bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reprogramming T Lymphocytes for Melanoma Adoptive Immunotherapy by T-Cell Receptor Gene Transfer with Lentiviral Vectors
Authors: Bobisse Sara , Rondina Maria , Merlo Anna , Tisato Veronica , Mandruzzato Susanna , Amendola Mario , Naldini Luigi , Willemsen Ralph A. , Debets Reno , Zanovello Paola , Rosato Antonio 
Published: December 2009

Abstract
T-cell receptor (TCR) gene transfer for cancer immunotherapy is limited by the availability of large numbers of tumor-specific T cells. TCR α and β chains were isolated from a highly lytic HLA-A2–restricted cytotoxic T lymphocyte (CTL) clone recognizing the melanoma-associated Melan-A/MART-1 antigen and inserted into a lentiviral vector carrying a bidirectional promoter capable of robust and coordinated expression of the two transgenes. Lentiviral vector–based gene delivery systems have shown increased transfer efficiency and transgene expression compared with the widely used γ-retroviral vectors. This vector performed more efficiently than a γ-retrovirus–based vector containing the same expression cassette, resulting in a T-cell population with 60% to 80% of transgenic TCR expression with mainly CD8+ intermediate effector phenotype. Transgenic T cells specifically produced cytokine in response to and killed antigen-expressing melanoma cells, retained an overlapping functional avidity in comparison with the TCR donor CTL clone, and exerted significant therapeutic effects in vivo upon adoptive transfer in melanoma-bearing severe combined immunodeficient mice. Optical imaging showed their accumulation in the tumor site. Overall, our results indicate that lentiviral vectors represent a valid tool for stable and high-intensity expression of transgenic TCR and support clinical exploitation of this approach for therapeutic application. [Cancer Res 2009;69(24):9385–94]
Gene Networks and microRNAs Implicated in Aggressive Prostate Cancer
Authors: Wang Liang , Tang Hui , Thayanithy Venugopal , Subramanian Subbaya , Oberg Ann L. , Cunningham Julie M. , Cerhan James R. , Steer Clifford J. , Thibodeau Stephen N. 
Published: December 2009

Abstract
Prostate cancer, a complex disease, can be relatively harmless or extremely aggressive. To identify candidate genes involved in causal pathways of aggressive prostate cancer, we implemented a systems biology approach by combining differential expression analysis and coexpression network analysis to evaluate transcriptional profiles using lymphoblastoid cell lines from 62 prostate cancer patients with aggressive phenotype (Gleason grade ≥ 8) and 63 prostate cancer patients with nonaggressive phenotype (Gleason grade ≤ 5). From 13,935 mRNA genes and 273 microRNAs (miRNA) tested, we identified significant differences in 1,100 mRNAs and 7 miRNAs with a false discovery rate (FDR) of &lt;0.01. We also identified a coexpression module demonstrating significant association with the aggressive phenotype of prostate cancer (P = 3.67 × 10−11). The module of interest was characterized by overrepresentation of cell cycle–related genes (FDR = 3.50 × 10−50). From this module, we further defined 20 hub genes that were highly connected to other genes. Interestingly, 5 of the 7 differentially expressed miRNAs have been implicated in cell cycle regulation and 2 (miR-145 and miR-331-3p) are predicted to target 3 of the 20 hub genes. Ectopic expression of these two miRNAs reduced expression of target hub genes and subsequently resulted in cell growth inhibition and apoptosis. These results suggest that cell cycle is likely to be a molecular pathway causing aggressive phenotype of prostate cancer. Further characterization of cell cycle–related genes (particularly, the hub genes) and miRNAs that regulate these hub genes could facilitate identification of candidate genes responsible for the aggressive phenotype and lead to a better understanding of prostate cancer etiology and progression. [Cancer Res 2009;69(24):9490–7]
Autocrine Bone Morphogenetic Protein-9 Signals through Activin Receptor-like Kinase-2/Smad1/Smad4 to Promote Ovarian Cancer Cell Proliferation
Authors: Herrera Blanca , van Dinther Maarten , ten Dijke Peter , Inman Gareth J. 
Published: December 2009

