bluuebunny/crossref_metadata_2025 huggingface dataset:
A Meta‐Analysis of the relationship between the Rorschach Ego Impairment Index (EII) and psychiatric severity
Authors: Diener Marc J. , Hilsenroth Mark J. , Shaffer Seth A. , Sexton James E.
Published: October 2010

The present study examined the relationship between the Rorschach Ego Impairment Index (EII) and psychiatric severity. Search procedures yielded 13 independent samples (total N = 1402, average n = 108, standard deviation = 90) for inclusion in the meta‐analysis. Inter‐rater reliability analyses demonstrated that coding of effect sizes and moderator variables was completed with good to excellent reliability. Results indicated that higher EII scores were associated with greater psychiatric severity, with an overall weighted effect size of r = 0.29, p = 0.000002 (95% confidence interval = 0.17–0.40), supporting the EII's validity as a measure of psychological impairment. Publication bias analyses did not indicate any significant cause for concern regarding the results. The data were demonstrably heterogeneous (Q = 56.82, p = 0.0000001), and results of post‐hoc tests indicated that effect sizes with dependent variables obtained via researcher ratings were significantly larger than any of the following: effect sizes with dependent variables obtained via clinician ratings, informant ratings, information about level of treatment or placement status or self‐report ratings (p's = 0.0005, 0.003, <0.001, <0.001, respectively). In addition, there was a trend for effect sizes based on performance‐based measures to be larger than those based on information about level of treatment or placement status (p = 0.098) as well as those based on self‐report measures (p = 0.076). Other moderator analyses were non‐significant (p 's > 0.10). Copyright © 2010 John Wiley & Sons, Ltd.

Key Practitioner Message:

• The Rorschach Ego Impairment Index (EII) demonstrated validity in measuring psychiatric severity across a range of normative, outpatient, residential, and inpatient samples.

• The degree of the EII's validity in assessing psychiatric severity compared favorably to the overall validity of the Rorschach and the MMPI.

• The EII appears to be most valid in capturing psychiatric severity as measured by researcher ratings of social competency or estimated ego impairment.
Can endogenous hyperinsulinaemia explain the increased risk of cancer development and mortality in type 2 diabetes: evidence from mouse models
Authors: LeRoith Derek
Published: October 2010

There is now convincing evidence of an increased risk of patients with obesity or type 2 diabetes developing cancer. To understand the possible causation, type 2 diabetic muscle lysine to arginine (MKR) mice were studied. Introduction of mammary tumour cell lines resulted in aggressive growth of the mammary tumours in the hyperinsulinaemic MKR female mice. Blocking the insulin receptor activation or reducing the hyperinsulinaemia reduced the mammary tumour burden. Thus, hyperinsulinaemia may be one of the factors in the increased breast cancer risk seen with obesity and type 2 diabetes. Copyright © 2010 John Wiley & Sons, Ltd.
Caspase 3 is not essential for the induction of anergy or multiple pathways of CD8+ T‐cell death
Authors: Murakami Kiichi , Liadis Nicole , Sarmiento Janice , Elford Alisha R. , Woo Minna , Nguyen Linh T. , Mak Tak W. , Ohashi Pamela S.
Published: October 2010

T‐cell death is a fundamental process that is intricately regulated at multiple phases during T‐cell differentiation, tolerance induction and the decline of the immune response. Caspase 3 is a crucial molecule regulating both mitochondrial and death receptor apoptotic pathways and therefore we were interested in examining the role of caspase 3 in T cells. Using P14 and H‐Y CD8+ TCR‐transgenic models, our analysis has shown that caspase 3 is not required for thymic negative selection. In addition, caspase 3 does not play a prominent role in the contraction phase following acute viral infection, nor clonal deletion of CD8+ T cells under tolerizing conditions. Surprisingly, our studies demonstrate that caspase 3 was not required for the induction of CD8+ T‐cell anergy in vivo, contrary to published reports using CD4+ T cells. Therefore, these results demonstrate that caspase 3 is not essential in CD8+ T cells for multiple forms of thymic or peripheral tolerance, nor the contraction phase after an acute anti‐viral response.
Tertiary lymphoid organs in renal allografts can be associated with donor‐specific tolerance rather than rejection
Authors: Brown Kathryn , Sacks Steven H. , Wong Wilson
Published: October 2010

Tertiary lymphoid organs can form at sites of chronic inflammation. Their presence has been mainly associated with tissue destruction. In transplantation, there is a dynamic immune response as in chronic inflammation. Indeed, the presence of tertiary lymphoid organs has been associated with chronic rejection. In addition to a destructive alloimmune response, secondary lymphoid organs are also important in transplant tolerance. We hypothesised that tertiary lymphoid organs may also form during transplantation tolerance as this process also requires an active local immune response. If so, their presence may enhance tolerance, resulting in better graft function rather than chronic rejection. Using a mouse kidney allograft model of tolerance, we demonstrate the formation of tertiary lymphoid organs within tolerated allografts. Tertiary lymphoid organs are supplied by high endothelial venules, and contain T and B cells, macrophages, DC, Foxp3+ T cells, donor MHC class II+ cells and recipient cells presenting donor‐derived allopeptides. Formation of tertiary lymphoid organs and the presence of immune cells within them are associated with superior graft function, suggesting that tertiary lymphoid organs act to amplify the prevailing immune response, be it a tolerant and beneficial immune response or the previously described destructive alloimmunity.
Facile and Efficient Synthesis of Benzoxazoles and Benzimidazoles: The Application of Hantzsch Ester 1,4‐Dihydropyridines in Reductive Cyclization Reactions
Authors: Xing Rui‐Guang , Li Ya‐Nan , Liu Qiang , Meng Qing‐Yuan , Li Jing , Shen Xiao‐Xia , Liu Zhengang , Zhou Bo , Yao Xiaojun , Liu Zhong‐Li
Published: October 2010

