bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurosteroid‐induced enhancement of short‐term facilitation involves a component downstream from presynaptic calcium in hippocampal slices
Authors: Schiess Adrian R. B. , Scullin Chessa S. , Partridge L. Donald
Published: August 2006

We used Magnesium Green AM to measure Ca2+ transients in Schaffer collateral presynaptic terminals simultaneously with postsynaptic field potentials (fEPSPs) to investigate the mechanism of neurosteroid enhancement of short‐term synaptic facilitation. Measurement of [Ca2+]i, isolated to presynaptic events, using the fluorescence ratio (ΔF/F0) demonstrated that at a constant stimulus intensity there was no change in the excitability of presynaptic fibres between paired stimuli or between ACSF and 1 μm pregnenolone sulphate (PREGS). Paired‐pulse facilitation (PPF) was correlated with residual Ca2+ ([Ca2+]res), and there was an additional increase in the ∫ΔF/F0 for the [Ca2+]res‐subtracted response to the second of paired stimuli, resulting primarily from a slowing of the decay time constant. In addition to the role of presynaptic [Ca2+]res in PPF, we observed a decrease in EC50 and a greater maximum for Hill function fits to fEPSP versusΔF/F0 during the second of paired responses. The enhancement of fEPSP PPF by PREGS did not result from an increase of ΔF/F0. The data presented here support a PREGS‐induced increase in presynaptic glutamate release from the second, but not the first, of a pair of stimuli for a given presynaptic [Ca2+] because: (a) there is actually a decrease in the ∫ΔF/F0 of the [Ca2+]res‐subtracted second response over that seen in ACSF; (b) PREGS causes no change in presynaptic Ca2+ buffering; and (c) there is a decrease in EC50 and an increase of ymax in the Hill function fits to ΔF/F0versus fEPSP data. We hypothesize that PREGS enhances short‐term facilitation by acting on the Ca2+‐dependent vesicle release machinery and that this mechanism plays a role in the cognitive effects of this sulphated neurosteroid.
Reversal of the TCR Stop Signal by CTLA-4
Authors: Schneider Helga , Downey Jos , Smith Andrew , Zinselmeyer Bernd H. , Rush Catherine , Brewer James M. , Wei Bin , Hogg Nancy , Garside Paul , Rudd Christopher E.
Published: August 2006

The coreceptor cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) is pivotal in regulating the threshold of signals during T cell activation, although the underlying mechanism is still not fully understood. Using in vitro migration assays and in vivo two-photon laser scanning microscopy, we showed that CTLA-4 increases T cell motility and overrides the T cell receptor (TCR)–induced stop signal required for stable conjugate formation between T cells and antigen-presenting cells. This event led to reduced contact periods between T cells and antigen-presenting cells that in turn decreased cytokine production and proliferation. These results suggest a fundamentally different model of reverse stop signaling, by which CTLA-4 modulates the threshold for T cell activation and protects against autoimmunity.
Structure of the Exon Junction Core Complex with a Trapped DEAD-Box ATPase Bound to RNA
Authors: Andersen Christian B. F. , Ballut Lionel , Johansen Jesper S. , Chamieh Hala , Nielsen Klaus H. , Oliveira Cristiano L. P. , Pedersen Jan Skov , Séraphin Bertrand , Hir Hervé Le , Andersen Gregers Rom
Published: August 2006

In higher eukaryotes, a multiprotein exon junction complex is deposited on spliced messenger RNAs. The complex is organized around a stable core, which serves as a binding platform for numerous factors that influence messenger RNA function. Here, we present the crystal structure of a tetrameric exon junction core complex containing the DEAD-box adenosine triphosphatase (ATPase) eukaryotic initiation factor 4AIII (eIF4AIII) bound to an ATP analog, MAGOH, Y14, a fragment of MLN51, and a polyuracil mRNA mimic. eIF4AIII interacts with the phosphate-ribose backbone of six consecutive nucleotides and prevents part of the bound RNA from being double stranded. The MAGOH and Y14 subunits lock eIF4AIII in a prehydrolysis state, and activation of the ATPase probably requires only modest conformational changes in eIF4AIII motif I.
Optimal processing of bone marrow trephine biopsy: the Hammersmith Protocol
Authors: Naresh K N , Lampert I , Hasserjian R , Lykidis D , Elderfield K , Horncastle D , Smith N , Murray-Brown W , Stamp G W
Published: August 2006

Specimens of bone marrow trephine biopsy (BMT) are transported and fixed in acetic acid–zinc–formalin fixative, decalcified in 10% formic acid–5% formaldehyde and processed with other specimens to paraffin-wax embedding. Sections, 1-μm-thick, are cut by experienced histotechnologists and used for haematoxylin and eosin, Giemsa, reticulin silver and other histological stains. Further, all immunohistochemical procedures used in the laboratory, including double immunostaining, can be used on these sections with no or minimal modifications. About 10 000 BMT specimens have been analysed using this procedure since 1997 and diseases involving the bone marrow have been classified successfully. More recently, standardised polymerase chain reaction-based analysis and mRNA in situ hybridisation studies have been conducted. Excellent morphology with good antigen, DNA and RNA preservation is offered by the Hammersmith Protocol.
Pancoast’s syndrome secondary to lung infection with cutaneous fistulisation caused byStaphylococcus aureus
Authors: Comet R , Monteagudo M , Herranz S , Gallardo X , Font B
Published: August 2006

