bluuebunny/crossref_metadata_2025_split huggingface dataset:
A High Molecular Weight Melanoma-Associated Antigen–Specific Chimeric Antigen Receptor Redirects Lymphocytes to Target Human Melanomas
Authors: Burns William R. , Zhao Yangbing , Frankel Timothy L. , Hinrichs Christian S. , Zheng Zhili , Xu Hui , Feldman Steven A. , Ferrone Soldano , Rosenberg Steven A. , Morgan Richard A. 
Published: April 2010

Abstract
Immunotherapy, particularly the adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL), is a very promising therapy for metastatic melanoma. Some patients unable to receive TIL have been successfully treated with autologous peripheral blood lymphocytes (PBL), genetically modified to express human leukocyte antigen (HLA) class I antigen–restricted, melanoma antigen–reactive T-cell receptors; however, substantial numbers of patients remain ineligible due to the lack of expression of the restricting HLA class I allele. We sought to overcome this limitation by designing a non–MHC-restricted, chimeric antigen receptor (CAR) targeting the high molecular weight melanoma-associated antigen (HMW-MAA), which is highly expressed on more than 90% of human melanomas but has a restricted distribution in normal tissues. HMW-MAA–specific CARs containing an antigen recognition domain based on variations of the HMW-MAA–specific monoclonal antibody 225.28S and a T-cell activation domain based on combinations of CD28, 4-1BB, and CD3ζ activation motifs were constructed within a retroviral vector to allow stable gene transfer into cells and their progeny. Following optimization of the HMW-MAA–specific CAR for expression and function in human PBL, these gene-modified T cells secreted cytokines, were cytolytic, and proliferated in response to HMW-MAA–expressing cell lines. Furthermore, the receptor functioned in both CD4+ and CD8+ cells, was non–MHC restricted, and reacted against explanted human melanomas. To evaluate this HMW-MAA–specific CAR in patients with metastatic melanoma, we developed a clinical-grade retroviral packaging line. This may represent a novel means to treat the majority of patients with advanced melanoma, most notably those unable to receive current ACT therapies. Cancer Res; 70(8); 3027–33. ©2010 AACR.
Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer
Authors: Ślusarz Anna , Shenouda Nader S. , Sakla Mary S. , Drenkhahn Sara K. , Narula Acharan S. , MacDonald Ruth S. , Besch-Williford Cynthia L. , Lubahn Dennis B. 
Published: April 2010

Abstract
Many botanical compounds have been proposed to prevent cancer. We investigated the cancer treatment and prevention abilities of apigenin, baicalein, curcumin, epigallocatechin 3-gallate (EGCG), genistein, quercetin, and resveratrol both in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice as well as in vitro in prostate cancer cell lines. In our experiments, these seven compounds act similarly to the Hedgehog antagonist cyclopamine, a teratogenic plant alkaloid, which had been previously shown to “cure” prostate cancer in a mouse xenograft model. With IC50 values ranging from &lt;1 to 25 μmol/L, these compounds can inhibit Gli1 mRNA concentration by up to 95% and downregulate Gli reporter activity by 80%. We show that four compounds, genistein, curcumin, EGCG, and resveratrol, inhibit Hedgehog signaling as monitored by real-time reverse transcription-PCR analysis of Gli1 mRNA concentration or by Gli reporter activity. Three compounds, apigenin, baicalein, and quercetin, decreased Gli1 mRNA concentration but not Gli reporter activity. Our results show that these compounds are also able to reduce or delay prostate cancer in vivo in TRAMP mice. All seven compounds, when fed in combination as pure compounds or as crude plant extracts, inhibit well-differentiated carcinoma of the prostate by 58% and 81%, respectively. In vitro, we show that all seven compounds also inhibit growth in human and mouse prostate cancer cell lines. Mechanistically, we propose the Hedgehog signaling pathway to be a direct or indirect target of these compounds. These botanicals at pharmacologic concentrations are potentially safer and less expensive alternatives to cyclopamine and its pharmaceutical analogues for cancer therapy. Cancer Res; 70(8); 3382–90. ©2010 AACR.
A Second Genetic Variant on Chromosome 15q24-25.1 Associates with Lung Cancer
Authors: Liu Pengyuan , Yang Ping , Wu Xifeng , Vikis Haris G. , Lu Yan , Wang Yian , Schwartz Ann G. , Pinney Susan M. , de Andrade Mariza , Gazdar Adi , Gaba Colette , Mandal Diptasri , Lee Juwon , Kupert Elena , Seminara Daniela , Minna John , Bailey-Wilson Joan E. , Spitz Margaret , Amos Christopher I. , Anderson Marshall W. , You Ming 
Published: April 2010

