bluuebunny/crossref_metadata_2025 huggingface dataset:
AlGaN/GaN-based power amplifiers for mobile radio applications: a review from the system supplier's perspective
Authors: Wiegner Dirk , Luz Gerhard , Jüschke Patrick , Machinal Robin , Merk Thomas , Seyfried Ulrich , Templ Wolfgang , Pascht Andreas , Quay Rüdiger , Van Raay Friedbert
Published: April 2010

This paper gives a summarized overview on the progress and achievements on AlGaN/GaN high electron mobility transistors (HEMT)-based power amplifiers (PAs) for mobile radio applications which have been achieved within two national funded German projects during a period of six years. Starting with a first 34 dBm (2.5 W, peak) amplifier in 2003 the impressive progress toward highly efficient S-band mobile radio PAs with up to >50 dBm (100 W) peak output power is described by means of some selected single- and multiband amplifier demonstrators. This progress has been mainly enabled by clear progress on GaN technology, device packaging, and PA design. Targeting at highly efficient single-band amplifier applications, a 2.7 GHz symmetrical Doherty amplifier with up to 45% drain efficiency at close to 45 dBm average output power under single-carrier W-CDMA (Wideband Code Division Multiple Access) operation using digital predistortion can be highlighted. In case of multiband capable amplifiers addressing software-defined radio applications, a class-AB-based demonstrator covering a frequency range from 1.8 to 2.7 GHz was realized. The amplifier showed >30% drain efficiency up to 2.5 GHz as well as up to 40 dBm average output power under single-carrier W-CDMA operation using proprietary digital predistortion. Finally, Alcatel-Lucent's activities on envelope tracking for future efficiency improved GaN-based amplifiers are described.
Shock melt veins of Tenham chondrite as a possible paleomagnetic recorder: Rock magnetism and high‐pressure minerals
Authors: Sato Yugo , Nakamura Norihiro
Published: April 2010

Heavily shocked meteorites of shock stages S5 and S6 contain shock‐induced melt veins (SMVs). SMVs might have reset the remanence of an asteroidal metamorphism at the time of giant collisions against a chondrite parent body. Here we present micropaleomagnetic and petrologic studies of SMVs in L6S5 Tenham chondrite with ∼500 μm thick black veins enclosing high‐pressure minerals such as ringwoodite. Paleomagnetic data show that the high‐temperature (HT, 200°C–650°C) and high‐coercivity (HC, 20–100 mT) stable components of SMVs formed a cluster even from different portions of SMV, whereas the stable HT component of surrounding host rock showed a scattered orientation under stereonet projection. The host rock HC components form a girdle between the mixing of SMVs and unknown overprints, tracing the magnetic susceptibility foliation. Magnetic force microscopy and backscattered electron images confirmed kamacite and taenite assemblages in iron sulfides as remanence‐carrying minerals in SMVs. Hysteresis data of SMVs revealed the presence of single‐domain (SD) FeNi metals with Mrs/Ms = ∼0.1 and Hrc/Hc = ∼2, although these parameters are only applicable to magnetite. Because the metastable ringwoodite in SMVs transforms back to olivine at 188°C for 1000 Myr (metamorphism) or at 900°C for 1 h (postshock heating), the preservation of ringwoodite suggests that SMVs have not experienced either thermal condition. The magnetic time‐temperature relation for SD FeNi metals suggested that 200°C unblocking temperature corresponds to the storage time of 100 years for kamacite and 4500 Myr for taenite at room temperature. The difference of HT components discards the possibility of postshock heating. Therefore, the SMV's remanence is a characteristic shock‐induced thermal remanence that has newly been acquired during hypervelocity collision under a cryptic magnetic field.
Motion of aurorae
Authors: Chaston Christopher. C. , Seki Kanako , Sakanoi Takeshi , Asamura Kazushi , Hirahara Masafumi
Published: April 2010

Using high resolution auroral imagery and particle measurements from the Reimei spacecraft we distinguish ‘Alfvénic’ and ‘quasi‐static’ auroral forms and implement a new multi‐scale wavelet analysis technique to examine how the vorticity in these forms varies as a function of scale transverse to the geomagnetic field. We find from this analysis that the complex motions of aurorae can be described by power‐laws relating spatial scale to optical vorticity. We demonstrate how these relationships naturally arise from the ‘conductance’ of geomagnetic field‐lines and the physics of Alfvén waves.
Influence of tidal range on the stability of coastal marshland
Authors: Kirwan Matthew L. , Guntenspergen Glenn R.
Published: April 2010

Early comparisons between rates of vertical accretion and sea level rise across marshes in different tidal ranges inspired a paradigm that marshes in high tidal range environments are more resilient to sea level rise than marshes in low tidal range environments. We use field‐based observations to propose a relationship between vegetation growth and tidal range and to adapt two numerical models of marsh evolution to explicitly consider the effect of tidal range on the response of the marsh platform channel network system to accelerating rates of sea level rise. We find that the stability of both the channel network and vegetated platform increases with increasing tidal range. Our results support earlier hypotheses that suggest enhanced stability can be directly attributable to a vegetation growth range that expands with tidal range. Accretion rates equilibrate to the rate of sea level rise in all experiments regardless of tidal range, suggesting that comparisons between accretion rate and tidal range will not likely produce a significant relationship. Therefore, our model results offer an explanation to widely inconsistent field‐based attempts to quantify this relationship while still supporting the long‐held paradigm that high tidal range marshes are indeed more stable.
Soil CO2flux and its controls during secondary succession
Authors: Wang Jin , Epstein Howard E. , Wang Lixin
Published: April 2010