Abstract
Bone morphogenetic proteins (BMPs) act as central regulators of ovarian physiology and may be involved in ovarian cancer development. In an effort to understand these processes, we characterized transforming growth factor β/BMP receptor and Smad expression in immortalized ovarian surface epithelial cells and a panel of ovarian cancer cell lines. These studies prompted us to evaluate the potential role of BMP9 signaling in ovarian cancer. Using small interfering RNA, ligand trap, inhibitor, and ligand stimulation approaches, we show that BMP9 acts as a proliferative factor for immortalized ovarian surface epithelial cells and ovarian cancer cell lines, signaling predominantly through an ALK2/Smad1/Smad4 pathway rather than through ALK1, the major BMP9 receptor in endothelial cells. Importantly, we find that some ovarian cancer cell lines have gained autocrine BMP9 signaling that is required for proliferation. Furthermore, immunohistochemistry analysis of an ovarian cancer tissue microarray reveals that ∼25% of epithelial ovarian cancers express BMP9, whereas normal human ovarian surface epithelial specimens do not. Our data indicate that BMP9 signaling through ALK2 may be a novel therapeutic target in ovarian cancer. [Cancer Res 2009;69(24):9254–62]
Differential Thymidylate Synthase Expression in Different Variants of Large-Cell Carcinoma of the Lung
Authors: Monica Valentina , Scagliotti Giorgio V. , Ceppi Paolo , Righi Luisella , Cambieri Alberto , Lo Iacono Marco , Saviozzi Silvia , Volante Marco , Novello Silvia , Papotti Mauro 
Published: December 2009

Abstract
Purpose: In non–small cell lung cancer, higher thymidylate synthase (TS) levels have been reported in squamous cell carcinoma (SCC) compared with adenocarcinoma (ADC). Data on TS expression in large-cell carcinoma (LCC) are scanty.
Experimental Design: TS mRNA and protein levels were analyzed in 42 surgical cases of pulmonary LCC, including 8 large-cell neuroendocrine carcinomas, and were compared with controls represented by ADC (n = 41), SCC (n = 30), and small-cell lung carcinoma (SCLC; n = 33). TS levels were also correlated with the expression of Ki67 and E2F1. Moreover, the reliability of TS expression analysis was assessed in 22 matched cytologic and surgical specimens of non–small cell lung cancer.
Results: TS mRNA levels of LCC were comparable with those of control SCC, but significantly higher than those of ADC (P &lt; 0.001) and lower than SCLC (P &lt; 0.001). A correlation between TS mRNA and protein levels was observed in control ADC and SCC, but not in LCC. Large-cell neuroendocrine carcinomas had the highest TS expression, whereas in non-neuroendocrine LCCs, TS protein levels were significantly higher (P = 0.02) in LCC immunoreactive for p63 and desmocollin3 (markers of squamous differentiation) than those expressing TTF-1 (a marker of ADC). Both E2F1 and Ki67 levels were not correlated with TS in LCCs. Finally, a linear correlation in TS protein levels was observed between matched cytologic and surgical specimens.
Conclusion: The pulmonary LCC immunoprofile may resemble that of SCCs or ADCs. This immunoprofile is associated with differential TS expression levels, which may support a more appropriate therapeutic strategy decision. (Clin Cancer Res 2009;15(24):7547–52)
Barriers to Integrating Gene Profiling for Stage II Colon Cancer
Authors: Kopetz Scott , Abbruzzese James L. 
Published: December 2009

Abstract
The identification of high-risk subsets of colon cancers has undergone extensive study over the years, and multidimensional gene signatures have shown promise for colon cancer. However, several hurdles need to be overcome in order to show the benefit of this approach and successfully apply them to the clinic. (Clin Cancer Res 2009;15(24):7451–2)
Nonfrontier Deforestation in the Eastern Amazon
Authors: de Almeida Arlete Silva , Stone Thomas A. , Vieira Ima Célia G. , Davidson Eric A. 
Published: December 2009