Both benzoxazole and benzimidazole are common heterocyclic scaffolds in biologically active and medicinally significant compounds. Reductive cyclization of ortho‐substituted nitrobenzene derivatives provides an attractive route to benzoxazole or benzimidazole ring formation. Unfortunately, only a few synthetic methods by reductive cyclization ofortho‐nitro compounds have been reported and the yields are rather low. In continuation of the development of biomimetic reductants in synthetically useful organic transformations, Hantzsch ester 1,4‐dihydropyridine (HEH), analogues of NAD(P)H, has attracted a considerable amount of attention. Hence, we wish to report that benzoxazoles and benzimidazoles can be efficiently synthesized by the reaction of ortho‐substituted nitrobenzene derivatives with HEH catalyzed by Pd/C. A range of functionalized ortho‐nitrophenyl esters or ortho‐nitrophenyl amides were efficiently reduced by HEH and cyclized to the corresponding benzoxazoles or benzimidazoles. Especially, working in the presence of the same substituents, benzimidazoles could be obtained in higher yields with respect to the corresponding benzoxazoles. Moreover, in the present work, the recycling of Pd/C was studied and was shown to maintain its high catalytic activity over five runs. On the basis of our experimental results and DFT calculations, a plausible reaction mechanism was proposed.
G‐Quadruplex‐Based DNAzymes Aptasensor for the Amplified Electrochemical Detection of Thrombin
Authors: Shen Bijun , Wang Qi , Zhu Dan , Luo Juanjuan , Cheng Guifang , He Pingang , Fang Yuzhi
Published: October 2010

A novel G‐quadruplex‐based DNAzymes aptasensor for the amplified electrochemical detection of thrombin has been described. The aptasensor utilized a combination of hemin and guanine‐rich thrombin‐binding aptamer (TBA) to form horseradish peroxidase (HRP)‐mimicking DNAzymes with peroxidase catalytic activity. In the presence of thrombin, the enzyme activity could be extensively promoted, thereby providing the amplified electrochemical readout signals for detecting thrombin. This aptasensor exhibited high sensitivity and selectivity for thrombin determination, which enabled the analysis of thrombin with a detection limit of 6×10–11 M. On the basis of results, this method could have broad applications in the detection of proteins and other biomolecules.
Depressive symptoms and executive functioning in stroke patients: a follow‐up study
Authors: Bour A. , Rasquin S. , Limburg M. , Verhey F.
Published: October 2010

Background

Cognitive and emotional sequellae are commonly observed in stroke patients and these symptoms often co‐occur. Diagnosis can be difficult since symptoms of depression and executive dysfunction overlap.

Objective

To study the longitudinal relationship between depressive symptoms and executive dysfunction in stroke patients.

Methods

The study comprises of 116 first‐ever stroke patients who were followed‐up for 2 years and who were assessed for emotional and cognitive sequellae after 1, 6, 12, and 24 months. Emotional disturbances were evaluated using the SCL‐90 depression subscale. Executive functions were assessed using compound scores of a combination of the interference scores of the Stroop Colour Word Test and the Concept Shifting Test.

Results

Twenty‐five patients suffered from both depressive symptoms and executive dysfunction, 28 patients were depressed with no signs of executive dysfunction, and 13 patients showed executive dysfunction with no depressive symptoms. Patients with executive dysfunction had higher mean SCL‐90‐D scores compared to patients with no executive dysfunction (30.9 (SD 11.7) versus 26.2 (SD 11.1, p = 0.037). Depressive symptoms were predictive for executive dysfunction in a regression analysis corrected for age, sex, and diabetes mellitus but not after additional correction for pre‐existent brain damage and other vascular risk factors. After 2 years 66.6 and 53.3% of patients with both depressive symptoms and executive dysfunction at baseline still had depressive symptoms and executive dysfunctions respectively and had worse prognostic outcome than patients with depressive symptoms or executive dysfunction alone.

Conclusions

Symptoms of depression and executive dysfunction are highly prevalent in stroke patients and often co‐occur. These patients are more at risk for poor stroke outcome, chronic depression, and cognitive deterioration. Copyright © 2010 John Wiley & Sons, Ltd.
Study of direction of cyclization of 1‐azolil‐4‐aryl/alkyl‐thiosemicarbazides
Authors: Siwek Agata , Wujec Monika , Dobosz Maria , Wawrzycka‐Gorczyca Irena
Published: October 2010

On a four series of 1‐azolil‐4‐aryl/alkyl‐thiosemicabazides, a study on the influence of azole moiety on the capability for intramolecular cyclization and its direction was carried out. It was found that for 4‐aryl/alkyl‐thiosemicabazides with triazole, imidazole, or pyrrole moiety at N‐1 nitrogen atom possible products were only s‐triazoles, both in alkaline and acidic medium. Successful dehydrocyclization of 1‐azolil‐4‐aryl/alkyl‐thiosemicarbazides leading to a thiadiazole has been documented only for a series of 1‐(4‐methyl‐1,2,3‐thiadiazol‐5‐yl‐carbonyl)‐4‐aryl/alkyl‐thiosemicarbazides. It can be speculative that the determination of pKa value of oxygen atom of 1‐azolil‐4‐aryl/alkyl‐thiosemicarbazide can be a very valuable parameter in the prediction of the possibility of dehydrocyclization to form thiadiazole. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:521–532, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20643
Family income and child cognitive and behavioural development in the United Kingdom: does money matter?
Authors: Violato Mara , Petrou Stavros , Gray Ron , Redshaw Maggie
Published: October 2010

