bluuebunny/crossref_metadata_2025_split huggingface dataset:
MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes
Authors: Vogl Thomas , Ludwig Stephan , Goebeler Matthias , Strey Anke , Thorey Irmgard S. , Reichelt Rudolf , Foell Dirk , Gerke Volker , Manitz Marie P. , Nacken Wolfgang , Werner Sabine , Sorg Clemens , Roth Johannes 
Published: August 2004

AbstractMRP14 (S100A9) is the major calcium-binding protein of neutrophils and monocytes. Targeted gene disruption reveals an essential role of this S100 protein for transendothelial migration of phagocytes. The underlying molecular mechanism comprises major alterations of cytoskeletal metabolism. MRP14, in complex with its binding partner MRP8 (S100A8), promotes polymerization of microtubules. MRP14 is specifically phosphorylated by p38 mitogen-activated protein kinase (MAPK). This phosphorylation inhibits MRP8/MRP14-induced tubulin polymerization. Phosphorylation of MRP14 is antagonistically regulated by binding of MRP8 and calcium. The biologic relevance of these findings is confirmed by the fact that MAPK p38 fails to stimulate migration of MRP14-/- granulocytes in vitro and MRP14-/- mice show a diminished recruitment of granulocytes into the granulation tissue during wound healing in vivo. MRP14-/- granulocytes contain significantly less polymerized tubulin, which subsequently results in minor activation of Rac1 and Cdc42 after stimulation of p38 MAPK. Thus, the complex of MRP8/MRP14 is the first characterized molecular target integrating MAPK- and calcium-dependent signals during migration of phagocytes.
Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells
Authors: Haberichter Sandra L. , Merricks Elizabeth P. , Fahs Scot A. , Christopherson Pamela A. , Nichols Timothy C. , Montgomery Robert R. 
Published: August 2004

Abstract
Type 3 von Willebrand disease (VWD) is a severe hemorrhagic defect in humans. We now identify the homozygous mutation in the Chapel Hill strain of canine type 3 VWD that results in premature termination of von Willebrand factor (VWF) protein synthesis. We cultured endothelium from VWD and normal dogs to study intracellular VWF trafficking and Weibel-Palade body formation. Weibel-Palade bodies could not be identified in the canine VWD aortic endothelial cells (VWD-AECs) by P-selectin, VWFpp, or VWF immunostaining and confocal microscopy. We demonstrate the reestablishment of Weibel-Palade bodies that recruit endogenous P-selectin by expressing wild-type VWF in VWD-AECs. Expression of mutant VWF proteins confirmed that VWF multimerization is not necessary for Weibel-Palade body creation. Although the VWF propeptide is required for the formation of Weibel-Palade bodies, it cannot independently induce the formation of the granule. These VWF-null endothelial cells provide a unique opportunity to examine the biogenesis of Weibel-Palade bodies in endothelium from a canine model of type 3 VWD.
Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants
Authors: Rosenberg Philip S. , Socié Gerard , Alter Blanche P. , Gluckman Eliane 
Published: August 2004

Abstract
Hematopoietic stem cell transplant (SCT) is currently the only therapy that can restore normal hematopoiesis in patients with Fanconi anemia (FA). Patients with FA have a high baseline risk of squamous cell cancers (SCCs) of the head, neck, and esophagus, and SCT conditioning may increase SCC incidence. We evaluated the risks of SCC and death in 145 patients with FA in the North American Survey (NAS) cohort who did not receive transplants, and 117 patients with FA in the Hôpital Saint Louis (SLH) cohort who did receive transplants. The age-specific hazard of SCC was 4.4-fold higher in patients who received transplants than in those who did not (P = .003), and SCCs occurred at significantly younger ages in the former (respective medians, 18 and 33 years, P = .004). Survival after SCC was similarly poor in both cohorts (P = .135, median, 13 months). The hazard of SCC increased at a greater than linear rate, to 4.4% per year by age 40 in NAS and 4.7% per year by 10 years after transplant in SLH. In SLH, the hazard of non-SCC death was biphasic, declining significantly (P = .004) from 7.1% per month during the first 6 months after transplant to 0.13% per month (1.6% per year) after the first year. Acute and chronic graft-versus-host diseases were significant SCC risk factors. Adverse event rates in these cohorts provide historical control rates to assess emerging therapies for FA.
Noninvasive MR imaging of magnetically labeled stem cells to directly identify neovasculature in a glioma model
Authors: Anderson Stasia A. , Glod John , Arbab Ali S. , Noel Martha , Ashari Parwana , Fine Howard A. , Frank Joseph A. 
Published: August 2004