Apical bronchial carcinoma is the most common cause of Pancoast’s syndrome. Of the many other causes reported, infection is a rare one. A literature review is presented and a case of Pancoast’s syndrome, secondary to apical lung pneumonia with bronchocutaneous fistulisation caused byStaphylococcus aureusinfection, is reported. Clinical and radiological resolution was achieved after treatment with antibiotics.
Multiprobe fluorescence in situ hybridisation: prognostic perspectives in superficial bladder cancer
Authors: Mian C , Lodde M , Comploj E , Lusuardi L , Palermo S , Mian M , Maier K , Pycha A
Published: August 2006

Aim:To establish independent prognostic factors on a chromosomal basis in superficial bladder cancer, using a multicolour fluorescence in situ hybridisation (FISH) probe mix.

Patients and methods:In 2002, voided urine from 75 consecutive patients (mean age 71.7, range 52–93) years under follow-up for superficial urothelial cancer was studied prospectively. The patients were observed for a mean (standard deviation (SD)) period of 39.3 (6.8) months (range 27–58) until July 2005. A multicolour FISH on liquid-based voided urinary cytology was carried out on all patients. Univariate analysis, using a log rank test, was used to determine the prognostic relevance of a low-risk pattern and a high-risk pattern. Progression-free survival time was calculated from the date of first diagnosis to first recurrence or progression according to the Kaplan–Meier product-limit method.

Results:One patient was lost to follow-up. 27 of the 74 remaining (36.8%) patients showed recurrent disease. In 9 (33.3%) patients with a low-risk pattern disease recurred after a mean (SD) observation time of 29.7 (1.9) months (range 8.3–52.3, median 30.8 (12.4)). 18 (66.7%) patients with a high-risk pattern developed recurrence within a mean (SD) of 17.6 (2.0) months (range 4–38.8, median 16.7 (11.6)). The Kaplan–Meier curve for progression-free survival showed marked differences between the low-risk and the high-risk groups.

Conclusion:Patients with a high-risk chromosomal pattern have a markedly shorter disease-free survival time and higher progression rate than patients with a low-risk pattern. High-risk patients can therefore be treated more aggressively to prevent tumour spreading.
Identification and chromosomal location of major genes for resistance toPyrenophorateresin a doubled-haploid barley population
Authors: Friesen T L , Faris J D , Lai Z , Steffenson B J
Published: August 2006

Net blotch, caused by Pyrenophora teres, is one of the most economically important diseases of barley worldwide. Here, we used a barley doubled-haploid population derived from the lines SM89010 and Q21861 to identify major quantitative trait loci (QTLs) associated with seedling resistance to P. teres f. teres (net-type net blotch (NTNB)) and P. teres f. maculata (spot-type net blotch (STNB)). A map consisting of simple sequence repeat (SSR) and amplified fragment length polymorphism (AFLP) markers was used to identify chromosome locations of resistance loci. Major QTLs for NTNB and STNB resistance were located on chromosomes 6H and 4H, respectively. The 6H locus (NTNB) accounted for as much as 89% of the disease variation, whereas the 4H locus (STNB resistance) accounted for 64%. The markers closely linked to the resistance gene loci will be useful for marker-assisted selection.Key words: disease resistance, Drechslera teres, molecular markers.
Molecular characterization and phylogenetic analysis of a novel glutenin gene (Dy10.1t) fromAegilops tauschii
Authors: Zhang Yanzhen , Li Qiaoyun , Yan Yueming , Zheng Jigang , An Xueli , Xiao Yinghua , Wang Aili , Pei Yuhe , Wang Haibo , Hsam Sai L.K , Zeller Friedrich J
Published: August 2006

A novel y-type high molecular mass glutenin subunit (HMM-GS) possessing a mobility that is slightly slower than that of the subunit Dy10 obtained by SDS–PAGE, named Dy10.1t, in the wild wheat Aegilops tauschii was identified by 1- and 2-dimensional gel electrophoresis, capillary electrophoresis, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI–TOF–MS). The gene encoding the HMM subunit Dy10.1twas amplified with allele-specific PCR primers, and the amplified products were cloned and sequenced. The coding domain of the Dy10.1tsubunit gene consisted of 1980 bp encoding a protein of 658 residues with an Mrsof 68 611 Da, which was similar to the Mrsdetermined by MALDI–TOF–MS. The deduced amino acid sequence indicated that Dy10.1tsubunit displayed a greater similarity to the Dy12 subunit, differing by only 8 amino acid substitutions. Six coding region single-nucleotide polymorphisms were discovered in the Dy10.1tgene by multiple alignments (1 per 330 bp), 1 in the N-terminal domain and the others in the central repeats. Five of them resulted in residue substitutions, whereas 3 created enzyme site changes. The homology and neighbour-joining trees constructed from code domain sequences of 20 x- and y-type glutenin genes from different Triticum species separated into 2 halves, which corresponded to the x-type and y-type HMM glutenin alleles. Phylogenetic analysis revealed that the Glu-1 gene duplication event probably occurred at about 16.83 million years ago, whereas the divergence times of A, B, and D genomes within x-type and y-type halves were before 7.047 and 10.54 million years ago, respectively.Key words: HMW glutenin genes, MALDI-TOF-MS, AS-PCR, cSNP, phylogenetic analysis, Aegilops tauschii.
Molecular and cytological characterization of ribosomal RNA genes inChenopodium quinoaandChenopodium berlandieri
Authors: Maughan P J , Kolano B A , Maluszynska J , Coles N D , Bonifacio A , Rojas J , Coleman C E , Stevens M R , Fairbanks D J , Parkinson S E , Jellen E N
Published: August 2006

