bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRAIL Death Receptor-4, Decoy Receptor-1 and Decoy Receptor-2 Expression on CD8+ T Cells Correlate with the Disease Severity in Patients with Rheumatoid Arthritis
Authors: Bisgin Atil , Terzioglu Ender , Aydin Cigdem , Yoldas Burcak , Yazisiz Veli , Balci Nilufer , Bagci Huseyin , Gorczynski Reginald M , Akdis Cezmi A , Sanlioglu Salih 
Published: August 2010

AbstractBackgroundRheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development.MethodsThe expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis.ResultsWhile no change was detected in the ratio of CD4+to CD8+T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+and CD8+T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+T cells, but not on CD4+T cells, were positively correlated with patients' DAS scores.ConclusionsOur data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis.
Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion
Authors: Shen Qingli , Cicinnati Vito R , Zhang Xiaoyong , Iacob Speranta , Weber Frank , Sotiropoulos Georgios C , Radtke Arnold , Lu Mengji , Paul Andreas , Gerken Guido , Beckebaum Susanne 
Published: August 2010

Abstract

Background
Micro-ribonucleic acid (miRNA)-199a-5p has been reported to be decreased in hepatocellular carcinoma (HCC) compared to normal tissue. Discoidin domain receptor-1 (DDR1) tyrosine kinase, involved in cell invasion-related signaling pathway, was predicted to be a potential target of miR-199a-5p by the use of miRNA target prediction algorithms. The aim of this study was to investigate the role of miR-199a-5p and DDR1 in HCC invasion.

Methods
Mature miR-199a-5p and DDR1 expression were evaluated in tumor and adjacent non-tumor liver tissues from 23 patients with HCC undergoing liver resection and five hepatoma cell lines by the use of real-time quantitative RT-PCR (qRT-PCR) analysis. The effect of aberrant miR-199a-5p expression on cell invasion was assessed in vitro using HepG2 and SNU-182 hepatoma cell lines. Luciferase reporter assay was employed to validate DDR1 as a putative miR-199a-5p target gene. Regulation of DDR1 expression by miR-199a-5p was assessed by the use qRT-PCR and western blotting analysis.

Results
A significant down-regulation of miR-199a-5p was observed in 65.2% of HCC tissues and in four of five cell lines. In contrast, DDR1 expression was significantly increased in 52.2% of HCC samples and in two of five cell lines. Increased DDR1 expression in HCC was associated with advanced tumor stage. DDR1 was shown to be a direct target of miR-199a-5p by luciferase reporter assay. Transfection of miR-199a-5p inhibited invasion of HepG2 but not SNU-182 hepatoma cells.

Conclusions
Decreased expression of miR-199a-5p contributes to increased cell invasion by functional deregulation of DDR1 activity in HCC. However, the effect of miR-199a-5p on DDR1 varies among individuals and hepatoma cell lines. These findings may have significant translational relevance for development of new targeted therapies as well as prognostic prediction for patients with HCC.
The association between ATM D1853N polymorphism and breast cancer susceptibility: a meta-analysis
Authors: Gao Lin-Bo , Pan Xin-Min , Sun Hong , Wang Xia , Rao Li , Li Li-Juan , Liang Wei-Bo , Lv Mei-Li , Yang Wen-Zhong , Zhang Lin 
Published: August 2010

Abstract

Background
Emerging evidence suggests that ataxia telangiectasia-mutated (ATM) is involved in numerous damage repair signaling pathways and cell-cycle checkpoints. Heterozygous carriers of ATM-mutations have an increased risk for the development of breast cancer. The purpose of this study is to evaluate the association between ATM exon39 5557G > A (D1853N, rs1801516) polymorphism and breast cancer susceptibility with the use of a meta-analysis.

Methods
By searching PubMed and Embase databases, a total of 9 epidemiological studies with 4,191 cases and 3,780 controls were identified. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for ATM D1853N polymorphism and breast cancer risk were calculated using fixed- or random-effects model based on the degree of heterogeneity among studies.

Results
No significant association between the ATM D1853N polymorphism and breast cancer risk was observed in overall analysis (GA versus GG: OR = 1.18; 95% CI, 0.90-1.53; AA versus GG: OR = 0.77; 95% CI, 0.58-1.03; dominant model: OR = 1.16; 95% CI, 0.89-1.51; and recessive model: OR = 0.78; 95% CI, 0.59-1.04, respectively).

