bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced visual functioning in autism: An ALE meta‐analysis
Authors: Samson Fabienne , Mottron Laurent , Soulières Isabelle , Zeffiro Thomas A.
Published: April 2011

Autistics often exhibit enhanced perceptual abilities when engaged in visual search, visual discrimination, and embedded figure detection. In similar fashion, while performing a range of perceptual or cognitive tasks, autistics display stronger physiological engagement of the visual system than do non‐autistics. To account for these findings, the Enhanced Perceptual Functioning Model proposes that enhanced autistic performance in basic perceptual tasks results from stronger engagement of sensory processing mechanisms, a situation that may facilitate an atypically prominent role for perceptual mechanisms in supporting cognition. Using quantitative meta‐analysis of published functional imaging studies from which Activation Likelihood Estimation maps were computed, we asked whether autism is associated with enhanced task‐related activity for a broad range of visual tasks. To determine whether atypical engagement of visual processing is a general or domain‐specific phenomenon, we examined three different visual processing domains: faces, objects, and words. Overall, we observed more activity in autistics compared to non‐autistics in temporal, occipital, and parietal regions. In contrast, autistics exhibited less activity in frontal cortex. The spatial distribution of the observed differential between‐group patterns varied across processing domains. Autism may be characterized by enhanced functional resource allocation in regions associated with visual processing and expertise. Atypical adult organizational patterns may reflect underlying differences in developmental neural plasticity that can result in aspects of the autistic phenotype, including enhanced visual skills, atypical face processing, and hyperlexia. Hum Brain Mapp, 2011 © 2011 Wiley‐Liss, Inc.
Deficiency of liver adipose triglyceride lipase in mice causes progressive hepatic steatosis
Authors: Wu Jiang Wei , Wang Shu Pei , Alvarez Fernando , Casavant Stéphanie , Gauthier Nicolas , Abed Lynda , Soni Krishnakant G. , Yang Gongshe , Mitchell Grant A.
Published: April 2011

Abstract:

Accumulation of cytoplasmic triacylglycerol (TG) underlies hepatic steatosis, a major cause of cirrhosis. The pathways of cytoplasmic TG metabolism are not well known in hepatocytes, but evidence suggests an important role in lipolysis for adipose triglyceride lipase (ATGL). We created mice with liver-specific inactivation of Pnpla2, the ATGL gene. These ATGLLKO mice had severe progressive periportal macrovesicular and pericentral microvesicular hepatic steatosis (73, 150, and 226 μmol TG/g liver at 4, 8, and 12 months, respectively). However, plasma levels of glucose, TG, and cholesterol were similar to those of controls. Fasting 3-hydroxybutyrate level was normal, but in thin sections of liver, beta oxidation of palmitate was decreased by one-third in ATGLLKO mice compared with controls. Tests of very low-density lipoprotein production, glucose, and insulin tolerance and gluconeogenesis from pyruvate were normal. Plasma alanine aminotransferase levels were elevated in ATGLLKO mice, but histological estimates of inflammation and fibrosis and messenger RNA (mRNA) levels of tumor necrosis factor-α and interleukin-6 were similar to or lower than those in controls. ATGLLKO cholangiocytes also showed cytoplasmic lipid droplets, demonstrating that ATGL is also a major lipase in cholangiocytes. There was a 50-fold reduction of hepatic diacylglycerol acyltransferase 2 mRNA level and a 2.7-fold increase of lipolysosomes in hepatocytes (P < 0.001), suggesting reduced TG synthesis and increased lysosomal degradation of TG as potential compensatory mechanisms. Conclusion: Compared with the hepatic steatosis of obesity and diabetes, steatosis in ATGL deficiency is well tolerated metabolically. ATGLLKO mice will be useful for studying the pathophysiology of hepatic steatosis. (HEPATOLOGY 2011;)
‘The Re Tea Corporation principle and junior creditors’ rights to participate in a scheme of arrangement – a view from Singapore'
Authors: Seah Chi‐Ling
Published: April 2011

This paper examines the application of the principle derived from Re Tea Corporation's case in recent schemes of arrangement to break negotiation deadlocks between senior and junior creditors of a financially distressed company. This paper argues against an overly technical application of the principle in Re Tea Corporation's case which might work injustice towards junior creditors by effectively shutting them out of a restructuring. This paper further explores how the holdout problem, which led to the formulation of the Re Tea Corporation principle in the first place, could be addressed while balancing the competing interests of junior claimants in a scheme of arrangement. Copyright © 2011 John Wiley & Sons, Ltd.
Fabrication of fibrinogen/P(LLA‐CL) hybrid nanofibrous scaffold for potential soft tissue engineering applications
Authors: He Chuanglong , Xu Xiaohong , Zhang Fan , Cao Lijun , Feng Wei , Wang Hongsheng , Mo Xiumei
Published: April 2011

