bluuebunny/crossref_metadata_2025 huggingface dataset:
The number of the genes in a functional category matters during rat liver regeneration after partial hepatectomy
Authors: Jiang Yun , Zhang Lian‐Xing , Chang Cui‐Fang , Wang Gai‐Ping , Shi Rui‐Jia , Yang Yan‐Jie , Xu Cun‐Shuan
Published: July 2011

Rat liver regeneration after partial hepatectomy (PH) is a good model to study the regulation of cell proliferation. We isolated hepatocytes from regenerating liver at different time points after PH and used microarray Rat Genome 230 2.0 chip to analyze the functional profiles of all up‐ or down‐regulated genes manually and with automatic gene ontological tools. We found that the transcript expressions of PH and sham operation group were apparently different. For PH group, in the priming phase (2–12 h), signaling, transcription, response to stimulus genes predominated in up‐regulated genes; in the proliferation phase (24–72 h), cell proliferation genes predominated; in the termination phase (120–168 h), differentiation and translation genes predominated; while metabolism genes predominated in the down‐regulated genes at all time points (2–168 h). These functional profiles are consistent with the cellular and molecular phenomenon observed during liver regeneration, and can be closely connected with the biological process. Moreover, the results indicated that not only the quantity of specific genes but also the number of the genes in the specific functional category was regulated during liver regeneration, which means the number of similar genes in a specific functional category matters as well as the regulation of the genes. The changes of the number of the regulated cell proliferation genes and metabolism genes during liver regeneration were similar to the expression patterns of some cell division genes and metabolism genes. J. Cell. Biochem. 112: 3194–3205, 2011. © 2011 Wiley Periodicals, Inc.
Protein kinase CK2 promotes cancer cell viability via up‐regulation of cyclooxygenase‐2 expression and enhanced prostaglandin E2 production
Authors: Yefi Roger , Ponce Daniela P. , Niechi Ignacio , Silva Eduardo , Cabello Pablo , Rodriguez Diego A. , Marcelain Katherine , Armisen Ricardo , Quest Andrew F.G. , Tapia Julio C.
Published: July 2011

Augmented expression of protein kinase CK2 is associated with hyperproliferation and resistance to apoptosis in cancer cells. Effects of CK2 are at least partially linked to signaling via the Wnt/β‐catenin pathway, which is dramatically enhanced in colon cancer. Cyclooxygenase‐2 (COX‐2), a Wnt/β‐catenin target gene, has been associated with enhanced cancer progression and metastasis. However, the possibility that a connection may exist between CK2 and COX‐2 has not been explored previously. Here we investigated changes in COX‐2 expression and activity upon CK2 modulation and evaluated how these changes affected cell viability. COX‐2 expression and cell viability decreased upon selective inhibition of COX‐2 with SC‐791 or CK2 with 2‐dimethylamino‐4,5,6,7‐tetrabromo‐1H‐benzimidazole (DMAT), both in human colon (HT29‐ATCC, HT29‐US, DLD‐1) and breast (ZR‐75) cancer cells, as well as in human embryonic kidney (HEK‐293T) cells. On the other hand, ectopic CK2α expression promoted up‐regulation of COX‐2 by activating the Wnt/β‐catenin pathway in HEK‐293T cells. Noteworthy, over‐expression of either CK2α, β‐catenin or COX‐2, as well as supplementation of the medium with prostaglandin E2 (PGE2), all were individually sufficient to overcome limitations in cell viability triggered by CK2 inhibition either upon addition of DMAT or over‐expression of a dominant negative CK2α variant. Altogether, these findings provide new insight to the role of CK2 in cancer by up‐regulating COX‐2 expression and thereby PGE2 production. J. Cell. Biochem. 112: 3167–3175, 2011. © 2011 Wiley Periodicals, Inc.
Two‐level hierarchical parallelization of second‐order Møller–plesset perturbation calculations in divide‐and‐conquer method
Authors: Katouda Michio , Kobayashi Masato , Nakai Hiromi , Nagase Shigeru
Published: July 2011

A two‐level hierarchical parallelization scheme including the second‐order Møller–Plesset perturbation (MP2) theory in the divide‐and‐conquer method is presented. The scheme is a combination of coarse‐grain parallelization assigning each subsystem to a group of processors, with fine‐grain parallelization, where the computational tasks for evaluating MP2 correlation energy of the assigned subsystem are distributed among processors in the group. Test calculations demonstrate that the present scheme shows high parallel efficiency and makes MP2 calculations practical for very large molecules. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Optimal scaling factors for CM1 and CM3 atomic charges in RM1‐based aqueous simulations
Authors: Vilseck Jonah Z. , Sambasivarao Somisetti V. , Acevedo Orlando
Published: July 2011