Abstract
Bone marrow-derived endothelial precursor cells incorporate into neovasculature and have been successfully used as vehicles for gene delivery to brain tumors. To determine whether systemically administered Sca1+ bone marrow cells labeled with superparamagnetic iron oxide nanoparticles can be detected by in vivo magnetic resonance imaging in a mouse brain tumor model, mouse Sca1+ cells were labeled in vitro with ferumoxides-poly-l-lysine complexes. Labeled or control cells were administered intravenously to glioma-bearing severe combined immunodeficient (SCID) mice. Magnetic resonance imaging (MRI) was performed during tumor growth. Mice that received labeled cells demonstrated hypointense regions within the tumor that evolved over time and developed a continuous dark hypointense ring at a consistent time point. This effect was not cleared by administration of a gadolinium contrast agent. Histology showed iron-labeled cells around the tumor rim in labeled mice, which expressed CD31 and von Willebrand factor, indicating the transplanted cells detected in the tumor have differentiated into endothelial-like cells. These results demonstrate that MRI can detect the incorporation of magnetically labeled bone marrow-derived precursor cells into tumor vasculature as part of ongoing angiogenesis and neovascularization. This technique can be used to directly identify neovasculature in vivo and to facilitate gene therapy by noninvasively monitoring these cells as gene delivery vectors. (Blood. 2005;105:420-425)
A supertree approach to shorebird phylogeny
Authors: Thomas Gavin H , Wills Matthew A , Székely Tamás 
Published: August 2004

Abstract
Background
Order Charadriiformes (shorebirds) is an ideal model group in which to study a wide range of behavioural, ecological and macroevolutionary processes across species. However, comparative studies depend on phylogeny to control for the effects of shared evolutionary history. Although numerous hypotheses have been presented for subsets of the Charadriiformes none to date include all recognised species. Here we use the matrix representation with parsimony method to produce the first fully inclusive supertree of Charadriiformes. We also provide preliminary estimates of ages for all nodes in the tree.

Results
Three main lineages are revealed: i) the plovers and allies; ii) the gulls and allies; and iii) the sandpipers and allies. The relative position of these clades is unresolved in the strict consensus tree but a 50% majority-rule consensus tree indicates that the sandpiper clade is sister group to the gulls and allies whilst the plover group is placed at the base of the tree. The overall topology is highly consistent with recent molecular hypotheses of shorebird phylogeny.

Conclusion
The supertree hypothesis presented herein is (to our knowledge) the only complete phylogenetic hypothesis of all extant shorebirds. Despite concerns over the robustness of supertrees (see Discussion), we believe that it provides a valuable framework for testing numerous evolutionary hypotheses relating to the diversity of behaviour, ecology and life-history of the Charadriiformes.
Recurrent Barrett's esophagus and adenocarcinoma after esophagectomy
Authors: Wolfsen Herbert C , Hemminger Lois L , DeVault Kenneth R 
Published: August 2004

Abstract
Background
Esophagectomy is considered the gold standard for the treatment of high-grade dysplasia in Barrett's esophagus (BE) and for noninvasive adenocarcinoma (ACA) of the distal esophagus. If all of the metaplastic epithelium is removed, the patient is considered "cured". Despite this, BE has been reported in patients who have previously undergone esophagectomy. It is often debated whether this is "new" BE or the result of an esophagectomy that did not include a sufficiently proximal margin. Our aim was to determine if BE recurred in esophagectomy patients where the entire segment of BE had been removed.

Methods
Records were searched for patients who had undergone esophagectomy for cure at our institution. Records were reviewed for surgical, endoscopic, and histopathologic findings. The patients in whom we have endoscopic follow-up are the subjects of this report.

