bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric properties of the Turkish Young Compensation Inventory
Authors: Karaosmanoğlu H. Alp , Soygüt Gonca , Kabul Asiye
Published: September 2011

The purpose of this study was to explore the psychometric properties of the Turkish version of the Young Compensation Inventory (YCI). Seven hundred and forty‐three patients participated in the study. Principal components analysis with equamax rotation was carried out, and seven definable factor structures emerged. Internal consistency analysis revealed statistically significant correlation coefficients. As to convergent validity, correlational analysis of theoretically related variables showed statistically significant coefficients. Furthermore, the discriminant validity assessed through t‐test analysis comparing clinical and non‐clinical samples (n = 516) yielded statistically significant differences. In overall evaluation, the Turkish YCI was found to have acceptable levels of reliability and validity. Copyright © 2011 John Wiley & Sons, Ltd.

Key Practitioner Message

The YCI is a self‐report questionnaire consisting of 48 items that assess the schema compensation strategies.

The Turkish YCI has acceptable levels of reliability and validity.

The Turkish YCI is ready to be used in both schema therapy practice and research settings in Turkey.
Erythema nodosum leprosum: Report of two cases
Authors: Aggarwal Roopak , Gupta Oneal , Beg Shaham , Prasad Rajni
Published: September 2011

Erythema nodosum leprosum (ENL) or type 2 lepra reaction is an inflammatory reaction, which may occur in the course of hanseniasis, may compel the patient to seek medical attention and may result in nerve function impairment and subsequent disability. Thus, recognition and timely management of these patients is critical in order to avoid permanent disability. Fine‐needle aspiration cytology is simple and effective tool that aids in the correct diagnosis and management of ENL. Herein, we present two cases of ENL, one with typical and another with atypical presentation. Diagn. Cytopathol. 2013;41:366–368. © 2011 Wiley Periodicals, Inc.
High sensitivity and positive predictive value of fine‐needle aspiration for uncommon thyroid malignancies
Authors: Dustin Simone M. , Jo Vickie Y. , Hanley Krisztina Z. , Stelow Edward B.
Published: September 2011

Fine‐needle aspiration (FNA) is a screening and diagnostic tool used to triage the management of thyroid nodules. While FNA has proved to be a sensitive means of detecting common thyroid malignancies, less is known about the sensitivity and positive predictive value (PPV) of FNA for uncommon thyroid malignancies, including anaplastic thyroid carcinomas, medullary thyroid carcinomas, lymphomas, metastatic carcinomas, and other malignancies. We reviewed our experience with these uncommon malignancies sampled by thyroid FNA and recorded interpretations according to the Bethesda System. We compared the FNA interpretations to the follow‐up cytology, histology, and flow cytometry. The sensitivity and PPV were as follows: anaplastic thyroid carcinoma (sensitivity 100%, PPV 89%), lymphoma (sensitivity 100%, PPV 100%), medullary thyroid carcinoma (sensitivity 83%, PPV 100%), metastatic carcinoma (sensitivity 80%, PPV 80%), and other malignancy (sensitivity 100%, PPV 100%). Four false‐negative and two false‐positive diagnoses were identified. While cases were nearly always triaged correctly, occasional pitfalls were encountered. Diagn. Cytopathol. 2011; © 2011 Wiley‐Liss, Inc.
Reciprocal actions of ATF5 and Shh in proliferation of cerebellar granule neuron progenitor cells
Authors: Lee Hae Young , Angelastro James M. , Kenney Anna Marie , Mason Carol A. , Greene Lloyd A.
Published: September 2011

Precise regulation of neuroprogenitor cell proliferation and differentiation is required for successful brain development, but the factors that contribute to this are only incompletely understood. The transcription factor ATF5 promotes proliferation of cerebral cortical neuroprogenitor cells and its down regulation permits their differentiation. Here, we examine the expression and regulation of ATF5 in cerebellar granule neuron progenitor cells (CGNPs) as well as the role of ATF5 in the transition of CGNPs to postmitotic cerebellar granule neurons (GCNs). We find that ATF5 is expressed by proliferating CGNPs in both the embryonic and postnatal cerebellar external granule layer (EGL) and in the rhombic lip, the embryonic structure from which the EGL arises. In contrast, ATF5 is undetectable in postmitotic GCNs. In highly enriched dissociated cultures of CGNPs and CGNs, ATF5 is expressed only in CGNPs. Constitutive ATF5 expression in CGNPs does not affect their proliferation or exit from the cell cycle. In contrast, in presence of sonic hedgehog (Shh), a mitogen for CGNPs, constitutively expressed ATF5 promotes CGNP proliferation and delays their cell cycle exit and differentiation. Conversely, ATF5 loss‐of‐function conferred by a dominant‐negative form of ATF5 significantly diminishes Shh‐stimulated CGNP proliferation and promotes differentiation. In parallel with its stimulation of CGNP proliferation, Shh enhances ATF5 expression by what appeared to be a posttranscriptional mechanism involving protein stabilization. These findings indicate a reciprocal interaction between ATF5 and Shh in which Shh stimulates ATF5 expression and in which ATF5 contributes to Shh‐stimulated CGNP expansion. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 789–804, 2012
Generating neuronal diversity in the Drosophila central nervous system
Authors: Lin Suewei , Lee Tzumin
Published: September 2011