The area of abandoned agricultural lands has substantially increased over the past several decades. These ubiquitous land use changes can be significant contributors to the dynamics of the global carbon budget. However, the effects of these land use dynamics (i.e., secondary succession) on carbon cycling, and particularly on soil CO2efflux, are rather sparsely addressed in the literature. Variations in soil CO2flux during secondary succession may explain the hypothesized shift from carbon source to carbon sink as succession proceeds. We investigated soil CO2flux of early, mid, and late succession ecosystems in northern Virginia from 2003 to 2006. Soil temperature, moisture, total carbon, total nitrogen, and soil C/N were measured along with soil CO2flux. Despite the wide array of changes in both physical conditions and vegetation composition/structure that occur during successional shifts, our results showed that soil CO2flux did not vary throughout succession. Our results support previous findings that soil temperature has a major influence on soil CO2flux, and we additionally found that the overall sensitivity of soil CO2flux to soil temperature did not change during succession. Soil moisture had a significant influence on soil CO2flux only at the two driest sites within the successional sequences (one early and one late successional site), where both root and microbial activities are potentially limited by soil water conditions. The monthly soil CO2fluxes were significantly different among successional stages in 9 out of the 12 months during the year. The soil CO2fluxes showed strong seasonality and differences among sites within seasons; however, these differences balanced out at the annual scale. The invariance in annual soil CO2fluxes throughout succession may indicate that soil CO2flux overall is independent of any shift from early succession carbon source to later succession carbon sink. Results also indicate that annual soil CO2budgets are likely determined by the climatic conditions under which succession proceeds. While the transient vegetation types of secondary succession alter the seasonal soil CO2fluxes, they may not affect the annual soil CO2output.
5‐aminoimidazole‐4‐carboxamide ribonucleoside and AMP‐activated protein kinase inhibit signalling through NF‐κB
Authors: Katerelos Marina , Mudge Stuart J , Stapleton David , Auwardt Russell B , Fraser Scott A , Chen C‐G , Kemp Bruce E , Power David A
Published: April 2010

Activation of nuclear factor‐kappa B (NF‐κB) is one of the most important pro‐inflammatory mechanisms in disease. In this study, we show that 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR), an intermediate in nucleoside metabolism, inhibits signalling by NF‐κB in three cell types, including bovine aortic endothelial cells (BAEC). The block in the NF‐κB signalling pathway occurred beyond degradation of IκB‐α and movement of p65 into the nucleus of BAEC. There was, however, reduced binding of NF‐κB from AICAR‐treated cells to a κB‐consensus oligonucleotide, suggesting that part of the mechanism was a reduction in NF‐κB DNA‐binding activity. Although AICAR is metabolized to ZMP and then adenosine, adenosine had no effect on activation of an NF‐κB reporter. ZMP, however, activates the metabolic stress‐sensing AMP‐activated protein kinase (AMPK). Transfection of active AMPK into BAEC reduced NF‐κB reporter activity compared with a kinase‐dead mutant, suggesting that part of the ability of AICAR to inhibit NF‐κB signalling is due to activation of AMPK. Inhibition of NF‐κB signalling may be important in the anti‐inflammatory action of drugs such as sulfasalazine and methotrexate, which led to the accumulation of AICAR within target cells.
Complement and the central nervous system: emerging roles in development, protection and regeneration
Authors: Rutkowski Martin J , Sughrue Michael E , Kane Ari J , Mills Steven A , Fang Shanna , Parsa Andrew T
Published: April 2010

As expanding research reveals the novel ability of complement proteins to promote proliferation and regeneration of tissues throughout the body, the concept of the complement cascade as an innate immune effector has changed rapidly. In particular, its interactions with the central nervous system have provided a wealth of information regarding the ability of complement proteins to mediate neurogenesis, synaptogenesis, cell migration, neuroprotection, proliferation and regeneration. At numerous phases of the neuronal and glial cell cycle, complement proteins exert direct or indirect influence over their behavior and fate. Neuronal stem cells differentiate and migrate in response to complement, and it prevents injury and death in adult cells in response to toxic agents. Furthermore, complement proteins promote survival via anti‐apoptotic actions, and can facilitate clearance and regeneration of injured tissues in various models of CNS disease. In summary, we highlight the protean abilities of complement proteins in the central nervous system, underscoring an exciting avenue of research that has yielded greater understanding of complement's role in central nervous system health and disease.
Anti‐idiotypic antibody mimicking a T‐antigen‐specific lectin inhibits human epithelial tumor cell proliferation
Authors: Sendra Victor G , Zlocowski Natacha , Nores Gustavo A , Irazoqui Fernando J
Published: April 2010

Cancer‐associated mucins show frequent alterations of oligosaccharide chain profile. Terminal structures may be deleted, thereby exposing normally ‘cryptic’ structures such as Tn (GalNAcα‐O‐Ser/Thr) and T antigen (Galβ1‐3GalNAcα‐O‐Ser/Thr). Overexpression of these commonly hidden glycoforms, and reduced level of naturally occurring anti‐T or anti‐Tn antibodies, is associated with epithelial tumor progression and aggressiveness. The lectin from the common edible mushroom Agaricus bisporus (ABL) shows high affinity binding to T antigen, and reversible noncytotoxic inhibitory effect on epithelial tumor cell proliferation. The aim of this study was to induce immune response with tumor‐associated glycan specificity and biological activity similar to those of ABL. An anti‐idiotypic (Id) antibody strategy was developed using ABL as first template. ABL was purified by affinity chromatography and assayed as immunogen in rabbit. Rabbit IgG was purified from anti‐ABL serum using a protein G column, and specific anti‐ABL IgG was obtained by affinity chromatography using immobilized ABL. Affinity‐purified anti‐ABL IgG contained an antibody fraction that recognizes the carbohydrate‐binding site of ABL. This IgG was used as immunogen in mouse to yield anti‐Id antibody recognizing tumor‐associated glycans such as Tn and T antigen. Competitive assays showed that α‐anomeric GalNAc is the main binding subsite of anti‐Id antibody in glycan recognition. Anti‐Id antibody bound human epithelial tumor cells, as shown by cell enzyme‐linked immunosorbent assay and immunofluorescence. Anti‐Id antibody raised by immunization with affinity‐purified anti‐ABL IgG had antiproliferative effect on human epithelial tumor cells through apoptosis induction similar to that of ABL. The anti‐Id immune response developed here has potential application in cancer therapy.
Recognition by toll‐like receptor 2 induces antigen‐presenting cell activation and Th1 programming during infection by Neospora caninum
Authors: Mineo Tiago WP , Oliveira Carlo JF , Gutierrez Fredy RS , Silva João S
Published: April 2010

