bluuebunny/crossref_metadata_2025_split huggingface dataset:
The matricellular protein CCN1 suppresses lung cancer cell growth by inducing senescence via the p53/p21 pathway
Authors: Jim Leu Shr‐Jeng , Sung Jung‐Sung , Chen Mei‐Yu , Chen Chih‐Wei , Cheng Jian‐Yu , Wang Tse‐Yen , Wang Jeng‐Jung 
Published: April 2013

AbstractCCN1, a secreted matrix‐associated molecule, is involved in multiple cellular processes. Previous studies have indicated that expression of CCN1 correlates inversely with the aggressiveness of non‐small‐cell lung carcinoma (NSCLC); however, the underlying mechanisms remain elusive. Using three NSCLC cell line systems, here we show that long‐term treatment of cells with the recombinant CCN1 protein led to a permanent cell cycle arrest in G1 phase; cells remained viable as judged by apoptotic assays. CCN1‐treated NSCLC cells acquired a phenotype characteristic of senescent cells, including an enlarged and flattened cell shape and expression of the senescence‐associated β‐galactosidase. Immunoblot analysis showed that addition of CCN1 increased the abundance of hypo‐phosphorylated Rb, as well as accumulation of p53 and p21. Silencing the expression of p53 or p21 by lentivirus‐mediated shRNA production in cells blocked the CCN1‐induced senescence. Furthermore, a CCN1 mutant defective for binding integrin α6β1 and co‐receptor heparan sulfate proteoglycans was incapable of senescence induction. Our finding that direct addition of CCN1 induces senescence in NSCLC cells provides a potential novel strategy for therapeutic intervention of lung cancers. J. Cell. Biochem. 114: 2082–2093, 2013. © 2013 Wiley Periodicals, Inc.
The inhibition of p85αPI3KSer83 phosphorylation prevents cell proliferation and invasion in prostate cancer cells
Authors: Feola Antonia , Cimini Annamaria , Migliucci Francesca , Iorio Rosamaria , Zuchegna Candida , Rothenberger Rodger , Cito Letizia , Porcellini Antonio , Unteregger Gerhard , Tombolini Vincenzo , Giordano Antonio , Di Domenico Marina 
Published: April 2013

AbstractPhosphoinositide 3‐kinase proteins are composed by a catalytic p110 subunit and a regulatory p85 subunit. There are three classes of PI3K, named class I–III, on the bases of the protein domain constituting and determining their specificity. The first one is the best characterized and includes a number of key elements for the integration of different cellular signals. Regulatory p85 subunit shares with the catalytic p110 subunit, a N‐terminal SH3 domain showing homology with the protein domain Rho‐GTP‐ase. After cell stimulation, all class I PI3Ks are recruited to the inner face of the plasma membrane, where they generate phosphatidylinositol‐3,4,5‐trisphosphate by direct phosphorylation of phosphatidylinositol‐4,5‐bisphosphate. All pathways trigger the control of different phenomena such as cell growth, proliferation, apoptosis, adhesion and migration through various downstream effectors. We have previously provided direct evidences that a Serine in position 83, adjacent to the N‐terminal SH3 domain of regulatory subunit of PI3K, is a substrate of PKA. The aim of this work is to confirm the role of p85αPI3KSer83 in regulating cell proliferation, migration and invasion in prostate cancer cells LNCaP. To this purpose cells were transfected with mutant forms of p85, where Serine was replaced by Alanine, where phosphorylation is prevented, or Aspartic Acid, to mimic the phosphorylated residue. The findings of this study suggest that identifying a peptide mimicking the sequence adjacent to Ser 83 may be used to produce antibodies against this residue that can be proposed as usefool tool for prognosis by correlating phosphorylation at Ser83 with tumor stage. J. Cell. Biochem. 114: 2114–2119, 2013. © 2013 Wiley Periodicals, Inc.
Gremlin aggravates hyperglycemia‐induced podocyte injury by a TGFβ/smad dependent signaling pathway
Authors: Li Guiying , Li Ying , Liu Shuxia , Shi Yonghong , Chi Yanqing , Liu Guijing , Shan Tieying 
Published: April 2013