Generating diverse neurons in the central nervous system involves three major steps. First, heterogeneous neural progenitors are specified by positional cues at early embryonic stages. Second, neural progenitors sequentially produce neurons or intermediate precursors that acquire different temporal identities based on their birth‐order. Third, sister neurons produced during asymmetrical terminal mitoses are given distinct fates. Determining the molecular mechanisms underlying each of these three steps of cellular diversification will unravel brain development and evolution. Drosophila has a relatively simple and tractable CNS, and previous studies on Drosophila CNS development have greatly advanced our understanding of neuron fate specification. Here we review those studies and discuss how the lessons we have learned from fly teach us the process of neuronal diversification in general. Developmental Dynamics 241:57–68, 2012. © 2011 Wiley Periodicals, Inc.
Transgenic zebrafish expressing green fluorescent protein in dopaminergic neurons of the ventral diencephalon
Authors: Xi Yanwei , Yu Man , Godoy Rafael , Hatch Gary , Poitras Luc , Ekker Marc
Published: September 2011

We have generated a line of transgenic zebrafish, Tg(dat:EGFP), in which the green fluorescent protein (GFP) is expressed under the control ofcis‐regulatory elements of thedopamine transporter(dat) gene. In Tg(dat:EGFP) fish, dopamine (DA) neurons are labeled with GFP, including those in ventral diencephalon (vDC) clusters, amacrine cells in the retina, in the olfactory bulb, in the pretectum, and in the caudal hypothalamus. In the vDC, DA neurons of groups 2–6 are correctly labeled with GFP, based on colocalization analyses. MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) treatments induced a modest but significant loss of DA neurons in groups 2–6 of the vDC. This transgenic line will be useful for the study of DA neuron development and in models of DA neuron loss. Developmental Dynamics 240:2539–2547, 2011. © 2011 Wiley‐Liss, Inc.
Expansion of a restricted residual host Treg‐cell repertoire is dependent on IL‐2 following experimental autologous hematopoietic stem transplantation
Authors: Bayer Allison L. , Chirinos Jackeline , Cabello Cecilia , Yang Jing , Matsutani Takaji , Malek Thomas R. , Levy Robert B.
Published: September 2011

We previously identified a population of residual Treg cells following autologous hematopoietic stem transplantation (HSCT), that rapidly undergoes significant expansion in lymphopenic transplant recipients prior to repopulation by donor de novo derived Treg cells. These CD4+Foxp3+ T cells provide protection from the development of autoimmune disease. Although ablative conditioning results in excess IL‐7 and IL‐15, IL‐2 is typically not found at high levels following autologous HSCT. We therefore examined the role of these three STAT‐5 signaling cytokines in the expansion of residual Treg cells after autologous HSCT. The present study found that the residual Treg cell population included surviving peripheral host Foxp3+CD4+ T cells whose expansion was critically dependent on IL‐2, which could be solely provided by surviving host cells. IL‐7 was found to contribute to Treg cell homeostasis, however, not as a growth factor but rather for their persistence. In conjunction with this expansion, TCR spectratype analyses revealed that the residual host Treg‐cell compartment differed from that present in non‐conditioned healthy mice since the residual host Treg cells exhibit a limited TCR diversity. Collectively, these data indicate that the proliferation of Treg and T effector (Teff) cells post‐HSCT utilize separate pools of cytokines which has important implications regarding the development of clinical strategies to elicit the desired immune responses in patients post‐transplant.
Palmitoylation of MICA, a ligand for NKG2D, mediates its recruitment to membrane microdomains and promotes its shedding
Authors: Agüera‐González Sonia , Gross Catharina C. , Fernández‐Messina Lola , Ashiru Omodele , Esteso Gloria , Hang Howard C. , Reyburn Hugh T. , Long Eric O. , Valés‐Gómez Mar
Published: September 2011

MICA and MICB (MHC‐class‐I‐related chain A/B) are transmembrane proteins expressed in pathological conditions that are ligands for NKG2D, an activating receptor found on cytotoxic lymphocytes. The recognition on target cells of NKG2D ligands leads to the activation of lysis and cytokine secretion by NK cells and T cells. Besides being expressed at the cell surface, MICA/B can be released as soluble proteins. Soluble NKG2D ligands downmodulate expression of the NKG2D receptor on lymphocytes, leading to a diminished cytotoxic response. Prior studies suggested that recruitment of MICA/B molecules to cholesterol‐enriched microdomains was an important factor regulating the proteolytic release of these molecules. We now show that recruitment of MICA to these microdomains depends on palmitoylation of two cysteine residues that allow MICA molecules to reside in the membrane in the same domains as caveolin‐1. Compared with WT molecules, nonpalmitoylated mutant MICA molecules were shed to the supernatant with low efficiency; however, both WT and mutant MICA were able to trigger NK cell cytotoxicity. These data suggest that the presence of NKG2D ligands at the plasma membrane is sufficient to activate cytotoxicity and reflect the need of different ligands to exploit different cellular pathways to reach the cell surface upon different stress situations.
Early B blasts acquire a capacity for Ig class switch recombination that is lost as they become plasmablasts
Authors: Marshall Jennifer L. , Zhang Yang , Pallan Lalit , Hsu Mei‐Chi , Khan Mahmood , Cunningham Adam F. , MacLennan Ian C. M. , Toellner Kai‐Michael
Published: September 2011