Neospora caninum is an apicomplexan parasite responsible for major economic losses due to abortions in cattle. Toll‐like receptors (TLRs) sense specific microbial products and direct downstream signaling pathways in immune cells, linking innate, and adaptive immunity. Here, we analyze the role of TLR2 on innate and adaptive immune responses during N. caninum infection. Inflammatory peritoneal macrophages and bone marrow‐derived dendritic cells exposed to N. caninum‐soluble antigens presented an upregulated expression of TLR2. Increased receptor expression was correlated to TLR2/MyD88‐dependent antigen‐presenting cell maturation and pro‐inflammatory cytokine production after stimulation by antigens. Impaired innate responses observed after infection of mice genetically deficient for TLR2(−/−) was followed by downregulation of adaptive T helper 1 (Th1) immunity, represented by diminished parasite‐specific CD4+ and CD8+ T‐cell proliferation, IFN‐γ:interleukin (IL)‐10 ratio, and IgG subclass synthesis. In parallel, TLR2−/− mice presented higher parasite burden than wild‐type (WT) mice at acute and chronic stages of infection. These results show that initial recognition of N. caninum by TLR2 participates in the generation of effector immune responses against N. caninum and imply that the receptor may be a target for future prophylactic strategies against neosporosis.
Dendritic cells expressing soluble CTLA4Ig prolong antigen‐specific skin graft survival
Authors: Ierino Francesco L , Mulley William , Dodge Natalie , Li Yu Qin , Mouhtouris Effie , Christiansen Dale , Sandrin Mauro S
Published: April 2010

Dendritic cells (DCs) and CTLA4Ig are important in regulating T‐cell responses and therefore represent potential therapeutic tools in transplantation. In this study, CTLA4Ig was expressed in a C57BL/6 murine DC line (JAWS II) by lentiviral transduction and these cells were used to examine T‐cell immunomodulatory effects in vitro and in vivo. A lower stimulation index to C57BL/6 was observed with splenocytes from BALB/c mice primed with JAWS II‐CTLA4Ig compared with control JAWS II‐green fluorescent protein (JAWS II‐GFP). Mice primed with JAWS II‐CTLA4Ig cells had significantly prolonged antigen‐specific C57BL/6 skin graft survival compared with either JAWS II‐GFP‐primed or naïve mice (median 13, 11 and 11 days, respectively, P=0.0001). Furthermore, JAWS II‐CTLA4Ig‐primed mice that had been previously transplanted with skin grafts were re‐transplanted with skin grafts 6 months later without immune manipulation. These mice demonstrated specific prolongation of second‐set rejection responses, indicating systemic immune modulation induced by genetically modified DC. The mechanism was not due to expression of indoleamine 2,3‐dioxygenase or induction of circulating regulatory T cells as assessed by flow cytometry of the peripheral blood lymphocytes. This potent effect demonstrated with skin grafts and second‐set responses highlights the potential use of this strategy for transplantation more generally.
Genome-wide analysis of diel gene expression in the unicellular N2-fixing cyanobacterium Crocosphaera watsonii WH 8501
Authors: Shi Tuo , Ilikchyan Irina , Rabouille Sophie , Zehr Jonathan P
Published: April 2010

Correction to: The ISME Journal (2010) 4, 621–632; doi:10.1038/ismej.2009.148; published online 28 January 2010 Since the publication of this paper, the authors have noticed an error in Figure 4. The correct figure is shown below. The authors would like to apologize for any inconvenience this may have caused.
Distributions of putative aerobic methanotrophs in diverse pelagic marine environments
Authors: Tavormina Patricia L , Ussler William , Joye Samantha B , Harrison Benjamin K , Orphan Victoria J
Published: April 2010

Correction to: The ISME Journal (2010) 4, 700–710; doi:10.1038/ismej.2009.155; published online 11 February 2010 Since the publication of this paper, the authors have noticed an error regarding a unit of measurement (μM) in the first paragraph under the heading ‘5′ exonuclease (Taqman) assay’, on page 5.
Target mRNA abundance dilutes microRNA and siRNA activity
Authors: Arvey Aaron , Larsson Erik , Sander Chris , Leslie Christina S , Marks Debora S
Published: April 2010

