bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of DNA repair and reductase activity in the cytotoxicity of the hypoxia-activated dinitrobenzamide mustard PR-104A
Authors: Gu Yongchuan , Patterson Adam V. , Atwell Graham J. , Chernikova Sophia B. , Brown J. Martin , Thompson Larry H. , Wilson William R. 
Published: June 2009

Abstract
PR-104 is a dinitrobenzamide mustard currently in clinical trial as a hypoxia-activated prodrug. Its major metabolite, PR-104A, is metabolized to the corresponding hydroxylamine (PR-104H) and amine (PR-104M), resulting in activation of the nitrogen mustard moiety. We characterize DNA damage responsible for cytotoxicity of PR-104A by comparing sensitivity of repair-defective hamster Chinese hamster ovary cell lines with their repair-competent counterparts. PR-104H showed a repair profile similar to the reference DNA cross-linking agents chlorambucil and mitomycin C, with marked hypersensitivity of XPF−/−, ERCC1−/−, and Rad51D−/− cells but not of XPD−/− or DNA-PKCS−/− cells. This pattern confirmed the expected dependence on the ERCC1-XPF endonuclease, implicated in unhooking DNA interstrand cross-links at blocked replication forks, and homologous recombination repair (HRR) in restarting collapsed forks. However, even under anoxia, the hypersensitivity of XPF−/−, ERCC1−/−, and Rad51D−/− cells to PR-104A itself was lower than for chlorambucil. To test whether this reflects inefficient PR-104A reduction, a soluble form of human NADPH:cytochrome P450 oxidoreductase was stably expressed in Rad51D−/− cells and their HRR-restored counterpart. This expression increased hypoxic metabolism of PR-104A to PR-104H and PR-104M as well as hypoxia-selective cytotoxicity of PR-104A and its dependence on HRR. We conclude that PR-104A cytotoxicity is primarily due to DNA interstrand cross-linking by its reduced metabolites, although under conditions of inefficient PR-104A reduction (low reductase expression or aerobic cells), a second mechanism contributes to cell killing. This study shows that hypoxia, reductase activity, and DNA interstrand cross-link repair proficiency are key variables that interact to determine PR-104A sensitivity. [Mol Cancer Ther 2009;8(6):1714–23]
IKKβ-mediated nuclear factor-κB activation attenuates smac mimetic–induced apoptosis in cancer cells
Authors: Bai Lang , Chen Wenshu , Chen Wenjie , Wang Xia , Tang Hong , Lin Yong 
Published: June 2009

Abstract
Smac mimetics (SM) have been recently reported to kill cancer cells through the extrinsic apoptosis pathway mediated by autocrine tumor necrosis factor (TNF). SM also activates nuclear factor-κB (NF-κB). However, how SM induces NF-κB and the role of NF-κB in SM-induced cancer cell death has not been well elucidated. We found that effective blockage of NF-κB had no detectable effect on SM compound 3 (SMC3)–induced TNF secretion, suggesting that the induction of TNF by SMC3 is independent of NF-κB. Conversely, SMC3-induced NF-κB activation was found to be mediated by autocrine TNF because this effect of SMC3 was effectively inhibited when TNF was blocked with either a TNF neutralizing antibody or TNF small interfering RNA. In addition, although SMC3 dramatically reduced c-IAP1 level, it had marginal effect on c-IAP2 expression, TNF-induced RIP modification, NF-κB activation, and downstream antiapoptosis NF-κB target expression. Furthermore, blocking NF-κB by targeting IKKβ or RelA substantially potentiated SMC3-induced cytotoxicity, suggesting that the NF-κB pathway inhibits SMC3-induced apoptosis in cancer cells. Our results show that through TNF autocrine, SM induces an IKKβ-mediated NF-κB activation pathway that protects cancer cells against SM-induced apoptosis, and thus, NF-κB blockage could be an effective approach for improving the anticancer value of SM. [Mol Cancer Ther 2009;8(6):1636–45]
Efficacy and pharmacodynamic effects of bosutinib (SKI-606), a Src/Abl inhibitor, in freshly generated human pancreas cancer xenografts
Authors: Messersmith Wells A. , Rajeshkumar N.V. , Tan Aik Choon , Wang Xiao Fei , Diesl Veronica , Choe Sung E. , Follettie Max , Coughlin Christina , Boschelli Frank , Garcia-Garcia Elena , Lopez-Rios Fernando , Jimeno Antonio , Hidalgo Manuel 
Published: June 2009