Coelectrospinning of native proteins and elastic synthetic polymers is an attractive technique to fabricate hybrid fibrous scaffolds that combine the bioactivity and mechanical features of each material component. In this study, hybrid fibrous scaffolds composed of synthetic P(LLA‐CL) elastomeric and naturally derived fibrinogen protein were fabricated and characterized for their bioactive and physiochemical properties. Fiber diameters of hybrid scaffolds increased with increasing P(LLA‐CL) content, and the shape of fibers changed from cylindrical shape on pure polymer scaffolds to flat structure on hybrid scaffolds. Characterizations of ATR‐FTIR, XRD, and thermal properties indicated that the hybrid scaffolds contain two different phases, one composed of pure fibrinogen and the other corresponding to a mixture of fibrinogen and P(LLA‐CL), and no obvious chemical reaction takes place between two components. The hybrid fibrous scaffolds showed tailorable degradation rates than pure P(LLA‐CL) and higher mechanical properties than pure fibrinogen, and both tensile strength and breaking strain increased with increasing P(LLA‐CL) content. In Vitro studies revealed that L929 cells on hybrid scaffolds achieved relatively higher level of cell attachment after 12 h of culture and significant increased cell proliferation rate after 7 days of culture, when compared with pure fibrinogen and P(LLA‐CL) scaffolds, and the cells exhibited a spreading polygonal shape on the hybrid fibrous surfaces compared to a round shape on surfaces of pure polymer scaffolds. Therefore, the fibrinogen/P(LLA‐CL) hybrid fibrous scaffolds possess the combined benefits of each individual component, which make it capable as scaffolds for soft tissue reconstruction. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Comparably accelerated vascularization by preincorporation of aortic fragments and mesenchymal stem cells in implanted tissue engineering constructs
Authors: Schumann Paul , von See Constantin , Kampmann Andreas , Lindhorst Daniel , Tavassol Frank , Kokemüller Horst , Bormann Kai‐Hendrik , Gellrich Nils‐Claudius , Rücker Martin
Published: April 2011

The demanding need for tissue replacement resulted in manifold approaches for the construction of different tissues. One common problem which hampers the clinical usage of tissue engineering constructs is a limited vascularization. In an attempt to accelerate the vascularization of tissue engineering constructs we compared the usage of bone marrow mesenchymal stem cells (bmMSCs) and fragments derived from the aorta in vivo. Tissue engineering constructs composed of PLGA scaffolds containing Matrigel (n = 8), aortic fragments embedded in Matrigel (n = 8), bmMSCs embedded in Matrigel (n = 8), and aortic fragments embedded in Matrigel combined with bmMSCs (n = 8) were implanted into dorsal skinfold chambers of balb/c mice and analyzed repetitively over 14 days. In all groups a weak inflammatory response was transiently apparent. Vascularization was significantly (p = 0.05) accelerated in bmMSC and aortic fragments containing constructs compared with Matrigel alone, demonstrated by a distinctly increased microvascular density throughout the whole experiment. The combination of bmMSCs and aortic fragments showed no additional effect compared with bmMSCs and aortic fragments alone. The accelerated vascularization and microvascular density of tissue engineering constructs triggered by bmMSCs and aortic fragments is comparable. Thus aortic fragments provide a new promising source for clinical relevant tissue engineering constructs. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Community‐level effects of individual and peer risk and protective factors on adolescent substance use
Authors: Monahan Kathryn , Egan Elizabeth A. , Van Horn M. Lee , Arthur Michael , Hawkins David
Published: April 2011

The association between community‐aggregated levels of individual and peer risk and protective factors and prevalence of adolescent substance use was examined in repeated cross‐sectional data among youth in 41 communities ranging in population from 1,578 to 106,221. The association between community levels of these risk and protective factors in 2000 and substance use 2 years later was examined by using within‐cohort analyses (e.g., sixth grade in 2000 predicting eighth grade in 2002) and cross‐cohort analyses (e.g., sixth grade in 2000 predicting sixth grade in 2002). In both within‐cohort and across‐cohort analyses, community‐aggregated levels of peer and individual risk and protective factors predicted adolescent substance use 2 years later, suggesting that focusing on elevated peer and individual risk factors and depressed peer and individual protective factors at the community level to guide the selection of preventive interventions may be a viable strategy for community efforts to prevent adolescent substance use. © 2011 Wiley Periodicals, Inc.
Social psychological dynamics of enhanced HIV risk reduction among peer interventionists
Authors: Dickson‐Gomez Julia , Weeks Margaret R. , Convey Mark , Li Jianghong
Published: April 2011

The authors present a model of interactive social psychological and relational feedback processes leading to human immunodeficiency virus (HIV) risk reduction behavior change among active drug users trained as Peer Health Advocates (PHAs). The model is supported by data from qualitative interviews with PHAs and members of their drug‐using networks in the Risk Avoidance Partnership (RAP) project. Results suggest three mutually reinforcing social psychological processes that motivate PHAs to provide HIV prevention intervention to their peers and to reduce their own risk behaviors: development of a prosocial identity, positive social reinforcement from drug users and community members, and cognitive dissonance associated with continued risk behavior while engaging in health advocacy. These processes directly influence peer interventionists' motivation and efficacy to continue giving intervention to their peers, and to reduce their HIV risk behaviors. The authors discuss implications of the model for continued research on effective HIV prevention in high‐risk groups. © 2011 Wiley Periodicals, Inc.
Psychological community integration among people with psychiatric disabilities and nondisabled community members
Authors: Yanos Philip T. , Stefanic Ana , Tsemberis Sam
Published: April 2011

This study examined individual and neighborhood predictors of the psychological community integration of people with psychiatric disabilities and nondisabled community members. One hundred twenty‐three adults (60 psychiatrically disabled, 63 general community residents), completed measures of sense of community, life satisfaction, psychiatric symptoms, and perceptions of neighborhood. Mental health consumers living in independent scatter‐site apartments did not differ from other community members in either sense of community or life satisfaction. Among mental health consumers, neither symptoms nor demographic variables predicted sense of community, whereas objective neighborhood characteristics did. Conversely, among community members, age and symptoms predicted sense of community while objective neighborhood characteristics did not; perceived neighborhood characteristics predicted sense of community in both samples. Findings suggest that consumers living in independent housing may achieve levels of psychological community integration comparable to other community members, and that neighborhood factors impact degree of community integration in this population. © 2011 Wiley Periodicals, Inc.
Positive traits versus previous trauma: racially different correlates with PTSD symptoms among hurricane katrina‐rita volunteers
Authors: Ai Amy L. , Plummer Carol , Kanno Hanae , Heo Grace , Appel Hoa B. , Simon Cassandra E. , Spigner Clarence
Published: April 2011