Abstract
A common variant on chromosomal region 15q24-25.1, marked by rs1051730, was found to be associated with lung cancer risk. Here, we attempted to confirm the second variant on 15q24-25.1 in several large sporadic lung cancer populations and determined what percentage of additional risk for lung cancer is due to the genetic effect of the second variant. SNPs rs1051730 and rs481134 were genotyped in 2,818 lung cancer cases and 2,766 controls from four populations. Joint analysis of these two variants (rs1051730 and rs481134) on 15q24-25.1 identified three major haplotypes (G_T, A_C, and G_C) and provided stronger evidence for association of 15q24-25.1 with lung cancer (P = 9.72 × 10−9). These two variants represent three levels of risk associated with lung cancer. The most common haplotype G_T is neutral; the haplotype A_C is associated with increased risk for lung cancer with 5.0% higher frequency in cases than in controls [P = 1.68 × 10−7; odds ratio (OR), 1.24; 95% confidence interval (95% CI), 1.14–1.35]; whereas the haplotype G_C is associated with reduced risk for lung cancer with 4.4% lower frequency in cases than in controls (P = 7.39 × 10−7; OR, 0.80; 95% CI, 0.73–0.87). We further showed that these two genetic variants on 15q24-25.1 independently influence lung cancer risk (rs1051730: P = 4.42 × 10−11; OR, 1.60; 95% CI, 1.46–1.74; rs481134: P = 7.01 × 10−4; OR, 0.81; 95% CI, 0.72–0.92). The second variant on 15q24-25.1, marked by rs481134, explains an additional 13.2% of population attributable risk for lung cancer. Cancer Res; 70(8); 3128–35. ©2010 AACR.
Immune Promotion of Epithelial-mesenchymal Transition and Generation of Breast Cancer Stem Cells
Authors: Reiman Jennifer M. , Knutson Keith L. , Radisky Derek C. 
Published: April 2010

Abstract
Elements of the immune system act as intimate regulators of cancer progression, inhibiting early stages of tumor growth, through immunosurveillance while facilitating later stages of tumor progression. Recent findings have revealed that activated CD8 T cells can stimulate mammary epithelial tumor cells to undergo epithelial-mesenchymal transition (EMT) and to acquire the greatly increased tumorigenic capability and chemotherapeutic resistance of breast cancer stem cells (BCSC). These studies provide a window to understanding how BCSC arise and are maintained within tumors, and how to best target these processes for therapeutic benefit. Cancer Res; 70(8); 3005–8. ©2010 AACR.
Blockade of CCN6 (WISP3) Activates Growth Factor–Independent Survival and Resistance to Anoikis in Human Mammary Epithelial Cells
Authors: Huang Wei , Gonzalez Maria E. , Toy Kathy A. , Banerjee Mousumi , Kleer Celina G. 
Published: April 2010

Abstract
CCN6 is a secreted cysteine-rich matricellular protein (36.9 kDa) that exerts growth-inhibitory functions in breast cancer. Reduction or loss of CCN6 protein has been reported in invasive carcinomas of the breast with lymph node metastasis and in inflammatory breast cancer. However, the mechanism by which CCN6 loss promotes breast cancer growth remains to be defined. In the present study, we developed lentiviral-mediated short hairpin RNA CCN6 knockdown (KD) in nontumorigenic mammary epithelial cells MCF10A and HME. We discovered that CCN6 KD protects mammary epithelial cells from apoptosis and activates growth factor–independent survival. In the absence of exogenous growth factors, CCN6 KD was able to promote growth under anchorage-independent conditions and triggered resistance to detachment-induced cell death (anoikis). On serum starvation, CCN6 KD was sufficient for activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Growth factor–independent cell survival was stunted in CCN6 KD cells when treated with either human recombinant CCN6 protein or the PI3K inhibitor LY294002. Targeted inhibition of Akt isoforms revealed that the survival advantage rendered by CCN6 KD requires specific activation of Akt-1. The relevance of our studies to human breast cancer is highlighted by the finding that low CCN6 protein levels are associated with upregulated expression of phospho-Akt-1 (Ser473) in 21% of invasive breast carcinomas. These results enable us to pinpoint one mechanism by which CCN6 controls survival of breast cells mediated by the PI3K/Akt-1 pathway. Cancer Res; 70(8); 3340–50. ©2010 AACR.
Cancer Inhibition through Circadian Reprogramming of Tumor Transcriptome with Meal Timing
Authors: Li Xiao-Mei , Delaunay Franck , Dulong Sandrine , Claustrat Bruno , Zampera Sinisa , Fujii Yoshiro , Teboul Michèle , Beau Jacques , Lévi Francis 
Published: April 2010

