bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Carbon Ion Beam on Putative Colon Cancer Stem Cells and Its Comparison with X-rays
Authors: Cui Xing , Oonishi Kazuhiko , Tsujii Hirohiko , Yasuda Takeshi , Matsumoto Yoshitaka , Furusawa Yoshiya , Akashi Makoto , Kamada Tadashi , Okayasu Ryuichi 
Published: April 2011

Abstract
Although carbon ion therapy facilities are expensive, the biological effects of carbon ion beam treatment may be better against cancer (and cancer stem cells) than the effects of a photon beam. To investigate whether a carbon ion beam may have a biological advantage over X-rays by targeting cancer stem–like cells, human colon cancer cells were used in vitro and in vivo. The in vitro relative biological effectiveness (RBE) values of a carbon ion beam relative to X-rays at the D10 values were from 1.63 to 1.74. Cancer stem–like CD133+, CD44+/ESA+ cells had a greater ability for colony and spheroid formation, as well as in vivo tumorigenicity compared with the CD133−, CD44−/ESA− cells. FACS (fluorescence-activated cell sorting) data showed that cancer stem–like cells were more highly enriched after irradiation with X-rays than carbon ion at doses that produced the same level of biological efficacy. A colony assay for cancer stem–like cells showed that RBE values calculated by the D10 levels were from 2.05 to 2.28 for the carbon ion beam relative to X-rays. The in vivo xenotransplant assay showed an RBE of 3.05 to 3.25, calculated from the slope of the dose–response curve for tumor growth suppression. Carbon ion irradiation with 15 Gy induced more severe xenograft tumor cell cavitation and fibrosis without significant enhancement of cells with putative cancer stem cell markers, CD133, ESA, and CD44, compared with 30 Gy X-rays, and marker positive cells were significantly decreased following 30 Gy carbon ion irradiation. Taken together, carbon ion beam therapy may have an advantage over photon beam therapy by improved targeting of putative colon cancer stem–like cells. Cancer Res; 71(10); 3676–87. ©2011 AACR.
Cancer-Associated Adipocytes Exhibit an Activated Phenotype and Contribute to Breast Cancer Invasion
Authors: Dirat Béatrice , Bochet Ludivine , Dabek Marta , Daviaud Danièle , Dauvillier Stéphanie , Majed Bilal , Wang Yuan Yuan , Meulle Aline , Salles Bernard , Le Gonidec Sophie , Garrido Ignacio , Escourrou Ghislaine , Valet Philippe , Muller Catherine 
Published: April 2011

Abstract
Early local tumor invasion in breast cancer results in a likely encounter between cancer cells and mature adipocytes, but the role of these fat cells in tumor progression remains unclear. We show that murine and human tumor cells cocultivated with mature adipocytes exhibit increased invasive capacities in vitro and in vivo, using an original two-dimensional coculture system. Likewise, adipocytes cultivated with cancer cells also exhibit an altered phenotype in terms of delipidation and decreased adipocyte markers associated with the occurrence of an activated state characterized by overexpression of proteases, including matrix metalloproteinase-11, and proinflammatory cytokines [interleukin (IL)-6, IL-1β]. In the case of IL-6, we show that it plays a key role in the acquired proinvasive effect by tumor cells. Equally important, we confirm the presence of these modified adipocytes in human breast tumors by immunohistochemistry and quantitative PCR. Interestingly, the tumors of larger size and/or with lymph nodes involvement exhibit the higher levels of IL-6 in tumor surrounding adipocytes. Collectively, all our data provide in vitro and in vivo evidence that (i) invasive cancer cells dramatically impact surrounding adipocytes; (ii) peritumoral adipocytes exhibit a modified phenotype and specific biological features sufficient to be named cancer-associated adipocytes (CAA); and (iii) CAAs modify the cancer cell characteristics/phenotype leading to a more aggressive behavior. Our results strongly support the innovative concept that adipocytes participate in a highly complex vicious cycle orchestrated by cancer cells to promote tumor progression that might be amplified in obese patients. Cancer Res; 71(7); 2455–65. ©2011 AACR.
Methylation of Retinoic Acid Receptor, Beta (RARB) Gene Increases Risk for Prostate Cancer in African-American Men
Authors: Rybicki B , Mitrache N , Do K , Jankowski M , Tang D , Rundle A , Bock C , Beebe-Dimmer J , Belinsky S 
Published: March 2011