This study compared risks and protective factors for acquiring symptoms of posttraumatic stress disorder (PTSD) between African‐American (n=299) and European‐American (n=206) student volunteers 3 months after Hurricanes Katrina and Rita (H‐KR). Respondents retrospectively provided information on peritraumatic emotional reactions and previous trauma that were recalled by H‐KR and H‐KR stressors. African‐American respondents reported higher levels of symptoms and higher rates of recollection of prior traumas during H‐KR than their European‐American counterparts. Hierarchical regression analyses found that previous trauma recollections predicted symptoms among European Americans but not among African Americans. Disaster‐related stressors, however, affected African Americans more than European Americans. Though negative emotions had negative outcomes for both groups, positive emotions and hope served as protective factors for African Americans. © 2011 Wiley Periodicals, Inc.
Social capital in promoting the psychosocial adjustment of chinese migrant children: interaction across contexts
Authors: Wu Qiaobing , Palinkas Lawrence A. , He Xuesong
Published: April 2011

Drawing upon a sample of 772 migrant children and their parents in Shanghai, China, this study investigated how the interactions of social capital embedded in a range of social contexts (i.e., family, school, peer, and community) influenced the psychosocial adjustment of Chinese migrant children. Results of multiple‐group structural equation modeling revealed a moderating effect of community social capital on the associations between other dimensions of social capital and child psychosocial adjustment. Family social capital showed stronger effects when there was higher community social capital, while school social capital appeared to be most influential for children with lower community social capital. Peer social capital showed comparable effects on psychosocial adjustment regardless of the stock of community social capital, but was most important for children with limited resources in both the community and school. Implications of the research findings for theory, practice, policy and future research are discussed. © 2011 Wiley Periodicals, Inc.
Rebuilding trust: a community, multiagency, state, and university partnership to improve behavioral health care for American Indian Youth, their families, and communities
Authors: Goodkind Jessica R. , Ross‐Toledo Kimberly , John Susie , Hall Janie Lee , Ross Lucille , Freeland Lance , Coletta Ernest , Becenti‐Fundark Twila , Poola Charlene , Roanhorse Regina , Lee Christopher
Published: April 2011

American Indian/Alaska Native youth represent the strength and survival of many Nations and Tribes. However, the aftermath of colonialism has resulted in numerous health disparities and challenges for Native youth, including the highest rate of suicide in the United States. With the aims of elucidating the causes of behavioral health disparities, eliminating them, and improving behavioral health care for Native youth, a partnership of providers, community members, and university faculty and staff completed a comprehensive literature review, conducted advisory meetings with 71 American Indian youth, parents, and elders, surveyed 25 service providers, and engaged in ongoing consultation with traditional practitioners. Results from the multiple sources were synthesized and are reported with 20 policy, provider, and research recommendations that recognize the importance of moving beyond exclusive reliance on western models of care and that seek to foster transformation of individuals, families, communities, behavioral health service systems of care, and social structures. © 2011 Wiley Periodicals, Inc.
Cellular modeling of cancer invasion: Integration of in silico and in vitro approaches
Authors: Kam Yoonseok , Rejniak Katarzyna A. , Anderson Alexander R.A.
Published: April 2011

Cancer invasion is one of the hallmarks of cancer and a prerequisite for cancer metastasis. However, the invasive process is very complex, depending on multiple correlated intrinsic and environmental factors, and thus is difficult to study experimentally in a fully controlled way. Therefore, there is an increased demand for interdisciplinary integrated approaches combining laboratory experiments with multiscale in silico modeling. In this review, we will summarize current computational techniques applicable to model cancer invasion in silico, with a special focus on a class of individual‐cell‐based models developed in our laboratories. We also discuss their integration with traditional and novel in vitro experimentation, including new invasion assays whose design was inspired by computational modeling. J. Cell. Physiol. 227: 431–438, 2012. © 2011 Wiley Periodicals, Inc.
Autophagy regulates hypoxia‐induced osteoclastogenesis through the HIF‐1α/BNIP3 signaling pathway
Authors: Zhao Yi , Chen Gang , Zhang Wei , Xu Ning , Zhu Jun‐Yi , Jia Jun , Sun Zhi‐Jun , Wang Yi‐Ning , Zhao Yi‐Fang
Published: April 2011

Previous studies have implicated that hypoxic stress could enhance osteoclast differentiation; however, the underlying mechanism remains poorly understood. Autophagy is a dynamic lysosomal degradation process that has emerged as an important regulator under hypoxic environment. In the present study, we demonstrate for the first time that autophagy regulates hypoxia‐induced osteoclastogenesis in vitro. We found that exposure of RAW264.7 cells to hypoxia (0.2% oxygen) resulted in enhanced osteoclast differentiation, accompanied by the observation of several specific features of autophagy, including appearance of membranous vacuoles, formation of acidic vesicular organelles, cleavage and recruitment of microtubule‐associated protein 1 light chain 3 (LC3) to autophagosomes, increase in autophagic flux, as well as up‐regulation of autophagy‐related gene (Atg) expression. Moreover, suppression of autophagy with DN‐Atg5K130R or 3‐methyladenine (3‐MA) significantly attenuated the osteoclast differentiation under hypoxic conditions, indicating the functional significance of autophagy in hypoxia‐induced osteoclastogenesis. The data also showed that the activation of autophagy under hypoxic conditions was caused by up‐regulated expression of hypoxia‐inducible factor‐1α (HIF‐1α)‐dependent Bcl‐2 adenovirus E1a 19 kDa interacting protein 3 (BNIP3). Importantly, knockdown of HIF‐1α or BNIP3 obviously abrogated hypoxia‐induced autophagy activation and osteoclastogenesis enhancement. Collectively, our results highlight the fact that autophagy is a pivotal regulator for hypoxia‐induced osteoclast differentiation, which may provide new insight into the pathological processes of osteoclastogenesis under hypoxic stress and help develop new therapeutic strategies for abnormal osteoclastogenesis. J. Cell. Physiol. 227: 639–648, 2012. © 2011 Wiley Periodicals, Inc.
Cementum protein 1 (CEMP1) induces a cementoblastic phenotype and reduces osteoblastic differentiation in periodontal ligament cells
Authors: Komaki Motohiro , Iwasaki Kengo , Arzate Higinio , Narayanan A. Sampath , Izumi Yuichi , Morita Ikuo
Published: April 2011

