bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perforin activity and immune homeostasis: the common A91V polymorphism in perforin results in both presynaptic and postsynaptic defects in function
Authors: Voskoboinik Ilia , Sutton Vivien R. , Ciccone Annette , House Colin M. , Chia Jenny , Darcy Phillip K. , Yagita Hideo , Trapani Joseph A. 
Published: May 2007

AbstractPerforin (PRF), a pore-forming protein expressed in cytotoxic lymphocytes, plays a key role in immune surveillance and immune homeostasis. The A91V substitution has a prevalence of 8% to 9% in population studies. While this variant has been suspected of predisposing to various disorders of immune homeostasis, its effect on perforin's function has not been elucidated. Here we complemented, for the first time, the cytotoxic function of perforin-deficient primary cytotoxic T lymphocytes (CTLs) with wild-type (hPRF-WT) and A91V mutant (hPRF-A91V) perforin. The cytotoxicity of hPRF-A91V–expressing cells was about half that of hPRF-WT–expressing counterparts and coincided with a moderate reduction in hPRF-A91V expression. By contrast, the reduction in cytotoxic function was far more pronounced (more than 10-fold) when purified proteins were tested directly on target cells. The A91V substitution can therefore be manifested by abnormalities at both the lymphocyte (presynaptic) and target cell (postsynaptic) levels. However, the severe intrinsic defect in activity can be partly rescued by expression in the physiological setting of an intact CTL. These findings provide the first direct evidence that hPRF-A91V is functionally abnormal and provides a rationale for why it may be responsible for disordered immune homeostasis if inherited with another dysfunctional perforin allele.
Mutation screen and association studies in the Diacylglycerol O-acyltransferase homolog 2 gene (DGAT2), a positional candidate gene for early onset obesity on chromosome 11q13
Authors: Friedel Susann , Reichwald Kathrin , Scherag André , Brumm Harald , Wermter Anne-Kathrin , Fries Hans-Rudolf , Koberwitz Kerstin , Wabitsch Martin , Meitinger Thomas , Platzer Matthias , Biebermann Heike , Hinney Anke , Hebebrand Johannes 
Published: May 2007

Abstract

Background

DGAT2 is a promising candidate gene for obesity because of its function as a key enzyme in fat metabolism and because of its localization on chromosome 11q13, a linkage region for extreme early onset obesity detected in our sample.
We performed a mutation screen in 93 extremely obese children and adolescents and 94 healthy underweight controls. Association studies were performed in samples of up to 361 extremely obese children and adolescents and 445 healthy underweight and normal weight controls. Additionally, we tested for linkage and performed family based association studies at four common variants in the 165 families of our initial genome scan.

Results
The mutation screen revealed 15 DNA variants, four of which were coding non-synonymous exchanges: p.Val82Ala, p.Arg297Gln, p.Gly318Ser and p.Leu385Val. Ten variants were synonymous: c.-9447A > G, c.-584C > G, c.-140C > T, c.-30C > T, IVS2-3C > G, c.812A > G, c.920T > C, IVS7+23C > T, IVS7+73C > T and *22C > T. Additionally, the small biallelic trinucleotide repeat rs3841596 was identified. None of the case control and family based association studies showed an association of investigated variants or haplotypes in the genomic region of DGAT2.

Conclusion
In conclusion, our results do not support the hypothesis of an important role of common genetic variation in DGAT2 for the development of obesity in our sample. Anyhow, if there is an influence of genetic variation in DGAT2 on body weight regulation, it might either be conferred by the less common variants (MAF < 0.1) or the detected, rare non-synonymous variants.
Neuronal expression of muskelin in the rodent central nervous system
Authors: Tagnaouti Nadia , Loebrich Sven , Heisler Frank , Pechmann Yvonne , Fehr Susanne , De Arcangelis Adèle , Georges-Labouesse Elisabeth , Adams Josephine C , Kneussel Matthias 
Published: May 2007

Abstract

Background
The kelch repeat protein muskelin mediates cytoskeletal responses to the extracellular matrix protein thrombospondin 1, (TSP1), that is known to promote synaptogenesis in the central nervous system (CNS). Muskelin displays intracellular localization and affects cytoskeletal organization in adherent cells. Muskelin is expressed in adult brain and has been reported to bind the Cdk5 activator p39, which also facilitates the formation of functional synapses. Since little is known about muskelin in neuronal tissues, we here analysed the tissue distribution of muskelin in rodent brain and analysed its subcellular localization using cultured neurons from multiple life stages.