Rapid production of neutralizing antibody can be critical for limiting the spread of infection. Such early antibody results when B‐cell blasts mature directly to plasmablasts without forming germinal centers. These extrafollicular responses can involve Ig class switch recombination (CSR), producing antibody that can readily disseminate through infected tissues. The present study identifies the differentiation stage where CSR occurs in an extrafollicular response induced by 4‐hydroxy‐3‐nitrophenyl acetyl (NP) conjugated to Ficoll (NP‐Ficoll). To do this, we took advantage of the antigen dose dependency of CSR in this response. Thus, while both 30 and 1 μg NP‐Ficoll induce plasmablasts, only the higher antigen dose induces CSR. Activation‐induce cytidine deaminase (AID) is critical for CSR and in keeping with this a proportion of NP‐specific B‐cell blasts induced by 30 μg NP‐Ficoll express AID. None of the B blasts responding to the non‐CSR‐inducing 1 μg dose of NP‐Ficoll express AID. We confirmed that CSR occurs in B blasts by demonstrating the presence of rearranged heavy‐chain transcripts in B blasts in the 30 μg response. CSR in this extrafollicular response is confined to B blasts, because NP‐specific plasmablasts, identified by expressing CD138 and Blimp‐1, no longer express AID and cannot undergo CSR.
Unravelling the T‐cell‐mediated autoimmune attack on CNS myelin in a new primate EAE model induced with MOG34–56 peptide in incomplete adjuvant
Authors: Jagessar S. Anwar , Heijmans Nicole , Blezer Erwin L. A. , Bauer Jan , Blokhuis Jeroen H. , Wubben Jacqueline A. M. , Drijfhout Jan W. , van den Elsen Peter J. , Laman Jon D. , Hart Bert A.'t
Published: September 2011

Induction of experimental autoimmune encephalomyelitis (EAE) has been documented in common marmosets using peptide 34–56 from human myelin/oligodendrocyte glycoprotein (MOG34‐56) in incomplete Freund's adjuvant (IFA). Here, we report that this EAE model is associated with widespread demyelination of grey and white matter. We performed an in‐depth analysis of the specificity, MHC restriction and functions of the activated T cells in the model, which likely cause EAE in an autoantibody‐independent manner. T‐cell lines isolated from blood and lymphoid organs of animals immunized with MOG34–56 displayed high production of IL‐17A and specific lysis of MOG34–56‐pulsed EBV B‐lymphoblastoid cells as typical hallmarks. Cytotoxicity was directed at the epitope MOG40–48 presented by the non‐classical MHC class Ib allele Caja‐E, which is orthologue to HLA‐E and is expressed in non‐inflamed brain. In vivo activated T cells identified by flow cytometry in cultures with MOG34–56, comprised CD4+CD56+ and CD4+CD8+CD56+ T cells. Furthermore, phenotypical analysis showed that CD4+CD8+CD56+ T cells also expressed CD27, but CD16, CD45RO, CD28 and CCR7 were absent. These results show that, in the MOG34–56/IFA marmoset EAE model, a Caja‐E‐restricted population of autoreactive cytotoxic T cells plays a key role in the process of demyelination in the grey and white matter.
Synthesis of New N‐Ethyl Dehydroamino Acid Derivatives: N‐Ethyl β,β‐Dibromo, N‐Ethyl β‐Bromo β‐Substituted, and N‐Ethyl β,β‐Disubstituted N‐Protected Dehydroamino Acid Methyl Esters
Authors: Monteiro Luís S. , Andrade Juliana J. , Suárez Ana C.
Published: September 2011

Recently, we reported the use of a sequence of alkylation and dehydration methodologies to obtain new non‐proteinogenic amino acids (N‐ethyl α,β‐dehydroamino acids) from the methyl esters of N‐(4‐nitrophenylsulfonyl) β‐hydroxy amino acids. Thus, it was possible to obtain for the first time, non‐natural amino acids that incorporate both N‐ethyl and α,β‐dehydro moieties. Herein, we report the application of this N‐alkylation procedure to several methyl esters of β,β‐dibromo and β‐bromo β‐substituted dehydroamino acids protected with standard amine protecting groups such as tert‐butyloxycarbonyl, benzyloxycarbonyl, and (4‐nitrobenzyl)oxycarbonyl, as well as acyl and sulfonyl groups. The procedure allows the synthesis of the methyl esters of N‐protected N‐ethyl β,β‐dibromo and N‐ethyl β‐bromo β‐substituted dehydroamino acids in fair to high yields. Some of these N‐ethylated dehydroamino acid derivatives were used as substrates in cross‐coupling reactions to give β,β‐disubstituted N‐ethyldehydroalanine derivatives.
Parieto‐frontal network in humans studied by cortico‐cortical evoked potential
Authors: Matsumoto Riki , Nair Dileep R. , Ikeda Akio , Fumuro Tomoyuki , LaPresto Eric , Mikuni Nobuhiro , Bingaman William , Miyamoto Susumu , Fukuyama Hidenao , Takahashi Ryosuke , Najm Imad , Shibasaki Hiroshi , Lüders Hans O.
Published: September 2011

Parieto‐frontal network is essential for sensorimotor integration in various complex behaviors, and its disruption is associated with pathophysiology of apraxia and visuo‐spatial disorders. Despite advances in knowledge regarding specialized cortical areas for various sensorimotor transformations, little is known about the underlying cortico‐cortical connectivity in humans. We investigated inter‐areal connections of the lateral parieto‐frontal networkin vivoby means of cortico‐cortical evoked potentials (CCEPs). Six patients with epilepsy and one with brain tumor were studied. With the use of subdural electrodes implanted for presurgical evaluation, network configuration was investigated by tracking the connections from the parietal stimulus site to the frontal site where the maximum CCEP was recorded. It was characterized by (i) a near‐to‐near and distant‐to‐distant, mirror symmetric configuration across the central sulcus, (ii) preserved dorso‐ventral organization (the inferior parietal lobule to the ventral premotor area and the superior parietal lobule to the dorsal premotor area), and (iii) projections to more than one frontal cortical sites in 56% of explored connections. These findings were also confirmed by the standardized parieto‐frontal CCEP connectivity map constructed in reference to the Jülich cytoarchitectonic atlas in the MNI standard space. The present CCEP study provided an anatomical blueprint underlying the lateral parieto‐frontal network and demonstrated a connectivity pattern similar to non‐human primates in the newly developed inferior parietal lobule in humans. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Hepatitis B Virus X (HBx) Induces Tumorigenicity of Hepatic Progenitor Cells in 3,5–Diethoxycarbonyl–1,4–Dihydrocollidine–Treated HBx Transgenic Mice
Authors: Wang Chao , Yang Wen , Yan He–Xin , Luo Tao , Zhang Jian , Tang Liang , Wu Fu–Quan , Zhang Hui–Lu , Yu Le–Xing , Zheng Long–Yi , Li Yu–Qiong , Dong Wei , He Ya–Qin , Liu Qiong , Zou Shan–Shan , Lin Yan , Hu Liang , Li Zhong , Wu Meng–Chao , Wang Hong–Yang
Published: September 2011