AbstractWhile interest in Amazonian deforestation mostly focuses on frontier areas, the amount of forest cover in areas already dominated by human settlement is also changing. Secondary forests play an increasingly important role for maintaining genetic diversity, hydrological functioning, and greenhouse gas emissions of altered landscapes, but secondary forests are also being converted to more intensive agricultural uses. Five dates of Landsat imagery from 1984 to 2002 were analyzed, covering 8000 km2 of the Zona Bragantina of the eastern part of the Brazilian state of Pará, which underwent its most intensive wave of deforestation several decades ago. However, even in this area of relatively long-term human occupation, ongoing decreases of forest cover were found, both in the small remaining areas of mature forest and in the more widespread areas of secondary forests, as human population increased and land use intensified. Although there was an initial increase in the area of secondary forest from 1984 to 1994, there has been a steady decline since then, from 75% secondary forest cover in 1994 to 54% in 2002. The amount of pasture was relatively stable from 1984 to 1994 but more recently has shown a steady increase, reaching 37% cover in 2002. The average rate of carbon loss over the 18-yr study period was 0.9 Mg C ha−1 yr−1 for the 8000 km2 study area. Forests in this long-settled region of eastern Amazonia continue to be degraded, resulting in the loss of ecosystem services and carbon stocks due to continued land-use change.
Spatial and Temporal Distribution of Latent Heating in the South Asian Monsoon Region
Authors: Zuluaga Manuel D. , Hoyos Carlos D. , Webster Peter J. 
Published: December 2009

Abstract
Information from the Tropical Rainfall Measuring Mission (TRMM) level 3 monthly 0.5° × 0.5° Convective and Stratiform Heating (CSH) product and TRMM Microwave Imager (TMI) 2A12 datasets is used to examine the four-dimensional latent heating (LH) structure over the Asian monsoon region between 1998 and 2006. High sea surface temperatures, ocean–land contrasts, and complex terrain produce large precipitation and atmospheric heating rates whose spatial and temporal characteristics are relatively undocumented. Analyses show interannual and intraseasonal LH variations with a large fraction of the interannual variability induced by internal intraseasonal variability. Also, the analyses identify a spatial dipole of LH anomalies between the equatorial Indian Ocean and the Bay of Bengal regions occurring during the summer active and suppressed phases of the monsoon intraseasonal oscillation. Comparisons made between the TRMM CSH and TMI 2A12 datasets indicate differences in the shape of the vertical profile of LH. A comparison of TRMM LH retrievals with sounding budget observations made during the South China Sea Monsoon Experiment shows a high correspondence in the timing of positive LH episodes during the rainy periods. Negative values of atmospheric heating, associated with radiative cooling and with upper-tropospheric cooling from nonsurface-precipitating clouds, are not captured by either of the TRMM datasets. In summary, LH algorithms based on satellite information are capable of representing the spatial and temporal characteristics of the vertically integrated heating in the Asian monsoon region. However, the vertical distribution of atmospheric heating is not captured accurately throughout different convective phases. It is suggested that satellite-derived radiative heating/cooling products are needed to supplement the LH products in order to give a better overall depiction of atmospheric heating.
Characterizing Warm-ENSO Variability in the Equatorial Pacific: An OLR Perspective*,+
Authors: Chiodi A. M. , Harrison D. E. 
Published: December 2009

Abstract
It is shown that space–time smoothed outgoing longwave radiation (OLR) indices of equatorial Pacific seasonal variability can give an interestingly different perspective on El Niño than is obtained from sea surface temperature (SST) indices or the Southern Oscillation index (SOI). In particular, the index defined by averaging over an eastern-central region exhibits strong event like character—more so than in any other El Niño–Southern Oscillation (ENSO) warm-phase index known to the authors. Although the historical record for OLR is much shorter than for SST or SOI, OLR offers a direct connection to anomalous atmospheric heating. It is suggested that the years identified as events by this OLR index deserve particular recognition; and it is noteworthy that they all meet the criteria for “El Niño” years. Other years, whose warm-ENSO status differs depending upon the index favored, are not particularly distinctive from an OLR perspective, and a case could be made that either the other years do not deserve special classification or that they should be identified as different from the OLR-distinguished El Niño years.
Climate Adjustments over Africa Accompanying the Indian Monsoon Onset
Authors: Camberlin P. , Fontaine B. , Louvet S. , Oettli P. , Valimba P. 
Published: December 2009

