bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes
Authors: Bonifaci Núria , Berenguer Antoni , Díez Javier , Reina Oscar , Medina Ignacio , Dopazo Joaquín , Moreno Víctor , Pujana Miguel Angel 
Published: December 2008

AbstractBackgroundRecent advances in whole-genome association studies (WGASs) for human cancer risk are beginning to provide the part lists of low-penetrance susceptibility genes. However, statistical analysis in these studies is complicated by the vast number of genetic variants examined and the weak effects observed, as a result of which constraints must be incorporated into the study design and analytical approach. In this scenario, biological attributes beyond the adjusted statistics generally receive little attention and, more importantly, the fundamental biological characteristics of low-penetrance susceptibility genes have yet to be determined.MethodsWe applied an integrative approach for identifying candidate low-penetrance breast cancer susceptibility genes, their characteristics and molecular networks through the analysis of diverse sources of biological evidence.ResultsFirst, examination of the distribution of Gene Ontology terms in ordered WGAS results identified asymmetrical distribution of Cell Communication and Cell Death processes linked to risk. Second, analysis of 11 different types of molecular or functional relationships in genomic and proteomic data sets defined the "omic" properties of candidate genes: i/ differential expression in tumors relative to normal tissue; ii/ somatic genomic copy number changes correlating with gene expression levels; iii/ differentially expressed across age at diagnosis; and iv/ expression changes afterBRCA1perturbation. Finally, network modeling of the effects of variants on germline gene expression showed higher connectivity than expected by chance between novel candidates and with known susceptibility genes, which supports functional relationships and provides mechanistic hypotheses of risk.ConclusionThis study proposes that cell communication and cell death are major biological processes perturbed in risk of breast cancer conferred by low-penetrance variants, and defines the common omic properties, molecular interactions and possible functional effects of candidate genes and proteins.
Hemolysis and hyperhomocysteinemia caused by cobalamin deficiency: three case reports and review of the literature
Authors: Acharya Utkarsh , Gau Jen-Tzer , Horvath William , Ventura Paolo , Hsueh Chung-Tsen , Carlsen Wayne 
Published: December 2008

Abstract
Concurrent hemolysis in patients with vitamin B12 deficiency is a well-recognized phenomenon and has been attributed to intramedullary destruction of erythrocytes (ineffective erythropoiesis). Recent studies revealed that homocysteine increased the risk of hemolysis in vitamin B12 deficiency in vitro and there is a high frequency (30%) of vitamin B12 deficiency in asymptomatic patients with homozygous methylene tetrahydrofolate reductase (MTHFR) C677T mutation, a known cause of hyperhomocysteinemia. Here we report three patients with MTHFR mutations and vitamin B12 deficiency presenting with hemolytic anemia and severely elevated homocysteine levels. Patients demonstrated complete resolution of hemolysis with simultaneous normalization of serum homocysteine levels after vitamin B12 treatments. We reviewed pertinent literature, and hypothesized that hemolytic anemia may be more prevalent in patients who have a coexisting MTHFR gene mutation and vitamin B12 deficiency possibly related to severely elevated homocysteine levels. The hemolysis in these cases occurred predominantly in peripheral blood likely due to the combined effects of structurally defective erythrocytes and homocysteine-induced endothelial damage with microangiopathy.
Increased expression of lipocalin-type prostaglandin D2synthase in osteoarthritic cartilage
Authors: Zayed Nadia , Li Xinfang , Chabane Nadir , Benderdour Mohamed , Martel-Pelletier Johanne , Pelletier Jean-Pierre , Duval Nicolas , Fahmi Hassan 
Published: December 2008

Abstract
Introduction
Prostaglandin D synthase (PGDS) is responsible for the biosynthesis of PGD and J series, which have been shown to exhibit anti-inflammatory and anticatabolic effects. Two isoforms have been identified: hematopoietic- and lipocalin-type PGDS (H-PGDS and L-PGDS, respectively). The aims of this study were to investigate the expressions of H-PGDS and L-PGDS in cartilage from healthy donors and from patients with osteoarthritis (OA) and to characterize their regulation by interleukin-1-beta (IL-1β) in cultured OA chondrocytes.

Methods
The expressions of H-PGDS and L-PGDS mRNA and protein in cartilage were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. Chondrocytes were stimulated with IL-1β, and the expression of L-PGDS was evaluated by real-time RT-PCR and Western blotting. The roles of de novo protein synthesis and of the signalling pathways mitogen-activated protein kinases (MAPKs), nuclear factor-kappa-B (NF-κB), and Notch were evaluated using specific pharmacological inhibitors.