The nucleolus organizer region (NOR) and 5S ribosomal RNA (rRNA) genes are valuable as chromosome landmarks and in evolutionary studies. The NOR intergenic spacers (IGS) and 5S rRNA nontranscribed spacers (NTS) were PCR-amplified and sequenced from 5 cultivars of the Andean grain crop quinoa (Chenopodium quinoa Willd., 2n = 4x = 36) and a related wild ancestor (C. berlandieri Moq. subsp. zschackei (Murr) A. Zobel, 2n = 4x = 36). Length heterogeneity observed in the IGS resulted from copy number difference in subrepeat elements, small re arrangements, and species-specific indels, though the general sequence composition of the 2 species was highly similar. Fifteen of the 41 sequence polymorphisms identified among the C. quinoa lines were synapomorphic and clearly differentiated the highland and lowland ecotypes. Analysis of the NTS sequences revealed 2 basic NTS sequence classes that likely originated from the 2 allopolyploid subgenomes of C. quinoa. Fluorescence in situ hybridization (FISH) analysis showed that C. quinoa possesses an interstitial and a terminal pair of 5S rRNA loci and only 1 pair of NOR, suggesting a reduction in the number of rRNA loci during the evolution of this species. C. berlandieri exhibited variation in both NOR and 5S rRNA loci without changes in ploidy.Key words: rDNA, NOR, IGS, 5S NTS, FISH, Chenopodium.
Somatic chimerism, genetic inheritance, and mapping of thefleshless berry(flb) mutation in grapevine (Vitis viniferaL.)
Authors: Fernandez L , Doligez A , Lopez G , Thomas M R , Bouquet A , Torregrosa L
Published: August 2006

The fleshless berry (flb) mutation of grapevine (Vitis vinifera L. 'Ugni Blanc') impairs the differentiation and division of inner mesocarp cells responsible for flesh in grapevine berries. In order to study the inheritance of the mutation and to map the flb locus, 5 segregating populations were created. Progeny plants were classified as mutant or wild type by scoring for the presence of an ovary phenotype associated with the Flb–phenotype at anthesis. Phenotypic segregation revealed the involvement of a single dominant allele that was heterozygous in the original mutant. Through bulk segregant analysis, microsatellite (simple sequence repeat (SSR)) markers linked to the mutation were identified, and the flb locus was assigned to linkage group 18. The locus position was then refined by analyzing individual progeny and the segregation of SSR markers in the target region with the closest marker 5.6 cM distant from the flb locus. All progeny with the Flb–ovary phenotype differed from the original fleshless berry mutant in that no berries formed after anthesis. Our data suggest that the original mutant plant was a chimera with the mutated allele present in only 1 cell layer (L2 layer) of the ovary and berry.Key words: Vitis vinifera, mutation, genetic mapping, chimerism.
Segregation of sperm mitochondria in two- and four-cell embryos of the blue musselMytilus edulis: implications for the mechanism of doubly uniparental inheritance of mitochondrial DNA
Authors: Cogswell Andrew T , Kenchington Ellen L.R , Zouros Eleftherios
Published: August 2006

Species of the family Mytilidae have 2 mitochondrial genomes, one that is transmitted through the egg and one that is transmitted through the sperm. In the Mytilus edulis species complex (M. edulis, M. galloprovincialis, and M. trossulus) there is also a strong mother-dependent sex-ratio bias in favor of one or the other sex among progeny from pair matings. In a previous study, we have shown that sperm mitochondria enter the egg and that their behavior during cell division is different depending on whether the egg originated from a female- or male-biased mother. Specifically, in eggs from females that produce mostly or exclusively daughters, sperm mitochondria disperse randomly among cells after egg division. In eggs from females that produce predominantly sons, sperm mitochondria tend to stay together in the same cell. Here, we extend these observations and show that in 2- and 4-cell embryos from male-biased mothers most sperm mitochondria are located near or at the cleavage furrow of the major cell, in contrast to embryos from female-biased mothers where there is no preferential association of sperm mitochondria with the cleavage furrow. This observation provides evidence for an early developmental mechanism through which sperm mitochondria are preferentially channeled into the primordial cells of male embryos, thus making the paternal mitochondrial genome the dominant mtDNA component of the male germ line.Key words: mussels, doubly uniparental inheritance of mtDNA, sperm mitochondria.
Insect mitochondrial genomics 2: the complete mitochondrial genome sequence of a giant stonefly,Pteronarcys princeps, asymmetric directional mutation bias, and conserved plecopteran A+T-region elements
Authors: Stewart James Bruce , Beckenbach Andrew T
Published: August 2006

