bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of neovascularization and its inhibition for allogeneic hematopoietic stem cell transplantation
Authors: Penack Olaf , Socié Gerard , van den Brink Marcel R. M. 
Published: January 2011

AbstractGVHD and tumor relapse are fundamental problems in allogeneic HSCT. Recent research has linked neovascularization to GVHD, tumor growth, and graft-versus-tumor (GVT) activity. Damage of the endothelium by the conditioning regimen provides the initiation stimulus for recruitment of donor-derived endothelial cells and their progenitors. During the early inflammatory phase of GVHD there is considerable neovascularization facilitating migration of inflammatory cells to target organs. In the course of GVHD, however, the vasculature itself becomes a target of alloreactive donor T cells. As a consequence, later stages of GVHD are characterized by fibrosis and rarefaction of blood vessels. Importantly, the inhibition of tumor-neovascularization by activated donor T cells that release antiangiogenic substances contributes to GVT and may be enhanced by pharmacologic inhibition of neovascularization. Furthermore, the therapeutic inhibition of neovascularization may improve immunotherapy for cancer by enhancing leukocyte infiltration in tumor tissue because of normalization of tumor vessels and stimulation of leukocyte–vessel wall interactions. These insights identify important mechanisms underlining the importance of neovascularization for allogeneic immune responses and move therapeutic approaches targeting neovascularization into the spotlight. This perspective covers current knowledge of the role of neovascularization during GVHD as well as GVT and its implications for HSCT.
Association between serum high-molecular-weight adiponectin level and the severity of chronic graft-versus-host disease in allogeneic stem cell transplantation recipients
Authors: Nakasone Hideki , Binh Phan Nguyen Thanh , Yamazaki Rie , Tanaka Yukie , Sakamoto Kana , Ashizawa Masahiro , Sato Miki , Terasako Kiriko , Kimura Shun-ichi , Kikuchi Misato , Kako Shinichi , Okuda Shinya , Oshima Kumi , Tanihara Aki , Nishida Junji , Abe Yasunori , Kanda Yoshinobu 
Published: January 2011

AbstractRecently, a growing body of evidence has suggested that adiponectin, which is secreted by adipose tissues, plays a critical role in obesity-related and autoimmune diseases. We compared the concentrations of adiponectin among 26 normal subjects and 34 allogeneic stem cell transplantation recipients. The concentrations of adiponectin were significantly higher in recipients with chronic graft-versus-host disease (cGVHD) than those in subjects without cGVHD (21.7 ± 11.0 vs 9.1 ± 6.1 μg/mL in females, P < .001; and 10.1 ± 6.8 vs 4.3 ± 2.9 μg/mL in males, P = .003). Multivariate analysis revealed that a higher concentration of adiponectin was associated with female sex (β-coefficient 8.2, P < .0001) and the severity of cGVHD (β-coefficient 6.6, 12.7, and 15.6, P < .01, each for mild, moderate, and severe cGVHD, respectively). In addition, adiponectin levels increased as cGVHD progressed, decreased as cGVHD improved, and did not change with stable cGVHD. In conclusion, adiponectin was associated with the severity of cGVHD and might play a role in the pathophysiology of cGVHD.
Discovery pipeline for epigenetically deregulated miRNAs in cancer: integration of primary miRNA transcription
Authors: Hulf Toby , Sibbritt Tennille , Wiklund Erik D , Bert Saul , Strbenac Dario , Statham Aaron L , Robinson Mark D , Clark Susan J 
Published: January 2011

AbstractBackgroundCancer is commonly associated with widespread disruption of DNA methylation, chromatin modification and miRNA expression. In this study, we established a robust discovery pipeline to identify epigenetically deregulated miRNAs in cancer.ResultsUsing an integrative approach that combines primary transcription, genome-wide DNA methylation and H3K9Ac marks with microRNA (miRNA) expression, we identified miRNA genes that were epigenetically modified in cancer. We find miR-205, miR-21, and miR-196b to be epigenetically repressed, and miR-615 epigenetically activated in prostate cancer cells.ConclusionsWe show that detecting changes in primary miRNA transcription levels is a valuable method for detection of local epigenetic modifications that are associated with changes in mature miRNA expression.
Optimization of glutathione production in batch and fed-batch cultures by the wild-type and recombinant strains of the methylotrophic yeast Hansenula polymorphaDL-1
Authors: Ubiyvovk Vira M , Ananin Vladimir M , Malyshev Alexander Y , Kang Hyun Ah , Sibirny Andriy A 
Published: January 2011

Abstract

Background
Tripeptide glutathione (gamma-glutamyl-L-cysteinyl-glycine) is the most abundant non-protein thiol that protects cells from metabolic and oxidative stresses and is widely used as medicine, food additives and in cosmetic industry. The methylotrophic yeast Hansenula polymorpha is regarded as a rich source of glutathione due to the role of this thiol in detoxifications of key intermediates of methanol metabolism. Cellular and extracellular glutathione production of H. polymorpha DL-1 in the wild type and recombinant strains which overexpress genes of glutathione biosynthesis (GSH2) and its precursor cysteine (MET4) was studied.

