bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired expression of p66Shc, a novel regulator of B-cell survival, in chronic lymphocytic leukemia
Authors: Capitani Nagaja , Lucherini Orso Maria , Sozzi Elisa , Ferro Micol , Giommoni Nico , Finetti Francesca , De Falco Giulia , Cencini Emanuele , Raspadori Donatella , Pelicci Pier Giuseppe , Lauria Francesco , Forconi Francesco , Baldari Cosima T. 
Published: January 2010

Abstract
Intrinsic apoptosis defects underlie to a large extent the extended survival of malignant B cells in chronic lymphocytic leukemia (CLL). Here, we show that the Shc family adapter p66Shc uncouples the B-cell receptor (BCR) from the Erk- and Akt-dependent survival pathways, thereby enhancing B-cell apoptosis. p66Shc expression was found to be profoundly impaired in CLL B cells compared with normal peripheral B cells. Moreover, significant differences in p66Shc expression were observed in patients with favorable or unfavorable prognosis, based on the mutational status of IGHV genes, with the lowest expression in the unfavorable prognosis group. Analysis of the expression of genes implicated in apoptosis defects of CLL showed an alteration in the balance of proapoptotic and antiapoptotic members of the Bcl-2 family in patients with CLL. Reconstitution experiments in CLL B cells, together with data obtained on B cells from p66Shc−/− mice, showed that p66Shc expression correlates with a bias in the Bcl-2 family toward proapoptotic members. The data identify p66Shc as a novel regulator of B-cell apoptosis which attenuates BCR-dependent survival signals and modulates Bcl-2 family expression. They moreover provide evidence that the p66Shc expression defect in CLL B cells may be causal to the imbalance toward the antiapoptotic Bcl-2 family members in these cells.
Overexpression of caveolin-1 in adult T-cell leukemia
Authors: Sawada Shigeki , Ishikawa Chie , Tanji Hiroe , Nakachi Sawako , Senba Masachika , Okudaira Taeko , Uchihara Jun-Nosuke , Taira Naoya , Ohshiro Kazuiku , Yamada Yasuaki , Tanaka Yuetsu , Uezato Hiroshi , Ohshima Koichi , Sasai Ken , Burgering Boudewijn M. T. , Duc Dodon Madeleine , Fujii Masahiro , Sunakawa Hajime , Mori Naoki 
Published: January 2010

AbstractCaveolin-1 is implicated in the regulation of signal pathways. Adult T-cell leukemia (ATL) is a T-cell malignancy causatively associated with human T-cell leukemia virus type 1 (HTLV-1). To determine the role of caveolin-1 in leukemogenesis, we examined caveolin-1 expression levels in HTLV-1–infected T-cell lines and ATL cells. These cells expressed high levels of caveolin-1 compared with uninfected T-cell lines and normal peripheral blood mononuclear cells (PBMCs). Caveolin-1–positive ATL cells were detected in ATL lymph nodes and skin lesions, and caveolin-1 was also detected in the plasma of patients with ATL. Infection of a human T-cell line, an epithelial cell line, and normal PBMCs with HTLV-1 induced caveolin-1 expression. The viral protein Tax transcriptionally activated caveolin-1 gene through nuclear factor-κB and cAMP response element binding protein signal pathways. HTLV-1–infected T-cell lines, and ATL cells are known to be resistant to transforming growth factor β (TGF-β)–induced growth inhibition. Caveolin-1 was colocalized with TGF-β type I receptor in HTLV-1–infected T-cell lines and suppressed TGF-β signaling. Caveolin-1 knockdown in an HTLV-1–infected T-cell line exhibited susceptibility to TGF-β. Thus, we describe a new function for Tax, repression of TGF-β signaling through caveolin-1 expression, which may play a critical role in ATL leukemogenesis.
Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms
Authors: Schaub Franz X. , Looser Renate , Li Sai , Hao-Shen Hui , Lehmann Thomas , Tichelli Andre , Skoda Radek C. 
Published: January 2010

