bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ras triggers acidosis-induced activation of the extracellular-signal-regulated kinase pathway in cardiac myocytes
Authors: Haworth Robert S. , Dashnyam Semjidmaa , Avkiran Metin 
Published: October 2006

In cardiac myocytes, sustained (3 min) intracellular acidosis activates the ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway and, through this pathway, increases sarcolemmal NHE (Na+/H+ exchanger) activity [Haworth, McCann, Snabaitis, Roberts and Avkiran (2003) J. Biol. Chem. 278, 31676–31684]. In the present study, we aimed to determine the time-dependence, pH-dependence and upstream signalling mechanisms of acidosis-induced ERK1/2 activation in ARVM (adult rat ventricular myocytes). Cultured ARVM were subjected to intracellular acidosis for up to 20 min by exposure to NH4Cl, followed by washout with a bicarbonate-free Tyrode solution containing the NHE1 inhibitor cariporide. After the desired duration of intracellular acidosis, the phosphorylation status of ERK1/2 and its downstream effector p90RSK (90 kDa ribosomal S6 kinase) were determined by Western blotting. This revealed a time-dependent transient phosphorylation of both ERK1/2 and p90RSK by intracellular acidosis (intracellular pH ∼6.6), with maximum activation occurring at 3 min and a return to basal levels by 20 min. When the degree of intracellular acidosis was varied from ∼6.8 to ∼6.5, maximum ERK1/2 phosphorylation was observed at an intracellular pH of 6.64. Inhibition of MEK1/2 [MAPK (mitogen-activated protein kinase)/ERK kinase 1/2) by pre-treatment of ARVM with U0126 or adenoviral expression of dominant-negative D208A-MEK1 protein prevented the phosphorylation of ERK1/2 by sustained intracellular acidosis, as did inhibition of Raf-1 with GW 5074 or ZM 336372. Interference with Ras signalling by the adenoviral expression of dominant-negative N17-Ras protein or with FPT III (farnesyl protein transferase inhibitor III) also prevented acidosis-induced ERK1/2 phosphorylation, whereas inhibiting G-protein signalling [by adenoviral expression of RGS4 or Lsc, the RGS domain of p115 RhoGEF (guanine nucleotide-exchange factor)] or protein kinase C (with bisindolylmaleimide I) had no effect. Our data show that, in ARVM, sustained intracellular acidosis activates ERK1/2 through proximal activation of the classical Ras/Raf/MEK pathway.
Oxidation and haem loss kinetics of poly(ethylene glycol)-conjugated haemoglobin (MP4): dissociation between in vitro and in vivo oxidation rates
Authors: Vandegriff Kim D. , Malavalli Ashok , Minn Charles , Jiang Eva , Lohman Jeff , Young Mark A. , Samaja Michele , Winslow Robert M. 
Published: October 2006

Haemoglobin-based oxygen carriers can undergo oxidation of ferrous haemoglobin into a non-functional ferric form with enhanced rates of haem loss. A recently developed human haemoglobin conjugated to maleimide-activated poly(ethylene glycol), termed MP4, has unique physicochemical properties (increased molecular radius, high oxygen affinity and low cooperativity) and lacks the typical hypertensive response observed with most cell-free haemoglobin solutions. The rate of in vitro MP4 autoxidation is higher compared with the rate for unmodified SFHb (stroma-free haemoglobin), both at room temperature (20–22 °C) and at 37 °C (P&lt;0.001). This appears to be attributable to residual catalase activity in SFHb but not MP4. In contrast, MP4 and SFHb showed the same susceptibility to oxidation by reactive oxygen species generated by a xanthine–xanthine oxidase system. Once fully oxidized to methaemoglobin, the rate of in vitro haem loss was five times higher in MP4 compared with SFHb in the fast phase, which we assign to the β subunits, whereas the slow phase (i.e. haem loss from α chains) showed similar rates for the two haemoglobins. Formation of MP4 methaemoglobin in vivo following transfusion in rats and humans was slower than predicted by its first-order in vitro autoxidation rate, and there was no appreciable accumulation of MP4 methaemoglobin in plasma before disappearing from the circulation. These results show that MP4 oxidation and haem loss characteristics observed in vitro provide information regarding the effect of poly(ethylene glycol) conjugation on the stability of the haemoglobin molecule, but do not correspond to the oxidation behaviour of MP4 in vivo.
Ubiquitin-binding domains
Authors: Hurley James H. , Lee Sangho , Prag Gali 
Published: October 2006