Cementum is a calcified tissue covering the tooth root surface, which functions as rigid tooth‐anchoring structure. Periodontal ligament is a unique non‐mineralized connective tissue, and is a source of mineralized tissue forming cells such as cementoblasts and osteoblasts. The CEMP1 is a novel cementum component the presence of which appears to be limited to cementoblasts and their progenitors. In order to understand the function of CEMP1, we investigated CEMP1 expression during the differentiation of human periodontal ligament cells. Immunomagnetically enriched alkaline phosphatase (ALP)‐positive periodontal ligament cells preferentially expressed CEMP1. CEMP1 expression was reduced when periodontal ligament cells differentiated to osteoblasts in vitro. Over‐expression of CEMP1 in periodontal ligament cells enhanced cementoblast differentiation and attenuated periodontal and osteoblastic phenotypes. Our data demonstrate for the first time that the CEMP1 is not only a marker protein for cementoblast‐related cells, but it also regulates cementoblast commitment in periodontal ligament cells. J. Cell. Physiol. 227: 649–657, 2012. © 2011 Wiley Periodicals, Inc.
Exercise training corrects control of spontaneous calcium waves in hearts from myocardial infarction heart failure rats
Authors: Kemi Ole J. , MacQuaide Niall , Hoydal Morten A. , Ellingsen Oyvind , Smith Godfrey L. , Wisloff Ulrik
Published: April 2011

Impaired cardiac control of intracellular diastolic Ca2+ gives rise to arrhythmias. Whereas exercise training corrects abnormal cyclic Ca2+ handling in heart failure, the effect on diastolic Ca2+ remains unstudied. Here, we studied the effect of exercise training on the generation and propagation of spontaneous diastolic Ca2+ waves in failing cardiomyocytes. Post‐myocardial infarction heart failure was induced in Sprague–Dawley rats by coronary artery ligation. Echocardiography confirmed left ventricular infarctions of 40 ± 5%, whereas heart failure was indicated by increased left ventricular end‐diastolic pressures, decreased contraction‐relaxation rates, and pathological hypertrophy. Spontaneous Ca2+ waves were imaged by laser linescanning confocal microscopy (488 nm excitation/505–530 nm emission) in 2 µM Fluo‐3‐loaded cardiomyocytes at 37°C and extracellular Ca2+ of 1.2 and 5.0 mM. These studies showed that spontaneous Ca2+ wave frequency was higher at 5.0 mM than 1.2 mM extracellular Ca2+ in all rats, but failing cardiomyocytes generated 50% (P < 0.01) more waves compared to sham‐operated controls at Ca2+ 1.2 and 5.0 mM. Exercise training reduced the frequency of spontaneous waves at both 1.2 and 5.0 mM Ca2+ (P < 0.05), although complete normalization was not achieved. Exercise training also increased the aborted/completed ratio of waves at 1.2 mM Ca2+ (P < 0.01), but not 5.0 mM. Finally, we repeated these studies after inhibiting the nitric oxide synthase with L‐NAME. No differential effects were found; thus, mediation did not involve the nitric oxide synthase. In conclusion, exercise training improved the cardiomyocyte control of diastolic Ca2+ by reducing the Ca2+ wave frequency and by improving the ability to abort spontaneous Ca2+ waves after their generation, but before cell‐wide propagation. J. Cell. Physiol. 227: 20–26, 2012. © 2011 Wiley Periodicals, Inc.
Potential role of HER2‐overexpressing exosomes in countering trastuzumab‐based therapy
Authors: Ciravolo Valentina , Huber Veronica , Ghedini Gaia C. , Venturelli Elisabetta , Bianchi Francesca , Campiglio Manuela , Morelli Daniele , Villa Antonello , Mina Pamela Della , Menard Sylvie , Filipazzi Paola , Rivoltini Licia , Tagliabue Elda , Pupa Serenella M.
Published: April 2011

Exosomes are endosome‐derived nanovesicles actively released into the extracellular environment and biological fluids, both under physiological and pathological conditions, by different cell types. We characterized exosomes constitutively secreted by HER2‐overexpressing breast carcinoma cell lines and analyzed in vitro and in vivo their potential role in interfering with the therapeutic activity of the humanized antibody Trastuzumab and the dual tyrosine kinase inhibitor (TKI) Lapatinib anti‐HER2 biodrugs. We show that exosomes released by the HER2‐overexpressing tumor cell lines SKBR3 and BT474 express a full‐length HER2 molecule that is also activated, although to a lesser extent than in the originating cells. Release of these exosomes was significantly modulated by the growth factors EGF and heregulin, two of the known HER2 receptor‐activating ligands and naturally present in the surrounding tumor microenvironment. Exosomes secreted either in HER2‐positive tumor cell‐conditioned supernatants or in breast cancer patients' serum bound to Trastuzumab. Functional assays revealed that both xenogeneic and autologous HER2‐positive nanovesicles, but not HER2‐negative ones, inhibited Trastuzumab activity on SKBR3 cell proliferation. By contrast, Lapatinib activity on SKBR3 cell proliferation was unaffected by the presence of autologous exosomes. Together, these findings point to the role of HER2‐positive exosomes in modulating sensitivity to Trastuzumab, and, consequently, to HER2‐driven tumor aggressiveness. J. Cell. Physiol. 227: 658–667, 2012. © 2011 Wiley Periodicals, Inc.
Urokinase induces stromal cell‐derived factor‐1 expression in human hepatocellular carcinoma cells
Authors: Hsu Wen‐Hsiu , Chen Cheng‐Nan , Huang Hai‐I , Lai Yi‐Liang , Teng Chun‐Yuh , Kuo Wu‐Hsien
Published: April 2011