Abstract
DNA methylation is an indicator of the initiation of prostate carcinogenesis and as such has utility as a marker of risk in pathologically negative prostate tissue samples. We conducted a matched case-control study nested in a historical cohort of over 6,000 men with pathologically benign prostate specimens identified between January 1991 and November 2002 with no previous history of prostate cancer. Eligible cases were diagnosed with prostate cancer at least one year after cohort entry. Controls were selected through incidence density sampling and matched to cases on date and age at cohort entry, race, and type of specimen. In 310 matched prostate cancer case-control pairs (65% white; 35% African American), we assayed the DNA of the benign prostate specimen for presence of methylation in a five-gene panel (APC, RARB, CCND2, RASSF1, MGMT) and then estimated the risk of developing prostate cancer associated with methylation at each gene for the whole sample and stratified by race. Overall, methylation of RARB had the strongest association with prostate cancer risk (HR = 1.94; 95% CI = 1.30 – 2.91). In race-stratified analyses, the majority of the increased risk associated with RARB was found in the African-American sample (HR = 3.40; 95% CI = 1.68–6.88). In addition, APC was also associated with increased risk for prostate cancer in the African-American sample (HR = 2.17; 95% CI = 1.09–4.29). In a model that included both genes, only RARB remained statistically significantly associated with prostate cancer (HR = 3.14; 95% CI = 1.54–6.44). In whites, methylation was not associated with prostate cancer for any of the five genes assayed. In summary, positive methylation status at RARB and APC in pathologically benign prostate is associated with significant increased risk for subsequent prostate cancer, but primarily in African-American men. Whether this race-specific risk is due to racial differences in environmental stimuli and/or biology is unclear, but further study of DNA methylation in the earliest stages of prostate carcinogenesis may help explain the disproportionate burden of this disease among African-American men.
Predictors and Health Consequences of Epigenetic Changes Associated with Excess Body Weight in Women of Child-bearing Age
Authors: Piyathilake C , Badiga S , Johanning G , Alvarez R , Partridge E 
Published: March 2011

Abstract
Background: Epigenetic alterations occurring during pregnancy have recently emerged as important factors for developmental programming of the fetus leading to obesity-related diseases in children. However, the role of excess body weight (EBW) in the modification of epigenetic patterns or its health consequences during child-bearing age is largely unknown. Because a lower degree of DNA methylation of long interspersed nucleotide element-1 (LINE-1) in PBMCs was shown to be associated with a higher risk of developing obesity-related diseases, for example cancer, the purpose of this study was to (1) evaluate the influence of indicators of obesity (BMI, WC, and % body fat) on PBMC LINE-1 methylation, (2) determine the predictors of PBMC LINE-1 methylation, and (3) determine the influence of PBMC LINE-1 methylation on biomarkers of obesity-related diseases.
Methods: The study population consisted of 470 child-bearing age women. We quantified the degree of PBMC LINE-1 methylation by pyrosequencing. Folate concentrations were measured using a microbiological assay. The degree of LINE-1 methylation (&gt; median vs. ≤ median) was the dependent variable in logistic models that specified BMI (&gt;25 vs. ≤ 25), WC (&gt;88 cm vs. ≤ 88 cm), or % body fat (&gt;33% vs. ≤ 33%) separately as the independent predictors of primary interest, adjusting for other relevant variables. The predictors and determinants of lower LINE-1 methylation were evaluated among women with EBW.
Results: Women with higher BMI, WC, or % body fat were 2.0, 1.9, and 1.8 times more likely to have lower LINE-1 methylation, respectively (P = 0.003, 0.005, and 0.01). The predictors and determinants of lower LINE-1 methylation yielded similar patterns with all three indicators of obesity. The following results are based on models run with BMI as the indicator for EBW. Women with higher plasma folate concentrations were less likely to have lower LINE-1 methylation (OR = 0.54, P = 0.0009). Higher LINE-1 methylation was associated with lower insulin resistance as indicated by HOMA (OR = 0.50, P = 0.02).
Conclusions: EBW-associated lower LINE-1 methylation in women of child-bearing age appears to have significant, and potentially transgenerational, health consequences. Higher folate status may exert beneficial effects on obesity-related health outcomes.
Runx2-Upregulated Receptor Activator of Nuclear Factor κB Ligand in Calcifying Smooth Muscle Cells Promotes Migration and Osteoclastic Differentiation of Macrophages
Authors: Byon Chang Hyun , Sun Yong , Chen Jianfeng , Yuan Kaiyu , Mao Xia , Heath Jack M. , Anderson Peter G. , Tintut Yin , Demer Linda L. , Wang Deli , Chen Yabing 
Published: April 2011