Results
Our data show that muskelin transcripts and polypeptides are expressed throughout the central nervous system with significantly high levels in hippocampus and cerebellum, a finding that resembles the tissue distribution of p39. At the subcellular level, muskelin is found in the soma, in neurite projections and the nucleus with a punctate distribution in both axons and dendrites. Immunostaining and synaptosome preparations identify partial localization of muskelin at synaptic sites. Differential centrifugation further reveals muskelin in membrane-enriched, rather than cytosolic fractions.

Conclusion
Our results suggest that muskelin represents a multifunctional protein associated with membranes and/or large protein complexes in most neurons of the central nervous system. These data are in conclusion with distinct roles of muskelin's functional interaction partners.
Requirement of aggregation propensity of Alzheimer amyloid peptides for neuronal cell surface binding
Authors: Bateman David A , McLaurin JoAnne , Chakrabartty Avijit 
Published: May 2007

Abstract

Background
Aggregation of the amyloid peptides, Aβ40 and Aβ42, is known to be involved in the pathology of Alzheimer's disease (AD). Here we investigate the relationship between peptide aggregation and cell surface binding of three forms of Aβ (Aβ40, Aβ42, and an Aβ mutant).

Results
Using confocal microscopy and flow cytometry with fluorescently labelled Aβ, we demonstrate a correlation between the aggregation propensity of the Alzheimer amyloid peptides and their neuronal cell surface association. We find that the highly aggregation prone Aβ42 associates with the surface of neuronal cells within one hour, while the less aggregation prone Aβ40 associates over 24 hours. We show that a double mutation in Aβ42 that reduces its aggregation propensity also reduces its association with the cell surface. Furthermore, we find that a cell line that is resistant to Aβ cytotoxicity, the non-neuronal human lymphoma cell line U937, does not bind either Aβ40 or Aβ42.

Conclusion
Taken together, our findings reveal that amyloid peptide aggregation propensity is an essential determinant of neuronal cell surface association. We anticipate that our approach, involving Aβ imaging in live cells, will be highly useful for evaluating the efficacy of therapeutic drugs that prevent toxic Aβ association with neuronal cells.
Hypoxia-inducible factor-1 (HIF-1) is involved in the regulation of hypoxia-stimulated expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and MCP-5 (Ccl12) in astrocytes
Authors: Mojsilovic-Petrovic Jelena , Callaghan Debbie , Cui Hong , Dean Clare , Stanimirovic Danica B , Zhang Wandong 
Published: May 2007

AbstractBackgroundNeuroinflammation has been implicated in various brain pathologies characterized by hypoxia and ischemia. Astroglia play an important role in the initiation and propagation of hypoxia/ischemia-induced inflammation by secreting inflammatory chemokines that attract neutrophils and monocytes into the brain. However, triggers of chemokine up-regulation by hypoxia/ischemia in these cells are poorly understood. Hypoxia-inducible factor-1 (HIF-1) is a dimeric transcriptional factor consisting of HIF-1α and HIF-1β subunits. HIF-1 binds to HIF-1-binding sites in the target genes and activates their transcription. We have recently shown that hypoxia-induced expression of IL-1β in astrocytes is mediated by HIF-1α. In this study, we demonstrate the role of HIF-1α in hypoxia-induced up-regulation of inflammatory chemokines, human monocyte chemoattractant protein-1 (MCP-1/CCL2) and mouse MCP-5 (Ccl12), in human and mouse astrocytes, respectively.MethodsPrimary fetal human astrocytes or mouse astrocytes generated from HIF-1α+/+and HIF-1α+/-mice were subjected to hypoxia (<2% oxygen) or 125 μM CoCl2for 4 h and 6 h, respectively. The expression of HIF-1α, MCP-1 and MCP-5 was determined by semi-quantitative RT-PCR, western blot or ELISA. The interaction of HIF-1α with a HIF-1-binding DNA sequence was examined by EMSA and supershift assay. HIF-1-binding sequence in the promoter of MCP-1 gene was cloned and transcriptional activation of MCP-1 by HIF-1α was analyzed by reporter gene assay.ResultsSequence analyses identified HIF-1-binding sites in the promoters of MCP-1 and MCP-5 genes. Both hypoxia and HIF-1α inducer, CoCl2, strongly up-regulated HIF-1α expression in astrocytes. Mouse HIF-1α+/-astrocytes had lower basal levels of HIF-1α and MCP-5 expression. The up-regulation of MCP-5 by hypoxia or CoCl2in HIF-1α+/+and HIF-1α+/-astrocytes was correlated with the levels of HIF-1α in cells. Both hypoxia and CoCl2also up-regulated HIF-1α and MCP-1 expression in human astrocytes. EMSA assay demonstrated that HIF-1 activated by either hypoxia or CoCl2binds to wild-type HIF-1-binding DNA sequence, but not the mutant sequence. Furthermore, reporter gene assay demonstrated that hypoxia markedly activated MCP-1 transcription but not the mutated MCP-1 promoter in transfected astrocytes.ConclusionThese findings suggest that both MCP-1 and MCP-5 are HIF-1 target genes and that HIF-1α is involved in transcriptional induction of these two chemokines in astrocytes by hypoxia.
Liquid versus gel handrub formulation: a prospective intervention study
Authors: Traore Ousmane , Hugonnet Stéphane , Lübbe Jann , Griffiths William , Pittet Didier 
Published: May 2007