Abstract
Recently, Src tyrosine kinase has emerged as an attractive target for anticancer therapy, and Src is overexpressed in pancreatic cancer. The purpose of the study was to investigate the in vivo efficacy and pharmacodynamic effects of bosutinib (SKI-606), a Src/Abl inhibitor, using a panel of human pancreatic tumor xenografts. Surgically resected human pancreatic tumors were implanted into female nude mice and randomized to bosutinib versus control. Src and other pathways were analyzed by Western Blot, IHC, and Affymetrix U133 Plus 2.0 gene arrays. Of 15 patient tumors, 3 patient tumors were found to be sensitive to bosutinib, defined as tumor growth of &lt;45% than that of control tumors. There were no definite differences between sensitive and resistant tumors in the baseline Src kinase pathway protein expression assessed by Western Blot. Caveolin-1 expression, as assessed by reverse transcription-PCR and immunohistochemistry, was frequently higher in sensitive cases. In sensitive tumors, bosutinib resulted in increased apoptosis. Phosphorylation of key signaling molecules downstream of Src, signal transducers and activators of transcription 3, and signal transducers and activators of transcription 3, were significantly inhibited by bosutinib. K-Top Scoring Pairs analysis of gene arrays gave a six-gene classifier that predicted resistance versus sensitivity in six validation cases. These results may aid the clinical development of bosutinib and other Src inhibitors in pancreas cancer. [Mol Cancer Ther 2009;8(6):1484–93]
Mutation-associated fusion cancer genes in solid tumors
Authors: Kaye Frederic J. 
Published: June 2009

Abstract
Chromosomal translocations and fusion oncogenes serve as the ultimate biomarker for clinicians as they show specificity for distinct histopathologic malignancies while simultaneously encoding an etiologic mutation and a therapeutic target. Previously considered a minor mutational event in epithelial solid tumors, new methodologies that do not rely on the detection of macroscopic cytogenetic alterations, as well as access to large series of annotated clinical material, are expanding the inventory of recurrent fusion oncogenes in both common and rare solid epithelial tumors. Unexpectedly, related assays are also revealing a high number of tandem or chimeric transcripts in normal tissues including, in one provocative case, a template for a known fusion oncogene. These observations may force us to reassess long-held views on the definition of a gene. They also raise the possibility that some rearrangements might represent constitutive forms of a physiological chimeric transcript. Defining the chimeric transcriptome in both health (transcription-induced chimerism and intergenic splicing) and disease (mutation-associated fusion oncogenes) will play an increasingly important role in the diagnosis, prognosis, and therapy of patients with cancer. [Mol Cancer Ther 2009;8(6):1399–408]
Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin
Authors: Zhou Qiong , Yan Bing , Hu Xiaowen , Li Xue-Bing , Zhang Jie , Fang Jing 
Published: June 2009

Abstract
Luteolin, a common dietary flavonoid, has been found to have antitumor properties and therefore poses special interest for the development of preventive and/or therapeutic agent for cancers. E-cadherin, a marker of epithelial cells, mediates cell-cell adhesion. Decreased expression of E-cadherin results in a loss of cell-cell adhesion and an increased cell invasion. Many studies have shown the antiproliferative activities of luteolin on cancer cells. However, the effects of luteolin on invasion of cancer cells remain unclear. In this article, we show that luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin. We found that Luteolin induced expression of E-cadherin through mdm2. Overexpression of mdm2 or knockdown of E-cadherin could restore invasion of PC3 cells after luteolin treatment. Luteolin inhibits mdm2 through AKT and overexpression of active AKT attenuated luteolin-induced expression of E-cadherin, suggesting that luteolin regulates E-cadherin through AKT/mdm2 pathway. The in vivo experiments showed that luteolin inhibited spontaneous lung metastasis of PC3 cells implanted onto the nude mice. These findings provide a new sight into the mechanisms that luteolin is against cancer cells, and suggest that molecular targeting of E-cadherin by luteolin may be a useful strategy for treatment of invasive prostate cancers. [Mol Cancer Ther 2009;8(6):1684–91]
Cross-Cultural Comparison of Student Attitudes toward Snakes
Authors: Özel Murat , Prokop Pavol , Uşak Muhammet 
Published: June 2009