Objective—
Clinical and experimental studies demonstrate the important roles of vascular smooth muscle cells (VSMC) in the pathogenesis of atherosclerosis. We have previously determined that the osteogenic transcription factor Runx2 is essential for VSMC calcification. The present study characterized Runx2-regulated signals and their potential roles in vascular calcification.

Methods and Results—

In vivo studies with atherogenic apolipoprotein E
−/−
mice demonstrated that increased oxidative stress was associated with upregulation of Runx2 and receptor activator of nuclear factor κB ligand (RANKL), which colocalized in the calcified atherosclerotic lesions and were juxtaposed to infiltrated macrophages and osteoclast-like cells that are positively stained for an osteoclast marker, tartrate-resistant acid phosphatase. Mechanistic studies using RNA interference, a luciferase reporter system, chromatin immunoprecipitation, and electrophoretic mobility shift assays indicated that Runx2 regulated the expression of RANKL via a direct binding to the 5′-flanking region of the RANKL. Functional characterization revealed that RANKL did not induce VSMC calcification, nor was RANKL required for oxidative stress–induced VSMC calcification. Using a coculture system, we demonstrated that VSMC-expressed RANKL induced migration as well as differentiation of bone marrow-derived macrophages into multinucleated, tartrate-resistant acid phosphatase–positive osteoclast-like cells. These effects were inhibited by the RANKL antagonist osteoprotegerin and with VSMC deficient in Runx2 or RANKL.

Conclusion—
We demonstrate that Runx2 directly binds to the promoter and controls the expression of RANKL, which mediates the crosstalk between calcifying VSMC and migration and differentiation of macrophages into osteoclast-like cells in the atherosclerotic lesions. Our studies provide novel mechanistic insights into the regulation and function of VSMC-derived RANKL in the pathogenesis of atherosclerosis and vascular calcification.
Signal Evolution and Infarction Risk for Apparent Diffusion Coefficient Lesions in Acute Ischemic Stroke Are Both Time- and Perfusion-Dependent
Authors: An Hongyu , Ford Andria L. , Vo Katie , Powers William J. , Lee Jin-Moo , Lin Weili 
Published: April 2011

Background and Purpose—
This study aimed to examine the temporal relationship between tissue perfusion and apparent diffusion coefficient (ADC) changes within 6 hours of ischemic stroke onset and how different reperfusion patterns may affect tissue outcome in ADC lesions.

Methods—

Thirty-one participants were sequentially imaged at 3 hours, 6 hours, and 1 month post-stroke. Three regions of interest (ROIs) were defined within initial ADC lesions: ROI (1)
reperf_3hour
hyperacute reperfusion (within 3 hours), ROI (2)
reperf_6hour
acute reperfusion (3 to 6 hours), and ROI (3)
nonreperf
no reperfusion (by 6 hours). For each ROI, changes in ADC (ΔADC) from 3 to 6 hours and risks of infarction were examined.

Results—

The magnitude of initial ADC reduction was similar in all 3 ROIs (
P
=0.51). ΔADC was strongly associated with reperfusion (
P
<0.0001) but not with initial ADC reduction (
P
=0.83). ΔADC in ROI (1)
reperf_3hour
and ROI (2)
reperf_6hour
was significantly larger than that of ROI (3)
nonreperf
(
P
<0.05). Positive ΔADC was obtained from 3 to 6 hours in ROI (1)
reperf_3hour
that had restored perfusion before 3 hours, demonstrating a temporal delay between reperfusion and ADC changes. Risks of infarction were significantly higher in ROI (3)
nonreperf
than those in ROI (1)
reperf_3hour
and ROI (2)
reperf_6hour
.