Mitochondrial (mt) genome sequences of insects are receiving renewed attention in molecular phylogentic studies, studies of mt-genome rearrangement, and other unusual molecular phenomena, such as translational frameshifting. At present, the basal neopteran lineages are poorly represented by mt-genome sequences. Complete mt-genome sequences are available in the databases for only the Orthoptera and Blatteria; 9 orders are unrepresented. Here, we present the complete mt-genome sequence of a giant stonefly, Pteronarcys princeps (Plecoptera; Pteronarcyidae). The 16 004 bp genome is typical in its genome content, gene organisation, and nucleotide composition. The genome shows evidence of strand-specific mutational biases, correlated with the time between the initiation of leading and the initiation of lagging strand replication. Comparisons with other insects reveal that this trend is seen in other insect groups, but is not universally consistent among sampled mt-genomes. The A+T region is compared with that of 2 stoneflies in the family Peltoperlidae. Conserved stem-loop structures and sequence blocks are noted between these distantly related families.Key words: mitochondrial genomics, directional mutation pressure, A+T-rich region, Plecoptera, stonefly.
Is headfirst ingestion essential in gape-limited predators? Prey-handling behavior of the anurophagous snake Rhabdophis tigrinus (Colubridae)
Authors: Mori Akira
Published: August 2006

Headfirst ingestion of prey is a common adaptive behavioral trait in gape-limited predators that swallow large prey whole. To ascertain this tendency during anurophagy, prey handling and direction of prey ingestion were investigated in Rhabdophis tigrinus (Boie, 1826), a snake that feeds mainly on anurans. Examinations of stomach contents of wild R. tigrinus revealed that this snake does not show a tendency for headfirst ingestion of large prey, unlike most other snake species. In the laboratory, direction of ingestion depended largely on initial bite position, and when R. tigrinus swallowed a frog rump-first, the snake grasped both hind limbs of the frog and aligned them side by side so that both were swallowed together simultaneously from their tips. A simple model test suggested that physical resistance in the buccal cavity incurred during transportation of frogs may not differ between headfirst and hind-first ingestion if the hind limbs of frogs are aligned and swallowed simultaneously. Laboratory experiments also demonstrated that ingestively naive hatchlings of R. tigrinus are able to perform the unique manipulation required to swallow frogs hind-first. It is suggested that this unique ingestion mode is an adaptation for anurophagy, and several possible functional advantages are discussed.
Prevalence, intensity, and geographic distribution of sinus worm (Skrjabingylus nasicola) infection in mink (Mustela vison) of central Ontario
Authors: Santi Stacey A. , Parker Glenn H. , Schaffner Natalie P. , Capodagli Liane , Persinger Michael A.
Published: August 2006

Mink (Mustela vison Schreber, 1777) skulls (n = 630) from 18 geographic regions throughout central Ontario were examined for levels of sinus worm (Skrjabingylus nasicola (Leuckart, 1842)) infection by exposing and counting adult worms present in each sinus cavity. Site differences in both infection prevalence (range 55.6%–100%) and infection intensity (2.4 ± 0.3 to 16.1 ± 2.2 worms per infected animal; mean ± SE) were found, but neither latitudinal nor longitudinal trends were apparent. Temporal differences in infection prevalence were not observed among selected regions sampled over two and three consecutive trapping seasons; however, at two of the three sites monitored, infection intensities increased approximately twofold. Juvenile animals of either sex indicated elevated levels of infection prevalence relative to adult males, while juvenile males, but not females, indicated significantly higher infection intensities than those seen in the adult male cohort. No bias toward left or right sinus location was noted in either prevalence or intensity of infections. Comparison of age- and sex-adjusted body mass failed to provide evidence for reduced physical condition in infected animals.
Comment on “Genetic analysis of 16th-century whale bones prompts a revision of the impact of Basque whaling on right and bowhead whales in the western North Atlantic”
Authors: Romero Aldemaro , Kannada Shelly
Published: August 2006

Rastogi et al. presented their genetic analysis of 16th-century whale bones found on a Basque whaling ship excavated from Red Bay, Labrador Peninsula, Canada. Based on the results from a very small sample, these authors concluded that whaling populations were already depleted before the onset of whaling. This is in direct contradiction to historical data. They also implied that the Basques were the only Europeans whaling in the North Atlantic before the onset of Yankee whaling and that there was a belief that Basque whalers historically killed equal numbers of right and bowhead whales. Here we present data based on historical and archaeological records generated by several authors using different methodologies, which clearly show that (i) Basques were not the only whalers that impacted cetacean populations in the North Atlantic; (ii) the number of whales killed by different peoples for approximately two centuries indicates that both right and bowhead whale population levels were much higher than typically assumed; and (iii) for many years there have been records published indicating that the Basques and others killed more bowhead whales than right whales, at least in the western North Atlantic.
Is winter diet quality related to body condition of white-tailed deer (Odocoileus virginianus)? An experiment using urine profiles
Authors: Sauvé Daniel G. , Côté Steeve D.
Published: August 2006