Scaling factors for atomic charges derived from the RM1 semiempirical quantum mechanical wavefunction in conjunction with CM1 and CM3 charge models have been optimized by minimizing errors in absolute free energies of hydration, ΔGhyd, for a set of 40 molecules. Monte Carlo statistical mechanics simulations and free energy perturbation theory were used to annihilate the solutes in gas and in a box of TIP4P water molecules. Lennard–Jones parameters from the optimized potentials for liquid simulations‐all atom (OPLS–AA) force field were utilized for the organic compounds. Optimal charge scaling factors have been determined as 1.11 and 1.14 for the CM1R and CM3R methods, respectively, and the corresponding unsigned average errors in ΔGhyd relative to experiment were 2.05 and 1.89 kcal/mol. Computed errors in aniline and two derivatives were particularly large for RM1 and their removal from the data set lowered the overall errors to 1.61 and 1.75 kcal/mol for CM1R and CM3R. Comparisons are made to the AM1 method which yielded total errors in ΔGhyd of 1.50 and 1.64 kcal/mol for CM1A*1.14 and CM3A*1.15, respectively. This work is motivated by the need for a highly efficient yet accurate quantum mechanical (QM) method to study condensed‐phase and enzymatic chemical reactions via mixed QM and molecular mechanical (QM/MM) simulations. As an initial test, the Menshutkin reaction between NH3 and CH3Cl in water was computed using a RM1/TIP4P‐Ew/CM3R procedure and the resultant ΔG‡, ΔGrxn, and geometries were in reasonable accord with other computational methods; however, some potentially serious shortcomings in RM1 are discussed. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
A comparison of neighbor search algorithms for large rigid molecules
Authors: Artemova Svetlana , Grudinin Sergei , Redon Stephane
Published: July 2011

Fast determination of neighboring atoms is an essential step in molecular dynamics simulations or Monte Carlo computations, and there exists a variety of algorithms to efficiently compute neighbor lists. However, most of these algorithms are general, and not specifically designed for a given type of application. As a result, although their average performance is satisfactory, they might be inappropriate in some specific application domains. In this article, we study the case of detecting neighbors between large rigid molecules, which has applications in, e.g., rigid body molecular docking, Monte Carlo simulations of molecular self‐assembly or diffusion, and rigid body molecular dynamics simulations. More precisely, we compare the traditional grid‐based algorithm to a series of hierarchy‐based algorithms that use bounding volumes to rapidly eliminate large groups of irrelevant pairs of atoms during the neighbor search. We compare the performance of these algorithms based on several parameters: the size of the molecules, the average distance between them, the cutoff distance, as well as the type of bounding volume used in the culling hierarchy (AABB, OBB, wrapped, or layered spheres). We demonstrate that for relatively large systems (> 100,000 atoms) the algorithm based on the hierarchy of wrapped spheres shows the best results and the traditional grid‐based algorithm gives the worst timings. For small systems, however, the grid‐based algorithm and the one based on the wrapped sphere hierarchy are beneficial. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
MyMolDB: A micromolecular database solution with open source and free components
Authors: Xia Bing , Tai Zheng‐Fu , Gu Yu‐Cheng , Li Bang‐Jing , Ding Li‐Sheng , Zhou Yan
Published: July 2011

Background:

To manage chemical structures in small laboratories is one of the important daily tasks. Few solutions are available on the internet, and most of them are closed source applications. The open‐source applications typically have limited capability and basic cheminformatics functionalities. In this article, we describe an open‐source solution to manage chemicals in research groups based on open source and free components. It has a user‐friendly interface with the functions of chemical handling and intensive searching.

Results:

MyMolDB is a micromolecular database solution that supports exact, substructure, similarity, and combined searching. This solution is mainly implemented using scripting language Python with a web‐based interface for compound management and searching. Almost all the searches are in essence done with pure SQL on the database by using the high performance of the database engine. Thus, impressive searching speed has been archived in large data sets for no external Central Processing Unit (CPU) consuming languages were involved in the key procedure of the searching.

Availability:

MyMolDB is an open‐source software and can be modified and/or redistributed under GNU General Public License version 3 published by the Free Software Foundation (Free Software Foundation Inc. The GNU General Public License, Version 3, 2007. Available at: http://www.gnu.org/licenses/gpl.html). The software itself can be found at http://code.google.com/p/mymoldb/. © 2011 Wiley Periodicals, Inc. J Comput Chem 2011
Increasing social capital and personal efficacy through small‐scale community events
Authors: Molitor Fred , Rossi Melissa , Branton Lisa , Field Julie
Published: July 2011

California's voter‐approved Children and Families Act of 1998 calls for money collected from tobacco taxes to support services for families with children up to 5 years of age. Sacramento County uses a portion of its allocation for small community grants with the specific intent of building social capital among neighbors and across communities. The evaluation of the 995 Community Building Initiative (CBI) events funded from July 2007 to June 2010 included randomly selecting parents from a larger population (n=29,607). Structured interviews with 538 parents identified those who had attended community events within the last 6 months and assessed hypothesized outcomes. Attending any community event was related to increased measures of social capital. However, those participating in a CBI event demonstrated the highest levels of familiarity with neighbors, neighborhood cohesion, and efficacy, as revealed through generalized linear mixed model analyses controlling for race/ethnicity, primary language, and education. © 2011 Wiley Periodicals, Inc.
The ecology of achievement among students diverse in ethnicity and ability
Authors: McMahon Susan D. , Keys Christopher B. , Berardi Luciano , Crouch Ronald
Published: July 2011

This longitudinal study uses an ecological framework to examine school and individual influences on academic achievement among African American and Latino students with and without disabilities who had recently transferred to more inclusive schools. The authors' ecological framework includes four domains: organizational policies and practices, school environment, student–school connections, and psychological symptoms. The authors tested a comprehensive model with 111 students from 16 schools over 3 years, as well as an organizational model with a smaller sample. Organizational policies and practices of inclusion and student–school connections of belonging each predicted higher academic achievement, and psychological symptoms of aggressive behavior predicted lower academic achievement across time. Their findings are consistent with and extend existing research through support of a comprehensive ecological model across time. Findings also yield significant implications for ecological theory and research in community psychology, school planning, intervention, and implementation of inclusive best practices for students with and without disabilities. © 2011 Wiley Periodicals, Inc.
Perceived neighborhood violence and use of verbal aggression, corporal punishment, and physical abuse by a national sample of parents in Israel
Authors: Winstok Zeev , Straus Murray A.
Published: July 2011