Conclusions—
Improvement in ADC did not occur coincidently with reperfusion but showed a temporal delay. Regions with similar initial ADC reductions at 3 hours had different evolution of ADC and infarction risks depending on when or if tissue reperfused. These findings provide a physiological basis for the observation that a single ADC measurement at a fixed time after stroke onset may not accurately predict tissue outcome.
I Did It: Unconscious Expectation of Sensory Consequences Modulates the Experience of Self-agency and Its Functional Signature
Authors: Gentsch Antje , Schütz-Bosbach Simone 
Published: March 2011

Abstract
The ability to recognize oneself in voluntary action is called the sense of agency and refers to the experience of causing one's own actions and their sensory consequences. This form of self-awareness is important not only for motor control but also for social interactions and the ascription of causal responsibility. Here, we examined the sense of agency at early and prereflective stages of action perception using ERPs. Subjects performed a visual forced-choice response task in which action effects were either caused by the subject or by the computer. In addition, to modulate the conscious experience of agency, action effects were subliminally primed by the presentation of congruent, incongruent, or neutral effect stimuli before the action. First, we observed sensorimotor attenuation in the visual ERP selectively for self-generated action effects. That is, the N1 component, a negative deflection around 100 msec after a visual stimulus, was smaller in amplitude for visual effects caused by the subject as compared with effects caused by the computer. Second, congruent effect priming enhanced the explicit judgment of agency and further reduced the N1 amplitude for self-generated effects, although effect primes were not consciously processed. Taken together, these results provide evidence of a top–down modulation of sensory processing of action effects by prior effect information and support the neurophysiological mechanism of sensorimotor attenuation as underlying self-registration in action. Our findings suggest that both efferent information and prior thoughts about the action consequence provide important cues for a prereflective form of the experience of being an agent.
Is Morality Unified? Evidence that Distinct Neural Systems Underlie Moral Judgments of Harm, Dishonesty, and Disgust
Authors: Parkinson Carolyn , Sinnott-Armstrong Walter , Koralus Philipp E. , Mendelovici Angela , McGeer Victoria , Wheatley Thalia 
Published: March 2011

AbstractMuch recent research has sought to uncover the neural basis of moral judgment. However, it has remained unclear whether “moral judgments” are sufficiently homogenous to be studied scientifically as a unified category. We tested this assumption by using fMRI to examine the neural correlates of moral judgments within three moral areas: (physical) harm, dishonesty, and (sexual) disgust. We found that the judgment of moral wrongness was subserved by distinct neural systems for each of the different moral areas and that these differences were much more robust than differences in wrongness judgments within a moral area. Dishonest, disgusting, and harmful moral transgression recruited networks of brain regions associated with mentalizing, affective processing, and action understanding, respectively. Dorsal medial pFC was the only region activated by all scenarios judged to be morally wrong in comparison with neutral scenarios. However, this region was also activated by dishonest and harmful scenarios judged not to be morally wrong, suggestive of a domain-general role that is neither peculiar to nor predictive of moral decisions. These results suggest that moral judgment is not a wholly unified faculty in the human brain, but rather, instantiated in dissociable neural systems that are engaged differentially depending on the type of transgression being judged.
Involvement of the Primary Motor Cortex in Controlling Movements Executed with the Ipsilateral Hand Differs between Left- and Right-handers
Authors: van den Berg Femke E. , Swinnen Stephan P. , Wenderoth Nicole 
Published: March 2011