During winter, boreal forest herbivores have access to only poor-quality forage. On Anticosti Island (Quebec, Canada), the ongoing reduction of balsam fir (Abies balsamea (L.) P. Mill.) owing to overbrowsing by white-tailed deer (Odocoileus virginianus (Zimmermann, 1780)) may force deer to include a higher proportion of white spruce (Picea glauca (Moench) Voss), a browse normally avoided, in their winter diet. We tested the hypotheses that (i) deer body condition during winter and (ii) the costs of detoxification of plant secondary metabolites in the winter diet could be estimated by monitoring the 3-methylhistidine / creatinine and glucuronic acid / creatinine ratios, respectively, in urine collected in snow from white-tailed deer fawns. Doubling the amount of white spruce in the winter diet of deer (from the current 20% under natural conditions to 40%) did not increase 3-methylhistidine / creatinine ratios but increased the glucuronic acid / creatinine ratio in urine, suggesting that a diet containing more spruce was more toxic. A weak positive relationship was observed between 3-methylhistidine and percent cumulative mass loss. There was no relationship between the 3-methylhistidine / creatinine ratio and the number of days left before death, as well as no relationship between the ratio of glucuronic acid / creatinine and percent cumulative mass loss. We conclude that the costs of detoxification of plant secondary metabolites in the winter diet of white-tailed deer in boreal forests could be monitored with glucuronic acid / creatinine ratios, but that 3-methylhistidine / creatinine ratios were weak indicators of deer body condition in winter.
Group Decision Making in Nest-Site Selection Among Social Insects
Authors: Visscher P. Kirk
Published: August 2006

The choice of a new nest site is ecologically critical for an insect colony. In swarm-founding social insects, or those that move as colonies from one site to another, this choice is one of the best-available examples of a distributed, nonhierarchical decision-making process in animals. In the few species of ants and bees that have been studied in detail, the main features of this collective decision making are strikingly similar, although some differences occur. Individual scouts discover potential nest sites and integrate multiple properties of these sites into assessments of their quality. The discovered sites then compete for a limited pool of nest-site scouts, and attrition of less-favored sites occurs by several mechanisms. Finally, the mass movement of the colony to the new site is triggered by a quorum-sensing mechanism when sufficient scouts are present at one of the alternatives. Movement itself is coordinated by different mechanisms in different insects.
Striatal opioid peptide gene expression differentially tracks short-term satiety but does not vary with negative energy balance in a manner opposite to hypothalamic NPY
Authors: Will Matthew J. , Vanderheyden William M. , Kelley Ann E.
Published: August 2006

It has long been known that central opioid systems play an important role in certain aspects of appetite and food intake, particularly with regard to the hedonic or rewarding impact of calorically dense food, such as fat and sugar. Ventral striatal enkephalin may be a key component of this system, as infusions of μ-opiate agonists into this region strongly increase feeding, whereas infusions of opiate antagonists decrease food intake. While pharmacological analysis has consistently supported such a role, direct measurement of enkephalin gene expression in relation to differing food motivational conditions has not been examined. In this study, the effects of a restricted laboratory chow diet (resulting in negative energy balance) as well has recent consumption of chow (short-term satiety) on striatal preproenkephalin (PPE) and prodynorphin (PD) mRNA expression were measured in rats, using both Northern blot analysis and in situ hybridization methods. As a comparison, hypothalamic (arcuate nucleus) neuropeptide Y (NPY) was also measured in these conditions. PPE expression was broadly downregulated throughout the striatum in animals that had recently consumed a meal, whereas it was unaffected by negative energy balance. Expression of an additional striatal peptide gene, PD, did not follow this pattern, although diet restriction caused a decrease in accumbens core dynorphin mRNA. Conversely, as expected, arcuate nucleus NPY mRNA expression was markedly upregulated by negative energy balance, but was unchanged by recent food consumption. This double dissociation between striatal and hypothalamic peptide systems suggests a specific role for striatal PPE in relatively short-term food motivational states, but not in long-term metabolic responses to diet restriction.
Asymmetric Dimethylarginine Predicts Major Adverse Cardiovascular Events in Patients With Advanced Peripheral Artery Disease
Authors: Mittermayer Friedrich , Krzyzanowska Katarzyna , Exner Markus , Mlekusch Wolfgang , Amighi Jasmin , Sabeti Schila , Minar Erich , Müller Markus , Wolzt Michael , Schillinger Martin
Published: August 2006

Objective—

Circulating concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, are elevated in conditions associated with increased cardiovascular risk. We investigated whether elevated ADMA concentrations predict major adverse cardiovascular events (MACE) in patients with advanced peripheral artery disease (PAD).

Methods and Results—

We prospectively enrolled 496 of 533 consecutive patients with PAD (median age 70 years, 279 males). ADMA and L-arginine were assessed at baseline by high performance liquid chromatography. The occurrence of MACE (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, carotid revascularization, death) was evaluated during a follow-up of median 19 months (interquartile range 11 to 25). One hundred eighty-two MACE were observed in 141 patients (28%). MACE occurred in 39% of the patients in the highest quartile and 26% of those in the lowest quartile of ADMA (
P
=0.016, log-rank test for all quartiles). Adjusted hazard ratios for occurrence of MACE for increasing quartiles of ADMA compared with the lowest quartile were 0.87 (95% confidence interval [CI], 0.51 to 1.48), 1.12 (95% CI, 0.62 to 1.90), and 1.70 (95% CI, 1.02 to 2.88), respectively. We observed no association between cardiovascular outcome and L-arginine.

