex , Vered Marilena , Talmi Yoav P. , Teicher Shlomo , Bedrin Lev
Published: April 2008

A protocol was created for prospective margin status evaluation of patients with Oral SCC. Margins are evaluated intra‐ and post‐operatively during three stages. Patients were divided into three groups: group 1 in which one margins were sampled randomly, group 2 with frozen sections taken from the surgical bed and 3 in which they were taken from the tumor specimen itself. Patients in group 3 showed the best correlation with final margin status and survival. J. Surg. Oncol. 2008;98:572–578. © 2008 Wiley‐Liss, Inc.
Assessing the optimal duration of chemotherapy in patients with colorectal liver metastases
Authors: White Rebekah R. , Schwartz Lawrence H. , Munoz Jose A. , Raggio Greer , Jarnagin William R. , Fong Yuman , D'Angelica Michael I. , Kemeny Nancy E.
Published: April 2008

Background and Objectives

Few studies have addressed the optimal duration of chemotherapy, particularly prior to liver resection for colorectal liver metastases (CLM). The purpose of this retrospective analysis was to evaluate time to maximal response in patients receiving systemic ± hepatic arterial infusion (HAI) chemotherapy alone for the treatment of CLM.

Methods

We reviewed 35 patients with CLM on clinical trials of HAI floxuridine/dexamethasone plus systemic oxaliplatin with 5‐fluorouracil/leucovorin or irinotecan (PUMP + SYSTEMIC). We retrospectively identified 35 patients with CLM who received first‐line systemic 5FU/leucovorin/oxaliplatin (FOLFOX) ± bevacizumab (SYSTEMIC) during the same time period. Measurable disease was evaluated on CT scans performed at 2‐month intervals. The sum of the products of bi‐dimensional tumor measurements for representative lesions was compared both to baseline imaging and between consecutive time points.

Results

In responders to therapy, mean cumulative tumor reduction increased from 61% at 2 months to 73% at 4 months in the PUMP + SYSTEMIC group (P < 0.01) and from 39% to 56% in the SYSTEMIC group (P < 0.01). No significant incremental tumor reduction occurred between 4 and 6 months in either group.

Conclusions

In responders to preoperative therapy, surgical resection should be considered after 2–4 months, when most patients have achieved maximal response. J. Surg. Oncol. 2008;97:601–604. © 2008 Wiley‐Liss, Inc.