Abstract
Somatic mutations in TET2 occur in patients with myeloproliferative neoplasms and other hematologic malignancies. It has been suggested that TET2 is a tumor suppressor gene and mutations in TET2 precede the acquisition of JAK2-V617F. To examine the order of events, we performed colony assays and genotyped TET2 and JAK2 in individual colonies. In 4 of 8 myeloproliferative neoplasm patients, we found that some colonies with mutated TET2 carried wild-type JAK2, whereas others were JAK2-V617F positive, indicating that TET2 occurred before JAK2-V617F. One of these patients carried a germline TET2 mutation. However, in 2 other patients, we obtained data compatible with the opposite order of events, with JAK2 exon 12 mutation preceding TET2 mutation in one case. Finally, in 2 of 8 patients, the TET2 and JAK2-V617F mutations defined 2 separate clones. The lack of a strict temporal order of occurrence makes it unlikely that mutations in TET2 represent a predisposing event for acquiring mutations in JAK2.
Machine learning methods for metabolic pathway prediction
Authors: Dale Joseph M , Popescu Liviu , Karp Peter D 
Published: January 2010

Abstract

Background
A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism.

Results
To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML) methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways.

Conclusions
ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations.
A pairwise residue contact area-based mean force potential for discrimination of native protein structure
Authors: Arab Shahriar , Sadeghi Mehdi , Eslahchi Changiz , Pezeshk Hamid , Sheari Armita 
Published: January 2010

Abstract

Background
Considering energy function to detect a correct protein fold from incorrect ones is very important for protein structure prediction and protein folding. Knowledge-based mean force potentials are certainly the most popular type of interaction function for protein threading. They are derived from statistical analyses of interacting groups in experimentally determined protein structures. These potentials are developed at the atom or the amino acid level. Based on orientation dependent contact area, a new type of knowledge-based mean force potential has been developed.

Results
We developed a new approach to calculate a knowledge-based potential of mean-force, using pairwise residue contact area. To test the performance of our approach, we performed it on several decoy sets to measure its ability to discriminate native structure from decoys. This potential has been able to distinguish native structures from the decoys in the most cases. Further, the calculated Z-scores were quite high for all protein datasets.

Conclusions
This knowledge-based potential of mean force can be used in protein structure prediction, fold recognition, comparative modelling and molecular recognition. The program is available at http://www.bioinf.cs.ipm.ac.ir/softwares/surfield
Intact fetal ovarian cord formation promotes mouse oocyte survival and development
Authors: Nicholas Cory R , Haston Kelly M , Pera Renee A Reijo 
Published: January 2010

Abstract
Background
Female reproductive potential, or the ability to propagate life, is limited in mammals with the majority of oocytes lost before birth. In mice, surviving perinatal oocytes are enclosed in ovarian follicles for subsequent oocyte development and function in the adult. Before birth, fetal germ cells of both sexes develop in clusters, or germline cysts, in the undifferentiated gonad. Upon sex determination of the fetal gonad, germ cell cysts become organized into testicular or ovarian cord-like structures and begin to interact with gonadal somatic cells. Although germline cysts and testicular cords are required for spermatogenesis, the role of cyst and ovarian cord formation in mammalian oocyte development and female fertility has not been determined.

Results
Here, we examine whether intact fetal ovarian germ and somatic cell cord structures are required for oocyte development using mouse gonad re-aggregation and transplantation to disrupt gonadal organization. We observed that germ cells from disrupted female gonad prior to embryonic day e13.5 completed prophase I of meiosis but did not survive following transplantation. Furthermore, re-aggregated ovaries from e13.5 to e15.5 developed with a reduced number of oocytes. Oocyte loss occurred before follicle formation and was associated with an absence of ovarian cord structure and ovary disorganization. However, disrupted ovaries from e16.5 or later were resistant to the re-aggregation impairment and supported robust oocyte survival and development in follicles.