Abstract
Unimanual motor tasks, specifically movements that are complex or require high forces, activate not only the contralateral primary motor cortex (M1) but evoke also ipsilateral M1 activity. This involvement of ipsilateral M1 is asymmetric, such that the left M1 is more involved in motor control with the left hand than the right M1 in movements with the right hand. This suggests that the left hemisphere is specialized for movement control of either hand, although previous experiments tested mostly right-handed participants. In contrast, research on hemispheric asymmetries of ipsilateral M1 involvement in left-handed participants is relatively scarce. In the present study, left- and right-handed participants performed complex unimanual movements, whereas TMS was used to disrupt the activity of ipsilateral M1 in accordance with a “virtual lesion” approach. For right-handed participants, more disruptions were induced when TMS was applied over the dominant (left) M1. For left-handed participants, two subgroups could be distinguished, such that one group showed more disruptions when TMS was applied over the nondominant (left) M1, whereas the other subgroup showed more disruptions when the dominant (right) M1 was stimulated. This indicates that functional asymmetries of M1 involvement during ipsilateral movements are influenced by both hand dominance as well as left hemisphere specialization. We propose that the functional asymmetries in ipsilateral M1 involvement during unimanual movements are primarily attributable to asymmetries in the higher-order areas, although the contribution of transcallosal pathways and ipsilateral projections cannot be completely ruled out.
Mechanisms Underlying the Emergence of Object Representations during Infancy
Authors: Scott Lisa S. 
Published: March 2011

Abstract
The effects of individual versus category training, using behavioral indices of stimulus discrimination and neural ERPs indices of holistic processing, were examined in infants. Following pretraining assessments at 6 months, infants were sent home with training books of objects for 3 months. One group of infants was trained with six different strollers labeled individually, and another group was trained with the same six strollers labeled at the category level (i.e., “stroller”). Infants returned for posttraining assessments at 9 months. Discrimination of objects was facilitated for infants trained with the individually labeled strollers but was unchanged after training at the category level. Relative to pretraining and to category-level training, individual-level training resulted in increased holistic processing of strollers recorded over occipital brain regions. These results suggest that labeling nonface objects individually, in infancy, facilitates discrimination and leads to the emergence of holistic neural representations not present with category-level labeling.
Choosing Our Words: Retrieval and Selection Processes Recruit Shared Neural Substrates in Left Ventrolateral Prefrontal Cortex
Authors: Snyder Hannah R. , Banich Marie T. , Munakata Yuko 
Published: March 2011

Abstract
When we speak, we constantly retrieve and select words for production in the face of multiple possible alternatives. Our ability to respond in such underdetermined situations is supported by left ventrolateral prefrontal cortical (VLPFC) regions, but there is active debate about whether these regions support (1) selection between competing alternatives, (2) controlled retrieval from semantic memory, or (3) selection and controlled retrieval in distinct subregions of VLPFC (selection in mid-VLPFC and controlled retrieval in anterior VLPFC). Each of these theories has been supported by some prior evidence but challenged by other findings, leaving the debate unresolved. We propose that these discrepancies in the previous literature reflect problems in the way that selection and controlled retrieval processes have been operationalized and measured. Using improved measures, we find that shared neural substrates in left VLPFC support both selection and controlled retrieval, with no dissociation between mid and anterior regions. Moreover, selection and retrieval demands interact in left VLPFC, such that selection effects are greatest when retrieval demands are low, consistent with prior behavioral findings. These findings enable a synthesis and reinterpretation of prior evidence and suggest that the ability to respond in underdetermined situations is affected by both selection and retrieval mechanisms for verbal material subserved by left VLPFC, and these processes interact in meaningful ways.
Transient Perceptual Neglect: Visual Working Memory Load Affects Conscious Object Processing
Authors: Emrich Stephen M. , Burianová Hana , Ferber Susanne 
Published: March 2011

AbstractVisual working memory (VWM) is a capacity-limited cognitive resource that plays an important role in complex cognitive behaviors. Recent studies indicate that regions subserving VWM may play a role in the perception and recognition of visual objects, suggesting that conscious object perception may depend on the same cognitive and neural architecture that supports the maintenance of visual object information. In the present study, we examined this question by testing object processing under a concurrent VWM load. Under a high VWM load, recognition was impaired for objects presented in the left visual field, in particular when two objects were presented simultaneously. Multivariate fMRI revealed that two independent but partially overlapping networks of brain regions contribute to object recognition. The first network consisted of regions involved in VWM encoding and maintenance. Importantly, these regions were also sensitive to object load. The second network comprised regions of the ventral temporal lobes traditionally associated with object recognition. Importantly, activation in both networks predicted object recognition performance. These results indicate that information processing in regions that mediate VWM may be critical to conscious visual perception. Moreover, the observation of a hemifield asymmetry in object recognition performance has important theoretical and clinical significance for the study of visual neglect.