This study investigates the extent to which family income is associated with an extensive range of child cognitive and behavioural outcomes in a cohort of almost 19 000 British children born between 2000 and 2001. Merging the economists' and developmental psychologists' approaches, it also attempts to identify the main mechanisms through which family economic resources translate into better developmental outcomes for children. The relative and joint relevance of three groups of mediating factors (parental stress, parental investment and other family‐related pathways), identified from the recent economic and psychological literature, are examined both in a cross‐sectional (‘mopping‐up’ approach) and in a panel data (fixed effects models) context. Results indicate a weak or absent direct effect of family economic resources on child development after controlling for potential mediating mechanisms. The study also identifies key mediating factors (e.g. maternal depression, a cognitively stimulating home environment, parenting practices and length of breastfeeding) that could be targeted by government initiatives in order to effectively improve children's intellectual development and behaviour beyond what income redistribution can achieve. Copyright © 2010 John Wiley & Sons, Ltd.
Kinetics of Charge‐Transfer Reactions at Nanoscopic Electrochemical Interfaces
Authors: Wang Yixian , Velmurugan Jeyavel , Mirkin Michael V.
Published: October 2010

After several decades of intensive studies, the questions about the magnitudes of rate constants of rapid heterogeneous electron transfer (ET) and ion transfer (IT) reactions remain open. The fabrication of nanometer‐sized metal electrodes and nanopipets enabled electrochemical studies of rapid charge transfer processes at solid/liquid and liquid/liquid nanointerfaces. The nanoelectrochemical techniques offer numerous advantages such as fast mass‐transfer rate and simplified analysis of data obtained under steady‐state conditions. At the same time, kinetic data obtained at nanointerfaces may be affected by double layer effects, deviations from classical electrochemical theory, and other size‐related phenomena. Nanoelectrochemical measurements are also plagued by difficulties in characterizing nanometer‐sized interfaces and conductor/insulator boundaries. In this review, we discuss the results of fast electron and ion transfer kinetics measurements at nanointerfaces, along with related reliability problems and some approaches to fixing them.
The Big Mac Index two decades on: an evaluation of burgernomics
Authors: Clements Kenneth W. , Lan Yihui , Seah Shi Pei
Published: October 2010

The Big Mac Index, introduced by The Economist magazine more than two decades ago, claims to provide the ‘true value’ of a large number of currencies. This paper assesses the economic value of this index. We show that (i) the index suffers from a substantial bias; (ii) once the bias is allowed for, the index tracks exchange rates reasonably well over the medium to longer term in accordance with relative purchasing power parity theory; (iii) the index is at least as good as the industry standard, the random walk model, in predicting future currency values for all but short‐term horizons; and (iv) future nominal exchange rates are more responsive than prices to currency mispricing. While not perfect, at a cost of less than $US10 per year, the index seems to provide good value for money. Copyright © 2011 John Wiley & Sons, Ltd.
Specific replication factors are targeted by different genotoxic agents to inhibit replication
Authors: Sharma Aparna , Kar Ananya , Kaur Manpreet , Ranade Sourabh M. , Sankaran Aparna , Misra Shashank , Rawat Kanchan , Saxena Sandeep
Published: October 2010

When mammalian cells experience DNA damaging stress, they block DNA replication to avoid erroneous replication of the damaged template. The cells that are unable to respond to DNA damage continue faulty DNA replication that results in incorporation of genomic lesions. To understand the regulation of replication machinery during stress, systemic studies have been carried out but they have been restricted to the evaluation of the mRNA levels and therefore have not been able to identify post‐transcriptional changes, vital for immediate blocking of the progressing DNA replication. We have recently discovered that an essential replication factor is downregulated by radiation stress. In this study, we have carried out a systematic evaluation of protein levels of entire replication apparatus after different types of DNA damage. We report that, independent of the status of p53 and retinoblastoma protein, mammalian cells choose targets that are essential for prereplication, preinitiation, and elongation phases of replication. We imposed different kinds of stress to discern whether similar or unique responses are invoked, and we propose a model for inhibition of replication machinery in which mammalian cells target specific essential replication factors based on the experienced stress. © 2010 IUBMB IUBMB Life, 62(10): 764–775, 2010
Improving the Wang–Landau algorithm for polymers and proteins
Authors: Swetnam Adam D. , Allen Michael P.
Published: October 2010

The 1/t Wang–Landau algorithm is tested on simple models of polymers and proteins. It is found that this method resolves the problem of the saturation of the error present in the original algorithm for lattice polymers. However, for lattice proteins, which have a rough energy landscape with an unknown energy minimum, it is found that the density of states does not converge in all runs. A new variant of the Wang–Landau algorithm that appears to solve this problem is described and tested. In the new variant, the optimum modification factor is calculated in the same straightforward way throughout the simulation. There is only one free parameter for which a value of unity appears to give near optimal convergence for all run lengths for lattice homopolymers when pull moves are used. For lattice proteins, a much smaller value of the parameter is needed to ensure rapid convergence of the density of states for energies discovered late in the simulation, which unfortunately results in poor convergence early on in the run. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011.
Cell surface N‐glycans‐mediated isolation of mouse neural stem cells
Authors: Hamanoue Makoto , Okano Hideyuki
Published: October 2010