Hepatitis B virus X (HBx) protein is implicated in hepatitis B virus (HBV)–associated liver carcinogenesis. However, it remains unclear whether HBx–expressing hepatic progenitor cells (HPCs) are attributed to liver tumor formation. In this study, by using HBx transgenic mice and a 3,5–diethoxycarbonyl–1,4–dihydrocollidine (DDC)–induced liver injury model, the relationship between HBx expression and tumorigenicity of HPCs was analyzed. Compared with control mice, an elevated number of EpCAM+ cells with characteristics of HPCs was observed in HBx mice after 1 month and 4 months of DDC diet feeding. All HBx transgenic mice developed liver tumors characterized by histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma after 7 months of DDC feeding. Notably, EpCAM+ HPCs isolated from premalignant HBx mice exposed to a DDC diet for 4 months formed subcutaneous mixed–lineage tumors (four out of six) in nonobese diabetic/severe–combined immunodeficient (NOD/SCID) mice, and none of the cells from wildtype (WT) induced tumor, indicating that HBx may induce malignant transformation of HPCs that contributes to tumorigenesis. We also found higher titers of circulating interleukin (IL)–6, activities of IL–6/STAT3, and Wnt/β–catenin signaling pathways in HBx transgenic mice, suggesting HBx may induce intrinsic changes in HPCs by way of the above signaling that enables HPCs with tumorigenicity potential. Finally, clinical evidence showed that high HBx expression in human HBV–related HCC was statistically associated with expansion of EpCAM+ or OV6+ tumor cells and aggressive clinicopathologic features.

Conclusion

: HBx induces intrinsic cellular transformation promoting the expansion and tumorigenicity of HPCs in DDC–treated mice, which may be a possible origin for liver cancer induced by chronic hepatitis infection. (Hepatology 2012)
IL28B Alleles Associated With Poor Hepatitis C Virus (HCV) Clearance Protect Against Inflammation and Fibrosis in Patients Infected With Non-1 HCV Genotypes
Authors: Bochud Pierre-Yves , Bibert Stéphanie , Kutalik Zoltán , Patin Etienne , Guergnon Julien , Nalpas Bertrand , Goossens Nicolas , Kuske Lorenz , Müllhaupt Beat , Gerlach Tillman , Heim Markus H. , Moradpour Darius , Cerny Andreas , Malinverni Raffaele , Regenass Stephan , Dollenmaier Guenter , Hirsch Hans , Martinetti Gladys , Gorgiewski Meri , Bourlière Marc , Poynard Thierry , Theodorou Ioannis , Abel Laurent , Pol Stanislas , Dufour Jean-François , Negro Francesco
Published: September 2011

Genetic polymorphisms near

IL28B

are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with

IL28B

polymorphisms has yet to be fully appreciated. We analyzed the association of

IL28B

polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at

IL28B

marker

rs8099917

—previously shown to be at risk of treatment failure—was associated with lower activity (

P

= 0.04), lower fibrosis (

P

= 0.02) with a trend toward lower fibrosis progression rate (

P

= 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (

P

= 0.003 for activity,

P

= 0.001 for fibrosis, and

P

= 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with

IL28B

genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively.

IL28B

polymorphisms were not predictive of the development of hepatocellular carcinoma.

Conclusion :

In chronic hepatitis C,

IL28B

variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes. (Hepatology 2012)
CD59 Incorporation Protects Hepatitis C Virus Against Complement-Mediated Destruction
Authors: Amet Tohti , Ghabril Marwan , Chalasani Naga , Byrd Daniel , Hu Ningjie , Grantham Ayslinn , Liu Ziqing , Qin Xuebin , He Johnny J. , Yu Qigui
Published: September 2011

Several enveloped viruses including human immunodeficiency virus type 1 (HIV-1), cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), Ebola virus, vaccinia virus, and influenza virus have been found to incorporate host regulators of complement activation (RCA) into their viral envelopes and, as a result, escape antibody-dependent complement-mediated lysis (ADCML). Hepatitis C virus (HCV) is an enveloped virus of the family

Flaviviridae

and incorporates more than 10 host lipoproteins. Patients chronically infected with HCV develop high-titer and crossreactive neutralizing antibodies (nAbs), yet fail to clear the virus, raising the possibility that HCV may also use the similar strategy of RCA incorporation to escape ADCML. The current study was therefore undertaken to determine whether HCV virions incorporate biologically functional CD59, a key member of RCA. Our experiments provided several lines of evidence demonstrating that CD59 was associated with the external membrane of HCV particles derived from either Huh7.5.1 cells or plasma samples from HCV-infected patients. First, HCV particles were captured by CD59-specific Abs. Second, CD59 was detected in purified HCV particles by immunoblot analysis and in the cell-free supernatant from HCV-infected Huh7.5.1 cells, but not from uninfected or adenovirus serotype 5 (Ad5) (a nonenveloped cytolytic virus)-infected Huh7.5.1 cells by enzyme-linked immunosorbent assay. Last, abrogation of CD59 function with its blockers increased the sensitivity of HCV virions to ADCML, resulting in a significant reduction of HCV infectivity. Additionally, direct addition of CD59 blockers into plasma samples from HCV-infected patients increased autologous virolysis.