Abstract
Rainfall and circulation changes accompanying the Indian monsoon onset are examined, focusing on the African continent and neighboring areas. The Indian Meteorological Department official monsoon onset dates over Kerala (MOK; on average on 1 June) are used. Composites are formed at a pentad (5 days) time scale to compare pre- and postonset conditions. Climate Prediction Center (CPC) Merged Analysis of Precipitation (CMAP) data for 1979–2007 indicate that a substantial rainfall decrease over several parts of Africa is associated with MOK. Significant rainfall anomalies, after removal of the mean seasonal cycle, are found in eastern Africa and the nearby western Indian Ocean. Indian monsoon onset dates over the period 1958–2001 are correlated at 0.55 with the cessation dates of the March–May rainy season (the long rains) averaged over Kenya and northern Tanzania. The rainy season cessation leads the onset by 12 days, on average. An early cessation of the March–May rains tends to precede an early onset over India. Over East Africa, the rainfall decrease is associated with a strengthening of the southerly winds (Somali jet) shortly before MOK, enhancing wind divergence and wind shear.
A weaker rainfall signal is noted over western Africa and the Gulf of Guinea. MOK coincides with a pause in the progression of the West African monsoon. The pause is associated with anomalous descent over the Sahel, culminating two to three pentads after MOK. Composite maps further indicate that MOK is followed over much of the African continent by a sea level pressure rise and, between India and North Africa, a westward propagation of easterly wind and positive geopotential height anomalies. Many of these signals are associated with Madden–Julian oscillations, but independent features, suggesting Rossby wave propagation over North Africa, are also found to connect MOK and West Africa. Overall, these results are indicative of a large-scale adjustment of the atmospheric dynamics across both eastern and western Africa in conjunction with the monsoon onset over India.
Ras-induced reactive oxygen species promote growth factor–independent proliferation in human CD34+ hematopoietic progenitor cells
Authors: Hole Paul S. , Pearn Lorna , Tonks Amanda J. , James Philip E. , Burnett Alan K. , Darley Richard L. , Tonks Alex 
Published: December 2009

Abstract
Excessive production of reactive oxygen species (ROS) is a feature of human malignancy and is often triggered by activation of oncogenes such as activated Ras. ROS act as second messengers and can influence a variety of cellular process including growth factor responses and cell survival. We have examined the contribution of ROS production to the effects of N-RasG12D and H-RasG12V on normal human CD34+ progenitor cells. Activated Ras strongly up-regulated the production of both superoxide and hydrogen peroxide through the stimulation of NADPH oxidase (NOX) activity, without affecting the expression of endogenous antioxidants or the production of mitochondrially derived ROS. Activated Ras also promoted both the survival and the growth factor–independent proliferation of CD34+ cells. Using oxidase inhibitors and antioxidants, we found that excessive ROS production by these cells did not contribute to their enhanced survival; rather, ROS promoted their growth factor–independent proliferation. Although Ras-induced ROS production specifically activated the p38MAPK oxidative stress response, this failed to induce expression of the cell-cycle inhibitor, p16INK4A; instead, ROS promoted the expression of D cyclins. These data are the first to show that excessive ROS production in the context of oncogene activation can promote proliferative responses in normal human hematopoietic progenitor cells.
Trisomy of Erg is required for myeloproliferation in a mouse model of Down syndrome
Authors: Ng Ashley P. , Hyland Craig D. , Metcalf Donald , Carmichael Catherine L. , Loughran Stephen J. , Di Rago Ladina , Kile Benjamin T. , Alexander Warren S. 
Published: December 2009

Abstract
Down syndrome is characterized by multiple phenotypic manifestations associated with trisomy of chromosome 21. The transient myeloproliferative disorder and acute megakaryocytic leukemia associated with Down syndrome are uniquely associated with mutations in the transcription factor GATA1; however, the identity of trisomic genes on chromosome 21 that predispose to these hematologic disorders remains unknown. Using a loss-of-function allele, we show that specific reduction to functional disomy of the Erg gene corrects the pathologic and hematologic features of myeloproliferation in the Ts(1716)65Dn mouse model of Down syndrome, including megakaryocytosis and progenitor cell expansion. Our data provide genetic evidence establishing the need for Erg trisomy for myeloproliferation in Ts(1716)65Dn mice and imply that increased ERG gene dosage may be a key consequence of trisomy 21 that can predispose to malignant hematologic disorders in Down syndrome.
Melav2, an elav-like gene, is essential for spermatid differentiation in the flatworm Macrostomum lignano
Authors: Sekii Kiyono , Salvenmoser Willi , De Mulder Katrien , Scharer Lukas , Ladurner Peter 
Published: December 2009