This study, based on an ecological perspective, examined the relation of perceived neighborhood violence, child misbehavior, parental attitudes to aggressive discipline tactics, and the actual use of aggressive discipline tactics. Research questions were: To what extent is perceived neighborhood violence associated with aggressive discipline by parents? What is the mechanism through which perceived neighborhood violence is linked to aggressive discipline? Data were obtained from a stratified probability sample of 1,649 women. Findings indicated that the more the study participants perceived their neighborhood as violent, the more frequent is the parental use of aggressive discipline. It seems that child misbehavior and parental approval of corporal punishment are affected by perceived neighborhood violence and, in turn, affect parental use of aggressive disciplines. Furthermore, the relationships of child misbehavior, parental approval of aggressive discipline, and the use of aggressive discipline are different in low and high levels of perceived neighborhood violence. © 2011 Wiley Periodicals, Inc.
Impacts of the duration of Head Start enrollment on children's academic outcomes: moderation effects of family risk factors and earlier outcomes
Authors: Lee Kyunghee
Published: July 2011

This study examined effects of the duration of Head Start enrollment on children's academic outcomes. Study questions are as follows: (a) Do Head Start children's baseline characteristics differ among those who entered at age 3 and enrolled in Head Start for 1 year, those who entered at age 4 and stayed for 1 year, and those who entered at age 3 and stayed for 2 years? (b) Do children's academic scores differ among the three groups? (c) Do these effects differ depending on the number of family risk factors and on children's scores at the beginning of the year? Findings indicate that children who entered Head Start at age 3 and stayed for 2 years showed higher academic outcomes than those enrolled later or for less time. Benefits were greater among children with more family risk factors and among those whose academic scores at the beginning of the study year were lower. © 2011 Wiley Periodicals, Inc.
The critical role of JNK in the ER‐mitochondrial crosstalk during apoptotic cell death
Authors: Verma Gaurav , Datta Malabika
Published: July 2011

Apoptosis or programmed cell death is an extremely coordinated phenomenon that involves the participation of a complex interacting crosstalk between the endoplasmic reticulum and mitochondria. This involves a series of signaling molecules like stress kinases, caspases, Bcl‐2 family of proteins, etc. that coordinately induce apoptosis by releasing apoptotic proteins from the mitochondria and mediate DNA damage of the cell. Among the stress kinases, JNK, a member of the MAPK family has been believed to be critically mediating these apoptotic phenomena. The involvement of JNK has been clouded by controversies because of its role both as a pro‐apoptotic and an anti‐apoptotic mediator. A very significant initiator of JNK activation is the pro‐inflammatory cytokine, IL‐1β, levels of which are significantly elevated in varied diseases especially diabetes where it is believed to significantly contribute to pancreatic β‐cell death. During apoptotic cell death, the endoplasmic reticulum and the mitochondrion participate in a relay of cellular events that determine the onset of the classical apoptotic pathways. Here we discuss the details of this ER‐mitochondrial crosstalk and the role of JNK herein that ultimately culminates into apoptotic cell death that is evident in various pathophysiological conditions. J. Cell. Physiol. 227: 1791–1795, 2012. © 2011 Wiley Periodicals, Inc.
mda‐7/IL‐24 differentially regulates soluble and nuclear clusterin in prostate cancer
Authors: Bhutia Sujit K. , Das Swadesh K. , Kegelman Timothy P. , Azab Belal , Dash Rupesh , Su Zhao‐zhong , Wang Xiang‐Yang , Rizzi Federica , Bettuzzi Saverio , Lee Seok‐Geun , Dent Paul , Grant Steven , Curiel David T. , Sarkar Devanand , Fisher Paul B.
Published: July 2011

Melanoma differentiation‐associated gene‐7/interleukin‐24 (mda‐7/IL‐24), a unique member of the IL‐10 gene family, displays a broad range of antitumor properties including cancer‐specific induction of apoptosis, inhibition of tumor angiogenesis, and modulation of anti‐tumor immune responses. Here, we identify clusterin (CLU) as a MDA‐7/IL‐24 interacting protein in DU‐145 cells and investigate the role of MDA‐7/IL‐24 in regulating CLU expression and mediating the antitumor properties of mda‐7/IL‐24 in prostate cancer. Ad.mda‐7 decreased expression of soluble CLU (sCLU) and increased expression of nuclear CLU (nCLU). In the initial phase of Ad.mda‐7 infection sCLU expression increased and CLU interacted with MDA‐7/IL‐24 producing a cytoprotective effect. Infection of stable clones of DU‐145 prostate cancer cells expressing sCLU with Ad.mda‐7 resulted in generation of nCLU that correlated with decreased cell viability and increased apoptosis. In the presence of mda‐7/IL‐24, sCLU‐DU‐145 cells displayed G2/M phase arrest followed by apoptosis. Similarly, Ad.mda‐7 infection decreased cell migration by altering cytoskeleton in sCLU‐DU‐145 cells. Ad.mda‐7‐treated sCLU‐DU‐145 cells displayed a significant reduction in tumor growth in mouse xenograft models and reduced angiogenesis when compared to the vector control group. Tumor tissue lysates demonstrated enhanced nCLU generated from sCLU with increased apoptosis in the presence of MDA‐7/IL‐24. Our findings reveal novel aspects relative to the role of sCLU/nCLU in regulating the anticancer properties of MDA‐7/IL‐24 that may be exploited for developing enhanced therapies for prostate cancer. J. Cell. Physiol. 227: 1805–1813, 2012. © 2011 Wiley Periodicals, Inc.
Possible role of RKIP in cytotrophoblast migration: immunohistochemical and in vitro studies
Authors: Ciarmela Pasquapina , Marzioni Daniela , Islam Md. Soriful , Gray Peter Clarke , Terracciano Luigi , Lorenzi Teresa , Todros Tullia , Petraglia Felice , Castellucci Mario
Published: July 2011