Results
Glutathione producing capacity of H. polymorpha DL-1 depending on parameters of cultivation (dissolved oxygen tension, pH, stirrer speed), carbon substrate (glucose, methanol) and type of overexpressed genes of glutathione and its precursor biosynthesis during batch and fed-batch fermentations were studied. Under optimized conditions of glucose fed-batch cultivation, the glutathione productivity of the engineered strains was increased from ~900 up to ~ 2300 mg of Total Intracellular Glutathione (TIG) or GSH+GSSGin, per liter of culture medium. Meantime, methanol fed-batch cultivation of one of the recombinant strains allowed achieving the extracellular glutathione productivity up to 250 mg of Total Extracellular Glutathione (TEG) or GSH+GSSGex, per liter of the culture medium.

Conclusions

H. polymorpha is an competitive glutathione producer as compared to other known yeast and bacteria strains (Saccharomyces cerevisiae, Candida utilis, Escherichia coli, Lactococcus lactis etc.) with good perspectives for further improvement especially for production of extracellular form of glutathione.
Plasmodium falciparum liver stage antigen-1 is cross-linked by tissue transglutaminase
Authors: Nicoll William S , Sacci John B , Rodolfo Carlo , Di Giacomo Giuseppina , Piacentini Mauro , Holland Zoe JM , Doerig Christian , Hollingdale Michael R , Lanar David E 
Published: January 2011

AbstractBackgroundPlasmodium falciparumsporozoites injected by mosquitoes into the blood rapidly enter liver hepatocytes and undergo pre-erythrocytic developmental schizogony forming tens of thousands of merozoites per hepatocyte. Shortly after hepatocyte invasion, the parasite starts to produce Liver Stage Antigen-1 (LSA-1), which accumulates within the parasitophorous vacuole surrounding the mass of developing merozoites. The LSA-1 protein has been described as a flocculent mass, but its role in parasite development has not been determined.MethodsRecombinant N-terminal, C-terminal or a construct containing both the N- and C- terminal regions flanking two 17 amino acid residue central repeat sequences (LSA-NRC) were subjected to in vitro modification by tissue transglutaminase-2 (TG2) to determine if cross-linking occurred. In addition, tissue sections ofP. falciparum-infected human hepatocytes were probed with monoclonal antibodies to the isopeptide ε-(γ-glutamyl)lysine cross-bridge formed by TG2 enzymatic activity to determine if these antibodies co-localized with antibodies to LSA-1 in the growing liver schizonts.ResultsThis study identified a substrate motif for (TG2) and a putative casein kinase 2 phosphorylation site within the central repeat region of LSA-1. The function of TG2 is the post-translational modification of proteins by the formation of a unique isopeptide ε-(γ-glutamyl)lysine cross-bridge between glutamine and lysine residues. When recombinant LSA-1 protein was crosslinkedin vitroby purified TG2 in a calcium dependent reaction, a flocculent mass of protein was formed that was highly resistant to degradation. The cross-linking was not detectably affected by phosphorylation with plasmodial CK2in vitro. Monoclonal antibodies specific to the very unique TG2 catalyzed ε- lysine cross-bridge co-localized with antibodies to LSA-1 in infected human hepatocytes providing visual evidence that LSA-1 was cross-linkedin vivo.ConclusionsWhile the role of LSA-1 is still unknown these results suggest that it becomes highly cross-linked which may aid in the protection of the parasite as it develops.
Variant Plasmodium ovale isolated from a patient infected in Ghana
Authors: Tordrup David , Virenfeldt Jakob , Andersen Felicie F , Petersen Eskild 
Published: January 2011