Abstract
Circadian disruption accelerates cancer progression, whereas circadian reinforcement could halt it. Mice with P03 pancreatic adenocarcinoma (n = 77) were synchronized and fed ad libitum (AL) or with meal timing (MT) from Zeitgeber time (ZT) 2 to ZT6 with normal or fat diet. Tumor gene expression profiling was determined with DNA microarrays at endogenous circadian time (CT) 4 and CT16. Circadian mRNA expression patterns were determined for clock genes Rev-erbα, Per2, and Bmal1, cellular stress genes Hspa8 and Cirbp, and cyclin A2 gene Ccna2 in liver and tumor. The 24-hour patterns in telemetered rest-activity and body temperature and plasma corticosterone and insulin-like growth factor-I (IGF-I) were assessed. We showed that MT inhibited cancer growth by ∼40% as compared with AL (P = 0.011) irrespective of calorie intake. Clock gene transcription remained arrhythmic in tumors irrespective of feeding schedule or diet. Yet, MT upregulated or downregulated the expression of 423 tumor genes, according to CT. Moreover, 36 genes involved in cellular stress, cell cycle, and metabolism were upregulated at one CT and downregulated 12 h apart. MT induced &gt;10-fold circadian expression of Hspa8, Cirbp, and Ccna2 in tumors. Corticosterone or IGF-I patterns played no role in tumor growth inhibition. In contrast, MT consistently doubled the circadian amplitude of body temperature. Peak and trough respectively corresponded to peak expressions of Hspa8 and Cirbp in tumors. The reinforcement of the host circadian timing system with MT induced 24-hour rhythmic expression of critical genes in clock-deficient tumors, which translated into cancer growth inhibition. Targeting circadian clocks represents a novel potential challenge for cancer therapeutics. Cancer Res; 70(8); 3351–60. ©2010 AACR.
Receptive Reason: Alexander of Aphrodisias on Material Intellect
Authors: Tuominen Miira 
Published: April 2010

AbstractAccording to Alexander of Aphrodisias, our potential intellect is a purely receptive capacity. Alexander also claims that, in order for us to actualise our intellectual potentiality, the intellect needs to abstract what is intelligible from enmattered perceptible objects. Now a problem emerges: How is it possible for a purely receptive capacity to perform such an abstraction? It will be argued that even though Alexander’s reaction to this question causes some tension in his theory, the philosophical motivation for it is a sound one. Rather than a calculation of actualities and potentialities, the doctrine of receptivity is supposed to explain how human beings come to grasp universal aspects of reality in an accurate manner.
The bay'a: Modern Political Uses of Islamic Ritual in the Arab World
Authors: Podeh Elie 
Published: April 2010

AbstractAccording to Islamic tradition, the bay'a (translated as investiture or an oath of allegiance) is an act by which a certain number of persons, acting individually or collectively, recognize the authority of another person as the head of a Muslim state. This article analyzes the different modern political uses of the bay'a in the Arab world. Based on research of seven Arab case studies—the Kingdom of Hijaz, Iraq, Syria, Jordan, Egypt, Lebanon and Saudi Arabia, the article presents three arguments: First, the bay'a evolved into an elastic term politically used in a variety of ways by different Arab regimes. Second, the evoking of the bay'a ritual has often been a response to a domestic necessity or crisis. Finally, the use of this traditional ritual, along modern Western symbolic artifacts, is an indication of the evolving hybrid nature of the Arab political culture, based on a market of a mixed reservoir of foreign and local rituals and symbols. The interplay between foreign and local artifacts depends on the state's specific historical circumstances, which include also the impact of the colonial period. Ultimately, the modern uses of the bay'a demonstrate that modernity, in its Western version, has not been adopted wholesale. The bay'a ritual has been kept almost intact only in Saudi Arabia—a territory which did not go through the colonial experience. In contrast, Iraq, Syria and Jordan, which were under colonial rule, used an adapted version of this instrument on a temporary and utilitarian basis.
The DECISIONS Study: A Nationwide Survey of United States Adults Regarding 9 Common Medical Decisions
Authors: Zikmund-Fisher Brian J. , Couper Mick P. , Singer Eleanor , Levin Carrie A. , Fowler Floyd J. , Ziniel Sonja , Ubel Peter A. , Fagerlin Angela 
Published: April 2010