Raf kinase inhibitor protein (RKIP) regulates growth and differentiation signaling of mitogen‐activated protein kinases (MAPK), GRK2 and NF‐kappaB pathways each of which regulates cytotrophoblast differentiation and normal placental development. We show here that RKIP is expressed in human normal and preeclampic placentas as detected by immunostaining. RKIP was detected in villous cytotrophoblast in normal placenta and switched to syncytiotrophoblast in pre‐eclampsia (PE)‐complicated pregnancies. RKIP was also localized in extravillous cytotrophoblast of cell islands and cell columns both in normal and in PE placentas, although staining was less uniform in the latter specimens. In order to test RKIP involvement in cytotrophoblast function, we performed in vitro studies on HTR‐8/SVneo cells, a first trimester cytotrophoblast cell line. We show that the RKIP inhibitor locostatin reduces ERK phosphorylation and impairs HTR‐8/SV neo cells motility in wound closure experiments. We also document the presence of GRK2 mRNA, the reduction of phosphorylated RKIP expression by locostatin and the induction of PAI mRNA expression in HTR‐8/SV neo cells, suggesting the involvement of GRK2 and NF‐kappaB pathways in these cells. In conclusion, our work provides evidence that RKIP is a novel factor expressed in cytotrophoblast cells where it likely regulates cell migration. J. Cell. Physiol. 227: 1821–1828, 2012. © 2011 Wiley Periodicals, Inc.
Activation of the p53 pathway induces α‐smooth muscle actin expression in both myeloid leukemic cells and normal macrophages
Authors: Secchiero Paola , Rimondi Erika , di Iasio Maria Grazia , Voltan Rebecca , Gonelli Arianna , Zauli Giorgio
Published: July 2011

A range of cell types of mesenchymal origin express α‐smooth muscle actin (α‐SMA), a protein that plays a key role in controlling cell motility and differentiation along the fibrocyte and myofibroblast lineages. Although α‐SMA is often expressed in stromal cells associated to a variety of cancers including hematological malignancies, up to now the role of anti‐cancer drugs on α‐SMA has not been deeply investigated. In this study, we demonstrated that Nutlin‐3, the small molecule inhibitor of the MDM2/p53 interactions, significantly up‐regulated the mRNA and protein levels of α‐SMA in normal macrophages as well as in p53wild‐type but not in p53mutated/null myeloid leukemic cells. The p53‐dependence of α‐SMA up‐regulation induced by Nutlin‐3 was demonstrated in experiments performed with siRNA for p53. Of note, Nutlin‐3 mediated up‐regulation of α‐SMA in OCI leukemic cells was accompanied by cell adhesion to plastic substrate and by reduced cell migratory response in transwell assays. Notably, the role of α‐SMA induction in the modulation of myeloid cell migration was clearly documented in α‐SMA gene knockdown experiments. In addition, Nutlin‐3 significantly up‐regulated α‐SMA expression in primary endothelial cells, but not in fibroblasts and mesenchymal stem cells (MSC). Conversely, transforming growth factor‐β1 up‐regulated α‐SMA in fibroblasts and MSC, but not in macrophages and endothelial cells. Taken together, these data indicate that Nutlin‐3 is a potent inducer of α‐SMA in both normal and leukemic myeloid cells as well as in endothelial cells. J. Cell. Physiol. 227: 1829–1837, 2012. © 2011 Wiley Periodicals, Inc.
Inhibitory regulation of osteoclast differentiation by interleukin‐3 via regulation of c‐Fos and Id protein expression
Authors: Oh Jaemin , Lee Myeung Su , Yeon Jeong‐Tae , Choi Sik‐Won , Kim Hun Soo , Shim Hyeok , Lee Sam Youn , Youn Byung Soo , Yokota Yoshifumi , Kim Jung Ha , Kwak Han Bok
Published: July 2011

Interleukin‐3 (IL‐3) is produced under various pathological conditions and is thought to be involved in the pathogenesis of inflammatory diseases; however, its function in bone homeostasis under normal conditions or nature of the downstream molecular targets remains unknown. Here we examined the effect of IL‐3 on osteoclast differentiation from mouse and human bone marrow‐derived macrophages (BMMs). Although IL‐3 can induce osteoclast differentiation of multiple myeloma bone marrow cells, IL‐3 greatly inhibited osteoclast differentiation of human BMMs isolated from healthy donors. These inhibitory effects of IL‐3 were only observed at early time points (days 0 and 1). IL‐3 inhibited the expression of c‐Fos and NFATc1 in BMMs treated with RANKL. However, IL‐3‐mediated inhibition of osteoclast differentiation was not completely reversed by ectopic expression of c‐Fos or NFATc1. Importantly, IL‐3 induced inhibitor of DNA binding/differentiation (Id)1 in hBMMs, while Id2 were sustained during osteoclast differentiation of mBMMs treated with IL‐3. Ectopic expression of NFATc1 in Id2‐deficient BMMs completely reversed the inhibitory effect of IL‐3 on osteoclast differentiation. Furthermore, inflammation‐induced bone erosion was markedly inhibited by IL‐3 administration. Taken together, our results suggest that IL‐3 plays an inhibitory role in osteoclast differentiation by regulating c‐Fos and Ids, and also exerts anti‐bone erosion effects. J. Cell. Physiol. 227: 1851–1860, 2012. © 2011 Wiley Periodicals, Inc.
The pro‐apoptotic effect of quercetin in cancer cell lines requires ERβ‐dependent signals
Authors: Bulzomi Pamela , Galluzzo Paola , Bolli Alessandro , Leone Stefano , Acconcia Filippo , Marino Maria
Published: July 2011