Abstract
Recent data have found that Plasmodium ovale can be separated in two distinct species: classic and variant P. ovale based on multilocus typing of different genes. This study presents a P. ovale isolate from a patient infected in Ghana together with an analysis of the small subunit RNA, cytochrome b, cytochrome c oxidase I, cysteine protease and lactate dehydrogenase genes, which show that the sample is a variant P. ovale and identical or highly similar to variant P. ovale isolated from humans in South-East Asia and Africa, and from a chimpanzee in Cameroon. The split between the variant and classic P. ovale is estimated to have occurred 1.7 million years ago.
A nuclear export signal within the structural Gag protein is required for prototype foamy virus replication
Authors: Renault Noémie , Tobaly-Tapiero Joelle , Paris Joris , Giron Marie-Lou , Coiffic Audrey , Roingeard Philippe , Saïb Ali 
Published: January 2011

Abstract

Background
The Gag polyproteins play distinct roles during the replication cycle of retroviruses, hijacking many cellular machineries to fulfill them. In the case of the prototype foamy virus (PFV), Gag structural proteins undergo transient nuclear trafficking after their synthesis, returning back to the cytoplasm for capsid assembly and virus egress. The functional role of this nuclear stage as well as the molecular mechanism(s) responsible for Gag nuclear export are not understood.

Results
We have identified a leptomycin B (LMB)-sensitive nuclear export sequence (NES) within the N-terminus of PFV Gag that is absolutely required for the completion of late stages of virus replication. Point mutations of conserved residues within this motif lead to nuclear redistribution of Gag, preventing subsequent virus egress. We have shown that a NES-defective PFV Gag acts as a dominant negative mutant by sequestrating its wild-type counterpart in the nucleus. Trans-complementation experiments with the heterologous NES of HIV-1 Rev allow the cytoplasmic redistribution of FV Gag, but fail to restore infectivity.

Conclusions
PFV Gag-Gag interactions are finely tuned in the cytoplasm to regulate their functions, capsid assembly, and virus release. In the nucleus, we have shown Gag-Gag interactions which could be involved in the nuclear export of Gag and viral RNA. We propose that nuclear export of unspliced and partially spliced PFV RNAs relies on two complementary mechanisms, which take place successively during the replication cycle.
Identification and Characterization of Seven New Exon 11-Associated Splice Variants of the Rat Mu Opioid Receptor Gene, OPRM1
Authors: Xu Jin , Xu Mingming , Rossi Grace C , Pasternak Gavril W , Pan Ying-Xian 
Published: January 2011

Background:The mouse mu opioid receptor (OPRM1) gene undergoes extensive alternative splicing at both the 3'- and 5'-ends of the gene. Previously, several C-terminal variants generated through 3' splicing have been identified in the rat OPRM1 gene. In both mice and humans 5' splicing generates a number of exon 11-containing variants. Studies in an exon 11 knockout mouse suggest the functional importance of these exon 11-associated variants in mediating the analgesic actions of a subset of mu opioids, including morphine-6β-glucuronide (M6G) and heroin, but not others such as morphine and methadone. We now have examined 5' splicing in the rat.Results:The current studies identified in the rat a homologous exon 11 and seven exon 11-associated variants, suggesting conservation of exon 11 and its associated variants among mouse, rat and human. RT-PCR revealed marked differences in the expression of these variants across several brain regions, implying region-specific mRNA processing of the exon 11-associated variants. Of the seven rat exon 11-associated variants, four encoded the identical protein as found in rMOR-1, two predicted 6 TM variants, and one, rMOR-1H2, generated a novel N-terminal variant in which a stretch of an additional 50 amino acids was present at the N-terminus of the previously established rMOR-1 sequence. When expressed in CHO cells, the presence of the additional 50 amino acids in rMOR-1H2 significantly altered agonist-induced G protein activation with little effect on opioid binding.Conclusion:The identification of the rat exon 11 and its associated variants further demonstrated conservation of 5′ splicing in OPRM1 genes among rodents and humans. The functional relevance of these exon 11 associated variants was suggested by the region-specific expression of their mRNAs and the influence of the N-terminal sequence on agonist-induced G protein coupling in the novel N-terminal variant, rMOR-1H2. The importance of the exon 11-associated variants in mice in M6G and heroin analgesia revealed in the exon 11 knockout mouse implies that these analogous rat variants may also play similar roles in rat. The complexity created by alternative splicing of the rat OPRM1 gene may provide important insights of understanding the diverse responses to the various mu opioids seen in rats.
Immunohistochemical profiles of claudin-3 in primary and metastatic prostatic adenocarcinoma
Authors: Bartholow Tanner L , Chandran Uma R , Becich Michael J , Parwani Anil V 
Published: January 2011

Abstract

Background
Claudins are integral membrane proteins that are involved in forming cellular tight junctions. One member of the claudin family, claudin-3, has been shown to be overexpressed in breast, ovarian, and pancreatic cancer. Here we use immunohistochemistry to evaluate its expression in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets).