The covalent modification of proteins by ubiquitination is a major regulatory mechanism of protein degradation and quality control, endocytosis, vesicular trafficking, cell-cycle control, stress response, DNA repair, growth-factor signalling, transcription, gene silencing and other areas of biology. A class of specific ubiquitin-binding domains mediates most of the effects of protein ubiquitination. The known membership of this group has expanded rapidly and now includes at least sixteen domains: UBA, UIM, MIU, DUIM, CUE, GAT, NZF, A20 ZnF, UBP ZnF, UBZ, Ubc, UEV, UBM, GLUE, Jab1/MPN and PFU. The structures of many of the complexes with mono-ubiquitin have been determined, revealing interactions with multiple surfaces on ubiquitin. Inroads into understanding polyubiquitin specificity have been made for two UBA domains, whose structures have been characterized in complex with Lys48-linked di-ubiquitin. Several ubiquitin-binding domains, including the UIM, CUE and A20 ZnF (zinc finger) domains, promote auto-ubiquitination, which regulates the activity of proteins that contain them. At least one of these domains, the A20 ZnF, acts as a ubiquitin ligase by recruiting a ubiquitin–ubiquitin-conjugating enzyme thiolester adduct in a process that depends on the ubiquitin-binding activity of the A20 ZnF. The affinities of the mono-ubiquitin-binding interactions of these domains span a wide range, but are most commonly weak, with Kd&gt;100 μM. The weak interactions between individual domains and mono-ubiquitin are leveraged into physiologically relevant high-affinity interactions via several mechanisms: ubiquitin polymerization, modification multiplicity, oligomerization of ubiquitinated proteins and binding domain proteins, tandem-binding domains, binding domains with multiple ubiquitin-binding sites and co-operativity between ubiquitin binding and binding through other domains to phospholipids and small G-proteins.
Influences of the breathing route on upper airway dynamics properties in normal awake subjects with constant mouth opening
Authors: Wang Wei , Verin Eric , Sériès Frédéric 
Published: October 2006

MB (mouth breathing) promotes the occurrence of sleep-disordered breathing even in non-apnoeic subjects. Considering that MO (mouth opening) contributes to an increase in UA (upper airway) collapsibility independently of MB, the aim of the present study was to assess the influence of breathing route on UA dynamics in the presence of MO. Bilateral anterior magnetic phrenic nerve stimulation was performed 2 s after expiratory onset in 12 healthy male subjects during wakefulness (age, 50±5 years; body mass index, 27.8±2.4 kg/m2) during MB through a mouthpiece and during exclusive NB (nasal breathing) with the same mouthpiece in place. Twitch-induced V̇I (instantaneous flow), Pph and Pes (pharyngeal and oesophageal pressures respectively) were recorded and the corresponding resistances were measured. A polynomial regression model, V̇I=k1Pd+k2Pd2, was used to characterize flow–pressure relationship and to determine the Pd value at which UA collapses. There was no difference in UA dynamic properties between NB and MB when UA collapse occurred above the pharyngeal catheter. For twitches where UA collapse occurred lower in the UA, pharyngeal resistance decreased from NB to MB (2.0±0.3 and 1.5±0.2 cmH2O·l−1·s respectively; P=0.02; values are means±S.D.), whereas closing pressure increased (−25.7±10.1 and −18.0±3.0 cmH2O respectively; P=0.04). We conclude that (i) in the presence of MO the dynamic properties of the proximal UA free of phasic activity do not differ between NB and MB, and (ii) MB decreases the upstream resistance and increases collapsibility of the distal UA.
Weakly null sequences in 𝐿₁
Authors: Johnson William , Maurey Bernard , Schechtman Gideon 
Published: October 2006

We construct a weakly null normalized sequence

{

f
i

}

i
=
1

∞

\{f_i\}_{i=1}^{\infty }

in

L
1

L_1

so that for each

ε
>
0

\varepsilon >0

, the Haar basis is

(
1
+
ε
)

(1+\varepsilon )