Conclusions
Thus, we demonstrate a critical window of oocyte development from e13.5 to e16.5 in the intact fetal mouse ovary, corresponding to the establishment of ovarian cord structure, which promotes oocyte interaction with neighboring ovarian somatic granulosa cells before birth and imparts oocytes with competence to survive and develop in follicles. Because germline cyst and ovarian cord structures are conserved in the human fetal ovary, the identification of genetic components and molecular mechanisms of pre-follicle stage germ and somatic cell structures may be important for understanding human female infertility. In addition, this work provides a foundation for development of a robust fetal ovarian niche and transplantation based system to direct stem cell-derived oocyte differentiation as a potential therapeutic strategy for the treatment of infertility.
Relationship between morphological features and kinetic patterns of enhancement of the dynamic breast magnetic resonance imaging and clinico-pathological and biological factors in invasive breast cancer
Authors: Fernández-Guinea Oscar , Andicoechea Alejandro , González Luis O , González-Reyes Salomé , Merino Antonio M , Hernández Luis C , López-Muñiz Alfonso , García-Pravia Paz , Vizoso Francisco J 
Published: January 2010

Abstract

Background
To investigate the relationship between the magnetic resonance imaging (MRI) features of breast cancer and its clinicopathological and biological factors.

Methods
Dynamic MRI parameters of 68 invasive breast carcinomas were investigated. We also analyzed microvessel density (MVD), estrogen and progesterone receptor status, and expression of p53, HER2, ki67, VEGFR-1 and 2.

Results
Homogeneous enhancement was significantly associated with smaller tumor size (T1: < 2 cm) (p = 0.015). Tumors with irregular or spiculated margins had a significantly higher MVD than tumors with smooth margins (p = 0.038). Tumors showing a maximum enhancement peak at two minutes, or longer, after injecting the contrast, had a significantly higher MVD count than those which reached this point sooner (p = 0.012). The percentage of tumors with vascular invasion or high mitotic index was significantly higher among those showing a low percentage (≤ 150%) of maximum enhancement before two minutes than among those ones showing a high percentage (>150%) of enhancement rate (p = 0.016 and p = 0.03, respectively). However, there was a significant and positive association between the mitotic index and the peak of maximum intensity (p = 0.036). Peritumor inflammation was significantly associated with washout curve type III (p = 0.042).

Conclusions
Variations in the early phase of dynamic MRI seem to be associated with parameters indicatives of tumor aggressiveness in breast cancer.
Gene expression profile of androgen modulated genes in the murine fetal developing lung
Authors: Bresson Eva , Seaborn Tommy , Côté Mélissa , Cormier Geneviève , Provost Pierre R , Piedboeuf Bruno , Tremblay Yves 
Published: January 2010

AbstractBackgroundAccumulating evidences suggest that sex affects lung development. Indeed, a higher incidence of respiratory distress syndrome is observed in male compared to female preterm neonates at comparable developmental stage and experimental studies demonstrated an androgen-related delay in male lung maturation. However, the precise mechanisms underlying these deleterious effects of androgens in lung maturation are only partially understood.MethodsTo build up a better understanding of the effect of androgens on lung development, we analyzed by microarrays the expression of genes showing a sexual difference and those modulated by androgens. Lungs of murine fetuses resulting from a timely mating window of 1 hour were studied at gestational day 17 (GD17) and GD18, corresponding to the period of surge of surfactant production. Using injections of the antiandrogen flutamide to pregnant mice, we hunted for genes in fetal lungs which are transcriptionally modulated by androgens.ResultsResults revealed that 1844 genes were expressed with a sexual difference at GD17 and 833 at GD18. Many genes were significantly modulated by flutamide: 1597 at GD17 and 1775 at GD18. Datasets were analyzed by using in silico tools for reconstruction of cellular pathways. Between GD17 and GD18, male lungs showed an intensive transcriptional activity of proliferative pathways along with the onset of lung differentiation. Among the genes showing a sex difference or an antiandrogen modulation of their expression, we specifically identified androgen receptor interacting genes, surfactant related genes in particularly those involved in the pathway leading to phospholipid synthesis, and several genes of lung development regulator pathways. Among these latter, some genes related to Shh, FGF, TGF-beta, BMP, and Wnt signaling are modulated by sex and/or antiandrogen treatment.ConclusionOur results show clearly that there is a real delay in lung maturation between male and female in this period, the latter pursuing already lung maturation while the proper is not yet fully engaged in the differentiation processes at GD17. In addition, this study provides a list of genes which are under the control of androgens within the lung at the moment of surge of surfactant production in murine fetal lung.
Malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart: a case report
Authors: Kitamura Masanori , Wada Naoki , Nagata Shigenori , Iizuka Norishige , Jin Yu-Fen , Tomoeda Miki , Yuki Michiko , Naka Norifumi , Araki Nobuhito , Yutani Chikao , Tomita Yasuhiko 
Published: January 2010