Results
L-PGDS and H-PGDS mRNAs were present in both healthy and OA cartilage, with higher levels of L-PGDS than H-PGDS (> 20-fold). The levels of L-PGDS mRNA and protein were increased in OA compared with healthy cartilage. Treatment of chondrocytes with IL-1β upregulated L-PGDS mRNA and protein expressions as well as PGD2 production in a dose- and time-dependent manner. The upregulation of L-PGDS by IL-1β was blocked by the translational inhibitor cycloheximide, indicating that this effect is indirect, requiring de novo protein synthesis. Specific inhibitors of the MAPK p38 (SB 203580) and c-jun N-terminal kinase (JNK) (SP600125) and of the NF-κB (SN-50) and Notch (DAPT) signalling pathways suppressed IL-1β-induced upregulation of L-PGDS expression. In contrast, an inhibitor of the extracellular signal-regulated kinase (ERK/MAPK) (PD98059) demonstrated no significant influence. We also found that PGD2 prevented IL-1β-induced upregulation of L-PGDS expression.

Conclusions
This is the first report demonstrating increased levels of L-PGDS in OA cartilage. IL-1β may be responsible for this upregulation through activation of the JNK and p38 MAPK and NF-κB signalling pathways. These data suggest that L-PGDS might have an important role in the pathophysiology of OA.
Filter survival time and requirement of blood products in patients with severe sepsis receiving drotrecogin alfa (activated) and requiring renal replacement therapy
Authors: Camporota Luigi , Corno Eleonora , Menaldo Eleonora , Smith John , Lei Katie , Beale Richard , Wyncoll Duncan 
Published: December 2008

Abstract
Introduction
Drotrecogin alfa (activated) (DrotAA) is licensed in the United States and the European Union for the treatment of severe sepsis with multiple organ failure. Patients with severe sepsis on renal replacement therapy (RRT), who typically receive additional anticoagulation to prevent circuit clotting, may be at higher risk of bleeding when DrotAA is administered in addition to standard anticoagulation. However, the effects of DrotAA on filter duration in the absence of additional anticoagulation have not been established. The aim of this study was to analyse the filter survival time (FST), and to quantify the requirement of packed red cells (PRC) and blood products during DrotAA infusion.

Methods
This was a single-centre, retrospective observational study conducted in an adult intensive care unit (ICU). Thirty-five patients with severe sepsis who had received both RRT and DrotAA were identified, and all relevant clinical and laboratory data were retrieved from the departmental electronic patient record. We compared haemofilter parameters, requirement of blood products and haemodynamic data recorded during RRT and the infusion of DrotAA with those recorded on RRT with standard anticoagulation after the DrotAA infusion had been completed (post-DrotAA).

Results
The proportion of filter changes due to filter clotting was similar during DrotAA infusion and with conventional anticoagulation post-DrotAA infusion. There was no difference in the FST and filter parameters during DrotAA in the presence or absence of additional anticoagulation with heparin or epoprostenol. A similar proportion of patients required red cell transfusion, although a greater proportion of patients received platelet and fresh frozen plasma during DrotAA infusion compared with the post-DrotAA period with no difference between medical and surgical patients.

Conclusions
Additional anticoagulation during DrotAA infusion does not appear to improve FST. The use of DrotAA in patients with severe sepsis requiring RRT is safe and is not associated with an increased need for PRC transfusion or major bleeding events.
Antimicrobial properties of melanocortins: comment to the manuscript “Anti-Candidaactivity of α-melanocyte-stimulating hormone (α-MSH) peptides” by Isabella Rauch et al.
Authors: Catania Anna , Lipton James M 
Published: December 2008

AbstractIn their report, Rauch et al. did not find candidacidal activity of α-melanocyte-stimulating hormone (α-MSH) in Sabouraud dextrose broth. The lack of killing activity by the natural α-MSH in broth medium may occur because of accelerated Candida replication or peptide degradation by fungal enzymes. It should be considered that in physiological conditions, there is sustained peptide release by host cells in an autocrine/paracrine manner. However, when the procedure described in the paper published in the Journal Leukocyte Biology was used, the investigation by Rauch et al. found that concentrations of α-MSH in the high micromolar range have candidacidal activity.
Delayed Ettringite Formation (DEF) Within Pre-Cast Concrete Cladding Panels on a Mid-Rise Commercial Office Building: A Case Study
Authors: French Warren R. , Schroeder Joshua S. 
Published: December 2008