Conclusion
Our results indicate that ATM D1853N polymorphism is not a risk factor for developing breast cancer.
Innate olfactory preferences in dung beetles
Authors: Dormont Laurent , Jay-Robert Pierre , Bessière Jean-Marie , Rapior Sylvie , Lumaret Jean-Pierre 
Published: August 2010

SUMMARYThe effects of insect larval diet on adult olfactory responses to host-plant or food volatiles are still debated. The induction of adult host preferences has been studied in insects with diverse ecologies, including parasitoids, flower-visitors and phytophagous species. We investigated this question for the first time in a coprophagous insect species. Larvae of the French scarab dung beetle Agrilinus constans were reared on four different artificial substrates containing dung from cattle, horse, sheep or wild boar, and responses of imagos to dung volatiles were then behaviourally tested in an olfactometer. We also reported the first analysis of the composition of different mammal dung volatiles. We showed that adult beetles were more attracted to cattle and sheep dung odours, and that larval feeding experience had no effect on the adult olfactory responses to dung volatiles. A second experiment showed that the presence of other insects inside the dung resource affects the process of dung selection by adults. We identified 64 chemical compounds from dung emissions, and showed that dung volatiles clearly differed among different mammal species, allowing olfactory discrimination by dung beetles. Our results suggest that resource selection in coprophagous insects may be based on innate olfactory preferences. Further experiments should examine whether Agrilinus adults can learn new dung odours, and whether larval diet may influence the behaviour of adults in other coprophagous species.
Lymph flux rates from various lymph sacs in the cane toad Rhinella marina: an experimental evaluation of the roles of compliance, skeletal muscles and the lungs in the movement of lymph
Authors: Hillman Stanley S. , Hedrick Michael S. , Drewes Robert C. , Withers Philip C. 
Published: August 2010

SUMMARY
A new method for quantitatively determining lymph flux from various lymphatic sacs of an anuran, the cane toad, was developed. This method used the dye dilution principle of CiVi=CfVf following injection of Evans Blue into specific lymph sacs and measuring its appearance in the venous circulation. The apparent lymph volume was 57 ml kg–1. The greatest rate of lymph return (0.5–0.8 ml kg–1 min–1) and best linear fit of Evans Blue appearance in the circulation with time followed injections into the subvertebral lymph sac, which has direct connections to both the anterior and posterior pairs of lymphatic hearts. Rate of lymph flux from the pair of posterior lymph hearts was three times greater than the anterior pair. Rates of lymph flux were only influenced by injection volume in the crural lymph sacs, implicating lymph sac compliance as the source of the pressure for lymph movement from these sacs. Femoral lymph sac fluxes were decreased by 60% following ablation of the tendons of the sphincter ani cloacalis, abdominal crenators and piriformis. This supports a role for these muscles in generating the pressure for vertical lymph movement. Femoral lymph sac fluxes were also decreased by 70% by the insertion of a coil in the subvertebral lymph sac, preventing normal compression and expansion of this sac by the lungs. This supports a role for lung ventilation in generating the pressure for vertical movement of lymph. Contrary to previous hypotheses, fluxes from the brachial sac were not influenced by insertion of the coil into the subvertebral sac. A haemorrhage equivalent to 50% of the blood volume did not change lymph flux rates from the femoral lymph sacs. These data provide the first experimental evidence that actual lymph fluxes in the cane toad Rhinella marina depend on lymph sac compliance, contraction of specific skeletal muscles and lung ventilation to move lymph laterally and vertically to the dorsally located lymphatic hearts.
An entomopathogenic Caenorhabditis briggsae
Authors: Abebe Eyualem , Jumba Miriam , Bonner Kaitlin , Gray Vince , Morris Krystalynne , Thomas W. Kelley 
Published: August 2010