Conclusion :

Our study, for the first time, demonstrates that CD59 is incorporated into both cell line-derived and plasma primary HCV virions at levels that protect against ADCML. This is also the first report to show that direct addition of RCA blockers into plasma from HCV-infected patients renders endogenous plasma virions sensitive to ADCML. (Hepatology 2012)
Training in context: Toward a person‐by‐situation view of voluntary training
Authors: Morrell Daniel L. , Korsgaard M. Audrey
Published: September 2011

The purpose of this field study of 327 nonfaculty university professionals was to examine the joint relationship of conscientiousness and context on two dependent variables: motivation and participation in voluntary training systems. Drawing on the principles of person‐by‐situation theories of personality, this study examined how the relationship between conscientiousness and training is moderated by social cues and managerial status. The findings from a field study indicated that the relationship between conscientiousness and motivation to learn was moderated by the favorableness of social cues from coworkers and supervisors. Results also indicated the relationship between conscientiousness and training participation was moderated by managerial status. The findings bolster research on the importance of situational factors on the decision to participate in voluntary training.
Modelling detention basins measured from high‐resolution light detection and ranging data
Authors: Wang Lei , Yu Jaehyung
Published: September 2011

The construction of stormwater detention basins is a best management practice to effectively control floods, to provide additional surface storage for excess floodwater and to compensate for the adverse effects of urban development. Traditional field‐based levelling survey methods are very time consuming and subject to human‐induced arbitrariness and error. This article presents an approach to modelling detention basins measured from light detection and ranging remote sensing data. A case study is illustrated by using the White Oak Bayou watershed of Harris County, Texas. The storage–stage curve obtained from the volumetric analysis is used in a modified detention basins routing model, which was developed by adding the weir structure control to the traditional hydrologic reservoir routing equations. The model simulation showed that the peak flow of the synthetic 100‐year reoccurrence event was effectively reduced and delayed by the detention basins. The comparison with the simulation results from the traditional reservoir routing model suggested that previous studies using the reservoir routing model were likely to underestimate the flood reduction effect of detention basins. The sensitivity analysis of the parameters showed that the detention basin design and evaluation should pay more attention on the weir height and river channel's roughness. Copyright © 2011 John Wiley & Sons, Ltd.
Oncogenic PIK3CA mutations in colorectal cancers and polyps
Authors: Whitehall Vicki L.J. , Rickman Celestine , Bond Catherine E. , Ramsnes Ingunn , Greco Sonia A. , Umapathy Aarti , McKeone Diane , Faleiro Rebecca J. , Buttenshaw Ron L. , Worthley Daniel L. , Nayler Sam , Zhao Zhen Zhen , Montgomery Grant W. , Mallitt Kylie‐Ann , Jass Jeremy R. , Matsubara Nagahide , Notohara Kenji , Ishii Tatsuhiro , Leggett Barbara A.
Published: September 2011

Oncogenic PIK3CA mutations contribute to colorectal tumorigenesis by activating AKT signaling to decrease apoptosis and increase tumor invasion. A synergistic association of PIK3CA mutation with KRAS mutation has been suggested to increase AKT signaling and resistance to antiepidermal growth factor receptor inhibitor therapy for advanced colorectal cancer, although studies have been conflicting. We sought to clarify this by examining PIK3CA mutation frequency in relation to other key molecular features of defined pathways of tumorigenesis. PIK3CA mutation was assessed by high resolution melt analysis in 829 colorectal cancer samples and 426 colorectal polyps. Mutations were independently correlated with clinicopathological features including patient age, sex and tumor location as well as molecular features including microsatellite instability, KRAS and BRAF mutation, MGMT methylation and the CpG Island Methylator Phenotype (CIMP). Mutation of the helical (Exon 9) and catalytic (Exon 20) domain mutation hotspots were also examined independently. Overall, PIK3CA mutation was positively correlated with KRAS mutation (p < 0.001), MGMT methylation (p = 0.007) and CIMP (p < 0.001). Novel, exon‐specific associations linked Exon 9 mutations to a subgroup of cancers characterized by KRAS mutation, MGMT methylation and CIMP‐Low, whilst Exon 20 mutations were more closely linked to features of serrated pathway tumors including BRAF mutation, microsatellite instability and CIMP‐High or Low. PIK3CA mutations were uncommonly, but exclusively, seen in tubulovillous adenomas (4/124, 3.2%) and 1/4 (25.0%) tubulovillous adenomas with a focus of cancer. These data provide insight into the molecular events driving traditional versus serrated pathway tumorigenesis.
Regulation of cell volume by glycosaminoglycans
Authors: Joerges Jelena , Schulz Tobias , Wegner Jeannine , Schumacher Udo , Prehm Peter
Published: September 2011