AbstractGremlin is a bone morphogenic protein (BMP) antagonist and is elevated in diabetic kidney tissues. In the early course of diabetic nephropathy (DN), podocyte are injured. We studied the protein and gene expression of gremlin in mice podocytes cultured in hyperglycemia ambient. The role of gremlin on podocyte injury and the likely signaling pathways involved were determined. Expression of gremlin was visualized by confocal microscopy. Recombinant mouse gremlin and small interfering RNA (siRNA) targeting to gremlin1 identified the role played by gremlin on podocytes. Study of canonical (smad2/3) and non‐canonical (p38MAPK and JNK1/2) transforming growth factor beta (TGFβ)/smad mediated signaling revealed the putative signaling mechanisms involved. Smad2/3 siRNA and TGFβ receptor inhibition (SB431542) were used to probe canonical TGFβ/smad signaling in gremlin‐induced podocyte injury. Apoptosis of podocytes was measured by TUNEL assay. Gremlin expression was enhanced in high glucose cultured mouse podocytes, and was localized predominantly in the cytoplasm and negligibly on the cell membrane. Not only expression of nephrin and synaptopodin were decreased on treatment with gremlin, but also synaptopodin rearrangement and nephrin relocalization were evident. Knockdown gremlin1 or smad2/3 by siRNA, and inhibition of TGFβR (SB431542) attenuated podocyte injury. Inhibition of canonical TGF‐β signal blocked the injury of gremlin on podocytes. In conclusion, gremlin was clearly elevated in high glucose cultured mouse podocytes, and likely employed endogenous canonical TGFβ1/Smad signaling to induce podocyte injury. Knockdown gremlin1 by siRNA may be clinically useful in the attenuation of podocyte injury. J. Cell. Biochem. 114: 2101–2113, 2013. © 2013 Wiley Periodicals, Inc.
Na+/H+ exchange is inactivated during mouse oocyte meiosis, facilitating glycine accumulation that maintains embryo cell volume
Authors: Zhou Chenxi , Fitzharris Greg , Alper Seth L. , Baltz Jay M. 
Published: April 2013

AbstractThe coupled action of the Na+/H+ exchanger NHE1 and the HCO3−/Cl− exchanger AE2 constitutes the principal mechanism for acute correction of decreased cell volume in mammalian somatic cells, while, when acting separately, they regulate intracellular pH. It was previously found that AE2 becomes inactivated during meiosis in mouse oocytes. Similarly, NHE1 activity stimulated by intracellular acidosis was present in preovulatory germinal vesicle stage (GV) mouse oocytes and then decreased during meiotic maturation. In contrast, NHE1 activity stimulated by decreased cell volume was low in GV oocytes but became active during meiotic maturation as the oocyte detached from the zona pellucida. It then decreased again in mature eggs similar to activity stimulated by acidosis. The subcellular localization of NHE1 was investigated with YFP‐tagged NHE1. Exogenous NHE1 expressed in GV oocytes localized to the plasma membrane and resulted in increased Na+/H+ exchanger activity, but only when co‐expressed with calcineurin homologous protein 1 (CHP1). When oocytes expressing functional NHE1 were matured to eggs, however, membrane localization of NHE1 and Na+/H+ exchanger activity were lost. It was unknown why NHE1 and AE2 activities are suppressed during meiotic maturation. Maintenance of cell volume in preimplantation embryos requires glycine accumulation via the GLYT1 transporter, a process unique to eggs and early embryos that is initiated during meiotic maturation. When NHE1 and AE2 activities were maintained in GV oocytes by exogenous expression, glycine accumulation was inhibited. We propose that NHE1‐mediated acute cell volume regulation is inactivated during meiotic maturation to allow preferential accumulation of glycine in eggs. J. Cell. Physiol. 228: 2042–2053, 2013. © 2013 Wiley Periodicals, Inc.
Epigallocatechin gallate inhibits growth and epithelial‐to‐mesenchymal transition in human thyroid carcinoma cell lines
Authors: De Amicis Francesca , Perri Anna , Vizza Donatella , Russo Alessandra , Panno Maria Luisa , Bonofiglio Daniela , Giordano Cinzia , Mauro Loredana , Aquila Saveria , Tramontano Donatella , Andò Sebastiano 
Published: April 2013