The isolation of neural stem cells (NSCs) has been hampered by the lack of valid cell‐surface antigens on NSCs, and novel valuable markers have been proposed. Glycan (oligosaccharide chain) is a potential candidate as a marker to isolate NSCs, because the species and the combination order of saccharides in glycan generate remarkable structural diversity and specificity. At present, the expression of hundreds of glycoconjugates with glycans have been found in the NSCs; however, just a few glycan‐epitopes have been identified as valuable cell‐surface markers. This review focused on the isolation of NSC using glycoprotein, especially complex type N‐glycans. The cell‐surface N‐glycan‐mediated isolation of NSCs is therefore expected to provide a comprehensive understanding of the biologic characteristics of NSCs in the brain, and thereby help to develop novel strategies in the field of regenerative medicine. J. Cell. Physiol. 226: 1433–1438, 2011. © 2010 Wiley‐Liss, Inc.
PINCH: More than just an adaptor protein in cellular response
Authors: Kovalevich Jane , Tracy Brittany , Langford Dianne
Published: October 2010

Particularly interesting new cysteine‐histidine‐rich protein (PINCH) is a LIM‐domain‐only adaptor protein involved in protein recruitment, subsequent assembly of multi‐protein complexes, and subcellular localization of these complexes. PINCH is developmentally regulated and its expression is critical for proper cytoskeletal organization and extracellular matrix adhesion. Although PINCH has no catalytic abilities, the PIP (PINCH–ILK–parvin) complex serves as a link between integrins and components of growth factor receptor kinase and GTPase signaling pathways. Accordingly, PINCH‐mediated signaling induces cell migration, spreading, and survival. Further research on the signaling cascades affected by PINCH is key to appreciating its biological significance in cell fate and systems maintenance, as the developmental functions of PINCH may extend to disease states and the cellular response to damage. PINCH is implicated in a diverse array of diseases including renal failure, cardiomyopathy, nervous system degeneration and demyelination, and tumorigenesis. This review presents evidence for PINCH's structural and functional importance in normal cellular processes and in pathogenesis. The current data for PINCH expression in nervous system disease is substantial, but due to the complex and ubiquitous nature of this protein, our understanding of its function in pathology remains unclear. In this review, an overview of studies identifying PINCH binding partners, their molecular interactions, and the potentially overlapping role(s) of PINCH in cancer and in nervous system diseases will be discussed. Many questions remain regarding PINCH's role in cells. What induces cell‐specific PINCH expression? How does PINCH expression contribute to cell fate in the central nervous system? More broadly, is PINCH expression in disease a good thing? Clarifying the ambiguous functions of PINCH expression in the central nervous system and other systems is important to understand more clearly signaling events both in health and disease. J. Cell. Physiol. 226: 940–947, 2011. © 2010 Wiley‐Liss, Inc.
The relationship between the Wnt/β‐catenin and TGF‐β/BMP signals in the intervertebral disc cell
Authors: Hiyama Akihiko , Sakai Daisuke , Tanaka Masahiro , Arai Fumiyuki , Nakajima Daisuke , Abe Koichiro , Mochida Joji
Published: October 2010

Degeneration of the lumbar intervertebral disc (IVD) is a cause of low back pain. In osteoarthritis patients, an increase in β‐catenin accumulation has been reported. However, the molecular mechanisms involved in IVD remain unclear. In the present study, we examined the relationship of Wnt/β‐catenin and transforming growth factor‐β (TGF‐β)/bone morphogenetic protein (BMP) signals in the IVDs. We found that treatment of nucleus pulposus (NP) cells with the Wnt/β‐catenin activator lithium chloride (LiCl) results in the increased expression of β‐catenin mRNA and protein, and cell proliferation is decreased due to the activation of the Wnt/β‐catenin signals through the suppression of c‐myc and cyclin‐D1. In addition, T‐cell‐specific transcription factor (TCF) promoter activity was found to increase the following stimulation with LiCl alone, and was further increased when BMP2 was added, in comparison to the control group. We further observed the effects of treatment with PD98059, a specific inhibitor of the mitogen‐activated protein kinase pathway, on TCF promoter activity in NP cells. These effects were largely attenuated by PD98059. Moreover, when transfected IVDs were co‐transfected with R‐Smad expression plasmids, there was a significant decrease in TCF reporter activity. We thereafter evaluated the effects of increased Wnt/β‐catenin activity on the transcriptional activity of the Smad binding element (SBE). As a result, LiCl suppressed the activity of SBE reporter activity. The present study demonstrates for the first time that there are opposing effects between the Wnt/β‐catenin and TGF‐β/BMP signals in IVDs, which is consistent with the Wnt/β‐catenin signals contributing to the pathogenesis of IVD degeneration. J. Cell. Physiol. 226: 1139–1148, 2011. © 2010 Wiley‐Liss, Inc.
Nestin(+) stem cells independently contribute to neural remodelling of the ischemic heart
Authors: Béguin Pauline C. , El‐Helou Viviane , Gillis Marc‐Antoine , Duquette Natacha , Gosselin Hugues , Brugada Ramon , Villeneuve Louis , Lauzier Dominique , Tanguay Jean‐Francois , Ribuot Christophe , Calderone Angelino
Published: October 2010

Recent studies have revealed the existence of multipotent nestin‐immunoreactive cells in the adult mammalian heart. These cells were recruited to infarct site following ischemic injury and differentiated to a vascular lineage leading to de novo blood vessel formation. Here, we show that a sub‐population of cardiac resident nestin(+) cells can further differentiate to a neuronal‐like fate in vivo following myocardial infarction. In the ischemically damaged rat heart, neurofilament‐M(+) fibres were detected innervating the peri‐infarct/infarct region and the preponderance of these fibres were physically associated with processes emanating from nestin(+) cells. One week after isogenic heterotopic cardiac transplantation, the beating transplanted rat heart was devoid of neurofilament‐M(+) fibre staining. The superimposition of an ischemic insult to the transplanted heart led to the de novo synthesis of neurofilament‐M(+) fibres by cardiac resident nestin(+) cells. Nerve growth factor infusion and the exposure of normal rats to intermittent hypoxia significantly increased the density of neurofilament‐M(+) fibres in the heart. However, these newly formed neurofilament‐M(+) fibres were not physically associated with nestin(+) processes. These data highlight a novel paradigm of reparative fibrosis as a subpopulation of cardiac resident nestin(+) cells directly contributed to neural remodelling of the peri‐infarct/infarct region of the ischemically damaged rat heart via the de novo synthesis of neurofilament‐M fibres. J. Cell. Physiol. 226: 1157–1165, 2011. © 2010 Wiley‐Liss, Inc.
Lack of association between stretch‐activated and volume‐activated Cl− currents in hepatocellular carcinoma cells
Authors: Mao Jianwen , Xu Bin , Li Hongzhi , Chen Lixin , Jin Xiaobao , Zhu Jiayong , Wang Weizhang , Zhu Linyan , Zuo Wanhong , Chen Weiqiang , Wang Liwei
Published: October 2010