Post‐transcriptional regulation by microRNAs and siRNAs depends not only on characteristics of individual binding sites in target mRNA molecules, but also on system‐level properties such as overall molecular concentrations. We hypothesize that an intracellular pool of microRNAs/siRNAs faced with a larger number of available predicted target transcripts will downregulate each individual target gene to a lesser extent. To test this hypothesis, we analyzed mRNA expression change from 178 microRNA and siRNA transfection experiments in two cell lines. We find that downregulation of particular genes mediated by microRNAs and siRNAs indeed varies with the total concentration of available target transcripts. We conclude that to interpret and design experiments involving gene regulation by small RNAs, global properties, such as target mRNA abundance, need to be considered in addition to local determinants. We propose that analysis of microRNA/siRNA targeting would benefit from a more quantitative definition, rather than simple categorization of genes as ‘target’ or ‘not a target.’ Our results are important for understanding microRNA regulation and may also have implications for siRNA design and small RNA therapeutics.
Activation of the MAPKs ERK1/2 by cell swelling in turbot hepatocytes
Authors: Fouchs Audrey , Ollivier Hélène , Haond Christophe , Roy Stella , Calvès Patrick , Pichavant‐Rafini Karine
Published: April 2010

Background information. Activation of MAPKs (mitogen‐activated protein kinases), in particular ERK1/2 (extracellular‐signal‐regulated kinase 1/2), has been reported to take place in a large variety of cell types after hypo‐osmotic cell swelling. Depending on cell type, ERK1/2 phosphorylation can then serve or not the RVD (regulatory volume decrease) process. The present study investigates ERK1/2 activation after aniso‐osmotic stimulations in turbot hepatocytes and the potential link between phosphorylation of these proteins and RVD.

Results. In turbot hepatocytes, Western‐blot analysis shows that a hypo‐osmotic shock from 320 to 240 mOsm·kg−1 induced a rapid increase in ERK1/2 phosphorylation, whereas a hyper‐osmotic shock from 320 to 400 mOsm·kg−1 induced no significant change in the phosphorylation of these proteins. The hypo‐osmotic‐induced ERK1/2 phosphorylation was significantly prevented when hypo‐osmotic shock was performed in the presence of the specific MEK (MAPK/ERK kinase) inhibitor PD98059 (100 μM). In these conditions, the RVD process was not altered, suggesting that ERK1/2 did not participate in this process in turbot hepatocytes. Moreover, the hypo‐osmotic‐induced activation of ERK1/2 was significantly prevented by breakdown of extracellular ATP by apyrase (10 units·ml−1), by inhibition of purinergic P2 receptors by suramin (100 μM) or by calcium depletion using EGTA (1 mM) and thapsigargin (1 μM).

Conclusions. In turbot hepatocytes, hypo‐osmotic swelling but not hyper‐osmotic shrinkage induced the activation of ERK1/2. However, these proteins do not seem to be involved in the RVD process. Their hypo‐osmotic‐induced activation is partially due to cascades of signalling events triggered by the binding of released ATP on purinergic P2 receptors and requires the presence of calcium.
Renal imino acid and glycine transport system ontogeny and involvement in developmental iminoglycinuria
Authors: Vanslambrouck Jessica M. , Bröer Angelika , Thavyogarajah Thuvaraka , Holst Jeff , Bailey Charles G. , Bröer Stefan , Rasko John E. J.
Published: April 2010

Renal maturation occurs post-natally in many species and reabsorption capacity at birth can vary substantially from the mature kidney. However, little is known regarding the maturation of amino acid transport mechanisms, despite the well-known physiological state of developmental iminoglycinuria. Commonly seen during early infancy, developmental iminoglycinuria is a transient version of the persistent inherited form of the disorder, referred to as iminoglycinuria, and manifests as a urinary hyperexcretion of proline, hydroxyproline and glycine. The transporters involved in developmental iminoglycinuria and their involvement in the improvement of renal reabsorption capacity remain unknown. qPCR (quantitative real-time PCR) and Western blot analysis in developing mouse kidney revealed that the expression of Slc6a18, Slc6a19, Slc6a20a and Slc36a2 was lower at birth (approx. 3.4-, 5.0-, 2.4- and 3.0-fold less than adult kidney by qPCR respectively) and increased during development. Furthermore, immunofluorescence confocal microscopy demonstrated the absence of apical expression of Slc6a18, Slc6a19, Slc6a20a and the auxiliary protein collectrin in kidneys of mice at birth. This correlated with the detection of iminoglycinuria during the first week of life. Iminoglycinuria subsided (proline reduction preceded glycine) in the second week of life, which correlated with an increase in the expression of Slc6a19 and Slc6a20a. Mice achieved an adult imino acid and glycine excretion profile by the fourth week, at which time the expression level of all transporters was comparable with adult mice. In conclusion, these results demonstrate the delayed expression and maturation of Slc6a18, Slc6a19, Slc6a20a and Slc36a2 in neonatal mice and thus the molecular mechanism of developmental iminoglycinuria.
S-Glutathionyl-(chloro)hydroquinone reductases: a novel class of glutathione transferases
Authors: Xun Luying , Belchik Sara M. , Xun Randy , Huang Yan , Zhou Huina , Sanchez Emiliano , Kang ChulHee , Board Philip G.
Published: April 2010