SUMMARY
Caenorhabditis elegans is a premier model organism upon which considerable knowledge of basic cell and developmental biology has been built. Yet, as is true for many traditional model systems, we have limited knowledge of the ecological context in which these systems evolved, severely limiting our understanding of gene function. A better grasp of the ecology of model systems would help us immensely in understanding the functionality of genes and evolution of genomes in an environmental context. Consequently, there are ongoing efforts to uncover natural populations of this model system globally. Here, we describe the discovery of a Caenorhabditis briggsae strain and its bacterial associate (Serratia sp.) that form an entomopathogenic complex in the wild. Laboratory experiments confirm that this nematode and its natural bacterial associate can penetrate, kill and reproduce in an insect host and that the bacterial associate can induce this insect pathogenic life cycle in other Caenorhabditis species, including C. elegans. Our findings suggest that this life history may be widespread in nature and critical to the understanding of the biology of this important model organism. Caenorhabditis–insect interaction could be a key factor in our quest for a better grasp of gene functionality in this important model species. The discovered association, consequently, would provide an ecological framework for functional genomics of Caenorhabditis.
Single source sound production and dynamic beam formation in echolocating harbour porpoises (Phocoena phocoena)
Authors: Madsen P. T. , Wisniewska D. , Beedholm K. 
Published: August 2010

SUMMARY
Echolocating toothed whales produce high-powered clicks by pneumatic actuation of phonic lips in their nasal complexes. All non-physeteroid toothed whales have two pairs of phonic lips allowing many of these species to produce both whistles and clicks at the same time. That has led to the hypothesis that toothed whales can increase the power outputs and bandwidths of clicks, and enable fast clicking and beam steering by acutely timed actuation of both phonic lip pairs simultaneously. Here we test that hypothesis by applying suction cup hydrophones on the sound-producing nasal complexes of three echolocating porpoises (Phocoena phocoena) with symmetrical pairs of phonic lips. Using time of arrival differences on three hydrophones, we show that all recorded clicks from these three porpoises are produced by the right pair of phonic lips with no evidence of simultaneous or independent actuation of the left pair. It is demonstrated that porpoises, despite actuation of only one sound source, can change their output and sound beam probably through conformation changes in the sound-producing soft tissues and nasal sacs, and that the coupling of the phonic lips and the melon acts as a waveguide for sound energy between 100 and 160 kHz to generate a forward-directed sound beam for echolocation.
Rh glycoprotein expression is modulated in pufferfish (Takifugu rubripes) during high environmental ammonia exposure
Authors: Michele Nawata C. , Hirose Shigehisa , Nakada Tsutomu , Wood Chris M. , Kato Akira 
Published: August 2010

SUMMARYRhesus (Rh) protein involvement in ammonia transport processes in freshwater fish has received considerable attention; however, parallel investigations in seawater species are scant. We exposed pufferfish to high environmental ammonia (HEA; 1 and 5 mmol l–1 NH4HCO3) and evaluated the patterns of ammonia excretion and gill Rh mRNA and protein expression. Gill H+-ATPase, NHE1, NHE2, NHE3, Na+/K+-ATPase (NKA), Na+/K+/2Cl– co-transporter (NKCC1) mRNA, H+-ATPase activity, NKA protein and activity, were also quantified. Activation of NKA by NH4+ was demonstrated in vitro. The downregulation of Rhbg mRNA and simultaneous upregulations of Rhcg1, H+-ATPase, NHE3, NKA, NKCC1 mRNA, H+-ATPase activity, and NKA protein and activity levels suggested that during HEA, ammonia excretion was mediated mainly by mitochondria-rich cells (MRCs) driven by NKA with basolateral NH4+ entry via NKA and/or NKCC1, and apical NH3 extrusion via Rhcg1. Reprotonation of NH3 by NHE3 and/or H+-ATPase would minimise back flux through the Rh channels. Downregulated Rhbg and Rhag mRNA observed in the gill during HEA suggests a coordinated protective response to minimise the influx of external ammonia via the pavement cells and pillar cells, respectively, while routing ammonia excretion through the MRCs. Exposure to hypercapnia (1% CO2 in air) resulted in downregulated gill and erythrocyte Rhag mRNA. Surprisingly, Rhag, Rhbg, Rhcg1 and Rhcg2 proteins responded to both hypercapnia and HEA with changes in their apparent molecular masses. A dual NH3/CO2 transport function of the pufferfish Rh proteins is therefore suggested. The results support and extend an earlier proposed model of pufferfish gill ammonia excretion that was based on immunolocalisation of the Rh proteins. Passive processes and/or Rhbg and Rhcg2 in the pavement cells may maintain basal levels of plasma ammonia but elevated levels may require active excretion via NKA and Rhcg1 in the MRCs.
Yolk testosterone shapes the expression of a melanin-based signal in great tits: an antioxidant-mediated mechanism?
Authors: Galván Ismael , Alonso-Alvarez Carlos 
Published: August 2010