Abstract
A rare case is presented of a 61-year-old man with a malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart. The primary tumor originated in the right thigh in 1982. Since then, the patient has had repeated local recurrences in spite of repeated surgical treatment and adjuvant chemotherapy. He has developed previous metastases of the lung and heart. The patient died of cardiac involvement.
Protein synthesis and degradation are required for the incorporation of modified information into the pre-existing object-location memory
Authors: Choi Jun-Hyeok , Kim Jung-Eun , Kaang Bong-Kiun 
Published: January 2010

Abstract
Although some reports indicate that protein synthesis dependent process may be induced by updating information, the role of protein synthesis and degradation in changing the content of pre-existing memory is yet unclear. In this study, we utilized an object rearrangement task, in which partial information related to a pre-existing memory is changed, promoting memory modification. Inhibitors of both protein synthesis and protein degradation impaired adequate incorporation of the altered information, each in a distinctive way. These results indicate that protein synthesis and degradation play key roles in memory modification.
An asymptomatic case of peritoneal encapsulation: case report and review of the literature
Authors: Al-Taan Omer S , Evans Martyn D , Shami Javid A 
Published: January 2010

Abstract
Peritoneal encapsulation is a rare congenital anomaly characterised by a thin membrane of peritoneum encasing the small bowel to form an accessory peritoneal sac. We present a case of peritoneal encapsulation diagnosed incidentally in an 82 year old man undergoing laparotomy for colonic cancer. The sac was easily excised and surgery was otherwise uneventful. A discussion of the case and a review of the literature are presented.
High prevalence of autoantibodies to RNA helicase A in Mexican patients with systemic lupus erythematosus
Authors: Vázquez-Del Mercado Monica , Palafox-Sánchez Claudia A , Muñoz-Valle Jose F , Orozco-Barocio Gerardo , Oregon-Romero Edith , Navarro-Hernández Rosa E , Salazar-Páramo Mario , Armendariz-Borunda Juan , Gámez-Nava Jorge I , Gonzalez-Lopez Laura , Chan Jason YF , Chan Edward KL , Satoh Minoru 
Published: January 2010

Abstract
Introduction
Autoantibodies to RNA helicase A (RHA) were reported as a new serological marker of systemic lupus erythematosus (SLE) associated with early stage of the disease. Anti-RHA and other autoantibodies in Mexican SLE patients and their correlation with clinical and immunological features were examined.

Methods
Autoantibodies in sera from 62 Mexican SLE patients were tested by immunoprecipitation of 35S-labeled K562 cell extract and enzyme-linked immunosorbent assay (anti-U1RNP/Sm, ribosomal P, β2GPI, and dsDNA). Anti-RHA was screened based on the immunoprecipitation of the 140-kDa protein, the identity of which was verified by Western blot using rabbit anti-RHA serum. Clinical and immunological characteristics of anti-RHA-positive patients were analyzed.