AbstractThere is an increasing amount of research focusing on the origin of the human fear of animals. However, other dimensions of human views of frightening animals have been largely neglected. This study investigated attitudes toward snakes. The Snake Attitude Questionnaire (SAQ), which consisted of 58 Likert-type items (Cronbach's α = 0.91), was administered in a sample of students from two countries (Turkey and Slovakia). Students showed negative attitudes toward snakes, especially within the Negativistic and Naturalistic dimensions. Turkish students showed more positive Scientistic and Naturalistic attitudes than Slovakian students, and females showed more negative attitudes toward snakes than males. Although biology majors had more positive attitudes, compared with nonbiology majors, knowledge of snakes and beliefs about untrue myths were similar between these two subgroups. Our research indicates that fear of snakes negatively influences other attitudinal dimensions (especially naturalistic and scientific attitudes) although no students had been injured by a snake. Keeping various pets at home was associated with less fear of snakes. Nature protection actions should combine direct contact with these controversial animals with interventions against belief in untrue myths about snakes.
Oryx and Crake and the New Nostalgia for Meat
Authors: Parry Jovian 
Published: June 2009

AbstractRecent years have seen the development of a new trend in gastronomic discourse toward acknowledging and even valorizing the role of animal slaughter in meat production. This development problematizes some of the ideas of influential theorists of meat such as Fiddes (1990) and Adams (1991): namely, that the animal in (post)modernity has been rendered invisible in the process of meat production and consumption (Adams, 1991), and that meat itself is a commodity with a declining reputation (Fiddes, 1990). This paper analyzes the role of nostalgia in this trend toward do-it-yourself (or at least witness-it-yourself) slaughter, and takes these developments in cultural tastes and feelings as a context within which to analyze the special significance of meat in Margaret Atwood's Oryx and Crake. In identifying this burgeoning nostalgia for meat and contextualizing it within a risk-reflexive, consumer-driven, dystopian near-future society of the author's own devising, Oryx and Crake foregrounds and illuminates these real-world developments in the meanings of meat.
Interrupting a History of Tolerance: Anti-Semitism and the Arabs
Authors: Hassan Riaz 
Published: June 2009

AbstractThe anti-Semitic rhetoric of many Islamist groups is qualitatively different from the reflective jurisprudence associated with the treatises of classical Islam. There is little evidence of any deep rooted anti-Semitism in the classical Islamic world. Jews have lived under Islamic rule for 14 centuries and in many lands, they were never free from discrimination but were rarely subjected to persecution as in Christian Europe. Most of the characteristic features of European-Christian anti-Semitism were absent from the Jewish-Muslim relations. This paper examines the growth of anti-Semitism in Arab-Muslim world and identifies some of the historical events which have contributed to this development.
The spatial genetic structure of bank vole (Myodes glareolus) and yellow-necked mouse (Apodemus flavicollis) populations: The effect of distance and habitat barriers
Authors: Kozakiewicz Michal , Gortat Tomasz , Panagiotopoulou Hanna , Gryczyńska–Siemiątkowska Alicja , Rutkowski Robert , Kozakiewicz Anna , Abramowicz Katarzyna 
Published: June 2009