SUMMARY
Conspicuous traits produced by melanin deposition in integuments are often involved in visual communication. The information content of melanin-based signals is unclear as their expression is tightly controlled by genes and, apparently, is less dependent on individual condition. In birds, high heritabilities have been attributed to melanin-based plumages, often on the basis of egg-swapping manipulations (cross-fostering experiments). However, it is well known that female birds can differentially transfer testosterone to the egg yolk. Furthermore, high testosterone levels have been related to high oxidative stress. As we recently found that oxidative stress experienced during development influences the expression of melanin-based traits, here we manipulated the level of yolk testosterone in great tits (Parus major) to assess the influence of this maternal effect on the expression of the black breast stripe, a well-known melanin-based signal. We predicted that fledglings hatched from eggs with high testosterone levels will not only show larger black stripes but also experience changes in their antioxidant machinery. Indeed, the size of the black stripe of great tits hatched from testosterone-injected eggs was almost double that of controls. Furthermore, the same individuals showed a trend to higher levels of circulating antioxidants, which suggests an adaptive response against some testosterone-induced oxidative challenge.
Simplified Method for International Normalized Ratio (INR) Derivation Based on the Prothrombin Time/INR Line: An International Study
Authors: Poller Leon , Ibrahim Saied , Keown Michelle , Pattison Albert , Jespersen Jørgen 
Published: August 2010

BACKGROUND
The need to perform local International Sensitivity Index (ISI) calibrations and in particular the requirement for a manual method for prothrombin time (PT) determination, have proved to be obstacles to application of the WHO scheme for PT standardization.

METHODS
We used international normalized ratio (INR) derived with a set of only 5 European Concerted Action on Anticoagulation (ECAA) lyophilized calibrant plasmas, certified manually by expert centers with reference thromboplastins, to determine a local PT/INR Line. We compared results of an independent set of validation plasmas with INRs from conventional ISI calibrations and with manually certified INRs.

RESULTS
The mean certified INR of 5 lyophilized validation plasmas was 2.41 with human thromboplastin, 2.04 with bovine/combined, and 2.80 with rabbit. With 42 human reagents, the mean observed INR of the validation plasmas was 2.68 (11.2% deviation from certified INR). Deviation was reduced to 0.4% with both local ISI calibration and the PT/INR Line. Eight results based on bovine/combined thromboplastin gave an INR deviation of 4.9%, becoming 0.5% after ISI calibration and 2.4% with the PT/INR Line. Six results with rabbit reagents deviated from certified INR by 2.5%. After ISI calibration, deviation became 1.1%, and with the PT/INR Line, 0.7%. The PT/INR Line gave similar results with both linear and orthogonal regression analysis. The total proportion of validation plasmas giving INR within 10% deviation from certified values was 42.5% with uncorrected INR, which increased to 92.1% with local ISI calibration and 93.2% with the PT/INR Line.

CONCLUSIONS
The PT/INR Line procedure with 5 ECAA calibrant plasmas successfully substitutes for local ISI calibrations in deriving reliable INRs.
Quality of Life in Hormone Receptor–Positive HER-2+ Metastatic Breast Cancer Patients During Treatment with Letrozole Alone or in Combination with Lapatinib
Authors: Sherrill Beth , Amonkar Mayur M. , Sherif Bintu , Maltzman Julie , O'Rourke Lisa , Johnston Stephen 
Published: August 2010

Abstract

Background.
A phase III trial compared lapatinib plus letrozole (L + Let) with letrozole plus placebo (Let) as first-line therapy for hormone receptor (HR)+ metastatic breast cancer (MBC) patients. The primary endpoint of progression-free survival (PFS) in patients whose tumors were human epidermal growth factor receptor (HER)-2+ was significantly longer for L + Let than for Let (8.2 months versus 3 months; p = .019). This analysis focuses on quality of life (QOL) in the HER-2+ population.

Methods.
QOL was assessed at screening, every 12 weeks, and at withdrawal using the Functional Assessment of Cancer Therapy–Breast (FACT–B). Changes from baseline were analyzed and the proportions of patients achieving minimally important differences in QOL scores were compared. Additional exploratory analyses evaluated how QOL changes reflected tumor progression status.