-equivalent to a block basis of every subsequence of

{

f
i

}

i
=
1

∞

\{f_i\}_{i=1}^{\infty }

. In particular, the sequence

{

f
i

}

i
=
1

∞

\{f_i\}_{i=1}^{\infty }

has no unconditionally basic subsequence. This answers a question raised by Bernard Maurey and H. P. Rosenthal in 1977. A similar example is given in an appropriate class of rearrangement invariant function spaces.
NMPP: a user-customized NimbleGen microarray data processing pipeline
Authors: Wang Xiangfeng , He Hang , Li Lei , Chen Runsheng , Deng Xing Wang , Li Songgang 
Published: October 2006

Abstract
Summary: NMPP package is a bundle of user-customized tools based on established algorithms and methods to process self-designed NimbleGen microarray data. It features a command-line-based integrative processing procedure that comprises five major functional components, namely the raw microarray data parsing and integrating module, the array spatial effect smoothing and visualization module, the probe-level multi-array normalization module, the gene expression intensity summarization module and the gene expression status inference module.
Availability:
Contact: Xiangfeng.Wang@Yale.edu
Supplementary information: The supplementary materials, figures, testing dataset, software instructions and a typical workflow of using NMPP package are accessible through the above homepage.
Interleukin-6 and vascular endothelial growth factor release by renal cell carcinoma cells impedes lymphocyte–dendritic cell cross-talk
Authors: Cabillic F , Bouet-Toussaint F , Toutirais O , Rioux-Leclercq N , Fergelot P , De La Pintière C Thomas , Genetet N , Patard J-J , Catros-Quemener V 
Published: October 2006

Summary
Anti-tumour T cell response requires antigen presentation via efficient immunological synapse between antigen presenting cells, e.g. dendritic cells (DC), and specific T cells in an adapted Th1 cytokine context. Nine renal cell carcinoma (RCC) primary culture cells were used as sources of tumour antigens which were loaded on DC (DC-Tu) for autologous T cell activation assays. Cytotoxic activity of lymphocytes stimulated with DC-Tu was evaluated against autologous tumour cells. Assays were performed with 75 grays irradiated tumour cells (Tu irr) and with hydrogen peroxide ± heat shock (Tu H2O2 ± HS) treated cells. DC-Tu irr failed to enhance cytotoxic activity of autologous lymphocytes in seven of 13 assays. In all these defective assays, irradiated tumour cells displayed high interleukin (IL)-6 and vascular endothelial growth factor (VEGF) release. Conversely, when tumour cells released low IL-6 levels (n = 4), DC-Tu irr efficiently enhanced CTL activity. When assays were performed with the same RCC cells treated with H2O2 + HS, DC-Tu stimulation resulted in improved CTL activity. H2O2 + HS treatment induced post-apoptotic cell necrosis of tumour cells, totally abrogated their cytokine release [IL-6, VEGF, transforming growth factor (TGF)-β1] and induced HSP70 expression. Taken together, data show that reduction in IL-6 and VEGF release in the environment of the tumour concomitantly to tumour cell HSP expression favours induction of a stronger anti-tumour CTL response.
Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high‐risk nondiabetic patients
Authors: CESARI M. , PESSINA A. C. , ZANCHETTA M. , DE TONI R. , AVOGARO A. , PEDON L. , DORIGATTI F. , MAIOLINO G. , ROSSI G. P. 
Published: October 2006

Abstract.Objective.  To investigate the association of plasma adiponectin levels with coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance (IR) in nondiabetic Caucasian patients.Design.  We measured plasma adiponectin levels, IR (HOMA index), and the CAD atherosclerotic burden (angiography‐based modified Duke Index score) in 400 nondiabetic patients undergoing coronary angiography. HT was diagnosed by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines or if patients were on antihypertensive treatment.Results.  Coronary artery disease was found in 62% of the patients and ruled out in the rest (non‐CAD group). Plasma adiponectin levels were inversely related to the CAD score (β = −0.12, P = 0.029) and predicted the coronary atherosclerotic burden independent of other cardiovascular risk factors. However, they were similar in NT and HT and showed no correlation with blood pressure values. In non‐CAD, but not in CAD patients, they were lower in patients with than without IR (8.3 ± 1.2 vs. 11.3 ± 1.3, respectively; P = 0.007).Conclusions.  In nondiabetic high‐risk Caucasian patients plasma adiponectin levels are inversely related to CAD severity and IR; however, they are not strongly related to blood pressure values.
Characterization of native and reconstituted exosome complexes from the hyperthermophilic archaeon Sulfolobus solfataricus
Authors: Walter Pamela , Klein Franziska , Lorentzen Esben , Ilchmann Anne , Klug Gabriele , Evguenieva‐Hackenberg Elena 
Published: October 2006