Cell volume is regulated by a delicate balance between ion distribution across the plasma membrane and the osmotic properties of intra‐ and extracellular components. Using a fluorescent calcein indicator, we analysed the effects of glycosaminoglycans on the cell volume of hyaluronan producing fibroblasts and hyaluronan deficient HEK cells over a time period of 30 h. Exogenous glycosaminoglycans induced cell blebbing after 2 min and swelling of fibroblasts to about 110% of untreated cell volume at low concentrations which decreased at higher concentrations. HEK cells did not show cell blebbing and responded by shrinking to 65% of untreated cell volume. Heparin induced swelling of both fibroblasts and HEK cells. Hyaluronidase treatment or inhibition of hyaluronan export led to cell shrinkage indicating that the hyaluronan coat maintained fibroblasts in a swollen state. These observations were explained by the combined action of the Donnan effect and molecular crowding. J. Cell. Biochem. 113: 340–348, 2012. © 2011 Wiley Periodicals, Inc.
Using hyperpolarized 3He MRI to evaluate treatment efficacy in cystic fibrosis patients
Authors: Sun Yanping , O'Sullivan Brian P. , Roche John P. , Walvick Ronn , Reno Austin , Baker Dawn , Mansour Joey K. , Albert Mitchell S.
Published: September 2011

Purpose:

To use hyperpolarized (HP) 3He MR imaging to assess functional lung ventilation in subjects with cystic fibrosis (CF) before and after treatment.

Materials and Methods:

We performed HP 3He static ventilation MRI scans on three subjects, using a Philips 3.0 Tesla (T) Achieva MRI scanner, before and after 11 days of in‐patient treatment with combined intravenous and inhaled therapies for pulmonary exacerbations of CF. We also collected spirometry data. We quantified pulmonary ventilation volume measured with HP 3He MRI using an advanced semi‐automated analysis technique.

Results:

Following 11 days of treatment with intravenous antibiotics, hypertonic saline, and rhDNase, HP 3He MR images in one subject displayed a 25% increase in total ventilation volume. Total ventilation volume in the other two subjects slightly decreased. All three subjects showed increases in FEV1 and FVC following treatment.

Conclusion:

In all subjects, the HP 3He MR images provided detailed information on precisely where in the lungs gas was reaching. These data provide additional support for the conclusion that HP noble gas MRI can be a powerful tool for evaluating lung ventilation in patients with cystic fibrosis, but also raise important questions about the correlation between spirometry and HP gas MRI measurements. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc.
Chronic administration of the neurotrophic agent cerebrolysin ameliorates the behavioral and morphological changes induced by neonatal ventral hippocampus lesion in a rat model of schizophrenia
Authors: Vázquez‐Roque Rubén Antonio , Ramos Brenda , Tecuatl Carolina , Juárez Ismael , Adame Anthony , de la Cruz Fidel , Zamudio Sergio , Mena Raúl , Rockenstein Edward , Masliah Eliezer , Flores Gonzalo
Published: September 2011

Neonatal ventral hippocampal lesion (nVHL) in rats has been widely used as a neurodevelopmental model to mimic schizophrenia‐like behaviors. Recently, we reported that nVHLs result in dendritic retraction and spine loss in prefrontal cortex (PFC) pyramidal neurons and medium spiny neurons of the nucleus accumbens (NAcc). Cerebrolysin (Cbl), a neurotrophic peptide mixture, has been reported to ameliorate the synaptic and dendritic pathology in models of aging and neurodevelopmental disorder such as Rett syndrome. This study sought to determine whether Cbl was capable of reducing behavioral and neuronal alterations in nVHL rats. The behavioral analysis included locomotor activity induced by novel environment and amphetamine, social interaction, and sensoriomotor gating. The morphological evaluation included dendritic analysis by using the Golgi‐Cox procedure and stereology to quantify the total cell number in PFC and NAcc. Behavioral data show a reduction in the hyperresponsiveness to novel environment‐ and amphetamine‐induced locomotion, with an increase in the total time spent in social interactions and in prepulse inhibition in Cbl‐treated nVHL rats. In addition, neuropathological analysis of the limbic regions also showed amelioration of dendritic retraction and spine loss in Cbl‐treated nVHL rats. Cbl treatment also ameliorated dendritic pathology and neuronal loss in the PFC and NAcc in nVHL rats. This study demonstrates that Cbl promotes behavioral improvements and recovery of dendritic neuronal damage in postpubertal nVHL rats and suggests that Cbl may have neurotrophic effects in this neurodevelopmental model of schizophrenia. These findings support the possibility that Cbl has beneficial effects in the management of schizophrenia symptoms. © 2011 Wiley Periodicals, Inc.
A retrospective study of surgical treatment of chronic radiation enteritis
Authors: Zhu Weiming , Gong Jianfeng , Li Yi , Li Ning , Li Jieshou
Published: September 2011

Background and aims

We assessed the role of surgery in the management of patients with intestinal obstruction or enterocutaneous fistula after chronic radiation enteritis (CRE) referred to our department, a specialist gastrointestinal surgical center, and analysis was made for the success of surgery.

Methods

A retrospective analysis was made of 156 patients receiving radiation therapy for malignancy from Jan 2000 to Nov 2010, among which 134 received surgery for intestinal or urinary complications. The demographic data, nutritional status, previous surgery, disease location and clinical manifestations, concomitant urinary complications, and surgical procedures were analyzed.

Results

Although malnutrition was prevalent (84/156, 53.9%) in this group of patients, the majority of them (101/134, 75.4%) recovered uneventfully after surgery following nutrition therapy, and resection and anastomosis (102/134) was the predominant surgical procedure for radiation injury to the ileocecal region. Sixteen patients received surgery for radiation‐induced urinary complications. There were 36 postoperative morbidities (26.87%), mainly wound complications (21/134), intestinal obstruction (5/134), and anastomotic dehiscence (3/134).