AbstractHabitat barriers are considered to be an important factor causing the local reduction of genetic diversity by dividing a population into smaller sections and preventing gene flow between them. However, the “barrier effect” might be different in the case of different species. The effect of geographic distance and water barriers on the genetic structure of populations of two common rodent species – the yellow-necked mouse (Apodemus flavicollis) and the bank vole (Myodes glareolus) living in the area of a lake (on its islands and on two opposite shores) was investigated with the use of microsatellite fragment analysis. The two studied species are characterised by similar habitat requirements, but differ with regard to the socio-spatial structure of the population, individual mobility, capability to cross environmental barriers, and other factors. Trapping was performed for two years in spring and autumn in north-eastern Poland (21°E, 53°N). A total of 160 yellow-necked mouse individuals (7 microsatellite loci) and 346 bank vole individuals (9 microsatellite loci) were analysed. The results of the differentiation analyses (FST and RST) have shown that both the barrier which is formed by a ca. 300 m wide belt of water (between the island and the mainland) and the actual distance of approximately 10 km in continuous populations are sufficient to create genetic differentiation within both species. The differences between local populations living on opposite lake shores are the smallest; differences between any one of them and the island populations are more distinct. All of the genetic diversity indices (the mean number of alleles, mean allelic richness, as well as the observed and expected heterozygosity) of the local populations from the lakeshores were significantly higher than of the small island populations of these two species separated by the water barrier. The more profound “isolation effect” in the case of the island populations of the bank vole, in comparison to the yellow-necked mouse populations, seems to result not only from the lower mobility of the bank vole species, but may also be attributed to other differences in the animals' behaviour.
Diet of the pulmonate gastropod Onchidella nigricans in the intertidal rocky shore, New Zealand
Authors: Alfaro Andrea 
Published: June 2009

AbstractGut content analyses and stable isotopes (δ13C and δ15N) were used to investigate the food consumption and assimilation of the pulmonate, Onchidella nigricans, within a rocky intertidal platform at Waiwera, northern New Zealand. Analyses of gut contents indicate that this species is a generalist herbivore, which may consume a variety of micro- and macro-algae, although small zooplankton may be ingested, when present. Gut contents of individuals collected from different intertidal habitats (bare rock, Hormosira banksii, green filaments, and coralline algae) reflected the dominant algal species within each habitat, suggesting that food availability does not restrict the grazer's distribution across its range. The radular morphology and small size of this gastropod also support the notion that O. nigricans is a non-selective microphagous feeder. However, stable isotopes on O. nigricans from the four habitats and the dominant algal food types indicate a strong assimilation preference for microalgae. The δ13C values (-15 to -13‰) of O. nigricans were consistent with signatures for intertidal grazers, but δ15N values (8 to 9‰) were relatively high, which may indicate the presence of bacteria and microfaunal detritus in the diet. Clusters of isotopic signatures of individuals from different habitats suggest feeding preferences, which also may be attributed to differences in detrital and bacterial consumption. This study illustrates the importance of using parallel techniques in diet studies.
Ultrastructural analysis of the fat body in workers of Attini ants (Hymenoptera: Formicidae)
Authors: Roma Gislaine , Bueno Odair , Camargo-Mathias Maria 
Published: June 2009

AbstractIn the present study a comparative morphological analysis of the fat body cells of ant workers of the basal Attini species Cyphomyrmex rimosus and Mycetarotes parallelus, and the derived species Acromyrmex disciger and Atta laevigata was conducted. The results revealed that the fat body is located mainly in the abdomen around organs (perivisceral) and near the integument (parietal). The main cells observed are spherical or polygonal trophocytes with a slightly rough surface. The oenocytes, another cell type found, are closely associated with trophocytes, and present a spherical or polygonal shape and a smoother surface. The morphometric analysis showed that the area of trophocytes and oenocytes of C. rimosus and M. parallelus is significantly smaller when compared to those of A. disciger and A. laevigata. In the cytoplasm of parietal and perivisceral trophocytes and oenocytes, electronlucent droplets (probably lipids) and electrondense granules (probably proteins) indicate the participation of these cells in the storage of these elements, while digestive vacuoles, residual bodies, and multivesicular bodies suggest a role in intracellular digestion. In perivisceral trophocytes and oenocytes of C. rimosus, the presence of mitochondria, lamellar rough endoplasmic reticulum, and Golgi complex suggests that these cells synthesize proteins. Based on these data, no significant differences were observed between the fat body cells of basal and derived ants, except regarding the larger size of trophocytes and oenocytes of the derived species A. disciger and A. laevigata.
The Depth Dependence of Shear Finestructure off Point Arena and near Pioneer Seamount
Authors: Kunze Eric , Kennelly Maureen A. , Sanford Thomas B. 
Published: June 2009