Abstract
This paper will present the findings of multiple forensic investigations on a fourteen-story office building located in Houston, Texas. During our initial survey, widespread cracking was observed within the concrete cladding panels that warranted a more extensive investigation. Construction of the building was completed in 1985; 17 years prior to our initial investigation. Exterior cladding components are comprised of pre-cast concrete panels over each of the floor lines, with a continuous, structurally glazed, horizontal window system at each floor level. The cladding panels are nonload bearing, pre-cast concrete panels, installed at the time of the building’s construction. The concrete panels are attached to the structure via steel plates that are welded and bolted to the building’s frame. It is intended that this paper will present the results of observations made at the site over a period of several years, as well as the results of testing conducted to assist in the evaluation. A system was developed to locate and catalog the visible anomalies on the panels; including cracks, exposed steel, spalls, pop-outs, and efflorescence on the panels. Full-depth cores were removed from select panels to perform a petrographic analysis and scanning electron microscopy/energy dispersive x-ray microanalysis (SEM/EDXA). The results revealed the presence of delayed ettringite formation (DEF) and alkali-silica reactivity (ASR), with varying degrees of severity. Specific conclusions will be derived related to the conditions at this project and how these anomalies have affected the cladding system performance. Current repair and maintenance provisions will be discussed, in addition to the necessary recladding that will be required in the future. Recommendations will be developed regarding construction practices so that the cladding panel failure observed may be avoided in the future.
Removal of Black Drum on Louisiana Reefs to Increase Survival of Eastern Oysters Crassostrea virginica
Authors: George Gerald J. , Brown Kenneth M. , Peterson Gary W. , Thompson Bruce A. 
Published: December 2008

Abstract
Black drum Pogonias cromis are large, molluscivorous fish that severely limit the abundance of eastern oysters Crassostrea virginica in the northern Gulf of Mexico. In field experiments, we tested two fish removal methods—baited trot lines and gill nets—near commercial oyster leases to determine whether the removal of black drum would increase eastern oyster survival. Both methods removed fish and increased oyster survival in the spring but not in the fall, when little mortality occurred. The numbers and biomass of black drum caught varied with gear type: 10-cm (bar mesh) gill nets landed the most fish, while trot lines and 10-cm gill nets were equally effective in landing the greatest biomass. Eastern oysters were more common in the diet of black drum in the spring than in the fall and increased in importance with fish size. Fish of 70–75 cm (standard length) had the greatest impact on oyster production. These fish can be removed most effectively with 12.5-cm gill nets, though trot lines are preferable because they require less effort and produce less bycatch. The removal techniques used here may also be successful in aiding other bivalve fisheries suffering from predation.
Transportation of Steelhead Kelts to Increase Iteroparity in the Columbia and Snake Rivers
Authors: Evans Allen F. , Wertheimer Robert H. , Keefer Matthew L. , Boggs Charles T. , Peery Christopher A. , Collis Ken 
Published: December 2008

Abstract
We tested the feasibility of transporting steelhead Oncorhynchus mykiss kelts (postspawned adults) around hydroelectric dams on the Snake and Columbia rivers to increase the returns of repeat spawners. Altogether, 5,878 kelts were collected, tagged with passive integrated transponder tags, and assigned to transported or in-river treatment groups at Lower Granite Dam (n = 5,320 [2002–2004]) on the Snake River and John Day Dam (n = 558 [2002]) on the Columbia River. Returns of repeat spawners differed by site and year: 11.1% (62/558) for the John Day Dam sample and 1.4% (27/1,959), 0.5% (6/1,241), and 0.8% (17/2,120) for the Lower Granite Dam samples in 2002, 2003, and 2004, respectively. Transportation tests indicated that kelts transported from the Snake River were approximately 2.3 times more likely to return than fish allowed to migrate in-river. Transport benefits were greatest for wild-origin female kelts, a demographic with high conservation value. There was no significant benefit for kelts transported from John Day Dam, although transported fish returned at a slighter higher rate (1.1 times). Comparisons between treatment groups (in-river versus transport) and locations (Snake River versus Columbia River) indicated that the greatest potential transport benefit may be for Snake River kelts owing to the population's low overall iteroparity rate and numerous potential kelt collection sites. The small sample sizes of returning fish limited our ability to examine more complex trends and environmental effects on return rates. Additional research is needed to fully evaluate the efficacy of kelt transportation in the context of regional steelhead recovery efforts.
Identification of a Small Subpopulation of Candidate Leukemia-Initiating Cells in the Side Population of Patients with Acute Myeloid Leukemia
Authors: Moshaver Bijan , van Rhenen Anna , Kelder Angèle , van der Pol Marjolein , Terwijn Monique , Bachas Costa , Westra August H. , Ossenkoppele Gert J. , Zweegman Sonja , Schuurhuis Gerrit Jan 
Published: December 2008