Results
Since 1995, 45 patients have undergone esophagectomy for cure for Barrett's dysplasia or localized ACA. Thirty-six of these 45 patients underwent endoscopy after surgery including 8/45 patients (18%) with recurrent Barrett's metaplasia or neoplasia after curative resection.

Conclusion
Recurrent Barrett's esophagus or adenocarcinoma after esophagectomy was common in our patients who underwent at least one endoscopy after surgery. This appears to represent the development of metachronous disease after complete resection of esophageal disease. Half of these patients have required subsequent treatment thus far, either repeat surgery or photodynamic therapy. These results support the use of endoscopic surveillance in patients who have undergone "curative" esophagectomy for Barrett's dysplasia or localized cancer.
Comparison of bovine leukemia virus (BLV) and CMV promoter-driven reporter gene expression in BLV-infected and non-infected cells
Authors: Harms Jerome S , Eakle Kurt A , Kuo Lillian S , Bremel Robert D , Splitter Gary A 
Published: August 2004

Abstract
Background
Viral promoters are used in mammalian expression vectors because they generally have strong activity in a wide variety of cells of differing tissues and species.

Methods
The utility of the BLV LTR/promoter (BLVp) for use in mammalian expression vectors was investigated through direct comparison to the CMV promoter (CMVp). Promoter activity was measured using luciferase assays of cell lines from different tissues and species stably transduced with BLVp or CMVp driven luciferase vectors including D17, FLK, BL3.1 and primary bovine B cells. Cells were also modified through the addition of BLV Tax expression vectors and/or BLV infection as well as treatment with trichostatin A (TSA).

Results
Results indicate the BLV promoter, while having low basal activity compared to the CMV promoter, can be induced to high-levels of activity similar to the CMV promoter in all cells tested. Tax or BLV infection specifically enhanced BLVp activity with no effect on CMVp activity. In contrast, the non-specific activator, TSA, enhanced both BLVp and CMVp activity.

Conclusion
Based on these data, we conclude the BLV promoter could be very useful for transgene expression in mammalian expression vectors.
Comprehensive analysis of pseudogenes in prokaryotes: widespread gene decay and failure of putative horizontally transferred genes
Authors: Liu Yang , Harrison Paul M , Kunin Victor , Gerstein Mark 
Published: August 2004

Abstract
Background
Pseudogenes often manifest themselves as disabled copies of known genes. In prokaryotes, it was generally believed (with a few well-known exceptions) that they were rare.

Results
We have carried out a comprehensive analysis of the occurrence of pseudogenes in a diverse selection of 64 prokaryote genomes. Overall, we find a total of around 7,000 candidate pseudogenes. Moreover, in all the genomes surveyed, pseudogenes occur in at least 1 to 5% of all gene-like sequences, with some genomes having considerably higher occurrence. Although many large populations of pseudogenes arise from large, diverse protein families (for example, the ABC transporters), notable numbers of pseudogenes are associated with specific families that do not occur that widely. These include the cytochrome P450 and PPE families (PF00067 and PF00823) and others that have a direct role in DNA transposition.

Conclusions
We find suggestive evidence that a large fraction of prokaryote pseudogenes arose from failed horizontal transfer events. In particular, we find that pseudogenes are more than twice as likely as genes to have anomalous codon usage associated with horizontal transfer. Moreover, we found a significant difference in the number of horizontally transferred pseudogenes in pathogenic and non-pathogenic strains of Escherichia coli.
Function-informed transcriptome analysis of Drosophila renal tubule
Authors: Wang Jing , Kean Laura , Yang Jingli , Allan Adrian K , Davies Shireen A , Herzyk Pawel , Dow Julian AT 
Published: August 2004

Abstract
Background
Comprehensive, tissue-specific, microarray analysis is a potent tool for the identification of tightly defined expression patterns that might be missed in whole-organism scans. We applied such an analysis to Drosophila melanogaster Malpighian (renal) tubule, a defined differentiated tissue.