AbstractWell‐differentiated papillary and follicular thyroid carcinoma are the most frequent types of thyroid cancer and the prognosis is generally favorable however, a number of patients develops recurrences. Epigallocatechin‐3‐gallate (EGCG), a major catechin in green tea, was shown to possess remarkable therapeutic potential against various types of human cancers, although data on thyroid cancer cells are still lacking. The aim of this study was to investigate the effect of EGCG on the proliferation and motility of human thyroid papillary (FB‐2) and follicular (WRO) carcinoma cell lines. Our results demonstrate that EGCG (10, 40, 60 μM) treatment inhibited the growth of FB‐2 and WRO cells in a dose‐dependent manner. These changes were associated with reduced cyclin D1, increased p21 and p53 expression. Furthermore, EGCG suppressed phosphorylation of AKT and ERK1/2. In addition EGCG treatment results in reduction of cell motility and migration. Changes in motility and migration in FB‐2 were associated with modulation in the expression of several proteins involved in cell adhesion and reorganization of actin cytoskeleton. After 24 h EGCG caused an increase of the E‐cadherin expression and a concomitant decrease of SNAIL, ZEB and the basic helix–loop–helix transcription factor TWIST. Besides expression of Vimentin, N‐cadherin and α5‐integrin was down‐regulated. These data well correlate with a reduction of MMP9 activity as evidenced by gelatin zymography. Our findings support the inhibitory role of EGCG on thyroid cancer cell proliferation and motility with concomitant loss of epithelial‐to‐mesenchymal cell transition markers. J. Cell. Physiol. 228: 2054–2062, 2013. © 2013 Wiley Periodicals, Inc.
Utilization of surface energetics approach to Understand protein interaction to ceramic hydroxyapatite
Authors: Aasim Muhammad , Bibi Noor Shad , Vennapusa Rami Reddy , Fernandez‐Lahore Marcelo 
Published: April 2013

AbstractBackgroundA surface thermodynamics approach can be utilized to understand protein interaction during adsorption chromatography. Ceramic hydroxyapatite has been widely used in the purification of biomolecules during downstream bio‐processing. Protein interaction with this adsorbent is a complicated process.ResultsIn this work, interaction between model proteins and an adsorbent (ceramic hydroxyapatite Type I) was studied via extended DLVO (Derjaguin, Landau, Verwey and Overbeek) theory. The surface energy parameters of proteins and adsorbent were determined from experimental contact angle and zeta potential values. In ceramic hydroxyapatite chromatography, protein adsorption takes place under mixed mode conditions i.e. cationic exchange and calcium chelation. The sample is loaded in low salt and eluted at increasing phosphate gradient. The XDLVO approach calculated the free energy of interaction as a function of distance, between the interacting surfaces under de‐binding conditions. The calculated interaction energy of the model proteins with CHT were correlated with the actual elution behavior. This revealed that all the proteins show minimum binding energies, i.e. |0.005| ± 0.002 kT under the observed conditions. These energy values are considered to be a cutoff between retaining and non‐retaining conditions. Higher energy values will explain binding and lower energies will explain elution (binding > |0.005| kT > elution).ConclusionKnowledge generated from these studies will assist understanding of adsorption of proteins to the process supports which could facilitate better bioprocess design and optimization. © 2013 Society of Chemical Industry
Conspecific Brood Parasitism in the White‐faced Ibis Plegadis chihi (Aves: Pelecaniformes) Revealed by Microsatellites' Based Kinship‐Reconstruction
Authors: de CASTRO e Souza ANDIARA SILOS MORAES , DEL LAMA SILVIA NASSIF , MIÑO CAROLINA ISABEL 
Published: April 2013