Both the urokinase‐type plasminogen activator (uPA) and the uPA receptor (uPAR) play important roles with regard to hepatocellular carcinoma (HCC) progression and metastasis. Notably, the stromal cell‐derived factor‐1 (SDF‐1) is an important chemokine involved in HCC pathology. However, the influence of uPA on SDF‐1 expression in human HCC cells remains unknown. We investigated the mechanisms underlying the modulation of SDF‐1 expression through uPA stimulation in human HCC SK‐Hep‐1 cells. SK‐Hep‐1 cells stimulation with uPA induced increases in the expression and secretion of SDF‐1. By using specific inhibitors and small interfering RNA, we have demonstrated that the activation of extracellular signal‐related kinase (ERK) and c‐Jun‐NH2‐terminal kinase (JNK) pathways are critical for uPA‐induced SDF‐1 expression. Transcription factor ELISA and chromatin immunoprecipitation assays suggest that uPA increase Sp1‐ and AP‐1‐DNA‐binding activities in SK‐Hep‐1 cells. Inhibition of Sp1 and AP‐1 activations by specific siRNAs blocked the uPA‐induced SDF‐1 promoter activity and expression. The effect of uPA on SK‐Hep‐1 signaling and SDF‐1 expression is mediated by uPAR. In summary, our findings serve to elucidate the uPA/uPAR downstream signaling, providing new insight into the function of uPA in HCC cells. J. Cell. Physiol. 227: 697–704, 2012. © 2011 Wiley Periodicals, Inc.
The tumor suppressor role of CTCF
Authors: Fiorentino Francesco Paolo , Giordano Antonio
Published: April 2011

CTCF is an evolutionary conserved and ubiquitously expressed protein that binds thousands of sites in the human genome. Ectopic expression of CTCF in various normal and tumoral human cell lines inhibits cell division and clonogenicity, with the consequence to consider CTCF a potential tumor‐suppressor factor. In this review article, we focused on the molecular mechanisms engaged by CTCF to modulate the expression of several key‐regulators of differentiation, cellular senescence, cell cycle control and progression, whose expression is frequently altered in tumors. Moreover, we discussed common features of CTCF at each tumor‐related DNA‐binding sequence, such as protein‐partners, post‐translational modifications, and distinctive epigenetic marks establishment. The investigation of the molecular mechanisms engaged by CTCF to modulate tumor‐related genes emphasizes the cell‐type dependency of its tumor suppressor role. Indeed, the ability of CTCF to bind their promoters strictly depends by cell‐type features as DNA methylation, BORIS‐binding and post‐translational modifications as PARYlation. J. Cell. Physiol. 227: 479–492, 2012. © 2011 Wiley Periodicals, Inc.
Cdk5 mediates vimentin ser56 phosphorylation during GTP‐induced secretion by neutrophils
Authors: Lee Ki‐Young , Liu Lijuan , Jin Yan , Fu Song‐bin , Rosales Jesusa L.
Published: April 2011

Secretion by neutrophils contributes to acute inflammation following injury or infection. Vimentin has been shown to be important for secretion by neutrophils but little is known about its dynamics during secretion, which is regulated by cyclin‐dependent kinase 5 (Cdk5). In this study, we sought to examine the vimentin dynamics and its potential regulation by Cdk5 during neutrophil secretion. We show that vimentin is a Cdk5 substrate that is specifically phosphorylated at Ser56. In response to neutrophil stimulation with GTP, vimentin Ser56 was phosphorylated and colocalized with Cdk5 in the cytoplasmic compartment. Vimentin pSer56 and Cdk5 colocalization was consistent with coimmunoprecipitation from stimulated cells. Vimentin Ser56 phosphorylation occurred immediately after stimulation, and a remarkable increase in phosphorylation was noted later in the secretory process. Decreased GTP‐induced vimentin Ser56 phosphorylation and secretion resulted from inhibition of Cdk5 activity by roscovitine or olomoucine or by depletion of Cdk5 by siRNA, suggesting that GTP‐induced Cdk5‐mediated vimentin Ser56 phosphorylation may be related to GTP‐induced Cdk5‐mediated secretion by neutrophils. Indeed, inhibition of vimentin Ser56 phosphorylation led to a corresponding inhibition of GTP‐induced secretion, indicating a link between these two events. While fMLP also induced vimentin Ser56 phosphorylation, such phosphorylation was unaffected by roscovitine, which nonetheless, inhibited secretion, suggesting that Cdk5 regulates fMLP‐induced secretion via a mechanism independent of Cdk5‐mediated vimentin Ser56 phosphorylation. These findings demonstrate the distinct involvement of Cdk5 in GTP‐ and fMLP‐induced secretion by neutrophils, and support the notion that specific targeting of Cdk5 may serve to inhibit the neutrophil secretory process. J. Cell. Physiol. 227: 739–750, 2012. © 2011 Wiley Periodicals, Inc.
PAI‐1 in tissue fibrosis
Authors: Ghosh Asish K. , Vaughan Douglas E.
Published: April 2011