Quercetin has potentially beneficial effects on disease prevention, including cancer. An intriguing issue regarding the mechanisms of action of quercetin is the ability of this drug to modulate estrogen receptor (ER) activities. In a previous study, we demonstrated that quercetin elicited apoptosis through an ERα‐dependent mechanism. However, the contribution of ERβ in quercetin‐induced apoptosis remains elusive. Here, we report that quercetin, at nutritionally relevant concentrations, mimicked the 17β‐estradiol (E2)‐induced apoptotic effect in both ERβ1‐transfected HeLa and in ERβ1‐containing DLD‐1 colon cancer cell lines by inducing the activation of p38. p38 activation is responsible for pro‐apoptotic activation of caspase‐3 and the cleavage of poly(ADP‐ribose) polymerase. Notably, no inactivation or downregulation of the survival kinases (i.e., AKT and ERK1/2) or the antiapoptotic protein Bcl‐2 was observed after quercetin stimulation. On the contrary, quercetin acted similarly to E2 by increasing the levels of the oncosuppressor protein PTEN and by impeding ERβ‐dependent cyclin D1 promoter activity, which subsequently resulted in the transcription of the estrogen‐responsive element remaining unchanged. As a whole, these data indicate that quercetin mimics the E2 effects in the presence of ERβ1, thus maintaining its anti‐carcinogenic potential. In addition, the quercetin pro‐apoptotic action in the presence of ERα may render it as a dual‐sided protective agent against E2‐related cancer in the reduction of tumour growth in organs that express ERα and/or ERβ. J. Cell. Physiol. 227: 1891–1898, 2012. © 2011 Wiley Periodicals, Inc.
Heterogeneity in apoptotic responses of microvascular endothelial cells to oxidative stress
Authors: Grinnell Katie , Duong Huetran , Newton Julie , Rounds Sharon , Choudhary Gaurav , Harrington Elizabeth O.
Published: July 2011

Oxidative stress contributes to disease and can alter endothelial cell (EC) function. EC from different vascular beds are heterogeneous in structure and function, thus we assessed the apoptotic responses of EC from lung and heart to oxidative stress. Since protein kinase Cδ (PKCδ) is activated by oxidative stress and is an important modulator of apoptosis, experiments assessed the level of apoptosis in fixed lung and heart sections of PKCδ wild‐type (PKCδ+/+) and null (PKCδ−/−) mice housed under normoxia (21% O2) or hyperoxia (∼95% O2). We noted a significantly greater number of TUNEL‐positive cells in lungs of hyperoxic PKCδ+/+ mice, compared to matched hearts or normoxic organs. We found that 33% of apoptotic cells identified in hyperoxic lungs of PKCδ+/+ mice were EC, compared to 7% EC in hyperoxic hearts. We further noted that EC apoptosis was significantly reduced in lungs of PKCδ−/− hyperoxic mice, compared to lungs of PKCδ+/+ hyperoxic mice. In vitro, both hyperoxia and H2O2 promoted apoptosis in EC isolated from microvasculature of lung (LMVEC), but not from the heart (HMVEC). H2O2 treatment significantly increased p38 activity in LMVEC, but not in HMVEC. Inhibition of p38 attenuated H2O2‐induced LMVEC apoptosis. Baseline expression of total PKCδ protein, as well as the caspase‐mediated, catalytically active PKCδ cleavage fragment, was higher in LMVEC, compared to HMVEC. PKCδ inhibition significantly attenuated H2O2‐induced LMVEC p38 activation. Conversely, overexpression of wild‐type PKCδ or the catalytically active PKCδ cleavage product greatly increased H2O2‐induced HMVEC caspase and p38 activation. We propose that enhanced susceptibility of lung EC to oxidant‐induced apoptosis is due to increased PKCδ → p38 signaling, and we describe a PKCδ‐centric pathway which dictates the differential response of EC from distinct vascular beds to oxidative stress. J. Cell. Physiol. 227: 1899–1910, 2012. © 2011 Wiley Periodicals, Inc.
Duplicated chromosomal fragments stabilize shortened telomeres in normal human IMR‐90 cells before transition to senescence
Authors: Zahnreich Sebastian , Krunic Damir , Melnikova Larissa , Szejka Agnes , Drossel Barbara , Sabatier Laure , Durante Marco , Ritter Sylvia , Fournier Claudia
Published: July 2011