Sphingobium chlorophenolicum completely mineralizes PCP (pentachlorophenol). Two GSTs (glutathione transferases), PcpC and PcpF, are involved in the degradation. PcpC uses GSH to reduce TeCH (tetrachloro-p-hydroquinone) to TriCH (trichloro-p-hydroquinone) and then to DiCH (dichloro-p-hydroquinone) during PCP degradation. However, oxidatively damaged PcpC produces GS-TriCH (S-glutathionyl-TriCH) and GS-DiCH (S-glutathionyl-TriCH) conjugates. PcpF converts the conjugates into TriCH and DiCH, re-entering the degradation pathway. PcpF was further characterized in the present study. It catalysed GSH-dependent reduction of GS-TriCH via a Ping Pong mechanism. First, PcpF reacted with GS-TriCH to release TriCH and formed disulfide bond between its Cys53 residue and the GS moiety. Then, a GSH came in to regenerate PcpF and release GS–SG. A TBLASTN search revealed that PcpF homologues were widely distributed in bacteria, halobacteria (archaea), fungi and plants, and they belonged to ECM4 (extracellular mutant 4) group COG0435 in the conserved domain database. Phylogenetic analysis grouped PcpF and homologues into a distinct group, separated from Omega class GSTs. The two groups shared conserved amino acid residues, for GSH binding, but had different residues for the binding of the second substrate. Several recombinant PcpF homologues and two human Omega class GSTs were produced in Escherichia coli and purified. They had zero or low activities for transferring GSH to standard substrates, but all had reasonable activities for GSH-dependent reduction of disulfide bond (thiol transfer), dehydroascorbate and dimethylarsinate. All the tested PcpF homologues reduced GS-TriCH, but the two Omega class GSTs did not. Thus PcpF homologues were tentatively named S-glutathionyl-(chloro)hydroquinone reductases for catalysing the GSH-dependent reduction of GS-TriCH.
Phosphorylation of Ser136 is critical for potent bone sialoprotein-mediated nucleation of hydroxyapatite crystals
Authors: Baht Gurpreet S. , O'Young Jason , Borovina Antonia , Chen Hong , Tye Coralee E. , Karttunen Mikko , Lajoie Gilles A. , Hunter Graeme K. , Goldberg Harvey A.
Published: April 2010

Acidic phosphoproteins of mineralized tissues such as bone and dentin are believed to play important roles in HA (hydroxyapatite) nucleation and growth. BSP (bone sialoprotein) is the most potent known nucleator of HA, an activity that is thought to be dependent on phosphorylation of the protein. The present study identifies the role phosphate groups play in mineral formation. Recombinant BSP and peptides corresponding to residues 1–100 and 133–205 of the rat sequence were phosphorylated with CK2 (protein kinase CK2). Phosphorylation increased the nucleating activity of BSP and BSP-(133–205), but not BSP-(1–100). MS analysis revealed that the major site phosphorylated within BSP-(133–205) was Ser136, a site adjacent to the series of contiguous glutamate residues previously implicated in HA nucleation. The critical role of phosphorylated Ser136 in HA nucleation was confirmed by site-directed mutagenesis and functional analyses. Furthermore, peptides corresponding to the 133–148 sequence of rat BSP were synthesized with or without a phosphate group on Ser136. As expected, the phosphopeptide was a more potent nucleator. The mechanism of nucleation was investigated using molecular-dynamics simulations analysing BSP-(133–148) interacting with the {100} crystal face of HA. Both phosphorylated and non-phosphorylated sequences adsorbed to HA in extended conformations with alternating residues in contact with and facing away from the crystal face. However, this alternating-residue pattern was more pronounced when Ser136 was phosphorylated. These studies demonstrate a critical role for Ser136 phosphorylation in BSP-mediated HA nucleation and identify a unique mode of interaction between the nucleating site of the protein and the {100} face of HA.
Cellular nucleic-acid-binding protein, a transcriptional enhancer of c-Myc, promotes the formation of parallel G-quadruplexes
Authors: Borgognone Mariana , Armas Pablo , Calcaterra Nora B.
Published: April 2010

G-rich sequences that contain stretches of tandem guanines can form four-stranded, intramolecular stable DNA structures called G-quadruplexes (termed G4s). Regulation of the equilibrium between single-stranded and G4 DNA in promoter regions is essential for control of gene expression in the cell. G4s are highly stable structures; however, their folding kinetics are slow under physiological conditions. CNBP (cellular nucleic-acid-binding protein) is a nucleic acid chaperone that binds the G4-forming G-rich sequence located within the NHE (nuclease hypersensitivity element) III of the c-Myc proto-oncogene promoter. Several reports have demonstrated that CNBP enhances the transcription of c-Myc in vitro and in vivo; however, none of these reports have assessed the molecular mechanisms responsible for this control. In the present study, by means of Taq polymerase stop assays, electrophoretic mobility-shift assays and CD spectroscopy, we show that CNBP promotes the formation of parallel G4s to the detriment of anti-parallel G4s, and its nucleic acid chaperone activity is required for this effect. These findings are the first to implicate CNBP as a G4-folding modulator and, furthermore, assign CNBP a novel mode-of-action during c-Myc transcriptional regulation.
Biosynthesis of heparan sulfate in EXT1-deficient cells
Authors: Okada Megumi , Nadanaka Satomi , Shoji Naoko , Tamura Jun-ichi , Kitagawa Hiroshi
Published: April 2010