Conclusions

Surgery is justified for patients with bowel obstruction or fistula after CRE. A comprehensive perioperative management, especially perioperative nutrition therapy was important for the success of the surgery. J. Surg. Oncol. 2012; 105:632–636. © 2011 Wiley Periodicals, Inc.
Innovations powered by laser plastic welding
Authors: Brunnecker Frank
Published: September 2011

Modern laser plastic welding is successfully competing with joining technologies in more and more areas of application. The technology is already well established in the automotive industry and in the medical technology sector with their zero‐error specifications.
Innovative manufacturing of 3D‐lightweight components
Authors: Brecher Christian , Dubratz Markus , Stimpfl Joffrey , Emonts Michael
Published: September 2011

Fibre‐reinforced plastics (or: fibre‐reinforced polymers, FRPs) – a group of materials with excellent and largely adjustable properties – have found their way into many industries over the past yearsn and have established themselves in various sectors. Continuous FRPs have a wide potential for lightweight designs due to their ability to withstand high mechanical loads despite their tare weight. Today's air and space technologies or the wind power industry are unimaginable without this material. Fibre‐reinforced components will form one of the most importantkey factors for the European industry with its energy‐efficient production to fulfil the increasing global demands e.g. energy efficiency, waste avoidance and reduction of CO2‐emissions.
Hepatocyte-derived MicroRNAs as Serum Biomarkers of Hepatic Injury and Rejection after Liver Transplantation
Authors: Farid Waqar R. R. , Pan Qiuwei , van der Meer Adriaan J. P. , de Ruiter Petra E. , Ramakrishnaiah Vedashree , de Jonge Jeroen , Kwekkeboom Jaap , Janssen Harry L. A. , Metselaar Herold J. , Tilanus Hugo W. , Kazemier Geert , van der Laan Luc J.W.
Published: September 2011

Recent animal and human studies have highlighted the potential of hepatocyte-derived microRNAs (HDmiRs) in serum as early, stable, sensitive, and specific biomarkers of liver injury. Their usefulness in human liver transplantation, however, has not been addressed. The aim of this study was to investigate serum HDmiRs as markers of hepatic injury and rejection in liver transplantation. Serum samples from healthy controls and liver transplant recipients (n = 107) and peritransplant liver allograft biopsy samples (n = 45) were analyzed via the real-time polymerase chain reaction quantification of HDmiRs (miR-122, miR-148a, and miR-194). The expression of miR-122 and miR-148a in liver tissue was significantly reduced with prolonged graft warm ischemia times. Conversely, the serum levels of these HDmiRs were elevated in patients with liver injury and positively correlated with aminotransferase levels. HDmiRs appear to be very sensitive because patients with normal aminotransferase values (<50 IU/L) had 6- to 17-fold higher HDmiR levels in comparison with healthy controls (P < 0.005). During an episode of acute rejection, serum HDmiRs were elevated up to 20-fold, and their levels appeared to rise earlier than aminotransferase levels. HDmiRs in serum were stable during repeated freezing and thawing. In conclusion, this study shows that liver injury is associated with the release of HDmiRs into the circulation. HDmiRs are promising candidates as early, stable, and sensitive biomarkers of rejection and hepatic injury after liver transplantation.
Liver Transpl 18:290–297, 2012.
© 2012 AASLD.
Long-Term Outcome of Hepatitis C Virus Infections Acquired After Pediatric Liver Transplantation
Authors: Venturi Carla , Bueno Javier , Castells Lluís , Quintero Jesus , Casas Isabel , Allende Helena , Martinez-Ibañez Vicente , Charco Ramón
Published: September 2011

The outcomes and characterization of hepatitis C virus (HCV) infections after pediatric liver transplantation (LT) have rarely been reported. We describe our experience with HCV infections after pediatric LT. Ten of 207 children (4.8%) who underwent LT at our institution (1985-2010) developed previously undiagnosed HCV disease. Eight received a liver graft before blood product and donor screening for HCV became available. The mean age at transplantation was 8.9 ± 4.3 years, and the median time from transplantation to the diagnosis of HCV was 15.1 years (range = 0.2-19.7 years). The genotypes were 1 (n = 8), 3 (n = 1), and undetermined (n = 1). At the time of this writing, all the patients were still alive with a mean follow-up of 7.3 ± 5.5 years after the diagnosis of HCV. Five patients did not receive treatment; 2 of these patients achieved spontaneous viral clearance (SVC). Four of the 5 treated patients achieved a sustained virological response, and 3 had an early virological response (EVR). Two of these 4 patients developed chronic rejection while they were on treatment, but this was resolved with a conversion from cyclosporine A to tacrolimus. The remaining patient was continuing treatment and had achieved EVR. In conclusion, despite the limitations of our series, de novo HCV infections after pediatric LT seem to have a slow histological progression. Even with genotype 1, the patients have a good long-term prognosis and respond well to treatment. Nevertheless, chronic rejection during antiviral therapy may develop. In addition, SVC may occur in this population. Liver Transpl, 2011. © 2011 AASLD.
Mining the malignant ascites proteome for pancreatic cancer biomarkers
Authors: Kosanam Hari , Makawita Shalini , Judd Bramford , Newman Alice , Diamandis Eleftherios P.
Published: September 2011