Abstract
Introduction
Hand hygiene is one of the cornerstones of the prevention of health care-associated infection, but health care worker (HCW) compliance with good practices remains low. Alcohol-based handrub is the new standard for hand hygiene action worldwide and usually requires a system change for its successful introduction in routine care. Product acceptability by HCWs is a crucial step in this process.

Methods
We conducted a prospective intervention study to compare the impact on HCW compliance of a liquid (study phase I) versus a gel (phase II) handrub formulation of the same product during daily patient care. All staff (102 HCWs) of the medical intensive care unit participated. Compliance with hand hygiene was monitored by a single observer. Skin tolerance and product acceptability were assessed using subjective and objective scoring systems, self-report questionnaires, and biometric measurements. Logistic regression was used to estimate the association between predictors and compliance with the handrub formulation as the main explanatory variable and to adjust for potential risk factors.

Results
Overall compliance (phases I and II) with hand hygiene practices among nurses, physicians, nursing assistants, and other HCWs was 39.1%, 27.1%, 31.1%, and 13.9%, respectively (p = 0.027). Easy access to handrub improved compliance (35.3% versus 50.6%, p = 0.035). Nurse status, working on morning shifts, use of the gel formulation, and availability of the alcohol-based handrub in the HCW's pocket were independently associated with higher compliance. Immediate accessibility was the strongest predictor. Based on self-assessment, observer assessment, and the measurement of epidermal water content, the gel performed significantly better than the liquid formulation.

Conclusion
Facilitated access to an alcohol-based gel formulation leads to improved compliance with hand hygiene and better skin condition in HCWs.
Global transcriptional responses of fission and budding yeast to changes in copper and iron levels: a comparative study
Authors: Rustici Gabriella , van Bakel Harm , Lackner Daniel H , Holstege Frank C , Wijmenga Cisca , Bähler Jürg , Brazma Alvis 
Published: May 2007

Abstract
Background
Recent studies in comparative genomics demonstrate that interspecies comparison represents a powerful tool for identifying both conserved and specialized biologic processes across large evolutionary distances. All cells must adjust to environmental fluctuations in metal levels, because levels that are too low or too high can be detrimental. Here we explore the conservation of metal homoeostasis in two distantly related yeasts.

Results
We examined genome-wide gene expression responses to changing copper and iron levels in budding and fission yeast using DNA microarrays. The comparison reveals conservation of only a small core set of genes, defining the copper and iron regulons, with a larger number of additional genes being specific for each species. Novel regulatory targets were identified in Schizosaccharomyces pombe for Cuf1p (pex7 and SPAC3G6.05) and Fep1p (srx1, sib1, sib2, rds1, isu1, SPBC27B12.03c, SPAC1F8.02c, and SPBC947.05c). We also present evidence refuting a direct role of Cuf1p in the repression of genes involved in iron uptake. Remarkable differences were detected in responses of the two yeasts to excess copper, probably reflecting evolutionary adaptation to different environments.