Abstract
High-resolution velocity profiles to depths of 1600 m were collected off Point Arena and near Pioneer Seamount, California. They reveal shear increasing with depth relative to the GM76 model spectrum. Using an empirical parameterization found to collapse microstructure data the “dissipation rate” and “eddy diffusivity” are estimated from these shears. Away from the seamount, dissipation rates are depth invariant at 3–6(×10−10 W kg−1). As a result, the eddy diffusivity increases with depth, approaching 0.2–0.3(×10−4 m2 s−1) below 1200-m depth. This may be a result of the proximity of the continental rise and sloping topography, but there is evidence that it is a general result for the abyssal ocean. Immediately above the seamount, there is a 300–400-m thick layer of elevated shear, corresponding to an eddy diffusivity of ∼ 10−4 m2 s−1. If this localized enhancement is typical of seamounts, topographically induced mixing is insufficient to significantly modify global average mixing.
Postsurgical Glenohumeral Arthritis in Young Adults
Authors: McNickle Allison G. , L'Heureux Daniel R. , Provencher Matthew T. , Romeo Anthony A. , Cole Brian J. 
Published: June 2009

Background Chondrolysis has been reported as a sequela of arthroscopic shoulder surgery. Although the causes have yet to be fully elucidated, basic science and clinical evidence suggest a multifactorial origin. Surgical treatment in young patients with glenohumeral chondrolysis is particularly challenging, with little outcome data. Hypothesis Glenohumeral chondrolysis has several causes and patterns of presentation. Biological resurfacing is a viable treatment option for symptomatic glenohumeral arthritis. Study Design Case series; Level of evidence, 4. Methods Twenty patients (mean age, 19.7 years; range, 13.1-33.8) were referred for management of extensive glenohumeral arthritis after arthroscopy glenohumeral surgery (mean time postoperatively, 26 months; range, 3-73). Sixteen patients had an intra-articular pain pump placed for 2 to 3 days; 2 patients demonstrated prominent implants; and 2 had thermal treatment. Patients underwent revision surgery, including 7 biological resurfacings of the glenoid and humeral head, 4 biological resurfacings of the humeral head alone, and 7 other procedures. Eight patients having biological resurfacing were assessed just before the revision surgery, at a mean time of 3.1 years after revision (range, 1.9-6.5), with the American Shoulder and Elbow Surgeon scale and Simple Shoulder Test, Short Form 12 (physical and mental components), and visual analog scale score for pain. Results Patient outcomes scores improved from 51 to 71 (American Shoulder and Elbow Surgeon scale, P < .01), 7 to 10 (Simple Shoulder Test, P < .02), and 5 to 3 (visual analog scale, P < .01). Preoperative range of motion demonstrated modest improvements from 119° to 132° of flexion, 42° to 41° of external rotation, and internal rotation from L2 to T12 level. Two patients required an additional surgery: 1 total shoulder arthroplasty and 1 capsular release with debridement. Conclusion Severe glenohumeral arthritis is a devastating postoperative complication of glenohumeral arthroscopy. Although not a universal finding, the use of glenohumeral pain pumps is a concern, as well as suboptimal anchor placement. Biological resurfacing permits modest functional improvement in a challenging shoulder condition.
Changing Sidestep Cutting Technique Reduces Knee Valgus Loading
Authors: Dempsey Alasdair R. , Lloyd David G. , Elliott Bruce C. , Steele Julie R. , Munro Bridget J. 
Published: June 2009

Background Common lower limb postures have been found when noncontact anterior cruciate ligament (ACL) injuries occur during sidestep cutting tasks. These same postures have been linked to knee loadings known to stress the ACL. Hypothesis Whole body technique modification would reduce knee loading. Study Design Controlled laboratory study. Methods Experienced team sport athletes were recruited for whole body sidestep cutting technique modification. Before and after a 6-week technique modification training, participants performed sidestep cutting tasks while ground-reaction force and motion data were collected. A kinematic and inverse dynamics model was used to calculate 3-dimensional knee loading during sidestep cutting. Results At initial foot contact, the participants placed their stance foot closer to the body’s midline and held their torso more upright, in line with the aims of the technique modification training. This was accompanied by significantly lower peak valgus moments in the weight acceptance phase of stance. Both postural changes were correlated with the change in peak valgus moment. Conclusion Whole body sidestep cutting technique modification resulted in reduced knee loading. Clinical Relevance Implementation of whole body technique modification may produce effective ACL injury prevention programs in sports involving sidestep cutting.