To assess why during in vitro aging of fibroblasts the maintenance of chromosomal stability is effective or occasionally fails, a detailed cytogenetic analysis was performed in normal human IMR‐90 fetal lung fibroblasts. The onset of senescence was inferred from proliferation activity, expression pattern of cell cycle regulating proteins, activity of β‐galactosidase, and morphological features. Over the period of proliferation, a moderate increase of non‐transmissible structural chromosomal aberrations was observed. In addition, using fluorescence in situ hybridization (mFISH and mBAND) techniques, we detected clonally expanding translocations in up to 70% of the analyzed metaphases, all involving one homolog of chromosome 9 as an acceptor. Notably, chromosomes are randomly involved as donor‐chromosomes of the translocated terminal acentric fragments. These fragments result from duplication because the donor chromosomes are apparently unchanged. Interstitial telomeric signals were detectable at fusion sites, most likely belonging to chromosome 9. Quantitative fluorescence in situ hybridization (QFISH) detecting telomere sequences, followed by mFISH technique revealed that already in young cells the respective telomeres of one chromosome 9 were particularly short. For the first time, we have observed dysfunctional telomeres of one specific chromosome in normal human cells that have been stabilized by duplicated terminal sequences. J. Cell. Physiol. 227: 1932–1940, 2012. © 2011 Wiley Periodicals, Inc.
Functional ion channels and cell proliferation in 3T3‐L1 preadipocytes
Authors: Zhang Xiao‐Hua , Zhang Ying‐Ying , Sun Hai‐Ying , Jin Man‐Wen , Li Gui‐Rong
Published: July 2011

Mouse 3T3‐L1 preadipocytes are widely used for metabolic study of obesity; however, their cellular physiology is not fully understood. The present study investigates functional ion channels and their role in the regulation of cell proliferation using whole‐cell patch voltage‐clamp, RT‐PCR, Western blot, and cell proliferation assay in undifferentiated 3T3‐L1 preadipocytes. We found three types of ionic currents present in 3T3‐L1 preadipocytes, including an inwardly‐rectifying K+ current (IKir, recorded in 15% of cells) inhibited by Ba2+, a Ca2+‐activated intermediate K+ current (IKCa, recorded in 44% of cells) inhibited by clotrimazole (or TRAM‐34) as well as a chloride current (ICl) inhibited by 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid (DIDS) in 12% of cells, which can be activated in all cells with hypotonic (0.8 T) insult, implicating a volume‐sensitive ICl (ICl.vol). RT‐PCR and Western blot analysis revealed the expression of KCa3.1 (for IKCa), Kir2.1 (for IKir), and Clcn3 (for ICl.vol). Blockade of IKCa with TRAM‐34 or ICl.vol with DIDS inhibited cell proliferation in a concentration‐dependent manner. Knockdown of KCa3.1 or Clcn3 with specific siRNAs also suppressed cell proliferation. Flow cytometry analysis showed that blockade or silencing of KCa3.1 or Clcn3 channels with corresponding blockers or siRNAs caused an accumulation of cells at the G0/G1 phase. These results demonstrate that three functional ion channel currents, IKCa, ICl.vol, and IKir, are heterogeneously present in 3T3‐L1 preadipocytes. IKCa and ICl.vol participate in the regulation of cell proliferation. J. Cell. Physiol. 227: 1972–1979, 2012. © 2011 Wiley Periodicals, Inc.
X‐rays of inner worlds: The mid‐twentieth‐century American Projective Test Movement
Authors: Lemov Rebecca
Published: July 2011

This essay begins to tell the neglected history of the projective test movement in the U.S. behavioral sciences from approximately 1941 to 1968. This cross‐disciplinary enterprise attempted to use projective techniques as “X‐ray” machines to see into the psyches of subjects tested around the world. The aim was to gather subjective materials en masse, pursuing data on a scope, scale, and manner rarely hazarded before in any science. In particular, the targeted data included the traces of the inner life and elusive aspects of subjective experience including dreams, life stories, and myriad test results from a battery of tests. This essay explores how the movement and the experimental data bank that resulted were unlikely yet telling sites for the practice and pursuit of the Cold War human sciences. To look closely at the encounters that resulted is to show how the most out‐of‐the‐way places and seemingly insignificant moments played a role in heady scientific ambitions and global geopolitical projects. At times, the projective test movement became a mirror of Cold War rationality itself, as tests were employed at the very limits of their possible extension. The essay argues for an off‐kilter centrality in the movement itself, shedding light on the would‐be unified social sciences after World War II and the “subjective turn” they took. © 2011 Wiley Periodicals, Inc.
The lateglacial Quercus expansion in the southern European Alps: rapid vegetation response to a late Allerød climate warming?
Authors: Finsinger W. , Lane C. S. , van Den Brand G. J. , Wagner‐Cremer F. , Blockley S. P. E. , Lotter A. F.
Published: July 2011

A pollen‐inferred vegetation shift, from pioneer birch–pine woodland to mixed pine–summergreen oak forests, in the southern Alpine forelands, is commonly attributed to a centennial‐scale warming that occurred between the Gerzensee Oscillation (GO) and the Younger Dryas. Two microtephra layers bracketing the Younger Dryas onset (the Laacher See Tephra and the Vedde Ash) improve the chronology at Lago Piccolo di Avigliana (northern Italy) and allowed accurate correlation with Central European records where the GO is clearly detected. We used pollen percentages, pollen accumulation rates (PARs) and plant macrofossils to assess the population dynamics of Quercus, and leaf‐cuticle analysis for a better taxonomic identification of Quercus. Our results indicate that the species that was locally present was probably Quercus robur. PARs suggest that the population expansion started as early as the Bølling and followed an exponential increase through time. We attribute this gradual shift to increasing summer temperatures and longer growing seasons which contrast with a gradually decreasing temperature trend as recorded in Greenland ice cores and in Central Europe. Breaks or set‐backs in the PAR record may indicate the biotic response to minor Lateglacial cooling events of different life‐history stages in the Quercus population. Copyright © 2011 John Wiley & Sons, Ltd.
Safety and efficacy of carboxymethylcellulose in the treatment of glottic insufficiency
Authors: Mallur Pavan S. , Morrison Michele P. , Postma Gregory N. , Amin Milan R. , Rosen Clark A.
Published: July 2011