Conclusions—

High ADMA plasma concentrations independently predict MACE in patients with advanced PAD. This indicates that ADMA may be a new cardiovascular risk marker in these patients.
Hyperhomocysteinemia Decreases Circulating High-Density Lipoprotein by Inhibiting Apolipoprotein A-I Protein Synthesis and Enhancing HDL Cholesterol Clearance
Authors: Liao Dan , Tan Hongmei , Hui Rutai , Li Zhaohui , Jiang Xiaohua , Gaubatz John , Yang Fan , Durante William , Chan Lawrence , Schafer Andrew I. , Pownall Henry J. , Yang Xiaofeng , Wang Hong
Published: August 2006

We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine β-synthase–/apolipoprotein E–deficient (CBS
−/−
/apoE
−/−
) mice. We observed that plasma homocysteine (Hcy) concentrations are negatively correlated with HDL-C and apolipoprotein A1 (apoA-I) in patients with CAD. We found the loss of large HDL particles, increased HDL-free cholesterol, and decreased HDL protein in CBS
−/−
/apoE
−/−
mice, and attenuated cholesterol efflux from cholesterol-loaded macrophages to plasma in CBS
−/−
/apoE
−/−
mice. ApoA-I protein was reduced in the plasma and liver, but hepatic apoA-I mRNA was unchanged in CBS
−/−
/apoE
−/−
mice. Moreover, Hcy (0.5 to 2 mmol/L) reduced the levels of apoA-I protein but not mRNA and inhibited apoA-1 protein synthesis in mouse primary hepatocytes. Further, plasma lecithin:cholesterol acyltransferase (LCAT) substrate reactivity was decreased, LCAT specific activity increased, and plasma LCAT protein levels unchanged in apoE
−/−
/CBS
−/−
mice. Finally, the clearance of plasma HDL cholesteryl ester, but not HDL protein, was faster in CBS
−/−
/apoE
−/−
mice, correlated with increased scavenger receptor B1, and unchanged ATP-binding cassette transporter A1 protein expression in the liver. These findings indicate that HHcy inhibits reverse cholesterol transport by reducing circulating HDL via inhibiting apoA-I protein synthesis and enhancing HDL-C clearance.
Impact of Time on Improvement of Outcome After Stroke
Authors: Kwakkel Gert , Kollen Boudewijn , Twisk Jos
Published: August 2006

Background and Purpose—

Longitudinal conducted studies show that neurologic and functional recovery show faster recovery in the first weeks poststroke. The aim of the present study was to study the effects of progress of time on observed improvements in motor strength, synergisms, and activities during the first 16 weeks poststroke.

Methods—

Based on data from a previous study, 101 patients with first-ever ischemic middle cerebral artery strokes were prospectively investigated during the first 16 weeks after stroke. Progress of time was categorized into 8 biweekly time intervals and was used as the independent covariate in a first-order longitudinal regression model. The biweekly time change (progress of time) was related to improvement in upper and lower limb motor recovery assessed with Fugl-Meyer score and Motricity Index, reduction in visuospatial inattention based on the letter cancellation task, and improvement in walking ability, dexterity, and activities of daily living measured with the Functional Ambulation Categories, Action Research Arm test, and Barthel Index.

Results—

Time explained a significant change of 8.4 (42%) measurement units on the Barthel Index for the first 10 weeks poststroke, 1.1 (22%) measurement units on Functional Ambulation Categories, and 19% on the Action Research Arm test for the first 6 and 8 weeks poststroke. Approximately 25% (for Fugl-Meyer-arm) to 26% (for Motricity Index-arm) of the significant change in measurements units was explained by time alone for the upper limb compared with 33% for Fugl-Meyer-leg and 39% for Motricity Index-leg of the lower limb. Time accounted for a reduction of 16% in the letter cancellation task. Observed associations did not change after controlling for covariates such as age, gender, hemisphere of stroke, type of stroke, or intervention.

Conclusion—

Progress of time is an independent covariate that reflects spontaneous recovery of body functions and activities explaining &16% to 42% of the observed improvements in the first 6 to 10 weeks after stroke onset.
Leukoaraiosis Is a Risk Factor for Symptomatic Intracerebral Hemorrhage After Thrombolysis for Acute Stroke
Authors: Neumann-Haefelin Tobias , Hoelig Silke , Berkefeld Joachim , Fiehler Jens , Gass Achim , Humpich Marek , Kastrup Andreas , Kucinski Thomas , Lecei Olivera , Liebeskind David S. , Rother Joachim , Rosso Charlotte , Samson Yves , Saver Jeffrey L. , Yan Bernhard
Published: August 2006

Background and Purpose—

The aim of the study was to evaluate whether leukoaraiosis (LA) is a risk factor for symptomatic intracerebral hemorrhage (sICH) in patients treated with thrombolysis for acute stroke.

Methods—

In this retrospective, multicenter analysis, we evaluated data from acute anterior circulation stroke patients (n=449; <6 hours after symptom onset) treated with thrombolysis. All patients had received standard magnetic resonance imaging evaluation before thrombolysis, including a high-quality T2-weighted sequence. For the analysis, LA in the deep white matter was dichotomized into absent or mild versus moderate or severe (corresponding to Fazekas scores of 0 to 1 versus 2 to 3).

Results—

The rate of sICH was significantly more frequent in patients with moderate to severe LA of the deep white matter (n=12 of 114; 10.5%) than in patients without relevant LA (n=13 of 335; 3.8%), corresponding to an odds ratio of 2.9 (95% CI, 1.29 to 6.59;
P
=0.015). In a logistic-regression analysis (including age, National Institutes of Health Stroke Scale score at presentation, and type of thrombolytic treatment), LA remained a significant independent risk factor (odds ratio, 2.9;
P
=0.03).