Stretch‐activated chloride currents (ICl,SA) have been considered to be a component of volume‐activated chloride currents (ICl,vol) for some time. This is due to a similarity in biophysical and pharmacological properties that involve a membrane curvature‐induced mechanism and rearrangement of the cytoskeleton induced by cell swelling or membrane stretch. In the present study, we demonstrated that current density, along with the time taken from the activation of currents to the peak, were significantly different between the two currents, in highly metastatic human hepatocellular carcinoma cells. In addition, the activation of ICl,vol or ICl,SA, induced maximally by hypotonic solutions or membrane stretch, respectively, did not affect the following activation of the other one. Moreover, neither inhibition of ICl,vol by sh‐ClC‐3 transfection, nor functional blocking of ICl,vol by intracellular dialysis of anti‐ClC‐3 antibody had an effect on the activation and properties of ICl,SA. Collectively, our results suggest that ICl,SA is different from ICl,vol in activation mechanism and/or in molecular entity responsible for formation of the currents. ClC‐3 is involved in the activation of ICl,vol, but not of ICl,SA. J. Cell. Physiol. 226: 1176–1185, 2011. © 2010 Wiley‐Liss, Inc.
Mechanistic insights into reprogramming to induced pluripotency
Authors: Ho Ritchie , Chronis Constantinos , Plath Kathrin
Published: October 2010

Induced pluripotent stem (iPS) cells can be generated from various embryonic and adult cell types upon expression of a set of few transcription factors, most commonly consisting of Oct4, Sox2, cMyc, and Klf4, following a strategy originally published by Takahashi and Yamanaka (Takahashi and Yamanaka, 2006, Cell 126: 663–676). Since iPS cells are molecularly and functionally similar to embryonic stem (ES) cells, they provide a source of patient‐specific pluripotent cells for regenerative medicine and disease modeling, and therefore have generated enormous scientific and public interest. The generation of iPS cells also presents a powerful tool for dissecting mechanisms that stabilize the differentiated state and are required for the establishment of pluripotency. In this review, we discuss our current view of the molecular mechanisms underlying transcription factor‐mediated reprogramming to induced pluripotency. J. Cell. Physiol. 226: 868–878, 2011. © 2010 Wiley‐Liss, Inc.
Vasodilator‐stimulated phosphoprotein deficiency potentiates PAR‐1‐induced increase in endothelial permeability in mouse lungs
Authors: Profirovic Jasmina , Han Jingyan , Andreeva Alexandra V. , Neamu Radu F. , Pavlovic Sasha , Vogel Stephen M. , Walter Ulrich , Voyno‐Yasenetskaya Tatyana A.
Published: October 2010

Vasodilator‐stimulated phosphoprotein (VASP) is implicated in the protection of the endothelial barrier in vitro and in vivo. The function of VASP in thrombin signaling in the endothelial cells (ECs) is not known. For the first time we studied the effects of VASP deficiency on EC permeability and pulmonary vascular permeability in response to thrombin receptor stimulation. We provided the evidence that VASP deficiency potentiates the increase in endothelial permeability induced by activation of thrombin receptor in cultured human umbilical vein endothelial cells (HUVECs) and isolated mouse lungs. Using transendothelial resistance measurement, we showed that siRNA‐mediated VASP downregulation in HUVECs leads to a potentiation of thrombin‐ and protease‐activated receptor 1 (PAR‐1) agonist‐induced increase in endothelial permeability. Compared to control cells, VASP‐deficient HUVECs had delayed endothelial junctional reassembly and abrogated VE‐cadherin cytoskeletal anchoring in the recovery phase after thrombin stimulation, as demonstrated by immunofluorescence studies and cell fractionation analysis, respectively. Measurement of the capillary filtration coefficient in isolated mouse lungs demonstrated that VASP−/− mice have increased microvascular permeability in response to infusion with PAR‐1 agonist compared to wild type mice. Lack of VASP led to decreased Rac1 activation both in VASP‐deficient HUVECs after thrombin stimulation and VASP−/− mouse lungs after PAR‐1 agonist infusion, indicating that VASP effects on thrombin signaling may be correlated with changes in Rac1 activity. This study demonstrates that VASP may play critical and complex role in the regulation of thrombin‐dependent disruption of the endothelial barrier function. J. Cell. Physiol. 226: 1255–1264, 2011. © 2010 Wiley‐Liss, Inc.
On the role of subtype selective adenosine receptor agonists during proliferation and osteogenic differentiation of human primary bone marrow stromal cells
Authors: Costa M. Adelina , Barbosa A. , Neto E. , Sá‐e‐Sousa A. , Freitas R. , Neves J.M. , Magalhães‐Cardoso T. , Ferreirinha F. , Correia‐de‐Sá P.
Published: October 2010