Objectives/Hypothesis:

No studies to date have examined the clinical safety and efficacy of carboxymethylcellulose (CMC) for vocal fold injection. The current study investigates the voice outcomes and complications of CMC injection.

Study Design:

Retrospective review.

Methods:

All patients who underwent CMC injection from three independent sites in a 1‐year period were reviewed. Voice outcomes in the form of voice handicap index‐10 (VHI‐10) and complications from injection were recorded.

Results:

Seventy‐eight patients with VHI‐10 results from 1 to 8 weeks after CMC injection were evaluated. Thirty‐eight patients were treated for vocal fold immobility, and 15 patients underwent treatment for hypomobility, 15 for vocal fold atrophy, seven for scar/sulcus, one for previous laryngeal fracture, one for functional dysphonia, and one for persistent granuloma. In 60 patients with available VHI‐10 data, overall improvement in voice was seen. There was a mean decrease in VHI‐10 of 7.48 (26.4 to 18.9, P < .05), correlating to a 19.9% decrease. Forty‐five patients (75%) showed a decrease in VHI‐10, nine (15%) showed an increase, and six (10%) showed no change. Statistically significant differences were seen for patients with immobility (decrease of 8.6, or 31%) and hypomobility (decrease of 10.7, or 37.8%). There were no complications of vocal fold stiffness, inflammatory reaction, or scar in the 78 patients during the total follow‐up period.

Conclusions:

CMC is a viable, safe, and efficacious material for the temporary treatment of glottic insufficiency in vocal fold immobility and hypomobility, with minimal risk of permanent adverse voice outcomes.
A Hölder continuity result for a class of obstacle problems under non standard growth conditions
Authors: Eleuteri Michela , Habermann Jens
Published: July 2011

We prove C0, α regularity for local minimizers u of functionals with p(x)‐growth of the type

in the class \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$K :=\lbrace w \in W^{1,p(\cdot )}(\Omega ;{\mathbb R}): w \ge \psi \rbrace$\end{document}, where the exponent function p : Ω → (1, ∞) is assumed to be continuous with a modulus of continuity satisfying

and 1 < γ1 ⩽ p(x) ≤ γ2 < +∞. Moreover, \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\psi \in W^{1,1}_{\textnormal {loc}}(\Omega )$\end{document} is a given obstacle function, whose gradient Dψ belongs to a Morrey space \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$L_{\textnormal {loc}}^{q,\lambda }(\Omega )$\end{document} with n − γ1 < λ < n and q > γ2. We do not assume any quantitative continuity of the integrand function f.
Synthesis and Characterizations of Regioregular Poly(3‐alkylthiophene) with Alter1483ting Dodecyl/1H,1H,2H,2H‐Perfluorooctyl Side Chains
Authors: Geng Yanfang , Tajima Keisuke , Hashimoto Kazuhito
Published: July 2011

A regioregular poly[4′‐dodecyl‐3‐(1H,1H,2H,2H‐perfluorooctyl)‐2,2′‐bithiophene] (P3DDFT) with alternating alkyl and semifluoroalkyl side chains were synthesized. Short ethylene spacer between perfluorohexyl part and thiophene did not largely affect the absorption and emission properties of the polythiophene backbone in comparison with poly(3‐dodecylthiophene) (P3DDT). P3DDFT showed a larger onset of the oxidation potential (+0.17 V) observed by cyclic voltamogram due to the electron withdrawing effect of the fluoroalkyl part. Thermal analysis and X‐ray diffraction patterns indicated that P3DDFT in the solid state forms a semicrystalline lamellar structure that is similar to that of P3DDT. Ultraviolet photoemission spectroscopy was also used to investigate their electron structure in the films. Comparison of hole mobilities in the films suggested that P3DDFT could have a less ordered packing structure compared to P3DDT both in the bulk and at the dielectric interface.

magnified image
Protein‐conjugated acrolein as a biochemical marker of brain infarction
Authors: Igarashi Kazuei , Kashiwagi Keiko
Published: July 2011

The relationship between acrolein (CH2=CH‐CHO) and brain infarction is the focus of this review. It has been found that acrolein is produced mainly within cells from polyamines by polyamine oxidases (PAOs), especially from spermine by spermine oxidase during cell damage, and that acrolein is more toxic than reactive oxygen species (ROS) in a cell culture system. Thus, the possibility that acrolein and PAOs are good biochemical markers of stroke was tested because there are no other reliable biochemical markers at the early stage of stroke. Levels of protein‐conjugated acrolein (PC‐Acro) and PAOs (acrolein‐producing enzymes) were significantly increased in the plasma of stroke patients. The multiplied value of PC‐Acro by PAOs was nearly parallel with the size of stroke. Furthermore, when the combined measurements of PC‐Acro, interleukin‐6 (IL‐6) and C‐reactive protein (CRP) were evaluated along with age using a receiver operating characteristic (ROC) curve, even silent brain infarction (SBI), which is a small brain infarction, was indicated with approximately 84% sensitivity and specificity. These findings clearly indicate that acrolein is strongly correlated with cell damage during brain infarction.
Practical second‐order reliability analysis applied to foundation engineering
Authors: Chan Chin Loong , Low Bak Kong
Published: July 2011