Methods
Tissue microarrays were immunohistochemically stained for claudin-3, with the staining intensities subsequently quantified and statistically analyzed using a one-way ANOVA with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Fifty-three cases of NAC, 17 cases of BPH, 35 cases of PIN, 107 cases of PCa, and 55 cases of Mets were analyzed in the microarrays.

Results
PCa and Mets had the highest absolute staining for claudin-3. Both had significantly higher staining than BPH (p < 0.05 in both cases) and NAC (p < 0.05 in both cases). PIN had a lower, but non-significant, staining score than PCa and Mets, but a statistically higher score than both BPH and NAC (p < 0.05 for both cases). No significant differences were observed between PCa, Mets, and PIN.

Conclusions
To our knowledge, this represents one of the first studies comparing the immunohistochemical profiles of claudin-3 in PCa and NAC to specimens of PIN, BPH, and Mets. These findings provide further evidence that claudin-3 may serve as an important biomarker for prostate cancer, both primary and metastatic, but does not provide evidence that claudin-3 can be used to predict risk of metastasis.
Evaluation of the respective influence of thyroid hormones and TSH on blood coagulation parameters after total thyroidectomy
Authors: Yango John , Alexopoulou Orsalia , Eeckhoudt Stephane , Hermans Cedric , Daumerie Chantal 
Published: January 2011

BackgroundSeveral hemostatic abnormalities have been described in hypothyroidism, such as modification of coagulation proteins and bleeding tendency. Although thyroid hormone deficiency is considered to be responsible for these changes, the underlying mechanisms have not yet been established.ObjectiveTo evaluate the respective influence of peripheral thyroid hormones (free thyroxine) and TSH on blood clotting by assessing coagulation parameters in patients with a history of total thyroidectomy for thyroid cancer, under three different conditions: induced hypothyroidism, euthyroid state, and following recombinant human TSH (rhTSH) administration.MethodsCoagulation parameters (platelet count, fibrinogen, international normalized ratio, prothrombin time, thrombin time, activated partial thromboplastin time (APTT), factor VIII activity ((FVIII:C), as well as von Willebrand factor antigen (VWF:Ag) and VWF activity using collagen binding assay (VWF:CBA)) were measured in patients with severe hypothyroidism following withdrawal of thyroid hormone replacement therapy, and in the same patients with euthyroidism after restoring replacement treatment (group A), and before and after administering rhTSH (group B).ResultsFVIII:C, VWF:Ag, and VWF:CBA were significantly decreased (P<0.001), whereas APTT was significantly increased (P<0.001) in patients with severe hypothyroidism compared with patients in the euthyroid state. No changes in clotting parameters were observed in patients who received rhTSH therapy.ConclusionThis prospective study shows that severe short-term hypothyroidism is associated with significantly lower levels of VWF:Ag, VWF:CBA, and FVIII:C. Administration of exogenous TSH has no effect on coagulation parameters. These findings suggest that thyroid hormone deficiency is likely to be the main cause of coagulation alterations in patients with hypothyroidism.
FABP 4 is associated with inflammatory markers and metabolic syndrome in morbidly obese women
Authors: Terra Ximena , Quintero Yunuen , Auguet Teresa , Porras Jose Antonio , Hernández Mercé , Sabench Fátima , Aguilar Carmen , Luna Anna María , del Castillo Daniel , Richart Cristobal 
Published: January 2011