HS (heparan sulfate) is synthesized by HS co-polymerases encoded by the EXT1 and EXT2 genes (exostosin 1 and 2), which are known as causative genes for hereditary multiple exostoses, a dominantly inherited genetic disorder characterized by multiple cartilaginous tumours. It has been thought that the hetero-oligomeric EXT1–EXT2 complex is the biologically relevant form of the polymerase and that targeted deletion of either EXT1 or EXT2 leads to a complete lack of HS synthesis. In the present paper we show, unexpectedly, that two distinct cell lines defective in EXT1 expression indeed produce small but significant amounts of HS chains. The HS chains produced without the aid of EXT1 were shorter than HS chains formed in concert with EXT1 and EXT2. In addition, biosynthesis of HS in EXT1-defective cells was notably blocked by knockdown of either EXT2 or EXTL2 (EXT-like), but not of EXTL3. Then, to examine the roles of EXTL2 in the biosynthesis of HS in EXT1-deficient cells, we focused on the GlcNAc (N-aetylglucosamine) transferase activity of EXTL2, which is involved in the initiation of HS chains by transferring the first GlcNAc to the linkage region. Although EXT2 alone synthesized no heparan polymers on the synthetic linkage region analogue GlcUAβ1-3Galβ1-O-C2H4NH-benzyloxycarbonyl, marked polymerization by EXT2 alone was demonstrated on GlcNAcα1-4GlcUAβ1-3Galβ1-O-C2H4N-benzyloxycarbonyl (where GlcUA is glucuronic acid and Gal is galactose), which was generated by transferring a GlcNAc residue using recombinant EXTL2 on to GlcUAβ1–3Galβ1-O-C2H4NH-benzyloxycarbonyl. These findings indicate that the transfer of the first GlcNAc residue to the linkage region by EXTL2 is critically required for the biosynthesis of HS in cells deficient in EXT1.
Regulation of Nicotiana tabacum osmotic stress-activated protein kinase and its cellular partner GAPDH by nitric oxide in response to salinity
Authors: Wawer Izabela , Bucholc Maria , Astier Jéremy , Anielska-Mazur Anna , Dahan Jennifer , Kulik Anna , Wysłouch-Cieszynska Aleksandra , Zaręba-Kozioł Monika , Krzywinska Ewa , Dadlez Michal , Dobrowolska Grażyna , Wendehenne David
Published: April 2010

Several studies focusing on elucidating the mechanism of NO (nitric oxide) signalling in plant cells have highlighted that its biological effects are partly mediated by protein kinases. The identity of these kinases and details of how NO modulates their activities, however, remain poorly investigated. In the present study, we have attempted to clarify the mechanisms underlying NO action in the regulation of NtOSAK (Nicotiana tabacum osmotic stress-activated protein kinase), a member of the SNF1 (sucrose non-fermenting 1)-related protein kinase 2 family. We found that in tobacco BY-2 (bright-yellow 2) cells exposed to salt stress, NtOSAK is rapidly activated, partly through a NO-dependent process. This activation, as well as the one observed following treatment of BY-2 cells with the NO donor DEA/NO (diethylamine-NONOate), involved the phosphorylation of two residues located in the kinase activation loop, one being identified as Ser158. Our results indicate that NtOSAK does not undergo the direct chemical modifications of its cysteine residues by S-nitrosylation. Using a co-immunoprecipitation-based strategy, we identified several proteins present in immunocomplex with NtOSAK in salt-treated cells including the glycolytic enzyme GAPDH (glyceraldehyde-3-phosphate dehydrogenase). Our results indicate that NtOSAK directly interacts with GAPDH in planta. Furthermore, in response to salt, GAPDH showed a transient increase in its S-nitrosylation level which was correlated with the time course of NtOSAK activation. However, GADPH S-nitrosylation did not influence its interaction with NtOSAK and did not have an impact on the activity of the protein kinase. Taken together, the results support the hypothesis that NtOSAK and GAPDH form a cellular complex and that both proteins are regulated directly or indirectly by NO.
Inhibition of dynamin‐2 confers endothelial barrier dysfunctions by attenuating nitric oxide production
Authors: Seerapu Hima bindu Reddy , Subramaniam Geetha Priya , Majumder Syamantak , Sinha Swaraj , Bisana Swathi , Mahajan Sahil , Kolluru Gopi Krishna , Muley Ajit , Siamwala Jamila H. , Illavazagan Govindan , Chatterjee Suvro
Published: April 2010

Hypoxia induces barrier dysfunctions in endothelial cells. Nitric oxide is an autacoid signalling molecule that confers protection against hypoxia‐mediated barrier dysfunctions. Dyn‐2 (dynamin‐2), a large GTPase and a positive modulator of eNOS (endothelial nitric oxide synthase), plays an important role in maintaining vascular homeostasis. The present study aims to elucidate the role of dyn‐2 in hypoxia‐mediated leakiness of the endothelial monolayer in relation to redox milieu. Inhibition of dyn‐2 by transfecting the cells with K44A, a dominant negative construct of dyn‐2, elevated leakiness of the endothelial monolayer under hypoxia. Sodium nitroprusside (nitric oxide donor) and uric acid (peroxynitrite quencher) were used to evaluate the role of nitric oxide and peroxynitrite in maintaining endothelial barrier functions under hypoxia. Administration of nitric oxide and uric acid recovered hypoxia‐mediated leakiness of K44A‐overexpressed endothelial monolayer. Our study confirms that inhibition of dyn‐2 induces leakiness in the endothelial monolayer by increasing the load of peroxynitrite under hypoxia.
Suppression of PTP1B in gastric cancer cells in vitro induces a change in the genome‐wide expression profile and inhibits gastric cancer cell growth
Authors: Wang Jinguo , Chen Xuehua , Liu Bingya , Zhu Zhenggang
Published: April 2010