Fibrosis is defined as a fibroproliferative or abnormal fibroblast activation‐related disease. Deregulation of wound healing leads to hyperactivation of fibroblasts and excessive accumulation of extracellular matrix (ECM) proteins in the wound area, the pathological manifestation of fibrosis. The accumulation of excessive levels of collagen in the ECM depends on two factors: an increased rate of collagen synthesis and or decreased rate of collagen degradation by cellular proteolytic activities. The urokinase/tissue type plasminogen activator (uPA/tPA) and plasmin play significant roles in the cellular proteolytic degradation of ECM proteins and the maintenance of tissue homeostasis. The activities of uPA/tPA/plasmin and plasmin‐dependent MMPs rely mostly on the activity of a potent inhibitor of uPA/tPA, plasminogen activator inhibitor‐1 (PAI‐1). Under normal physiologic conditions, PAI‐1 controls the activities of uPA/tPA/plasmin/MMP proteolytic activities and thus maintains the tissue homeostasis. During wound healing, elevated levels of PAI‐1 inhibit uPA/tPA/plasmin and plasmin‐dependent MMP activities, and, thus, help expedite wound healing. In contrast to this scenario, under pathologic conditions, excessive PAI‐1 contributes to excessive accumulation of collagen and other ECM protein in the wound area, and thus preserves scarring. While the level of PAI‐1 is significantly elevated in fibrotic tissues, lack of PAI‐1 protects different organs from fibrosis in response to injury‐related profibrotic signals. Thus, PAI‐1 is implicated in the pathology of fibrosis in different organs including the heart, lung, kidney, liver, and skin. Paradoxically, PAI‐1 deficiency promotes spontaneous cardiac‐selective fibrosis. In this review, we discuss the significance of PAI‐1 in the pathogenesis of fibrosis in multiple organs. J. Cell. Physiol. 227: 493–507, 2012. © 2011 Wiley Periodicals, Inc.
Regulation of endothelial barrier function by TGF‐β type I receptor ALK5: Potential role of contractile mechanisms and heat shock protein 90
Authors: Antonov Alexander S. , Antonova Galina N. , Fujii Makiko , ten Dijke Peter , Handa Vaishali , Catravas John D. , Verin Alexander D.
Published: April 2011

Multifunctional cytokine transforming growth factor‐beta (TGF‐β1) plays a critical role in the pathogenesis of acute lung inflammation by controlling endothelial monolayer permeability. TGF‐β1 regulates endothelial cell (EC) functions via two distinct receptors, activin receptor‐like kinase 1 (ALK1) and activin receptor‐like kinase 5 (ALK5). The precise roles of ALK1 and ALK5 in the regulation of TGF‐β1‐induced lung endothelium dysfunction remain mostly unknown. We now report that adenoviral infection with constitutively active ALK5 (caALK5), but not caALK1, induces EC retraction and that this receptor predominantly controls EC permeability. We demonstrate that ubiquitinated ALK5 and phosphorylated heat shock protein 27 (phospho‐Hsp27) specifically accumulate in the cytoskeleton fraction, which parallels with microtubule collapse, cortical actin disassembly and increased EC permeability. We have found that ALK1 and ALK5 interact with heat shock protein 90 (Hsp90). Moreover, the Hsp90 inhibitor radicicol (RA) prevents accumulation of ubiquitinated caALK5 and phospho‐Hsp27 in the cytoskeletal fraction and restore the decreased EC permeability induced by caALK5. We hypothesize that specific translocation of ubiquitinated ALK5 receptor into the cytoskeleton compartment due to its lack of degradation is the mechanism that causes the divergence of caALK1 and caALK5 signaling. J. Cell. Physiol. 227: 759–771, 2012. © 2011 Wiley Periodicals, Inc.
Biological AFM: where we come from – where we are – where we may go
Authors: Casuso Ignacio , Rico Felix , Scheuring Simon
Published: April 2011

Biological atomic force microscopy (AFM) is a fast growing and advancing field. This review's objective is to overview the state of the art and to retrace achievements of biological AFM as presented by past and present research, and wishes to give a (subjective) outlook where AFM may go in the upcoming years. The following areas of interest are discussed: High‐resolution imaging, cell imaging, single molecule force spectroscopy, cell mechanical measurements, combined AFM instrumentation, and AFM instrumentation. Of all these topics, particular representative examples are shown, each of them standing for a variety of achievements by many research groups. Copyright © 2011 John Wiley & Sons, Ltd.
Outcomes of hepatic resection for huge hepatocellular carcinoma (≥10 cm in diameter)
Authors: Yamashita Yo‐ichi , Taketomi Akinobu , Shirabe Ken , Aishima Shinichi , Tsuijita Eiji , Morita Kazutoyo , Kayashima Hiroto , Maehara Yoshihiko
Published: April 2011

Background

The object of the current study was to review the outcomes of hepatic resection for hepatocellular carcinoma (HCC) ≥ 10 cm.

Methods

Between 1995 and 2007, fifty‐three patients with HCC ≥ 10 cm underwent hepatic resection, and clinical data were compared to those of patients with non‐surgical treatment (n = 12). Surgical results for HCC ≥ 10 cm were compared to those of patients with HCC < 10 cm (n = 412). The independent poor prognostic factors of the patients with HCC ≥ 10 cm were identified.

Results

Overall survival was significantly better in patients with hepatic resection for HCC ≥ 10 cm than in those with non‐surgical treatment (P < 0.01). Survival rates of patients with hepatic resection for HCC ≥ 10 cm were 35% at 5 years. Morbidity and mortality rate were statistically equal. The independent poor prognostic factors of patients with hepatic resection for HCC ≥ 10 cm were revealed: T4 status, macroscopic tumor thrombus in portal vein (VP+), and the use of intra‐operative transfusion.