Abstract
In acute myeloid leukemia (AML), apart from the CD34+CD38− compartment, the side population (SP) compartment contains leukemic stem cells (LSCs). We have previously shown that CD34+CD38− LSCs can be identified using stem cell-associated cell surface markers, including C-type lectin-like molecule-1 (CLL-1), and lineage markers, such as CD7, CD19, and CD56. A similar study was performed for AML SP to further characterize the SP cells with the aim of narrowing down the putatively very low stem cell fraction. Fluorescence-activated cell sorting (FACS) analysis of 48 bone marrow and peripheral blood samples at diagnosis showed SP cells in 41 of 48 cases that were partly or completely positive for the markers, including CD123. SP cells in normal bone marrow (NBM) were completely negative for markers, except CD123. Further analysis revealed that the SP fraction contains different subpopulations: (a) three small lymphoid subpopulations (with T-, B-, or natural killer-cell markers); (b) a differentiated myeloid population with high forward scatter (FSChigh) and high sideward scatter (SSChigh), high CD38 expression, and usually with aberrant marker expression; (c) a more primitive FSClow/SSClow, CD38low, marker-negative myeloid fraction; and (d) a more primitive FSClow/SSClow, CD38low, marker-positive myeloid fraction. NBM contained the first three populations, although the aberrant markers were absent in the second population. Suspension culture assay showed that FSClow/SSClow SP cells were highly enriched for primitive cells. Fluorescence in situ hybridization (FISH) analyses showed that cytogenetically abnormal colonies originated from sorted marker positive cells, whereas the cytogenetically normal colonies originated from sorted marker-negative cells. In conclusion, AML SP cells could be discriminated from normal SP cells at diagnosis on the basis of expression of CLL-1 and lineage markers. This reveals the presence of a low-frequency (median, 0.0016%) SP subfraction as a likely candidate to be enriched for leukemia stem cells.
Disclosure of potential conflicts of interest is found at the end of this article.
Serum Monocyte Chemoattractant Protein-1 Concentrations Associate With Diabetes Status but Not Arterial Stiffness in Children With Type 1 Diabetes
Authors: Zineh Issam , Beitelshees Amber L. , Silverstein Janet H. , Haller Michael J. 
Published: December 2008

OBJECTIVE
The relationship between circulating markers of inflammation and arterial stiffness in children with type 1 diabetes is not well studied. We tested whether inflammatory monocyte chemoattractant protein (MCP)-1 concentrations correlate with arterial stiffness or type 1 diabetes status.

RESEARCH DESIGN AND METHODS
MCP-1 concentrations and radial tonometry data were available for 98 children with type 1 diabetes and 55 healthy control subjects. Arterial stiffness was calculated as augmentation index corrected for a heart rate of 75 (AI75). Correlation between MCP-1 and AI75 and differences in MCP-1 concentrations between case and control subjects were tested.

RESULTS
MCP-1 was significantly higher in children with type 1 diabetes than in control subjects (P &lt; 0.001). However, there were no correlations between MCP-1 and AI75 in the overall sample or upon stratification by type 1 diabetes status (range P = 0.28–0.66).

CONCLUSIONS
Circulating MCP-1 was not associated with arterial stiffness but was significantly elevated in children with type 1 diabetes, indicating a proinflammatory state in children as young as 10 years. The clinical significance of MCP-1 elevation in type 1 diabetes needs further investigation.
Radioligand Binding Characterization of Neuronal Nicotinic Acetylcholine Receptors
Authors: Anderson David J. 
Published: December 2008