Results
The transcriptome of the D. melanogaster Malpighian tubule is highly reproducible and significantly different from that obtained from whole-organism arrays. More than 200 genes are more than 10-fold enriched and over 1,000 are significantly enriched. Of the top 200 genes, only 18 have previously been named, and only 45% have even estimates of function. In addition, 30 transcription factors, not previously implicated in tubule development, are shown to be enriched in adult tubule, and their expression patterns respect precisely the domains and cell types previously identified by enhancer trapping. Of Drosophila genes with close human disease homologs, 50 are enriched threefold or more, and eight enriched 10-fold or more, in tubule. Intriguingly, several of these diseases have human renal phenotypes, implying close conservation of renal function across 400 million years of divergent evolution.

Conclusions
From those genes that are identifiable, a radically new view of the function of the tubule, emphasizing solute transport rather than fluid secretion, can be obtained. The results illustrate the phenotype gap: historically, the effort expended on a model organism has tended to concentrate on a relatively small set of processes, rather than on the spread of genes in the genome.
Improving identification of differentially expressed genes in microarray studies using information from public databases
Authors: Kim Richard D , Park Peter J 
Published: August 2004

AbstractWe demonstrate that the process of identifying differentially expressed genes in microarray studies with small sample sizes can be substantially improved by extracting information from a large number of datasets accumulated in public databases. The improvement comes from more reliable estimates of gene-specific variances based on other datasets. For a two-group comparison with two arrays in each group, for example, the result of our method was comparable to that of a t-test analysis with five samples in each group or to that of a regularized t-test analysis with three samples in each group. Our results are further improved by weighting the results of our approach with the regularized t-test results in a hybrid method.
Regulation of Steroidogenesis by p53 in Macaque Granulosa Cells and H295R Human Adrenocortical Cells
Authors: Cherian-Shaw Mary , Das Rituparna , VandeVoort Catherine A. , Chaffin Charles L. 
Published: August 2004

AbstractOvulation and formation of a functional corpus luteum in primates involve cascades of events, including increased progesterone synthesis and changes in granulosa cell proliferation. However, critical gaps remain in our understanding of how an ovulatory gonadotropin surge initiates these processes. To more fully elucidate changes in the cell cycle during luteal formation, the actions of the tumor suppressor p53 were examined. Rhesus macaque granulosa cells were isolated during controlled ovarian stimulation protocols before (nonluteinized) or after (luteinized) an ovulatory gonadotropin stimulus. Phosphorylated p53 protein was detected in the cytoplasm of granulosa cells before and after human chorionic gonadotropin (hCG) treatment, whereas granulosa cells from hormonally controlled rats did not express p53 before or after hCG. Treatment of nonluteinized macaque granulosa cells with hCG and the p53 inhibitor pifithrin-α (PFT) in vitro did not alter markers of the cell cycle, including proliferating cell nuclear antigen, p21, and human double minute (HDM)-2 expression compared with hCG alone. Levels of pregnenolone and progesterone increased 2- and 4-fold, respectively, within 6 h of hCG treatment, whereas PFT completely blocked this hCG-induced effect. Estradiol was increased transiently (&gt;10-fold) by hCG plus PFT relative to levels after hCG alone. PFT also inhibited hCG-induced increases in steroidogenic acute regulatory protein and 3β-hydroxysteroid dehydrogenase mRNAs. Similar results were obtained using the human adrenocortical cell line H295R, suggesting that p53 may have a general function in primate steroidogenesis. These data indicate that p53 plays a key role in luteinization of the primate ovarian follicle though the regulation of steroidogenic enzymes leading to progesterone synthesis.
Evidence for a Novel Intrapituitary Autocrine/Paracrine Feedback Loop Regulating Growth Hormone Synthesis and Secretion in Grass Carp Pituitary Cells by Functional Interactions between Gonadotrophs and Somatotrophs
Authors: Zhou Hong , Wang Xinyan , Ko Wendy K. W. , Wong Anderson O. L. 
Published: August 2004