Conclusions—

LA of the deep white matter is an independent risk factor for sICH after thrombolytic treatment for acute stroke.
Similarity of Semantic Relations
Authors: Turney Peter D.
Published: August 2006

There are at least two kinds of similarity. Relational similarity is correspondence between relations, in contrast with attributional similarity, which is correspondence between attributes. When two words have a high degree of attributional similarity, we call them synonyms. When two pairs of words have a high degree of relational similarity, we say that their relations are analogous. For example, the word pair mason:stone is analogous to the pair carpenter:wood. This article introduces Latent Relational Analysis (LRA), a method for measuring relational similarity. LRA has potential applications in many areas, including information extraction, word sense disambiguation, and information retrieval. Recently the Vector Space Model (VSM) of information retrieval has been adapted to measuring relational similarity, achieving a score of 47% on a collection of 374 college-level multiple-choice word analogy questions. In the VSM approach, the relation between a pair of words is characterized by a vector of frequencies of predefined patterns in a large corpus. LRA extends the VSM approach in three ways: (1) The patterns are derived automatically from the corpus, (2) the Singular Value Decomposition (SVD) is used to smooth the frequency data, and (3) automatically generated synonyms are used to explore variations of the word pairs. LRA achieves 56% on the 374 analogy questions, statistically equivalent to the average human score of 57%. On the related problem of classifying semantic relations, LRA achieves similar gains over the VSM.
Mao, Tibet, and the Korean War
Authors: Sheng Michael M.
Published: August 2006

In October 1950 the Chinese leader Mao Zedong embarked on a two-front war. He sent troops to Korea and invaded Tibet at a time when the People's Republic of China was burdened with many domestic problems. The logic behind Mao's risky policy has baffled historians ever since. By drawing on newly available Chinese and Western documents and memoirs, this article explains what happened in October 1950 and why Mao acted as he did. The release of key documents such as telegrams between Mao and his subordinates enables scholars to understand Chinese policymaking vis-à-vis Tibet much more fully than in the past. The article shows that Mao skillfully used the conflicts for his own purposes and consolidated his hold over the Chinese Communist Party.
Rethinking the Linkage between Tibet and the China-India Border Conflict: A Realist Approach
Authors: Hoffmann Steven A.
Published: August 2006

This article assesses the dynamic political and military relationships among Tibet, China, and India in the late 1950s and early 1960s. By examining the three governments' calculations and security interests, the article shows that the relationships among the three are best understood from a realist perspective. The focus in the article is on the Sino-Indian dispute over the territory known as “Assam Himalaya,” located on the far eastern end of the Sino-Indian border, between southeastern Tibet and northeast India. The article covers a relatively lengthy period, from 1913 to 1962, but in doing so it shows that territorial claims and the desire for secure borders were the key concern of all the countries involved—Tibet, China, India under British imperial rule, post-1947 India, and the United States.
Cultivating Consensus and Creating Conflict
Authors: Epstein Rachel A.
Published: August 2006

In Central and Eastern Europe, economic reform consistent with Bretton Woods and European Union (EU) demands has replicated not only the rules and institutions that prevail in Western societies but also their patterns of consensus and conflict. Although central bank policy has been largely depoliticized in the 2004 accession states through the institutionalization of central bank independence, agricultural interests were mobilized—in some instances against the EU—in the course of accession negotiations. This article argues that as they engage in the explicit transfer of economic policy to post-communist states, international institutions simultaneously transmit beliefs about who has legitimate claims on the state. The methods through which international institutions help construct new markets in transition states have consequences for the development of domestic cleavages and for the cultivation of political support for economic integration.
Does Lootable Wealth Breed Disorder?
Authors: Snyder Richard
Published: August 2006

This article proposes a political economy of extraction framework that explains political order and state collapse as alternative outcomes in the face of lootable wealth. Different types of institutions of extraction can be built on lootable resources—with divergent effects on political stability. If rulers are able to forge institutions of extraction that give them control of revenues generated by lootable resources, then these resources can contribute to political order by providing the income with which to govern. Conversely, the breakdown or absence of such institutions increases the risk of civil war by making it easier for rebels to organize. The framework is used to explain two puzzling cases that experienced sharply contrasting political trajectories in the face of lootable resources: Sierra Leone and Burma. A focus on institutions of extraction provides a stronger understanding of the wide range of political outcomes—from chaos, to dictatorship, to democracy—in resource-rich countries.
Expression of tumor-associated antigens in acute myeloid leukemia: implications for specific immunotherapeutic approaches
Authors: Greiner Jochen , Schmitt Michael , Li Li , Giannopoulos Krzysztof , Bosch Katrin , Schmitt Anita , Dohner Konstanze , Schlenk Richard F. , Pollack Jonathan R. , Dohner Hartmut , Bullinger Lars
Published: August 2006