Results.
Among the 1,286 patients randomized, 219 had HER-2+ tumors. Baseline QOL scores were comparable in the two arms. Mean changes in QOL scores were generally stable over time for patients who stayed on study. The average change from baseline on the FACT-B total score in both arms was positive at all scheduled visits through week 48. There was no significant difference between the two treatment arms in the percentage of QOL responders.

Conclusion.
The addition of lapatinib to letrozole led to a significantly longer PFS interval while maintaining QOL during treatment, when compared with letrozole alone, thus confirming the clinical benefit of the combination therapy in the HR+ HER-2+ MBC patient population. This all oral regimen provides an effective option in this patient population, delaying the need for chemotherapy and its accompanying side effects.
Does Sunscreen Prevent Epidermal Growth Factor Receptor (EGFR) Inhibitor–Induced Rash? Results of a Placebo-Controlled Trial from the North Central Cancer Treatment Group (N05C4)
Authors: Jatoi Aminah , Thrower Abby , Sloan Jeff A. , Flynn Patrick J. , Wentworth-Hartung Nicole Lea , Dakhil Shaker R. , Mattar Bassam I. , Nikcevich Daniel A. , Novotny Paul , Sekulic Aleksandar , Loprinzi Charles L. 
Published: August 2010

Abstract

Purpose.
Rash occurs in &gt;50% of patients prescribed epidermal growth factor receptor (EGFR) inhibitors. This study was undertaken to determine whether sunscreen prevents or mitigates these rashes.

Methods.
This placebo-controlled, double-blinded trial enrolled rash-free patients starting an EGFR inhibitor. Patients were randomly assigned to sunscreen with a sun protection factor of 60 applied twice a day for 28 days versus placebo. They were then monitored for rash and quality of life (Skindex-16) during the 4-week intervention and for an additional 4 weeks.

Results.
Fifty-four patients received sunscreen, and 56 received placebo; the arms were balanced at baseline. During the 4-week intervention, physician-reported rash occurred in 38 (78%) and 39 (80%) sunscreen-treated and placebo-exposed patients, respectively (p = 1.00); no significant differences in rash rates emerged over the additional 4 weeks. There were no significant differences in rash severity, and patient-reported outcomes of rash yielded similar conclusions. Adjustment for sun intensity by geographical zone, season, and use of photosensitivity medications did not yield a significant difference in rash across study arms (p = .20). Quality of life scores declined but remained comparable between arms.

Conclusions.
Sunscreen, as prescribed in this trial, did not prevent or attenuate EGFR inhibitor–induced rash.
Nuclear Hormone Retinoid X Receptor (RXR) Negatively Regulates the Glucose-Stimulated Insulin Secretion of Pancreatic β-Cells
Authors: Miyazaki Satsuki , Taniguchi Hidenori , Moritoh Yusuke , Tashiro Fumi , Yamamoto Tsunehiko , Yamato Eiji , Ikegami Hiroshi , Ozato Keiko , Miyazaki Jun-ichi 
Published: August 2010

OBJECTIVE
Retinoid X receptors (RXRs) are members of the nuclear hormone receptor superfamily and are thought to be key regulators in differentiation, cellular growth, and gene expression. Although several experiments using pancreatic β-cell lines have shown that the ligands of nuclear hormone receptors modulate insulin secretion, it is not clear whether RXRs have any role in insulin secretion.

RESEARCH DESIGN AND METHODS
To elucidate the function of RXRs in pancreatic β-cells, we generated a double-transgenic mouse in which a dominant-negative form of RXRβ was inducibly expressed in pancreatic β-cells using the Tet-On system. We also established a pancreatic β-cell line from an insulinoma caused by the β-cell–specific expression of simian virus 40 T antigen in the above transgenic mouse.

RESULTS
In the transgenic mouse, expression of the dominant-negative RXR enhanced the insulin secretion with high glucose stimulation. In the pancreatic β-cell line, the suppression of RXRs also enhanced glucose-stimulated insulin secretion at a high glucose concentration, while 9-cis-retinoic acid, an RXR agonist, repressed it. High-density oligonucleotide microarray analysis showed that expression of the dominant-negative RXR affected the expression levels of a number of genes, some of which have been implicated in the function and/or differentiation of β-cells.

CONCLUSIONS
These results suggest that endogenous RXR negatively regulates the glucose-stimulated insulin secretion. Given these findings, we propose that the modulation of endogenous RXR in β-cells may be a new therapeutic approach for improving impaired insulin secretion in type 2 diabetes.