AbstractDescribed in this unit are radioligand binding protocols for three neuronal nicotinic acetylcholine receptor (nAChR) subtypes. Detailed descriptions of binding protocols are presented for the two predominant CNS subtypes of nAChRs, α4β2 and α7, as well as the ganglionic α3β4 nAChR. [3H]Cytisine is utilized for α4β2 nAChRs, while [3H]methyllycaconitine is utilized for α7 nAChRs, both in rat brain. α3β4 nAChRs in IMR‐32 cells are labeled with [3H]epibatidine. Reference data are presented, as well as commentary on the current state of neuronal nicotinic receptor research.Curr. Protoc. Pharmacol. 43:1.8.1‐1.8.15. © 2008 by John Wiley & Sons, Inc.
Models of Anxiety: Ultrasonic Vocalizations of Isolated Rat Pups
Authors: Groenink Lucianne , Verdouw P. Monika , van Oorschot Ruud , Olivier Berend 
Published: December 2008

AbstractDescribed in this unit is the ultrasonic distress vocalization test in rat pups. This test is a reliable method for detecting anxiolytic properties of test compounds. In this test, ultrasonic vocalizations (30 to 50 kHz) are elicited by separating rat pups of 9 to 11 days of age from their mother and littermates for a brief period of time. The test can be performed under two different stress conditions. Pups are placed in isolation in either a warm (37°C) or cold (18°C) environment for 5 min. The total number and duration of ultrasonic calls emitted by the pups during this period is used as an index of anxiety. Established anxiolytic compounds, including benzodiazepines, serotonin1A receptor agonists, and selective serotonin reuptake inhibitors (SSRIs), consistently reduce the number and cumulative duration of these ultrasonic distress vocalizations. Curr. Protoc. Pharmacol. 43:5.18.1‐5.18.14. © 2008 by John Wiley & Sons, Inc.
A Model of Cystitis Pain in the Mouse
Authors: Leventhal Liza , Strassle Brian 
Published: December 2008

AbstractInterstitial cystitis (IC) is a chronic pelvic‐perineal pain syndrome of unknown etiology that mainly targets the lower urinary tract. It is characterized by urinary frequency and urgency, inflammation, stiffening of the bladder wall, and visceral pain. Pain is the most prominent feature of IC and current treatments provide limited relief. To facilitate the identification of novel therapeutic options for IC, efforts are being made to identify more predictive rodent models. A well‐characterized rat model is based on administration of cyclophosphamide (CP). The protocol described in this unit replicates this model in mice, demonstrating that CP increases both spontaneous and evoked pain behaviors in this species. This mouse model can be used for understanding disease etiology as well as for the pharmacological evaluation of novel therapeutics for the treatment of IC pain. Curr. Protoc. Pharmacol. 43:5.52.1‐5.52.11. © 2008 by John Wiley & Sons, Inc.
Murine Retroviral Bone Marrow Transplantation Models for the Study of Human Myeloproliferative Disorders
Authors: Gavrilescu L. Cristina , Van Etten Richard A. 
Published: December 2008

AbstractHuman myeloproliferative diseases are common hematologic disorders characterized by clonal overproduction of maturing myeloid or erythroid cells, often caused by expression of a mutant, dysregulated tyrosine kinase (TK). These diseases can be accurately modeled in laboratory mice by the retroviral transfer of a mutant TK gene into murine hematopoietic stem and progenitor cells, followed by transplantation of these cells into irradiated recipient mice. This yields a model system for analyzing the molecular pathophysiology of these conditions and provides a platform for testing therapies, particularly molecularly targeted new chemical entities (NCEs). The Basic Protocol in this unit describes the preparation of mouse bone marrow cells to express the relevant human oncogene before transplanting them into irradiated recipient mice. An alternate protocol describes a similar technique that allows specific induction of lymphoproliferative disease by some TKs. Support protocols for generating and titering retroviral stocks are also included. Curr. Protoc. Pharmacol. 43:14.10.1‐14.10.28. © 2008 by John Wiley & Sons, Inc.
Synthesis of Alkyne‐ and Azide‐Modified Oligonucleotides and Their Cyclization by the CuAAC (Click) Reaction
Authors: El‐Sagheer Afaf H. , Brown Tom 
Published: December 2008

AbstractThe Cu(I)‐catalyzed alkyne‐azide cycloaddition (CuAAC) reaction has been used to synthesize cyclic mini‐DNA duplexes. The reaction is carried out on 5′‐alkyne‐3′‐azide‐labeled hairpin loop oligonucleotides and proceeds in high yield under mild conditions in as little as 5 min. The resultant duplexes have very high thermal stability and their CD spectra are characteristic of normal B‐DNA. Curr. Protoc. Nucleic Acid Chem. 35:4.33.1‐4.33.21. © 2008 by John Wiley & Sons, Inc.