Purines are important modulators of bone cell biology. ATP is metabolized into adenosine by human primary osteoblast cells (HPOC); due to very low activity of adenosine deaminase, the nucleoside is the end product of the ecto‐nucleotidase cascade. We, therefore, investigated the expression and function of adenosine receptor subtypes (A1, A2A, A2B, and A3) during proliferation and osteogenic differentiation of HPOC. Adenosine A1(CPA), A2A(CGS21680C), A2B(NECA), and A3(2‐Cl‐IB‐MECA) receptor agonists concentration‐dependently increased HPOC proliferation. Agonist‐induced HPOC proliferation was prevented by their selective antagonists, DPCPX, SCH442416, PSB603, and MRS1191. CPA and NECA facilitated osteogenic differentiation measured by increases in alkaline phosphatase (ALP) activity. This contrasts with the effect of CGS21680C which delayed HPOC differentiation; 2‐Cl‐IB‐MECA was devoid of effect. Blockade of the A2Breceptor with PSB603 prevented osteogenic differentiation by NECA. In the presence of the A1antagonist, DPCPX, CPA reduced ALP activity at 21 and 28 days in culture. At the same time points, blockade of A2Areceptors with SCH442416 transformed the inhibitory effect of CGS21680C into facilitation. Inhibition of adenosine uptake with dipyridamole caused a net increase in osteogenic differentiation. The presence of all subtypes of adenosine receptors on HPOC was confirmed by immunocytochemistry. Data show that adenosine is an important regulator of osteogenic cell differentiation through the activation of subtype‐specific receptors. The most abundant A2Breceptor seems to have a consistent role in cell differentiation, which may be balanced through the relative strengths of A1or A2Areceptors determining whether osteoblasts are driven into proliferation or differentiation. J. Cell. Physiol. 226: 1353–1366, 2011. © 2010 Wiley‐Liss, Inc.
Constitutive overexpression of Id‐1 in mammary glands of transgenic mice results in precocious and increased formation of terminal end buds, enhanced alveologenesis, delayed involution
Authors: Shin Dong‐Hui , Jang Si‐Hyong , Kang Byeong‐Cheol , Kim Hyun‐Jun , Oh Seung Hyun , Kong Gu
Published: October 2010

Inhibitor of differentiation‐1 (Id‐1) has been shown to play an essential role in cell proliferation, invasion, migration, and anti‐apoptosis. However, the effect of Id‐1 in mammary gland development remains unknown. Here, we generated MMTV‐Id‐1 transgenic mice to study the role of Id‐1 in mammary gland development. In virgin mice, Id‐1 overexpression led to precocious development and delayed regression of terminal end buds (TEBs) compared with wild‐type mice. The number of BrdU‐positive cells and the expression of Wnt signaling molecules, β‐catenin and cyclin D1, which regulate ductal extension and TEB formation in virgin, were statistically higher in Id‐1 transgenic mice than in wild‐type mice. Id‐1 also had an effect on the formation and proliferation of lobuloalveolar structures during early and mid‐pregnancy. Id‐1 transgenic mice had more lobulated and prominent alveolar budding than wild‐type mice and had significantly greater counts of lobuloalveolar structures in early pregnancy. The expression of BrdU, β‐catenin, and cyclin D1 was also predominantly increased in Id‐1 transgenic mice. Moreover, Id‐1 transgenic mice showed delayed involution. Id‐1 regulated the expression levels of anti‐apoptotic Bcl‐2 and pro‐apoptotic Bax, and resulted in delay of apoptotic peak during postlactational involution. We also found that Id‐1 was able to modulate expression of the regulators of Wnt/β‐catenin signaling such as phospho‐Akt, BMP2, FGF3, and RAR‐β in tubuloalveolar development of mammary glands. Taken together, our results suggest that Id‐1 plays a pivotal role in mammary gland development through Wnt signaling‐mediated acceleration of precocity and alveologenesis and Bcl‐2 family members‐mediated delay of involution. J. Cell. Physiol. 226: 1340–1352, 2011. © 2010 Wiley‐Liss, Inc.
Embryonal carcinoma cell induction of miRNA and mRNA changes in co‐cultured prostate stromal fibromuscular cells
Authors: Vêncio Eneida F. , Pascal Laura E. , Page Laura S. , Denyer Gareth , Wang Amy J. , Ruohola‐Baker Hannele , Zhang Shile , Wang Kai , Galas David J. , Liu Alvin Y.
Published: October 2010

The prostate stromal mesenchyme controls organ‐specific development. In cancer, the stromal compartment shows altered gene expression compared to non‐cancer. The lineage relationship between cancer‐associated stromal cells and normal tissue stromal cells is not known. Nor is the cause underlying the expression difference. Previously, the embryonal carcinoma (EC) cell line, NCCIT, was used by us to study the stromal induction property. In the current study, stromal cells from non‐cancer (NP) and cancer (CP) were isolated from tissue specimens and co‐cultured with NCCIT cells in a trans‐well format to preclude heterotypic cell contact. After 3 days, the stromal cells were analyzed by gene arrays for microRNA (miRNA) and mRNA expression. In co‐culture, NCCIT cells were found to alter the miRNA and mRNA expression of NP stromal cells to one like that of CP stromal cells. In contrast, NCCIT had no significant effect on the gene expression of CP stromal cells. We conclude that the gene expression changes in stromal cells can be induced by diffusible factors synthesized by EC cells, and suggest that cancer‐associated stromal cells represent a more primitive or less differentiated stromal cell type. J. Cell. Physiol. 226: 1479–1488, 2011. © 2010 Wiley‐Liss, Inc.
Protein acetylation within the cellular response to radiation
Authors: Averbeck Nicole B. , Durante Marco
Published: October 2010