Conclusion

Hepatic resections for HCC ≥ 10 cm are safe and efficacious. Minimizing intra‐operative blood loss and the establishment of an effective systemic treatment for patients with HCC ≥ 10 cm in T4 appear to be critical. J. Surg. Oncol. 2011; 104:292–298. © 2011 Wiley‐Liss, Inc.
Unresectable peritoneal carcinomatosis from colorectal cancer: A single center experience
Authors: Hompes Daphne , Boot Henk , van Tinteren Harm , Verwaal Victor
Published: April 2011

Background and objectives

For unresectable peritoneal carcinomatosis (PC) median overall survival (OS) is 5–6 months. This article analyzes patients with PC from colorectal cancer (CRC) uneligible for debulking and hyperthermic intra‐peritoneal chemotherapy, describing patient‐ and tumor‐related factors possibly affecting survival.

Patients and Methods

From 2005 to 2009, 43 patients presented with unresectable PC from CRC: male/female ratio was 29/14, median age was 57.1 years (range 34.8–76.8). “Unresectability” was defined as: six to seven abdominal regions affected by PC, involvement of mesentery or small bowel in the PC, presence of liver metastases, retroperitoneal lymph nodes, vascular invasion, and/or neural invasion.

Results

Median time interval between diagnosis of the primary tumor and diagnosis of PC was 7.2 months (range 0.0–102.3). Primary tumors were right‐sided in >50% and had been previously resected in >58%, 74.4% of PC occurred synchronously. Ascites was present at primary diagnosis in 37.2%. In 70% of cases, six to seven abdominal regions were affected and in 58.1% PC involved small bowel/mesentery. Systemic disease was present in 16.3%. In 18.6% of patients, a palliative diversion or ostomy was constructed.

Median OS was 6.3 months (range 0.4–33.1). Thirty‐one patients (72.1%) received palliative chemotherapy. Median OS was 9.3 months (range 0.9–33.1) with versus 3.1 months (range 0.4–6.5) without chemotherapy (P = 0.000), with less favorable patient and tumor characteristics in the latter group. No other factors clearly influenced OS.

Conclusion

Palliative chemotherapy results in better OS, but this is probably attributable to factors influencing the patient's general condition. J. Surg. Oncol. 2011; 104: 269–273. © 2011 Wiley‐Liss, Inc.
Class II radical hysterectomy for stage I–IIA cervix cancer: Prognostic factors associated to recurrence and survival in a northeast Brazil experience
Authors: Bezerra Artur Lício Rocha , Martins Mário Rino , Bezerra Simone Maria Muniz da Silva , Figueiroa José Natal , Batista Thales Paulo
Published: April 2011

Background

The main aim of this study was describe the author's experience with class II radical hysterectomy and pelvic lymphadenectomy to treat stage I–IIA cervix cancer and reexamine some prognostic factors associated with disease recurrence and patient survival in this data from northeast Brazil.

Methods

A cross‐sectional study was carried out on patients treated at our Centers from January 2001 to December 2008. Statistical analyses were performed using conventional methods.

Results

Eighty‐eight patients were selected to analysis. Over the 7.3‐year follow‐up, 80 (91%) patients were alive and 8 (9%) disease recurrences were observed. Overall 1‐, 2‐, and 5‐year patients survival was 96.5%, 95.3%, and 84%, respectively. Recurrence was associated to tumor size ≥1 cm (P = 0.021) and compromised vaginal margin (P = 0.020). Lower survivals were associated to tumor size ≥1 cm (P = 0.038), compromised vaginal margin (P < 0.001), and lymph node metastasis (P = 0.024). Postoperative complications (n = 11) included wound infection (5.7%), partial wound dehiscence (3.4%), and bladder atony (3.4%).

Conclusions

Class II radical hysterectomy has provided appropriated disease control of cervix cancer with low morbidity in our experience. Furthermore, tumor size and compromised vaginal margin were significantly associated to recurrence. These factors and lymph node metastasis were also associated to lower 5‐year survival according to our analysis. J. Surg. Oncol. 2011; 104:255–259. © 2011 Wiley‐Liss, Inc.
Origin and maintenance of the intestinal cancer stem cell
Authors: Davies Emma J. , Marsh Victoria , Clarke Alan R.
Published: April 2011

Colorectal cancer is one of the most common cancers in the western world and its incidence is steadily increasing. Understanding the basic biology of both the normal intestine and of intestinal tumorigenesis is vital for developing appropriate and effective cancer therapies. However, relatively little is known about the normal intestinal stem cell or the hypothetical intestinal cancer stem cell, and there is much debate surrounding these areas. This review briefly describes our current understanding of the properties of both the intestinal stem cell and the intestinal cancer stem cell. We also discuss recent theories regarding the origin of the intestinal cancer stem cell, and the signals required for its maintenance and proliferation. Finally, we place the relevance of cancer stem cell research into context by discussing potential clinical applications of targeting the intestinal cancer stem cell. © 2011 Wiley‐Liss, Inc.
Proteasomal non‐catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas
Authors: Matsuyama Yasushi , Suzuki Motoshi , Arima Chinatsu , Huang Qin Miao , Tomida Shuta , Takeuchi Toshiyuki , Sugiyama Ryoji , Itoh Yasutomo , Yatabe Yasushi , Goto Hidemi , Takahashi Takashi
Published: April 2011