The expression of tumor-associated antigens (TAAs) might play a critical role in the control of minimal residual disease (MRD) in acute myeloid leukemia (AML), and therefore might be associated with clinical outcome in AML. In a DNA microarray analysis of 116 AML samples, we found a significant correlation between high mRNA levels of G250/CA9 and longer overall survival (P = .022), a similar trend with high mRNA levels of PRAME (P = .103), and a hint for RHAMM/HMMR. In contrast, for other TAAs like WT1, TERT, PRTN3, BCL2, and LAMR1, we found no correlation with clinical outcome. High expression of at least 1 of the 3 TAAs, RHAMM/HMMR, PRAME, or G250/CA9, provided the strongest favorable prognostic effect (P = .005). Specific T-cell responses were detected in 8 (47%) of 17 patients with AML in complete remission for RHAMM/HMMR-R3 peptide, in 7 (70%) of 10 for PRAME-P3 peptide, and in 6 (60%) of 10 for newly characterized G250/CA9-G2 peptide, a significant increased immune response compared with patients with AML patients who had refractory disease (P < .001). Furthermore, we could demonstrate specific lysis of T2 cells presenting these epitope peptides. In conclusion, expression of the TAAs RHAMM/HMMR, PRAME, and G250/CA9 can induce strong antileukemic immune responses, possibly enabling MRD control. Thus, these TAAs represent interesting targets for polyvalent immunotherapeutic approaches in AML.
BCR ubiquitination controls BCR-mediated antigen processing and presentation
Authors: Drake Lisa , McGovern-Brindisi Erica M. , Drake James R.
Published: August 2006

BCR-mediated antigen processing occurs at immunologically relevant antigen concentrations and hinges on the trafficking of antigen-BCR (Ag-BCR) complexes to class II–containing multivesicular bodies (MVBs) termed MIICs. However, the molecular mechanism underlying the trafficking of Ag-BCR complexes to and within MIICs is not well understood. In contrast, the trafficking of the epidermal growth factor receptor (EGFR) to and within MVBs occurs via a well-characterized ubiquitin-dependent mechanism, which is blocked by acute inhibition of proteasome activity. Using a highly characterized antigen-specific model system, it was determined that the immunoglobulin heavy chain subunit of the IgM BCR of normal (ie, nontransformed) B cells is ubiquitinated. Moreover, acute inhibition of proteasome activity delays the formation of ubiquitinated ligand–BCR complexes, alters the intracellular trafficking of internalized Ag-BCR complexes, and selectively blocks the BCR-mediated processing and presentation of cognate antigen, without inhibiting the endocytosis, processing, and presentation of non–cognate antigen internalized by fluidphase endocytosis. These results demonstrate that the trafficking of Ag-BCR complexes to and within MVB-like antigen processing compartments occurs via a molecular mechanism with similarities to that used by the EGFR, and establishes the EGFR as a paradigm for the further analysis of Ag-BCR trafficking to and within MIICs.
Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy
Authors: Schmitt E , Gehrmann M , Brunet M , Multhoff G , Garrido C
Published: August 2006

Stress or heat shock proteins (HSPs) are the most conserved proteins present in both prokaryotes and eukaryotes. Their expression is induced in response to a wide variety of physiological and environmental insults. These proteins play an essential role as molecular chaperones by assisting the correct folding of nascent and sress-accumulated misfolded proteins, and preventing their aggregation. HSPs have a dual function depending on their intracellular or extracellular location. Intracellular HSPs have a protective function. They allow the cells to survive lethal conditions. Various mechanisms have been proposed to account for the cytoprotective functions of HSPs. Several HSPs have also been demonstrated to directly interact with various components of the tightly regulated programmed cell death machinery, upstream and downstream of the mitochondrial events. On the other hand, extracellular located or membrane-bound HSPs mediate immunological functions. They can elicit an immune response modulated either by the adaptive or innate immune system. This review will focus on HSP27, HSP70, and HSP90. We will discuss the dual role of these HSPs, protective vs. immunogenic properties, making a special emphasis in their utility as targets in cancer therapy.
Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages: new therapeutic strategies
Authors: Aquaro Stefano , Svicher Valentina , Schols Dominique , Pollicita Michela , Antinori Andrea , Balzarini Jan , Perno Carlo Federico
Published: August 2006

Monocyte-derived macrophages (M/M) are considered the second cellular target of HIV-1 and a crucial virus reservoir. M/M are widely distributed in all tissues and organs, including the CNS, where they represent the most common HIV-infected cells. Differently from activated CD4+ T lymphocytes, M/M are resistant to the cytopathic effect of HIV and survive HIV infection for a long time. Moreover, HIV-1 replication in M/M is a key pathogenetic event during the course of HIV-1 infection. Overall findings strongly support the clinical relevance of anti-HIV drugs in M/M. Nucleoside RT inhibitors (NRTIs) are more active against HIV in M/M than in CD4+ T lymphocytes. Their activity is further boosted by the presence of an additional monophosphate group (i.e., a phosphonate group, as in the case of Tenofovir), thus overcoming the bottleneck of the low phosphorylation ability of M/M. In contrast, the antiviral activity of non-NRTIs (not affecting the DNA chain elongation) in M/M is similar to that in CD4+ T lymphocytes. Protease inhibitors are the only clinically approved drugs acting at a late stage of the HIV lifecycle. They are able to interfere with HIV replication in HIV-1 chronically infected M/M, even if at concentrations greater than those observed in HIV-1 chronically infected CD4+ T lymphocytes. Finally, several new drugs have been shown to interfere efficiently with HIV replication in M/M, including entry inhibitors. A better understanding of the activity of the anti-HIV drugs in M/M may represent a key element for the design of effective anti-HIV chemotherapy.