Post‐translational protein modification represents a fundamental tool within the control of protein functions. While phosphorylation is the longest known of these modifications, several more were identified. Among these, acetylation was originally discovered as an important modification of histones within the process of transcription. Later it was revealed that histone acetylation also plays a crucial role in DNA repair, and that histones are not the only target for transient acetylation within these processes. Although there is no doubt that protein acetylation is essential, its function and even more its regulation is still not fully elucidated. Here we will discuss how protein acetylation occurs within the cellular response to radiation, a well characterized DNA‐damaging environmental stressor and further want to draw the attention to open questions within the field of protein acetylation. J. Cell. Physiol. 226: 962–967, 2011. © 2010 Wiley‐Liss, Inc.
A comprehensive characterization study of human bone marrow mscs with an emphasis on molecular and ultrastructural properties
Authors: Karaöz Erdal , Okçu Alparslan , Gacar Gülçin , Sağlam Özlem , Yürüker Sinan , Kenar Halime
Published: October 2010

Human bone marrow‐derived mesenchymal stem cells (hBM‐MSCs) continue to draw attention of researchers in the fields of basic science and medicine due to their indispensible regenerative, reparative, angiogenic, anti‐apoptotic, and immunosuppressive properties, all of which collectively point out their enormous therapeutic potential. There is still, however, a need for further investigation of their characteristics to broaden their field of use and learn much more about how to control their fate and improve their therapeutic effectiveness. hBM‐MSCs were extensively characterized in terms of their growth characteristics, genetic stability, and differentiation capability to the mesodermal and ectodermal cell lineages; a special emphasis was given to their phenotypic and ultrastructural properties. Expression of embryonic stem cell markers Oct4, Rex‐1, FoxD‐3, Sox2, and Nanog was shown with real‐time PCR. Transmission electron microscopy revealed the ultrastructural characteristics of hBM‐MSCs; they had pale, irregularly shaped and large euchromatic nuclei, and two distinct areas in their cytoplasm: an intensely stained inner zone rich in mitochondria and rough endoplasmic reticulum (rER) with dilated cisternae and a relatively peripheral zone poor in organelles. hBM‐MSCs expressed adipogenic (adipophilin and PPARγ), myogenic (desmin, myogenin, α‐SMA), neurogenic (γ‐enolase, MAP2a,b, c‐fos, nestin, NF‐H, NF‐L, GFAP, β3‐tubulin), osteogenic (osteonectin, osteocalcin, osteopontin, Runx‐2, type I collagen), and chondrogenic (type II collagen, SOX9) markers either at RNA or protein level even under basal conditions, without any stimulation towards differentiation. The differentiation potential of hBM‐MSCs to adipogenic, osteogenic, and neurogenic lineages was shown by using the relevant differentiation factors. J. Cell. Physiol. 226: 1367–1382, 2011. © 2010 Wiley‐Liss, Inc.
Mechanisms of transforming growth factor β induced cell cycle arrest in palate development
Authors: Iordanskaia Tatiana , Nawshad Ali
Published: October 2010

Immaculate and complete palatal seam disintegration, which takes place at the last phase of palate development, is essential for normal palate development. And in absence of palatal midline epithelial seam (MES) disintegration, cleft palate may arise. It has been established that transforming growth factor (TGF) β induces both epithelial mesenchymal transition (EMT) and/or apoptosis during MES disintegration. It is likely that MES might cease cell cycle to facilitate cellular changes prior to undergoing transformation or apoptosis, which has never been studied before. This study was designed to explore whether TGFβ, which is crucial for palatal MES disintegration, is capable of inducing cell cycle arrest. We studied the effects of TGFβ1 and TGFβ3, potent negative regulators of the cell cycle, on p15ink4b activity in MES cells. We surprisingly found that TGFβ1, but not TGFβ3, plays a major role in activation of the p15ink4b gene. In contrast, following successful cell cycle arrest by TGFβ1, it is TGFβ3 but not TGFβ1 that causes later cellular morphogenesis, such as EMT and apoptosis. Since TGFβ signaling activates Smads, we analyzed the roles of three Smad binding elements (SBEs) on the p15ink4b mouse promoter by site specific mutagenesis and found that these binding sites are functional. The ChIP assay demonstrated that TGFβ1, not TGFβ3, promotes Smad4 binding to two 5' terminal SBEs but not the 3' terminal site. Thus, TGFβ1 and TGFβ3 play separate yet complimentary roles in achieving cell cycle arrest and EMT/apoptosis and cell cycle arrest is a prerequisite for later cellular changes. J. Cell. Physiol. 226: 1415–1424, 2011. © 2010 Wiley‐Liss, Inc.
Testosterone attenuates morpho‐functional alterations by 2‐methoxyestradiol exposure and induces differentiation in C6 cells
Authors: Manca Paolo , Chisu Valentina
Published: October 2010

2‐Methoxyestradiol (2ME) is a cytotoxic drug that interacts with tubulin and alters microtubule dynamics. It has been reported that testosterone (T) has a neuroprotective effect against oxidative stress and induces differentiation in mouse C1300 neuroblastoma cells. Here, we investigated the ability of T to attenuate the cytotoxic effects of 2ME and to induce cell differentiation in an immortalized rat glial cell line, known as C6. C6 cells were exposed for 5 days to 5 µM 2ME, 50 nM T, or both. We evaluated the morphological changes, growth rate, vitality, catalase activity, and glial fibrillary acidic protein (GFAP) immunoreactivity in control and treated C6 cells. Western blot analyses were used to quantify expression of tyrosinated tubulin (Tyr‐Tub), acetylated tubulin (Acet‐Tub), total α‐tubulin (TOT‐Tub), and GFAP. After 2ME exposure, the cells displayed a globular, shrunken shape, and retraction or absence of cytoplasmic processes; moreover, 2ME treatment significantly decreased cell growth, cell viability, catalase activity, and expression of both Tyr‐Tub and Acet‐Tub. However, when T was added, the cells exhibited a glial‐like shape, elongated cell processes, and enhanced cell growth, cell vitality, catalase activity, and GFAP immunoreactivity. Densitometric values of Tyr‐Tub, Acet‐Tub, and GFAP increased significantly when T was present, while Tot‐Tub values were unaltered. These results indicate that, in C6 cells, T: (i) attenuated the morpho‐functional changes caused by 2ME exposure; (ii) induced glial differentiation; and (iii) exerted a direct action on the microtubule system. J. Cell. Physiol. 226: 1510–1518, 2011. © 2010 Wiley‐Liss, Inc.
The roles of pathogen small RNAs
Authors: Zhou Yexin , Xie Jianping
Published: October 2010