SummaryThe eukaryotic exosome is a protein complex with essential functions in processing and degradation of RNA. Exosome‐like complexes were recently found in Archaea. Here we characterize the exosome of Sulfolobus solfataricus. Two exosome fractions can be discriminated by density gradient centrifugation. We show that the Cdc48 protein is associated with the exosome from the 30S−50S fraction but not with the exosome of the 11.3S fraction. While only some complexes contain Cdc48, the archaeal DnaG‐like protein was found to be a core exosome subunit in addition to Rrp4, Rrp41, Rrp42 and Csl4. Assays with depleted extracts revealed that the exosome is responsible for major ribonucleolytic activity in S. solfataricus. Various complexes consisting of the Rrp41‐Rrp42 hexameric ring and Rrp4, Csl4 and DnaG were reconstituted. Dependent on their composition, different complexes showed variations in RNase activity indicating functional interdependence of the subunits. The catalytic activity of these complexes and of the native exosome can be ascribed to the Rrp41‐Rrp42 ring, which degrades RNA phosphorolytically. Rrp4 and Csl4 do not exhibit any hydrolytic RNase activity, either when assayed alone or in context of the complex, but influence the activity of the archaeal exosome.
Structure‐based mutagenesis of SigE verifies the importance of hydrophobic and electrostatic residues in type III chaperone function
Authors: Knodler Leigh A. , Bertero Michela , Yip Calvin , Strynadka Natalie C. J. , Steele‐Mortimer Olivia 
Published: October 2006

SummaryDespite sharing little sequence identity, most type III chaperones display a similar homodimeric structure characterized by negative charges distributed broadly over their entire surface, interspersed with hydrophobic patches. Here we have used SigE from Salmonella as a model for class IA type III chaperones to investigate the role of these surface‐exposed residues in chaperone function. SigE is essential for the stability, secretion and translocation of its cognate effector, SopB (SigD). We analysed the effect of mutating nine conserved hydrophobic and electronegative surface‐exposed amino acids of SigE on SopB binding, stability, secretion and translocation. Six of these mutations affected some aspect of SigE function (Leu14, Asp20, Leu22, Leu23, Ile25 and Asp51) and three were without effect (Leu54, Glu92 and Glu99). Our results highlight that both hydrophobic and electronegative surfaces are required for the function of SigE and provide an important basis for the prediction of side‐chain requirements for other chaperone–effector pairs.
The Vibrio motor proteins, MotX and MotY, are associated with the basal body of Na+‐driven flagella and required for stator formation
Authors: Terashima Hiroyuki , Fukuoka Hajime , Yakushi Toshiharu , Kojima Seiji , Homma Michio 
Published: October 2006

SummaryThe four motor proteins PomA, PomB, MotX and MotY, which are believed to be stator proteins, are essential for motility by the Na+‐driven flagella of Vibrio alginolyticus. When we purified the flagellar basal bodies, MotX and MotY were detected in the basal body, which is the supramolecular complex comprised of the rotor and the bushing, but PomA and PomB were not. By antibody labelling, MotX and MotY were detected around the LP ring. These results indicate that MotX and MotY associate with the basal body. The basal body had a new ring structure beneath the LP ring, which was named the T ring. This structure was changed or lost in the basal body from a ΔmotX or ΔmotY strain. The T ring probably comprises MotX and MotY. In the absence of MotX or MotY, we demonstrated that PomA and PomB were not localized to a cell pole. From the above results, we suggest that MotX and MotY of the T ring are involved in the incorporation and/or stabilization of the PomA/PomB complex in the motor.
A new domain of conjugative relaxase TrwC responsible for efficient oriT‐specific recombination on minimal target sequences
Authors: César Carolina Elvira , Machón Cristina , De La Cruz Fernando , Llosa Matxalen 
Published: October 2006