Pancreatic cancer (PC) is one of the most lethal malignancies and disease‐specific biomarkers are desperately needed for better diagnosis, prognosis, monitoring treatment efficacy and for accelerating the development of novel targeted therapeutics. Being an advanced stage manifestation and a proximal fluid in contact with cancer tissues, the ascitic fluid presents itself as a promising rich source of biomarkers. Herein, we present a comprehensive proteomic analysis of pancreatic ascitic fluid. To fractionate the complex ascites proteome, we adopted a multi‐dimensional chromatographic approach that included size‐exclusion, ion‐exchange and lectin‐affinity chromatographic techniques. Our detailed proteomic analysis with high‐resolution Orbitrap® mass spectrometer resulted in the identification of 816 proteins. We followed rigorous filtering criteria that consisted of PC‐specific information obtained from three publicly available databases (Oncomine, Protein Atlas and Unigene) to segregate 20 putative biomarker candidates for future validation. Since these proteins are of membranous and extra‐cellular origin, most are glycosylated, and many of them are over‐expressed in cancer tissues, the probability of these proteins entering the peripheral blood circulation is high. Their validation as serological PC biomarkers in the future is highly warranted.
ErbB2/Her‐2 regulates the expression of Akt2 in prostate cancer cells
Authors: Le Page Cécile , Koumakpayi Ismaël Hervé , Péant Benjamin , Delvoye Nathalie , Saad Fred , Mes‐Masson Anne‐Marie
Published: September 2011

BACKGROUND

We have previously reported that ErbB family members regulate the signaling pathway leading to Akt and NF‐kappaB activation in prostate cancer cells. In this study, the regulation of Akt2 expression in LNCaP, DU145, and PC‐3 prostate cancer cell lines was investigated.

METHODS

Akt‐2 expression was analyzed by western‐blotting and Q‐PCR in cell lines. We also analyzed the Akt‐2 protein expression in a tissue microarray from 64 prostate cancer patients. Akt‐2 promoter activity was assessed and analyzed by luciferase assay.

RESULTS

A concomitant over‐expression of Her‐2 and Akt2 expression was observed by western‐blotting and quantitative‐PCR in prostate cancer cell lines. A significant correlation between Her‐2 and Akt2 protein expression was also observed by immunohistochemistry assay on prostate cancer tissues. In LNCaP cells, over‐expression of Akt2 protein and mRNA was decreased by Her‐2 pharmacologic inhibitors as well as small interfering RNA (siRNA) specific to Her‐2. Cloning of the AKT2 promoter in a luciferase reporter plasmid further showed that Akt2 over‐expression in cell lines is associated with increased AKT2 promoter activity suggesting that Her‐2 modulates a signaling pathway involving AKT2 gene regulation.

CONCLUSION

This study reveals a novel mechanism of Akt2 regulation in prostate cancer cells. Prostate 72:777–788, 2012. © 2011 Wiley Periodicals, Inc.
Phase II study of personalized peptide vaccination for castration‐resistant prostate cancer patients who failed in docetaxel‐based chemotherapy
Authors: Noguchi Masanori , Moriya Fukuko , Suekane Shigetaka , Matsuoka Kei , Arai Gaku , Matsueda Satoko , Sasada Tetsuro , Yamada Akira , Itoh Kyogo
Published: September 2011

BACKGROUND

Docetaxel‐based chemotherapy (DBC) showed limited clinical efficacy for castration‐resistant prostate cancer (CRPC) patients. To explore cancer vaccine as a new treatment modality, we conducted a phase II study of personalized peptide vaccine (PPV) for DBC‐resistant CRPC patients.

METHODS

Twenty DBC‐resistant CRPC patients and 22 patients with no prior DBC, as a control, were treated with PPV using peptides chosen from 31 peptides in patients, respectively. Cytokines, inflammatory markers, and immune responses were measured as candidate biomarkers. DBC‐resistant CRPC patients without PPV was set as a historical control for evaluation of clinical benefit of PPV.

RESULTS

Median overall survival (OS) time from the first vaccination was 14.8 months or not reached in DBC‐resistant CRPC patients and patients with no prior DBC (log‐rank; P = 0.07), respectively. Median OS time from the first day of progression disease was 17.8 and 10.5 months in DBC‐resistant CRPC patients receiving PPV and those with no PPV (P = 0.1656), respectively. Elevated IL‐6 levels before vaccination was an unfavorable factor for OS of DBC‐resistant CRPC patients (P = 0.0161, hazard ratio (HR): 0.024, 95% CI:0.001–0.499) as well as all 42 patients with PPV(P = 0.0011, HR: 0.212, 95% CI:0.068–0.661) by multivariable analysis.

CONCLUSIONS

Further clinical study of PPV is recommended for DBC‐resistant CRPC patients, because of the safety and possible prolongation of MST. Control of elevated IL‐6 by combined therapy may provide much better clinical outcome. Prostate 72:834–845, 2012. © 2011 Wiley Periodicals, Inc.
Predicting flexible loop regions that interact with ligands: The challenge of accurate scoring
Authors: Danielson Matthew L. , Lill Markus A.
Published: September 2011

Flexible loop regions play a critical role in the biological function of many proteins and have been shown to be involved in ligand binding. In the context of structure‐based drug design, using or predicting an incorrect loop configuration can be detrimental to the study if the loop is capable of interacting with the ligand. Three protein systems, each with at least one flexible loop region in close proximity to the known binding site, were selected for loop prediction using the CorLps program; a six residue loop region from phosphoribosylglycinamide formyltransferase (GART), two nine residue loop regions from cytochrome P450 (CYP) 119, and an 11 residue loop region from enolase were selected for loop prediction. The results of this study indicate that the statistically based DFIRE scoring function implemented in the CorLps program did not accurately rank native‐like predicted loop configurations in any protein system. In an attempt to improve the ranking of the native‐like predicted loop configurations, the MM/GBSA and the optimized MM/GBSA‐dsr scoring functions were used to re‐rank the predicted loops with and without bound ligand. In general, single snapshot MM/GBSA scoring provided the best ranking of native‐like loop configurations. Based on the scoring function analyses presented, the optimal ranking of native‐like loop configurations is still a difficult challenge and the choice of the “best” scoring function appears to be system dependent. Proteins 2012; © 2011 Wiley Periodicals, Inc.