Abstract

Background
Failure of sperm differentiation is one of the major causes of male sterility. During spermiogenesis, spermatids undergo a complex metamorphosis, including chromatin condensation and cell elongation. Although the resulting sperm morphology and property can vary depending on the species, these processes are fundamental in many organisms. Studying genes involved in such processes can thus provide important information for a better understanding of spermatogenesis, which might be universally applied to many other organisms.

Results
In a screen for genes that have gonad-specific expression we isolated an elav-like gene, melav2, from Macrostomum lignano, containing the three RNA recognition motifs characteristic of elav-like genes. We found that melav2 mRNA was expressed exclusively in the testis, as opposed to the known elav genes, which are expressed in the nervous system. The RNAi phenotype of melav2 was characterized by an aberrant spermatid morphology, where sperm elongation often failed, and an empty seminal vesicle. Melav2 RNAi treated worms were thus male-sterile. Further analysis revealed that in melav2 RNAi treated worms precocious chromatin condensation occurred during spermatid differentiation, resulting in an abnormally tightly condensed chromatin and large vacuoles in round spermatids. In addition, immunostaining using an early-spermatid specific antibody revealed that melav2 RNAi treated worms had a larger amount of signal positive cells, suggesting that many cells failed the transition from early spermatid stage.

Conclusion
We characterize a new function for elav-like genes, showing that melav2 plays a crucial role during spermatid differentiation, especially in the regulation of chromatin condensation and/or cell elongation.
Cytosolic N-terminal arginine-based signals together with a luminal signal target a type II membrane protein to the plant ER
Authors: Boulaflous Aurélia , Saint-Jore-Dupas Claude , Herranz-Gordo Marie-Carmen , Pagny-Salehabadi Sophie , Plasson Carole , Garidou Frédéric , Kiefer-Meyer Marie-Christine , Ritzenthaler Christophe , Faye Loïc , Gomord Véronique 
Published: December 2009

Abstract

Background
In eukaryotic cells, the membrane compartments that constitute the exocytic pathway are traversed by a constant flow of lipids and proteins. This is particularly true for the endoplasmic reticulum (ER), the main "gateway of the secretory pathway", where biosynthesis of sterols, lipids, membrane-bound and soluble proteins, and glycoproteins occurs. Maintenance of the resident proteins in this compartment implies they have to be distinguished from the secretory cargo. To this end, they must possess specific ER localization determinants to prevent their exit from the ER, and/or to interact with receptors responsible for their retrieval from the Golgi apparatus. Very few information is available about the signal(s) involved in the retention of membrane type II protein in the ER but it is generally accepted that sorting of ER type II cargo membrane proteins depends on motifs mainly located in their cytosolic tails.

Results
Here, using Arabidopsis glucosidase I as a model, we have identified two types of signals sufficient for the location of a type II membrane protein in the ER. A first signal is located in the luminal domain, while a second signal corresponds to a short amino acid sequence located in the cytosolic tail of the membrane protein. The cytosolic tail contains at its N-terminal end four arginine residues constitutive of three di-arginine motifs (RR, RXR or RXXR) independently sufficient to confer ER localization. Interestingly, when only one di-arginine motif is present, fusion proteins are located both in the ER and in mobile punctate structures, distinct but close to Golgi bodies. Soluble and membrane ER protein markers are excluded from these punctate structures, which also do not colocalize with an ER-exit-site marker. It is hypothesized they correspond to sites involved in Golgi to ER retrotransport.

Conclusion
Altogether, these results clearly show that cytosolic and luminal signals responsible for ER retention could coexist in a same type II membrane protein. These data also suggest that both retrieval and retention mechanisms govern protein residency in the ER membrane. We hypothesized that mobile punctate structures not yet described at the ER/Golgi interface and tentatively named GERES, could be involved in retrieval mechanisms from the Golgi to the ER.