Results
Anti-RHA was detected in 23% (14/62) of patients, a prevalence higher than that of anti-Sm (13%, 8/62). Prevalence and levels of various autoantibodies were not clearly different between anti-RHA (+) vs. (-) cases, although there was a trend of higher levels of anti-RHA antibodies in patients without anti-U1RNP/Sm (P = 0.07). Both anti-RHA and -Sm were common in cases within one year of diagnosis; however, the prevalence and levels of anti-RHA in patients years after diagnosis did not reduce dramatically, unlike a previous report in American patients. This suggests that the high prevalence of anti-RHA in Mexican patients may be due to relatively stable production of anti-RHA.

Conclusions
Anti-RHA was detected at high prevalence in Mexican SLE patients. Detection of anti-RHA in races in which anti-Sm is not common should be clinically useful. Racial difference in the clinical significance of anti-RHA should be clarified in future studies.
Lipopolysaccharide suppresses HIV-1 replication in human monocytes by protein kinase C-dependent heme oxygenase-1 induction
Authors: Devadas Krishnakumar , Hewlett Indira K , Dhawan Subhash 
Published: January 2010

Abstract
The host factor HO-1 plays a pivotal role in LPS-mediated suppression of HIV-1 replication.
LPS is an important component of the Gram-negative bacteria cell wall. It activates monocytes and induces multiple host immune and inflammatory responses. Interestingly, in spite of inducing host-inflammatory responses, LPS also protects monocyte-derived macrophages from infection by HIV-1. In this report, we have shown that LPS treatment of human monocyte-derived macrophages markedly suppressed HIV-1 replication, even on addition to infected cells 24 h after infection. Inhibition of HIV-1 replication was associated with PKC-dependent induction of HO-1, a cytoprotective enzyme known to catabolize heme. Pretreatment with the PKC inhibitor Go 6976 not only substantially inhibited LPS-mediated induction of HO-1 but also attenuated LPS-induced suppression of HIV replication. Significant reduction of HIV replication by inhibitors of JNK, NF-κB, and PI3K was independent of a LPS-mediated anti-HIV effect. Specificity of HO-1 was confirmed by substantial reversal of LPS-induced viral replication by pretreatment of cells with SnPP IX, an inhibitor of HO-1 enzyme activity. These results demonstrate a previously undefined function of HO-1 as a host defense mechanism in LPS-mediated inhibition of HIV-1 replication.
Nuclear Factor-κB Contributes to Anaplastic Thyroid Carcinomas through Up-Regulation of miR-146a
Authors: Pacifico Francesco , Crescenzi Elvira , Mellone Stefano , Iannetti Alessio , Porrino Nunzio , Liguoro Domenico , Moscato Fortunato , Grieco Michele , Formisano Silvestro , Leonardi Antonio 
Published: January 2010

Abstract
Context: Micro-RNAs (miRNAs) have been recently involved in the modulation of several biological activities including cancer. Many human tumors show deregulated expression of miRNAs targeting oncogenes and/or tumor suppressors, thus identifying miRNAs as new molecular targets for cancer therapy.
Objectives: Nuclear factor (NF)-κB is strongly activated in human anaplastic thyroid carcinomas (ATCs). Because the regulation of miRNA expression is under control of RNA polymerase II-dependent transcription factors, we stably inactivated NF-κB in the ATC-derived FRO cell line and analyzed its miRNA profile in comparison with the parental counterpart by using a miRNA chip microarray.
Results: The analysis revealed that a number of miRNAs were differentially expressed in the two cell lines. Among others, the miR-146a showed a strong down-regulation that was confirmed by quantitative real time RT-PCR. The expression of miR-146a was almost undetectable in mouse embryonic fibroblasts isolated from the RelA knockout mice and was restored after reexpression of RelA, thus indicating that miR-146a transcription was controlled by NF-κB. The inhibition of miR-146a expression in FRO cells decreased their oncogenic potential and increased the susceptibility to chemotherapeutic drug-induced apoptosis. No difference was found in the growth rate between untransfected and miR-146a-null FRO cells. Importantly, the miR-146a resulted in overexpression of human ATC specimens compared with the normal thyroid tissue.
Conclusions: Our results show that NF-κB contributes to anaplastic thyroid cancer up-regulating the expression of miR-146a.