AbstractGonadotropin (GTH) and GH released from the pituitary are known to interact at multiple levels to modulate the functions of the gonadotrophic and somatotrophic axes. However, their interactions at the pituitary level have not been fully characterized. In this study, autocrine/paracrine regulation of GH synthesis and secretion by local interactions between gonadotrophs and somatotrophs was examined using grass carp pituitary cells as a cell model. Exogenous GTH and GH induced GH release and GH mRNA expression in carp pituitary cells. Removal of endogenous GTH and GH by immunoneutralization with GTH and GH antisera, respectively, suppressed GH release, GH production, and GH mRNA levels. GH antiserum also blocked the stimulatory effects of exogenous GTH on GH release and GH mRNA levels. In reciprocal experiments, GH release and GH mRNA expression induced by exogenous GH was significantly reduced by GTH antiserum. In addition, exogenous GH was found to be inhibitory to basal GTH release and treatment with GH antiserum elevated GTH secretion at low doses but suppressed GTH production at high doses. These results suggest that local interactions between gonadotrophs and somatotrophs may form an intrapituitary feedback loop to regulate GH release and synthesis. In this model, GTH released from gonadotrophs induces GH release and GH production in neighboring somatotrophs. GH secreted maintains somatotroph sensitivity to GTH stimulation, and at the same time, inhibits basal GTH release in gonadotrophs. This feedback loop may represent a novel mechanism regulating GH release and synthesis in lower vertebrates.
Minireview: GNAS: Normal and Abnormal Functions
Authors: Weinstein Lee S. , Liu Jie , Sakamoto Akio , Xie Tao , Chen Min 
Published: August 2004

Abstract
GNAS is a complex imprinted gene that uses multiple promoters to generate several gene products, including the G protein α-subunit (Gsα) that couples seven-transmembrane receptors to the cAMP-generating enzyme adenylyl cyclase. Somatic activating Gsα mutations, which alter key residues required for the GTPase turn-off reaction, are present in various endocrine tumors and fibrous dysplasia of bone, and in a more widespread distribution in patients with McCune- Albright syndrome. Heterozygous inactivating Gsα mutations lead to Albright hereditary osteodystrophy. Gsα is imprinted in a tissue-specific manner, being primarily expressed from the maternal allele in renal proximal tubules, thyroid, pituitary, and ovary. Maternally inherited mutations lead to Albright hereditary osteodystrophy (AHO) plus PTH, TSH, and gonadotropin resistance (pseudohypoparathyroidism type 1A), whereas paternally inherited mutations lead to AHO alone. Pseudohypoparathyroidism type 1B, in which patients develop PTH resistance without AHO, is almost always associated with a GNAS imprinting defect in which both alleles have a paternal-specific imprinting pattern on both parental alleles. Familial forms of the disease are associated with a mutation within a closely linked gene that deletes a region that is presumably required for establishing the maternal imprint, and therefore maternal inheritance of the mutation results in the GNAS imprinting defect. Imprinting of one differentially methylated region within GNAS is virtually always lost in pseudohypoparathyroidism type 1B, and this region is probably responsible for tissue-specific Gsα imprinting. Mouse knockout models show that Gsα and the alternative Gsα isoform XLαs that is expressed from the paternal GNAS allele may have opposite effects on energy metabolism in mice.
Minireview: PRKAR1A: Normal and Abnormal Functions
Authors: Bossis Ioannis , Stratakis Constantine A. 
Published: August 2004

AbstractThe type 1α regulatory subunit (RIα) of cAMP-dependent protein kinase (PKA) (coded by the PRKAR1A gene) is the main component of type I PKA, which regulates most of the serine-threonine kinase activity catalyzed by the PKA holoenzyme in response to cAMP. Carney complex (CNC), or the complex of spotty skin pigmentation, myxomas, and endocrine overactivity, is a multiple endocrine (and not only) neoplasia syndrome that is due to PRKAR1A-inactivating mutations. The R1α protein and PRKAR1A mRNA have been found to be up-regulated in a series of cell lines and human and rodent neoplasms, suggesting this molecule’s involvement in tumorigenesis and its potential role in cell cycle regulation, growth, and/or proliferation. Alterations in PKA activity elicit a variety of effects depending on the tissue, developmental stage, degree of differentiation, and cAMP levels. In addition, RIα may have functions independent of PKA. The presence of inactivating germline mutations and the loss of its wild-type allele in some CNC lesions indicate that PRKAR1A might function as a tumor suppressor gene in these tissues, but could PRKAR1A be a classic tumor suppressor gene? Probably not, and this review explains why.