Background Patient involvement is required before patients’ preferences can be reflected in the medical care they receive. Furthermore, patients are a vital link between physicians’ assessments of patients’ needs and actual implementation of appropriate care. Yet no study has specifically examined how and when a representative sample of patients considered, discussed, and made medical decisions. Objective To identify decision prevalence and decision-making processes regarding 1) initiation of prescription medications for hypertension, hypercholesterolemia, or depression; 2) screening tests for colorectal, breast, or prostate cancer; and 3) surgeries for knee or hip replacement, cataracts, or lower back pain. Design Computer-assisted telephone interview survey. Setting Nationally representative sample of US adults in households with telephones. Participants 3010 English-speaking adults age 40 and older identified using a stratified random sample of telephone numbers. Measurements Estimated prevalence of medical decisions, defined as the patient having initiated medications, been screened, or had surgery within the past 2 years or having discussed these actions with a health care provider during the same interval, as well as decision-specific data regarding patient knowledge, attitudes and patient-provider interactions. Results 82.2% of the target population reported making at least 1 medical decision in the preceding 2 years. The proportion of decisions resulting in patient action varied dramatically both across decision type (medications [61 %] v. screening [83%] v. surgery [44%]; P < 0.001), and within each category (e.g., blood pressure medications [76%] v. cholesterol medications [55%] vs. depression medications [48%]; P < 0.001). Respondents reported making more decisions if they had a primary care provider or poorer health status and fewer decisions if they had lower education, were male, or were under age 50. Limitations Retrospective self-reports may incorporate recall biases. Conclusions Medical decisions with significant life-saving, quality of life, and cost implications are a pervasive part of life for most US adults. The DECISIONS dataset provides a rich research environment for exploring factors influencing when and how patients make common medical decisions.
Recognising ‘social’ and ‘non-social’ emotions in self and others: A study of autism
Authors: Williams David , Happé Francesca 
Published: April 2010

Studies of emotion processing in autism have produced mixed results, with fewer studies observing autism-specific deficits than might be imagined. In the current study, 21 individuals with autism and 21 age- and ability-matched, learning disabled comparison participants were tested for their ability to (a) recognise, in others, expressions of ‘social’ emotions (e.g., embarrassment) and ‘non-social’ emotions (e.g., happiness) and; (b) report their own previous experiences of each of these emotions. In line with predictions, amongst both groups of participants, social emotions were more difficult to recognise and report than non-social emotions. Also amongst both groups, the ability to report social emotion-experience was significantly associated with the ability to recognise social emotions in others, independent of age and verbal ability. However, contrary to predictions, no between-group differences in levels or patterns of performance on the experimental tasks were observed. In light of previous research, these results suggest either that emotion-processing is not as specifically impaired in autism as is traditionally thought to be the case, or that individuals with autism are implementing compensatory strategies to succeed on experimental tasks in the absence of emotion-processing competence.
Genomic organization of duplicated short wave-sensitive and long wave-sensitive opsin genes in the green swordtail, Xiphophorus helleri
Authors: Watson Corey T , Lubieniecki Krzysztof P , Loew Ellis , Davidson William S , Breden Felix 
Published: April 2010

AbstractBackgroundLong wave-sensitive (LWS) opsin genes have undergone multiple lineage-specific duplication events throughout the evolution of teleost fishes.LWSrepertoire expansions in live-bearing fishes (family Poeciliidae) have equipped multiple species in this family with up to fourLWSgenes. Given that color vision, especially attraction to orange male coloration, is important to mate choice within poeciliids,LWSopsins have been proposed as candidate genes driving sexual selection in this family. To date the genomic organization of these genes has not been described in the family Poeciliidae, and little is known about the mechanisms regulating the expression ofLWSopsins in any teleost.ResultsTwo BAC clones containing the complete genomic repertoire ofLWSopsin genes in the green swordtail fish,Xiphophorus helleri, were identified and sequenced. Three of the fourLWSloci identified here were linked in a tandem array downstream of two tightly linked short wave-sensitive 2 (SWS2) opsin genes. The fourthLWSopsin gene, containing only a single intron, was not linked to the other three and is the product of a retrotransposition event. Genomic and phylogenetic results demonstrate that theLWSgenes described here share a common evolutionary origin with those previously characterized in other poeciliids. Using qualitative RT-PCR and MSP we showed that each of theLWSandSWS2opsins, as well as three other cone opsin genes and a single rod opsin gene, were expressed in the eyes of adult female and maleX. helleri, contributing to six separate classes of adult retinal cone and rod cells with average λmaxvalues of 365 nm, 405 nm, 459 nm, 499 nm, 534 nm and 568 nm. Comparative genomic analysis identified two candidate teleost opsin regulatory regions containing putative CRX binding sites and hormone response elements in upstream sequences ofLWSgene regions of seven teleost species, includingX. helleri.ConclusionsWe report the first complete genomic description ofLWSandSWS2genes in poeciliids. These data will serve as a reference for future work seeking to understand the relationship betweenLWSopsin genomic organization, gene expression, gene family evolution, sexual selection and speciation in this fish family.
Polymorphisms in the gene encoding bovine interleukin-10 receptor alpha are associated with Mycobacterium avium ssp. paratuberculosis infection status
Authors: Verschoor Chris P , Pant Sameer D , You Qiumei , Schenkel Flavio S , Kelton David F , Karrow Niel A 
Published: April 2010