SummaryWe show that relaxase TrwC promotes recombination between two directly repeated oriTs while related relaxases TraI of F and pKM101 do not. Efficient recombination required also relaxosome accessory protein TrwA even after deletion of TrwA binding sites at oriT, suggesting that the effect of TrwA is mediated by protein–protein interactions. TrwC relaxase domain was necessary but not sufficient to catalyse recombination efficiently. Full recombinase activity was obtained with the N‐terminal 600 residues of TrwC. The minimal target sequences required for recombination were different at each of the two involved oriTs: oriT1 could be reduced to the nic site and TrwC binding site, while oriT2 required an extended sequence including a set of iterons that are not required for conjugation. TrwC‐mediated integration of a transferred DNA into a resident oriT copy required a complete oriT in the recipient. We observed dramatic changes in the efficiency of recombination between tandem oriTs linked to the direction of plasmid replication and transcription through oriT1. We propose that recombination is triggered by the generation of a single‐stranded DNA at oriT1 that causes TrwC nicking. The resulting TrwC‐DNA complex reacts with oriT2, excising the intervening DNA. This intermediate can be resolved by host‐encoded replication functions.
Meningococcal biofilm formation: structure, development and phenotypes in a standardized continuous flow system
Authors: Lappann Martin , Haagensen Janus A. J. , Claus Heike , Vogel Ulrich , Molin Søren 
Published: October 2006

SummaryWe show that in a standardized in vitro flow system unencapsulated variants of genetically diverse lineages of Neisseria meningitidis formed biofilms, that could be maintained for more than 96 h. Biofilm cells were resistant to penicillin, but not to rifampin or ciprofloxacin. For some strains, microcolony formation within biofilms was observed. Microcolony formation in strain MC58 depended on a functional copy of the pilE gene encoding the pilus subunit pilin, and was associated with twitching of cells. Nevertheless, unpiliated pilE mutants formed biofilms showing that attachment and accumulation of cells did not depend on pilus expression. Mutation and complementation analysis revealed that the type IV pilus‐associated protein PilX, which was recently shown to mediate interbacterial aggregation, indirectly supported microcolony formation by contributing to pilus expression. A large number of PilX alleles was identified among genetically diverse meningococcal strains. PilX alleles differed in their propensity to support autoaggregation of cells in suspension, but not in their ability to support microcolony formation within biofilms in the continuous flow system.
Wolbachia‐induced unidirectional cytoplasmic incompatibility and the stability of infection polymorphism in parapatric host populations
Authors: FLOR M. , HAMMERSTEIN P. , TELSCHOW A. 
Published: October 2006

AbstractWolbachiaare intracellular, maternally inherited bacteria that are widespread among arthropods and commonly induce a reproductive incompatibility between infected male and uninfected female hosts known as unidirectional cytoplasmic incompatibility (CI). If infected and uninfected populations occur parapatrically, CI acts as a post‐zygotic isolation barrier. We investigate the stability of such infection polymorphisms in a mathematical model with two populations linked by migration. We determine critical migration rates below which infected and uninfected populations can coexist. Analytical solutions of the critical migration rate are presented for mainland‐island models. These serve as lower estimations for a more general model with two‐way migration. The critical migration rate is positive if eitherWolbachiacauses a fecundity reduction in infected female hosts or its transmission is incomplete, and is highest for intermediate levels of CI. We discuss our results with respect to local adaptations of theWolbachiahost, speciation, and pest control.
The origin of theChorthippus parallelushybrid zone: chromosomal evidence of multiple refugia for Iberian populations
Authors: BELLA J. L. , SERRANO L. , ORELLANA J. , MASON P. L. 
Published: October 2006

AbstractA study of the variation in pattern and frequency of constitutive heterochromatin and nucleolar organizing regions of the X chromosomes of maleChorthippus parallelusgrasshoppers in 25 populations within the Iberian peninsula requires us to revise our interpretation of the biogeography and evolutionary history of this species. Hybridization between the subspeciesCp erythropusandCp parallelus, previously only known from populations in the Pyrenean cols, is shown to extend at least 400 km further into north‐west Spain. A novel X‐chromosome variant is described that appears to be close to fixation in 18 populations, mainly from the centre and south of Spain. Our findings indicate a possible independent origin for each of three distinct, nonderivative X variants present in Spain: the northernCp erythropusandCp parallelusvariants, and a central‐southernCp erythropusvariant. The first two are distinguished by interstitial and distal C bands, respectively, whereas the central‐southern form has neither. This central‐southern form is probably the current representative of the ancestral Iberian X variant. The pattern of variation supports the hypotheses of multiple refugia for Iberian populations and that more hybrid zones exist between these chromosomal variants.