Conclusion
The considerable evolutionary distance between budding and fission yeast resulted in substantial diversion in the regulation of copper and iron homeostasis. Despite these differences, the conserved regulation of a core set of genes involved in the uptake of these metals provides valuable clues to key features of metal metabolism.
Role of endogenous interferon and LPS in the immunomodulatory effects of bovine lactoferrin in murine peritoneal macrophages
Authors: Puddu Patrizia , Carollo Maria Grazia , Belardelli Filippo , Valenti Piera , Gessani Sandra 
Published: May 2007

AbstractLactoferrin (Lf) plays an important role in host defense against infection and excessive inflammation. Although the mechanisms underlying its immunomodulatory properties have not been fully elucidated yet, recent evidence suggests that some of these effects may be related to its capacity to form complexes with LPS. We report that the culture of resting mouse peritoneal macrophages (PM) with bovine Lf (bLf), prior to infection with the vesicular stomatitis virus (VSV), resulted in a significant reduction of virus yield with respect to control cultures. The antiviral activity of bLF was related to its capacity of inducing IFN-α/β expression, which in turn inhibited VSV replication. Indeed, the accumulation of IFN-β but not of IFNα1-2 transcripts was up-modulated markedly early after bLf addition. Furthermore, bLf did not exert any antiviral activity in the presence of neutralizing antibodies to IFN-α/β in PM from wild-type mice, as well as in PM from mice genetically defective for the response to IFN. The antiviral activity of bLf relied on its intrinsic capacity to bind LPS, as this protein did not induce IFN expression in PM from LPS-hyporesponsive mice. It is interesting that this LPS-binding property was dispensable for the production of TNF-α, which also occurred in LPS-hyporesponsive mice. Overall, these results indicate that some of the immunomodulatory effects ascribed to Lf may be related to its capacity to favor Type I IFN expression and argue in favor of an important role of the LPS-binding feature and TLR4 in some of the effects ascribed to this molecule.
Language and Social Identity
Authors: Pomerantz Anne 
Published: May 2007

Language and Social Identity. Richard K. Blot, ed. Westport, CT: Praeger Publishers, 2003. 295 pp.Identity in Narrative:. Study of Immigrant Discourse. Anna De Fina. Amsterdam: John Benjamins, 2003. 251 pp.Negotiation of Identities in Multilingual Contexts. Aneta Pavlenko and Adrian Blackledge, eds.Clevedon, UK: Multilingual Matters, 2004. 349 pp.
Reevaluation of Eastern Oyster Dredge Efficiency in Survey Mode: Application in Stock Assessment
Authors: Powell Eric N. , Ashton-Alcox Kathryn A. , Kraeuter John N. 
Published: May 2007

Abstract
Dredge efficiency measurements were conducted in 2003 by comparing paired dredge and diver samples taken on eastern oyster Crassostrea virginica beds in the New Jersey waters of Delaware Bay. We evaluated whether ancillary data collected during the tow could be used to estimate dredge efficiency rather than periodically conducting costly field experiments. With the exception of market-size eastern oysters, dredge efficiency did not vary between the time when it was last measured (2000) and 2003. Dredge efficiencies were lower upbay in both studies. Capture efficiency was significantly greater for live eastern oysters than for boxes (dead, articulated valves) and significantly greater for boxes than for cultch (shell clumps, shells, and shell fragments without attached live eastern oysters or boxes) in both studies. In the single significant exception, dredge efficiency was significantly lower for market-size eastern oysters in 2003. Survey quantification of eastern oyster abundance by calibrating dredge performance requires recognition that dredge efficiencies are spatially variable and that this spatial variability is nonrandom. An analysis that focused on tow-based variables and variables describing fishing effort during the preceding 3 years revealed a suite of variables providing substantive information about the between-tow variation in dredge efficiency. These variables described aspects of catch volume, industry effort, and cultch availability. Each increased with increasing dredge efficiency. Selected subsets of these variables used in multiple-regression equations with data from an independent data set from the 2003 stock survey reproduced the estuarine gradient in dredge efficiency as well as the gradient in dredge efficiency from the highest values (for live eastern oysters) to the lowest values (for cultch). In only one case (market-size animals) did the efficiencies predicted from survey data using the multiple-regression equations diverge significantly from direct measurements. These analyses provide some confidence that estimates of dredge efficiency can be attained from tow-specific data.
Angler Exploitation of Redband Trout in Eight Idaho Desert Streams
Authors: Schill Daniel J. , LaBar George W. , Elle F. Steven , Mamer Elizabeth R. J. M. 
Published: May 2007