ObjectiveThe adipocyte/macrophage fatty acid-binding protein 4 (FABP4) has been described as a biomarker for adiposity and metabolic syndrome (MS). The aims of this study were to assess the relationship between FABP4 and inflammatory cytokines related to obesity, and to evaluate FABP4 mRNA expression in visceral and subcutaneous adipose tissue in non-diabetic morbidly obese women versus healthy lean women.MethodsWe analyzed circulating levels of FABP4 in 81 Spanish women: 38 lean (body mass index (BMI)<25 kg/m2) and 43 morbidly obese (BMI>40 kg/m2). We took 30 follow-up blood samples at 6 and 12 months after bariatric surgery. We assessed FABP4 gene expression in samples of subcutaneous abdominal and visceral adipose tissue. Adipose tissue mRNA expression was determined by real-time RT-PCR.ResultsIn morbidly obese women, plasma FABP4 levels were significantly higher than in non-obese patients. These levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA2-IR), and plasma glucose and insulin levels. Post-operative FABP4 levels decreased by a maximum of 30% after 12 months. We also found an inverse association between FABP4 and adiponectin levels, and positive correlations between FABP4 and circulating leptin, tumor necrosis factor (TNF) receptors, C-reactive protein (CRP) and interleukin 6 levels. Linear regression analysis revealed that FABP4 was more closely related to HOMA2-IR than adiponectin, CRP, TNF-RI, or leptin. Furthermore, high circulating FABP4 levels were associated with the presence of MS. FABP4 mRNA expression in visceral adipose tissue was related to its circulating levels in morbidly obese women.ConclusionsOur results indicate that serum FABP4 is associated with inflammatory factors related to obesity and MS in non-diabetic morbidly obese women.
What Do Prostate Cancer Patients Die Of?
Authors: Riihimäki Matias , Thomsen Hauke , Brandt Andreas , Sundquist Jan , Hemminki Kari 
Published: January 2011

AbstractBackground.A recent rise in the incidence of prostate cancer and a more favorable outcome have increased the proportions of other causes of death in affected men. Extending the survival of prostate cancer patients thus requires knowledge of all causes of death.Methods.Data on the population, cancers, and causes of death were gathered from the nationwide Swedish Family-Cancer Database. A Cox regression model, comparing prostate cancer patients with all other men, was applied. Hazard ratios (HR) were calculated both for the underlying cause and for dying with a specific cause listed among multiple causes of death.Findings.Among 686,500 observed deaths, 62,500 were prostate cancer patients. For underlying causes other than prostate cancer, the highest cause-specific HRs were found for external causes (HR, 1.24; 95% confidence interval [CI], 1.16–1.31), diseases of the pulmonary circulation (HR, 1.22; 95% CI, 1.09–1.37), and heart failure (HR, 1.18; 95% CI, 1.11–1.24). For specific multiple causes, the highest HRs were found for anemia (HR, 2.28; 95% CI, 2.14–2.42), diseases of the pulmonary circulation (HR, 1.61; 95% CI, 1.55–1.68), and urinary system disease (HR, 1.90; 95% CI, 1.84–1.96).Interpretations.Prostate cancer patients have a higher risk for dying from various causes other than prostate cancer, including external causes and heart failure. Mechanisms have been proposed linking these elevated risks to both cancer and treatment. More attention should be paid to comorbidities in men with prostate cancer. The present study fulfills a gap in the knowledge of death causes in prostate cancer patients.
Polymorphic microsatellite markers in the invasive shrub Buddleja davidii (Scrophulariaceae)1
Authors: Schreiter Susanne , Ebeling Susan K. , Durka Walter 
Published: January 2011

• Premise of the study: Microsatellite primers were developed for the invasive plant Buddleja davidii, a Chinese shrub that is an invader in most other continents.• Methods and Results: An invasive population was analyzed using eight di‐ and tetranucleotide microsatellite loci. The number of alleles per locus ranged from 5 to 14. Due to polyploidy, exact genotypes could not be determined. Progeny arrays were used to study the outcrossing rate using presence/absence data of alleles resulting in an estimate of multilocus outcrossing rate of 93%. The markers were successfully tested in five congeneric species.• Conclusions: The results indicate the utility of these loci in future studies of population genetics and breeding systems in B. davidii and in congeneric species.
Development and characterization of microsatellite markers for Sagittaria trifolia var. sinensis (Alismataceae)
Authors: Wu Zhi‐Hua , Wang Shu‐Zhen , Hu Ji‐Hong , Li Feng , Ke Wei‐Dong , Ding Yi 
Published: January 2011

• Premise of the study: Microsatellite markers were developed for the aquatic plant Sagittaria trifolia var. sinensis to assess its genetic diversity and population structure. Cross‐species transferability was assayed in eight congeneric species.• Methods and Results: Seventeen microsatellite markers were isolated and characterized in Sagittaria trifolia var. sinensis using Fast Isolation by AFLP of Sequence COntaining Repeats (FIASCO) protocol. Across the evaluated populations, 14 of the markers showed polymorphisms with 3 to 11 alleles per locus; the observed and expected heterozygosity (Ho and HE) ranged from 0.0000 to 0.6364 and from 0.0000 to 0.8386, respectively. Nine of the loci were successfully amplified in the congeneric species.• Conclusions: These markers will be useful for further investigation of population genetics in Sagittaria trifolia var. sinensis and related research in Sagittaria species.