Abstract

Background
Johne's disease is a chronic inflammatory bowel disease (IBD) of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). Since this pathogen has been implicated in the pathogenesis of human IBDs, the goal of this study was to assess whether single nucleotide polymorphism (SNPs) in several well-known candidate genes for human IBD are associated with susceptibility to MAP infection in dairy cattle.

Methods
The bovine candidate genes, interleukin-10 (IL10), IL10 receptor alpha/beta (IL10RA/B), transforming growth factor beta 1 (TGFB1), TGFB receptor class I/II (TGFBR1/2), and natural resistance-associated macrophage protein 1 (SLC11A1) were sequenced for SNP discovery using pooled DNA samples, and the identified SNPs were genotyped in a case-control association study comprised of 242 MAP negative and 204 MAP positive Holstein dairy cattle. Logistic regression was used to determine the association of SNPs and reconstructed haplotypes with MAP infection status.

Results
A total of 13 SNPs were identified. Four SNPs in IL10RA (984G > A, 1098C > T, 1269T > C, and 1302A > G) were tightly linked, and showed a strong additive and dominance relationship with MAP infection status. Haplotypes AGC and AAT, containing the SNPs IL10RA 633C > A, 984G > A and 1185C > T, were associated with an elevated and reduced likelihood of positive diagnosis by serum ELISA, respectively.

Conclusions
SNPs in IL10RA are associated with MAP infection status in dairy cattle. The functional significance of these SNPs warrants further investigation.
Genetic transformation of cotton with a harpin-encoding gene hpa Xoo confers an enhanced defense response against different pathogens through a priming mechanism
Authors: Miao Weiguo , Wang Xiben , Li Ming , Song Congfeng , Wang Yu , Hu Dongwei , Wang Jinsheng 
Published: April 2010

AbstractBackgroundThe soil-borne fungal pathogenVerticillium dahliaeKleb causesVerticilliumwilt in a wide range of crops including cotton (Gossypium hirsutum). To date, most upland cotton varieties are susceptible toV. dahliaeand the breeding for cotton varieties with the resistance toVerticilliumwilt has not been successful.ResultsHpa1Xoois a harpin protein fromXanthomonas oryzaepv.oryzaewhich induces the hypersensitive cell death in plants. Whenhpa1Xoowas transformed into the susceptible cotton line Z35 throughAgrobacterium-mediated transformation, the transgenic cotton line (T-34) with an improved resistance toVerticillium dahliaewas obtained. Cells of the transgenic T-34, when mixed with the conidia suspension ofV. dahliae, had a higher tolerance toV. dahliaecompared to cells of untransformed Z35. Cells of T-34 were more viable 12 h after mixing withV. dahliaeconidia suspension. Immunocytological analysis showed that Hpa1Xoo, expressed in T-34, accumulated as clustered particles along the cell walls of T-34. In response to the infection caused byV. dahliae, the microscopic cell death and the generation of reactive oxygen intermediates were observed in leaves of T-34 and these responses were absent in leaves of Z35 inoculated withV. dahliae. Quantitative RT-PCR analysis indicated that five defense-related genes,ghAOX1, hin1, npr1, ghdhg-OMT, andhsr203J, were up-regulated in T-34 inoculated withV. dahliae. The up-regulations of these defense-relate genes were not observed or in a less extent in leaves of Z-35 after the inoculation.ConclusionsHpa1Xooaccumulates along the cell walls of the transgenic T-34, where it triggers the generation of H2O2as an endogenous elicitor. T-34 is thus in a primed state, ready to protect the host from the pathogen. The results of this study suggest that the transformation of cotton withhpa1Xoocould be an effective approach for the development of cotton varieties with the improved resistance against soil-borne pathogens.