PTP1B (protein tyrosine phosphatase 1B) is a member of the superfamily of PTPs (protein tyrosine phosphatases) and has been implicated in cancer pathogenesis. However, the role of PTP1B in gastric cancer is still unknown. Here, we first detected the PTP1B expression in six gastric cancer cell lines and in the immortalized gastric mucosal epithelial cell line GES‐1 by RT‐PCR and Western blot. Then, we measured the change of the genome‐wide expression profile in MKN28 gastric cancer cells transfected with a plasmid expressing PTP1B‐specific small interfering RNA by microarray analysis. Our results showed that PTP1B was overexpressed in gastric cancer cells, and inhibition of PTP1B expression dramatically inhibited gastric cancer cell growth in vitro and in vivo. In addition, microarray analysis revealed that inhibition of PTP1B induced changes in the genome‐wide expression profile. These changes may be related to cell growth. Taken together, our data suggested that PTP1B may be a candidate oncogene in gastric cancer.
Role of leukaemia inhibitory factor in the induction of pluripotent stem cells in mice
Authors: Xu Jie , Wang Feng , Tang Zhouping , Zhan Yanqiang , Zhang Jinping , Yan Qiuyue , Xiong Yongjie , Xie Xuewei , Wu Jun , Zhang Suming
Published: April 2010

iPS (induced pluripotent stem) cells can be induced from somatic cells in mice by genetic manipulation. Most previously established mouse iPS cell lines have been derived using feeder layers supplemented with exogenous LIF (leukaemia inhibitory factor). Although a feeder‐free induction system has been developed in recent studies, LIF is still required for reprogramming, but its role in the generation of mouse iPS cells has remained elusive. In this study, we investigated its contribution to the induction of pluripotency. Our results showed that LIF activates AP (alkaline phosphatase) through a c‐Myc‐dependent mechanism. Moreover, it acts as a protective factor during the transition from AP‐positive colonies to Oct3/4‐positive cells. These findings illustrate a mechanism by which LIF may integrate signalling into reprogramming.
Selecting exercise regimens and strains to modify obesity and diabetes in rodents: an overview
Authors: Ghosh Sanjoy , Golbidi Saeid , Werner Isa , Verchere Bruce C. , Laher Ismail
Published: April 2010

Exercise is part of a healthy lifestyle and frequently is an important component in combating chronic diseases, such as obesity and diabetes. Understanding the molecular events initiated by regular exercise is best studied in laboratory animals, with mice and rats being favoured for a number of reasons. However, the wide variety of rodent strains available for biomedical research often makes it challenging to select an animal strain suitable for studying specific disease outcomes. In the present review we focus on exercise as a management strategy for obesity and diabetes and we discuss: (i) exercise paradigms in humans shown to ameliorate signs and symptoms of obesity and diabetes; (ii) different rodent strains in terms of their advantages, disadvantages and limitations when using specific forms of exercise; (iii) the strengths and weaknesses of commonly used laboratory methods for rodent exercise; and (iv) the unintended consequences of exercise that are often manifested by increased hormonal and oxidative stress responses.
A translational approach to micro-inflammation in end-stage renal disease: molecular effects of low levels of interleukin-6
Authors: Memoli Bruno , Salerno Simona , Procino Alfredo , Postiglione Loredana , Morelli Sabrina , Sirico Maria Luisa , Giordano Francesca , Ricciardone Margherita , Drioli Enrico , Andreucci Vittorio E. , de Bartolo Loredana
Published: April 2010

Inflammation plays a key role in the progression of cardiovascular disease, the leading cause of mortality in ESRD (end-stage renal disease). Over recent years, inflammation has been greatly reduced with treatment, but mortality remains high. The aim of the present study was to assess whether low (<2 pg/ml) circulating levels of IL-6 (interleukin-6) are necessary and sufficient to activate the transcription factor STAT3 (signal transducer and activator of transcription 3) in human hepatocytes, and if this micro-inflammatory state was associated with changes in gene expression of some acute-phase proteins involved in cardiovascular mortality in ESRD. Human hepatocytes were treated for 24 h in the presence and absence of serum fractions from ESRD patients and healthy subjects with different concentrations of IL-6. The specific role of the cytokine was also evaluated by cell experiments with serum containing blocked IL-6. Furthermore, a comparison of the effects of IL-6 from patient serum and rIL-6 (recombinant IL-6) at increasing concentrations was performed. Confocal microscopy and Western blotting demonstrated that STAT3 activation was associated with IL-6 cell-membrane-bound receptor overexpression only in hepatocytes cultured with 1.8 pg/ml serum IL-6. A linear activation of STAT3 and IL-6 receptor expression was also observed after incubation with rIL-6. Treatment of hepatocytes with 1.8 pg/ml serum IL-6 was also associated with a 31.6-fold up-regulation of hepcidin gene expression and a 8.9-fold down-regulation of fetuin-A gene expression. In conclusion, these results demonstrated that low (<2 pg/ml) circulating levels of IL-6, as present in non-inflamed ESRD patients, are sufficient to activate some inflammatory pathways and can differentially regulate hepcidin and fetuin-A gene expression.
Activation of peripheral blood mononuclear cells and extracellular matrix and inflammatory gene profile in acute myocardial infarction
Authors: Fang Lu , Du Xiao-Jun , Gao Xiao-Ming , Dart Anthony M.
Published: April 2010

Inflammation and ECM (extracellular matrix) remodelling play important roles in LV (left ventricular) remodelling following acute MI (myocardial infarction). Previous studies show elevated plasma MMP (matrix metalloproteinase) levels in patients with acute MI, but their sources are not clear. The recruitment of mononuclear cells into the infarcted myocardium is critical for inflammatory responses, but their exact roles in LV remodelling have not been fully investigated, as it is difficult to isolate and study the function of regional inflammatory cells. To address these questions, we isolated PBMCs (peripheral blood mononuclear cells) from blood samples of patients with acute MI or stable angina, or healthy controls (n=14, 8 and 12 respectively). PBMCs were cultured for 24 h and the MMP9 level in the culture medium was measured by gelatin zymography, and MMP9 gene expression was measured by real-time PCR. Two superarrays (ECM and adhesion molecules, and common cytokines; 84 genes included in each array) were employed to screen gene expression profiles by PBMCs in five patients with acute MI and five controls. We found that MMP9 expression by PBMCs at both the mRNA and protein levels was increased 2-fold (both P<0.05) in patients with acute MI compared with the two control groups. Notably, MMP2 was not expressed by PBMCs. Superarray screening revealed that PBMCs not only expressed MMPs, TIMPs (tissue inhibitors of metalloproteinases) and matrix proteins, but also served as an important source of cell adhesion molecules, inflammatory cytokines and growth factors. A total of 42 genes were differentially expressed in patients with acute MI compared with controls. Expression of selected genes was confirmed by real-time PCR. In conclusion, PBMCs constitute a key cellular source for elevated plasma MMP9, but not for MMP2. PBMCs also contribute to systemic and regional inflammation and matrix remodelling in acute MI.
A new lubrication theory to derive far-field axial pressure difference due to force singularities in cylindrical or annular vessels
Authors: Navardi Shahin , Bhattacharya Sukalyan
Published: April 2010