Abstract
We estimated angler exploitation rate for redband trout Oncorhynchus mykiss gairdneri in reaches of eight desert streams in southern Idaho using angler-reported catches of 716 jaw-tagged fish. Only two tagged redband trout were reported as harvested by anglers during the angling season. Estimates of annual angler exploitation for seven of the eight study reaches in question equate to 0.0% and from 3.4% to 5.7% on the Sinker Creek reach, depending on the assumed rate of angler tag reporting. Exploitation for the eight study reaches combined was 0.6–0.9%. Our results indicate that jaw tagging did not markedly reduce survival or catchability of redband trout. We conclude that redband trout residing in streams within southern Idaho are virtually unexploited and that angler harvest is well below levels observed on other Idaho redband trout fisheries in more accessible montane environments.
Observational Evidence of Spatial and Temporal Structure in a Sympatric Anadromous (Winter Steelhead) and Resident Rainbow Trout Mating System on the Olympic Peninsula, Washington
Authors: McMillan John R. , Katz Stephen L. , Pess George R. 
Published: May 2007

AbstractWe documented the spawning distribution and male mating tactics of sympatric anadromous rainbow trout Oncorhynchus mykiss (winter steelhead) and resident rainbow trout in the Calawah and Sol Duc River basins, Washington. Snorkel surveys and in situ behavioral observations were used to determine the spatial and temporal distribution patterns and male mating tactics of anadromous, resident, and hatchery residual fish across the spawning season. In general, male steelhead entered our survey reaches earlier than female steelhead, and both entered earlier than the wild resident and hatchery residual forms. Spatially, wild residents represented the greatest proportion of the population in the middle and upper survey reaches. Those differences coincided with mating attempts primarily between male and female steelhead early in the spawning season and primarily between female steelhead and wild resident males at the end of the season. Most of the mating attempts that we observed involved a single female and a single male steelhead, but attempts commonly included multiple male steelhead, wild resident males, or both, and behavioral tactics differed between forms. The patterns suggest a strong temporal structure and a lesser spatial structure to the distribution of O. mykiss during the spawning season, which has important implications for future studies of this complex species.
Essential Facility Access in Europe: Building a Test for Antitrust Policy
Authors: Castaldo Angelo , Nicita Antonio 
Published: May 2007

Abstract
This paper investigates the evolution of competition policy decisions in the US and, particularly, in the EU, concerning mandatory access to an essential facility held by a dominant firm. Based on some recent and controversial EU antitrust decisions, we outline a comprehensive test for identifying an essential facility and consequently imposing a mandatory access obligation on dominant firms.
Cost Effectiveness of R&D and Strategic Trade Policy
Authors: Kujal Praveen , Ruiz Juan M. 
Published: May 2007

Abstract
We analyze how the cost-effectiveness of R&D influences the incentives for governments to impose export subsidies. Governments first impose an export subsidy, or a tax. After observing export policy, firms invest in cost reducing R&D and subsequently compete in the market. Governments subsidize exports under Cournot competition. Under Bertrand competition and for linear demands and constant marginal costs, export subsidies are positive whenever R&D is sufficiently cost-effective at reducing marginal costs, and negative otherwise. The trade policy reversal found in models without endogenous sunk costs disappears if R&D is sufficiently cost-effective. Thus, output subsidies seem more robust than implied by the recent literature.
The use of in vitro culture to improve the propagation of Rhododendron ponticum subsp. baeticum (Boiss. & Reuter)
Authors: Cantos Manuel , Linán Juana , García José , García-Linán María , Domínguez Miguel , Troncoso Antonio 
Published: May 2007

AbstractRhododendron ponticum subsp. baeticum is endemic in the southern region of the Iberian Peninsula. The relict populations of this species are vulnerable, due mainly to difficult conditions for the establishment of seedlings, resulting in a virtual lack of sexual recruitment. In order to preserve the surviving populations, in vitro culture methods have been applied for both the sexual and the agamic propagation of the species. The in vitro germination of seeds was high when conducted with Anderson’s medium without plant growth regulators. The self-rooted seedlings obtained were easily transplanted to outside conditions. The presence of growth regulators in the medium interfered with the development of the seedlings, causing heavy callus formation. The in vitro growth of explants took place readily in Anderson’s medium plus 0.072 mg L−1 of BA and 0.036 mg L−1 of NAA although the explants did not form roots. Rooting was achieved by the basal dipping of the explants in hydroalcoholic solutions of 500 mg L−1 IAA during the outside transplanting process. Therefore, the combination of in vitro grown explants together with ex vitro rooting, results in a good method for the agamic propagation of Rhododendron ponticum subsp. baeticum.