A practical and efficient approach of implementing second‐order reliability method (SORM) is presented and illustrated for cases related to foundation engineering involving explicit and implicit limit state functions. The proposed SORM procedure is based on an approximating paraboloid fitted to the limit state surface in the neighborhood of the design point and can be easily carried out in a spreadsheet. Complex mathematical operations are relegated to relatively simple user‐created functions. The failure probability is calculated automatically based on the reliability index and principal curvatures of the limit state surface using established closed‐form SORM formulas. Four common foundation engineering examples are analyzed using the proposed method and discussed: immediate settlement of a flexible rectangular foundation, bearing capacity of a shallow footing, axial capacity of a vertical single pile, and deflection of a pile under lateral load. Comparisons with Monte Carlo simulations are made. In the case of the laterally loaded pile, the friction angle of the soil is represented as a one‐dimensional random field, and pile deflections are computed based on finite element analysis on a stand‐alone computer package. The implicit limit state function is approximated via the response surface method using two quadratic models. Copyright © 2011 John Wiley & Sons, Ltd.
Direct detection of a single evoked action potential with MRS in Lumbricus terrestris
Authors: Poplawsky Alexander J. , Dingledine Raymond , Hu Xiaoping P.
Published: July 2011

Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background‐subtracted FID exhibited a systematic change, with a peak phase difference of (−1.2 ± 0.3) × 10–5 radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. Copyright © 2011 John Wiley & Sons, Ltd.
Genome‐wide array‐based copy number profiling in human placentas from unexplained stillbirths
Authors: Harris R. Alan , Ferrari Francesca , Ben‐Shachar Shay , Wang Xiaoling , Saade George , Van Den Veyver Ignatia , Facchinetti Fabio , Aagaard‐Tillery Kjersti
Published: July 2011

Objective

Accumulating evidence suggests that genomic structural variations, particularly copy number variations (CNV), are a common occurrence in humans that may bear phenotypic consequences for living individuals possessing the variant. While precise estimates vary, large‐scale karyotypic abnormalities are present in 6–12% of stillbirths (SB). However, due to inherent limitations of conventional cytogenetics, the contribution of genomic aberrations to stillbirth is likely underrepresented. High‐resolution copy number variant analysis by genomic array‐based profiling may overcome such limitations.

Methods

Prospectively acquired SB cases > 22 weeks underwent classification of ‘unexplained’ stillbirth by Wigglesworth and Aberdeen criteria after extensive testing and rigorous multidisciplinary audit. Genome‐wide analysis was conducted using high‐resolution Illumina single nucleotide polymorphism (SNP) arrays (Human CNV370‐Duo) on placental and fetal samples. Potential alternate detection methods were completed by one or more of three independent means (quantitative PCR, Illumina1M, or Agilent105K comparative genomic hybridization arrays).

Results

In our cohort of 54 stillbirths, 29 met strict unexplained criteria. Among these, we identified 24 putative novel CNVs. Subsequent interrogation detected 18 of 24 CNVs (75%) in placental samples, 8 of which were also confirmed in available fetal samples; none were present in maternal blood.

Conclusion

We describe the potential of whole‐genome placental profiling to identify small genomic imbalances, which might contribute to a small proportion of well‐characterized, unexplained stillbirths. Copyright © 2011 John Wiley & Sons, Ltd.
Electronic database to detect drug–drug interactions between antidepressants and oral anticancer drugs from a cancer center in Singapore: implications to clinicians
Authors: Chan Alexandre , Yap Kevin Yi‐Lwern , Koh Dorothy , Low Xiu Hui , Cheung Yin Ting ,   from the Onco‐Informatics (onco‐informatics.com) Group
Published: July 2011

Background

Electronic drug interaction databases are often utilized in clinical practice to detect for possible drug–drug interactions between drug pairs. It is uncertain, however, whether most of these detections interactions are clinically important in practice. To demonstrate these issues, this study utilized a comprehensive drug–drug interaction (DDI) electronic database to elucidate the prevalence of DDIs at a cancer centre between antidepressants and oral anticancer drugs (ACDs).

Methods

Drug utilization reports were retrieved to determine the patients who were prescribed with antidepressants oral ACDs between 2006 and 2009 at a cancer center. Medication records of these patients were retrospectively examined using OncoRx, an internet‐based oncology‐specific database that allows the identification of DDIs.

Results

Out of 910 users of antidepressants, about one‐third (281 patients, 30.9%) used an oral ACD and an antidepressant concomitantly. From these patients, about one‐fifth (21.0%) had potential DDIs. These patients were users of 17 potentially interacting drug pairs. Ten out of the 17 drug pairs could potentially cause pharmacokinetic interactions, and the rest were pharmacodynamic interactions, with only three out of the 17 drug pairs were clinically documented to cause interacting events.

Conclusion

The lack of screening conditions may have led to an over detection of DDI combinations by electronic DDI databases. Many of the detected interactions may not deem high significance in clinical practice. This study exposed a major weakness of current electronic DDI databases for detecting oral ACDs and antidepressants DDIs. Copyright © 2011 John Wiley & Sons, Ltd.