Regulatory small RNAs (sRNAs), also known as non‐coding RNA, are not translated into proteins and widespread in prokaryotes and eukaryotes. sRNAs involve in multiple fundamental cellular events. They are emerging regulatory elements that are gaining momentum. Knowledge of sRNA largely originates from eukaryotes. Prokaryotic sRNAs, particularly those of pathogen are only recently explored. The main types, function, and methodology to predict pathogen sRNAs are summarized in this review. Special focus is sRNAs regulating pathogen gene expression, particularly that of Mycobacterium tuberculosis, which is hitherto the most successful pathogen afflicting mankind. J. Cell. Physiol. 226: 968–973, 2011. © 2010 Wiley‐Liss, Inc.
Cell growing density affects the structural and functional properties of Caco‐2 differentiated monolayer
Authors: Natoli Manuela , Leoni Bruno D. , D'Agnano Igea , D'Onofrio Mara , Brandi Rossella , Arisi Ivan , Zucco Flavia , Felsani Armando
Published: October 2010

The human intestinal Caco‐2 cell line has been extensively used as a model of the intestinal barrier. However, it is widely reported in literature that culture‐related conditions, as well as the different Caco‐2 cell lines utilized in different laboratories, often lead to problems of reproducibility making difficult to compare results. We developed a new cell‐maintenance protocol in which Caco‐2 cells were subcultured at 50% of confluence instead of 80% of confluence, as usually suggested. Using this new protocol, Caco‐2 cells retained a higher proliferation potential resulting in a cell population, which, on reaching confluence, was able to differentiate almost synchronously, forming a more homogeneous and polarized cell monolayer, as compared to that obtained using a high cell growing density. This comparison has been done by analyzing the gene expression and the structural characteristics of the 21‐days differentiated monolayers by microarrays hybridization and by confocal microscopy. We then investigated if these differences could also modify the effects of toxicants on 21‐days‐differentiated cells. We analyzed the 2 h‐acute toxicity of CuCl2 in terms of actin depolymerization and metallothionein 2A (MT2A) and heat shock protein 70 (HSPA1A) genes induction. Copper treatment resulted in different levels of actin depolymerization and gene expression induction in relationship with culture protocol, the low‐density growing cells showing a more homogeneous and stronger response. Our results suggest that cell growing density could influence a number of morphological and physiological properties of differentiated Caco‐2 cells and these effects must be taken in account when these cells are used as intestinal model. J. Cell. Physiol. 226: 1531–1543, 2011. © 2010 Wiley‐Liss, Inc.
Peptidoglycan induces interleukin‐6 expression through the TLR2 receptor, JNK, c‐Jun, and AP‐1 pathways in microglia
Authors: Lin Hsiao‐Yun , Tang Chih‐Hsin , Chen Jia‐Hong , Chuang Jing‐Yuan , Huang Ssu‐Ming , Tan Tzu‐Wei , Lai Chih‐Ho , Lu Dah‐Yuu
Published: October 2010

We recently reported that peptidoglycan (PGN), a cell wall component of the Gram‐positive bacterium, induces NF‐κB activation and microglia activation. However, PGN‐regulated AP‐1 activation and cytokine expression in microglia remains unclear. This study investigated how PGN influences the signaling pathway involved in IL‐6 production in microglia. IL‐6 mRNA and protein level up‐regulation were increased by PGN in a concentration‐ and time‐dependent manner. In addition, PGN increased toll‐like receptor‐2 (TLR2) expression, but not TLR4 receptor up‐regulation. Administration of TLR2 siRNA or TLR2 neutralized antibody effectively inhibited PGN‐induced IL‐6 expression. In contrast, PGN‐induced IL‐6 mRNA and protein up‐regulation were attenuated by the SAPK/JNK (c‐Jun N‐terminal kinases) inhibitor SP600125. Treatment of microglia with PGN increased levels of JNK phosphorylation and c‐Jun phosphorylation, and up‐regulated of JNK kinase activity. Treatment of microglia with AP‐1 inhibitors (Tanshinone IIA and curcumin) effectively reduced PGN‐induced IL‐6 expression. PGN also significantly increased c‐Fos and phospho‐c‐Jun translocation to nucleus. In line with this, PGN also increased AP‐1‐DNA complexes formation, as determined by the electrophoretic mobility shift assay. Furthermore, PGN also increased IL‐6 transcription activity determined by transfection with IL‐6 promoter construct plasmid. Co‐transfection with dominant negative mutant of JNK (DN‐JNK), or treatment with SP600125, curcumin, or Tanshinone IIA effectively antagonized PGN‐increased IL‐6 transcription activity. Our data demonstrate that PGN‐induced IL‐6 expression is mediated by AP‐1 activation through the TLR2 and JNK/c‐Jun pathways in microglia. J. Cell. Physiol. 226: 1573–1582, 2011. © 2010 Wiley‐Liss, Inc.