In simulations of creeping flow, the effect of suspended particles on a fluid is often represented by force singularities responsible for singular Stokesian solutions, which are infinite at the sphere center and decay far from the particle. In this article, we consider such singular fields centered at a point inside a cylindrical or annular conduit containing highly viscous medium. Across an unbounded infinite domain, these singular flows cannot produce a finite pressure difference as they decay to zero far from the center. However, in the presence of bounding cylindrical surfaces, the reflected flow from the walls creates a finite pressure difference between the far fields across the force singularity along the axial direction. To quantify the effect of the reflected flow, we present a new lubrication analysis, which, on the one hand, identifies the specific singular fields capable of producing axial pressure difference and, on the other hand, provides explicit expressions for the far-field pressure. Though we specifically focus on cylindrical or annular geometry, the outlined approach can also be extended to other confinements. Thus, the general formulation can be used in larger context to quantify the effect of small particles on wall-bounded fluid medium.
Effect of ultraviolet radiation on slow-relaxation processes in ferroelectric capacitance structures
Authors: Petrov P. K. , Alford N. McN , Kozyrev A. , Gaidukov M. , Altynnikov A. , Vasilevskiy A. , Konoplev G. , Tumarkin A. , Gagarin A.
Published: April 2010

The effects of ultraviolet (UV) irradiation on the relaxation processes in Ba0.3Sr0.7TiO3 thin film capacitors were experimentally investigated in a range of wavelengths λ=(310–400) nm. It was observed that irradiation with a specific wavelength reduces the time of slow capacitance relaxation up to three orders of magnitude in comparison with relaxation time in the “dark” regime. It was also observed that at a certain wavelength of UV irradiation there was a maximum in the leakage current of the capacitors. This wavelength corresponded exactly with a minimum in the relaxation time of the capacitance. It was shown that the decrease in the ferroelectric film thickness resulted in a shift in τ(λ)minima and I(λ)maxima towards the shorter wavelengths. Phenomena observed are analyzed using Bouguer’s law.
Resistivity recovery in Gd5Si2.09Ge1.91 by annealing
Authors: Hadimani R. L. , Jiles D. C.
Published: April 2010

Irreversible change in resistivity occurs in Gd5(SixGe1−x)4 (with 0.41<x<0.575) each time the material is cycled through its first order transition temperature. This results in a progressive increase in resistivity with no apparent recovery. Results showed that the resistivity does recover if the material is left for an extended period of time at room temperature. We postulate that the recovery time decreases with temperature, and a model has been developed here to explain the recovery in resistivity when the samples are held at elevated temperatures over a period of time, and this has been verified experimentally by holding a Gd5Si2.09Ge1.91 at 360 K.
FeNi-based magnetic layered nanostructures: Magnetic properties and giant magnetoimpedance
Authors: Kurlyandskaya G. V. , Svalov A. V. , Fernandez E. , Garcia-Arribas A. , Barandiaran J. M.
Published: April 2010

Magnetic properties and the magnetoimpedance (MI) effect were studied for a series of [Fe20Ni80/Ti]n/Fe20Ni80 (n=0 to 5) nanostructures, prepared by dc magnetron sputtering. The thickness of the FeNi layers was selected as 170 nm in order to avoid the appearance of the “transcritical” state that takes place for thicker layers. First, the influence of the Ti layer thickness was determined for n=1 trilayers, with Ti layers ranging from 2 to 20 nm. The minimum coercivity corresponded to a Ti layer of about 6 nm. Second, the magnetic properties and MI responses were studied for different [FeNi/Ti]n/FeNi structures at a fixed Ti layer thickness of 6 nm. The complex impedance was measured for a frequency range of 1–300 MHz. The highest value of the MI was obtained in the sample [FeNi/Ti]5/FeNi with the largest total thickness.
Magnetoimpedance and magnetodielectric properties of single phase 45PMN-20PFW-35PT ceramics
Authors: Ramachandran B. , Sudarshan N. , Rao M. S. Ramachandra
Published: April 2010

Phase pure and dense polycrystalline 45PMN-20PFW-35PT sample has been synthesized using a columbite precursor method. Structure and surface morphology of the samples were studied using x-ray diffraction and scanning electron microscope. The sample showed the expected reduction in dielectric constant and polarization (Pmax=17 μC/cm2) compared with that of the parent compound, 65PMN-35PT (Pmax=22 μC/cm2). The sample is also found to be paramagnetic, which is confirmed by magnetization measurements as a function of temperature and an applied magnetic field. The sample was also tested for magnetoelectric coupling by measuring its dielectric constant and impedance at different applied magnetic fields. The observed colossal negative magnetodielectrics (177%) and colossal positive magnetoimpedance (130%) effect at 7 MHz, which is due to piezoelectric radial vibration. This is an indirect confirmation of the coupling between the electric and magnetic order parameters.