We previously identified PSMD2, a subunit of the 19S regulatory complex of proteasomes, as a constituent of a signature associated with the acquisition of metastatic phenotype and poor prognosis in lung cancers. In the present study, we found that knockdown of PSMD2 decreased proteasome activity, and induced growth inhibition and apoptosis in lung cancer cell lines. These effects of siRNA‐mediated PSMD2 inhibition were associated with changes in the balance between phosphorylated AKT and p38, as well as with induction of p21. In addition, patients with higher PSMD2 expression had poorer prognosis and a small fraction of lung cancer specimens carried increased copies of PSMD2. Notably, our findings clearly illustrate that lung adenocarcinomas can be divided into two groups; those with and without general upregulation of proteasome pathway genes including PSMD2. This general upregulation was significantly more prevalent in the non‐terminal respiratory unit (non‐TRU)‐type, a recently proposed genetically and clinicopathologically relevant expression profile‐defined classification of adenocarcinomas (P < 0.001 by Fisher's exact test). Patients with adenocarcinomas with general upregulation had significantly shorter survival after potentially curative resection (P = 0.0001 by log‐rank test) independent of disease stage, as shown by multivariate Cox regression analysis. Our results suggest that PSMD2 may be a good molecular target candidate and that other co‐regulated proteasome pathway genes and/or their common regulator(s) might also be potential targets, warranting future study including elucidation of the underlying common regulatory mechanism. © 2011 Wiley‐Liss, Inc.
Mechanistic basis for the chemopreventive effects of black raspberries at a late stage of rat esophageal carcinogenesis
Authors: Wang Li‐Shu , Dombkowski Alan A. , Seguin Claire , Rocha Claudia , Cukovic Daniela , Mukundan Anju , Henry Cassandra , Stoner Gary D.
Published: April 2011

The present study used a postinitiation protocol to investigate molecular mechanisms by which black raspberries (BRBs) influence the late stages of N‐nitrosomethylbenzylamine (NMBA)‐induced esophageal tumorigenesis in rats. F344 rats were injected with NMBA and then fed either control diet or a diet containing 5% BRB powder. Control rats were injected with DMSO/water (20:80), the vehicle for NMBA. Esophagi from control, NMBA‐ and NMBA + BRB‐treated rats were collected at 35 wk for histopathological, molecular, and immunohistochemical analyses. Treatment with 5% BRBs reduced the number of dysplastic lesions and the number and size of esophageal papillomas in NMBA‐treated rats. When compared to esophagi from control rats, NMBA treatment led to the differential expression of 4807 genes in preneoplastic esophagus (PE) and 17 846 genes in esophageal papillomas. Dietary BRBs modulated 626 of the 4807 differentially expressed genes in PE and 625 of the 17 846 differentially expressed genes in esophageal papillomas towards normal levels of expression. In both PE and in papillomas, BRBs modulated the mRNA expression of genes associated with carbohydrate and lipid metabolism, cell proliferation and death, and inflammation. In these same tissues, BRBs modulated the expression of proteins associated with proliferation, apoptosis, inflammation, angiogenesis, and both cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Interestingly, matrix metalloproteinases involved in tissue invasion and metastasis, and proteins associated with cell–cell adhesion, were also modulated by BRBs. This is the first report of the effects of berries on the expression of genes associated with the late stages of rat esophageal carcinogenesis. © 2011 Wiley‐Liss, Inc.
Ultraviolet B radiation activates NF‐κB and induces iNOS expression in HR‐1 hairless mouse skin: Role of IκB kinase‐β
Authors: Chang Eun‐Jin , Kundu Joydeb Kumar , Liu Lijia , Shin Jun‐Wan , Surh Young‐Joon
Published: April 2011

Exposure to ultraviolet B (UVB) radiation is known to cause inflammatory tissue damage and skin cancer. One of the molecular links between inflammation and cancer is the eukaryotic transcription factor nuclear factor‐kappaB (NF‐κB), which is known to regulate expression of various pro‐inflammatory genes including inducible nitric oxide synthase (iNOS). The present study was aimed at elucidating the molecular mechanisms underlying UVB‐induced NF‐κB activation and iNOS expression in hairless mouse skin. Irradiation of male HR‐1 hairless mouse skin with UVB (5 kJ/m2) resulted in increased degradation of IκBα, nuclear translocation of p65 and p50, and the DNA binding of NF‐κB. Exposure to UVB radiation induced the phosphorylation and the catalytic activity of an upstream kinase IκB kinase‐β (IKKβ). Pharmacological inhibition of IKKβ attenuated UVB‐induced NF‐κB activation in mouse skin. Irradiation of mouse skin with UVB also increased phosphorylation of extracellular signal‐regulated kinase (ERK) and p38 mitogen‐activated protein (MAP) kinase. Pretreatment with SC‐514, a specific inhibitor of IKKβ, attenuated UVB‐induced phosphorylation of ERK and p38 MAP kinase. A kinetic study showed that UVB significantly increased the expression of iNOS in mouse skin at 6 h postirradiation, which was abrogated by pretreatment with SC‐514. In conclusion, the upstream kinase IKKβ is involved in UVB‐induced activation of MAP kinases and NF‐κB, and expression of iNOS in mouse skin. © 2011 Wiley‐Liss, Inc.
Exploring genomic profiles of hepatocellular carcinoma
Authors: Woo Hyun Goo , Park Eun Sung , Thorgeirsson Snorri S. , Kim Yoon Jun
Published: April 2011

Gene expression profiling using microarray technologies provides a powerful approach to understand complex biological systems and the pathogenesis of diseases. In the field of liver cancer research, a number of genome‐wide profiling studies have been published. These studies have provided gene sets, that is, signature, which could classify tumors and predict clinical outcomes such as survival, recurrence, and metastasis. More recently, the application of genomic profiling has been extended to identify molecular targets, pathways, and the cellular origins of the tumors. Systemic and integrative analyses of multiple data sets and emerging new technologies also accelerate the progress of the cancer genomic studies. Here, we review the genomic signatures identified from the genomic profiling studies of hepatocellular carcinoma (HCC), and categorize and characterize them into prediction, phenotype, function, and molecular target signatures according to their utilities and properties. Our classification of the signatures would be helpful to understand and design studies with extended application of genomic profiles. © 2011 Wiley‐Liss, Inc.