AbstractThe white‐faced ibis Plegadis chihi Vieillot, 1817 (Pelecaniformes: Threskiornithidae) is a socially monogamous colonially breeding bird in which behavioral and ecological observations suggest the occurrence of conspecific brood parasitism (CBP). We inferred aspects of the genetic mating system of P. chihi in nature, using a genetic approach in the absence of parental information. We used five heterologous microsatellite loci and a multiple‐step methodological approach to infer kinship patterns among 104 pairs of nestlings sampled inside 80 nests in a breeding colony from southern Brazil. The estimated effective population size was 69 white‐faced ibises (95% CI: 50–98), enough to ensure long‐term population survival. Kinship patterns were identified for 38% of the analyzed pairs: 60% of the diagnosed pairs were identified as full‐siblings, 2.5% as half‐siblings and 37.5% as unrelated individuals. CBP could explain the presence of unrelated nestlings within broods, in agreement with available non‐genetic evidence. The presence of half‐siblings within broods could indicate extra‐pair paternity. Results suggest that a non‐strictly monogamous genetic mating system may be present in the white‐faced ibis. This study is the first molecular approach to better characterize the reproductive behavior of P. chihi in the wild. Our findings set the stage for further research to investigate the possible causes and consequences of alternative reproductive strategies in this species. J. Exp. Zool. 319A:277–284, 2013. © 2013 © 2013 Wiley Periodicals, Inc.
Biomolecular Identification of Beta‐Defensin‐Like Peptides From the Skin of the Soft‐Shelled Turtle Apalone spinifera
Authors: BENATO F. , DALLA VALLE L. , SKOBO T. , ALIBARDI L. 
Published: April 2013

AbstractNumerous bacteria are frequently observed in the superficial corneocytes forming the corneous layer of the soft‐shelled turtle Apalona spinifera. The resistance to bacterial penetration through the living epidermis in this turtle suggests the presence of an antimicrobial barrier, possibly derived from the presence of anti‐microbial peptides in the epidermis. Four beta‐defensin‐like peptides, named As‐BD‐1 to 4, have been characterized from skin tissues using molecular and bioinformatics methods. The precursor peptides contain the beta‐defensin motif with the typical cysteine localization pattern. The analysis of the expression for the four different beta‐defensin‐like proteins show that these molecules are expressed in the skin (epidermis and dermis) of the carapace, neck, digit, and tail but are apparently not expressed in the liver or intestine under normal conditions. These data suggest that in the skin of the soft‐shelled turtle there are potential effective anti‐microbial peptides against epidermal bacteria. J. Exp. Zool. (Mol. Dev. Evol.) 320B:210–217, 2013. © 2013 Wiley Periodicals, Inc.
Exploring Instructional Strategies in Student Leadership Development Programming
Authors: Jenkins Daniel M. 
Published: April 2013

AbstractThe author explored 24 commonly used instructional strategies in student leadership development programming recently profiled in the leadership education literature. Through a national web‐based survey, this study asked leadership educators teaching classroom‐based academic credit‐bearing undergraduate leadership studies courses how often they used certain instructional strategies. Leadership educators showed a preference for discussion‐based pedagogies as well as instructional strategies that promoted conceptual understanding and personal growth. Although the infrequent use of tests and quizzes in leadership education was anticipated, the sparse use of highly experiential skill‐building activities such as simulation, role play, and games was surprising.
Effectiveness of MR angiography for the primary diagnosis of acute pulmonary embolism: Clinical outcomes at 3 months and 1 year
Authors: Schiebler Mark L. , Nagle Scott K. , François Christopher J. , Repplinger Michael D. , Hamedani Azita G. , Vigen Karl K. , Yarlagadda Rajkumar , Grist Thomas M. , Reeder Scott B. 
Published: April 2013

PurposeTo determine the effectiveness of MR angiography for pulmonary embolism (MRA‐PE) in symptomatic patients.Materials and MethodsWe retrospectively reviewed all patients whom were evaluated for possible pulmonary embolism (PE) using MRA‐PE. A 3‐month and 1‐year from MRA‐PE electronic medical record (EMR) review was performed. Evidence for venous thromboembolism (VTE) (or death from PE) within the year of follow‐up was the outcome surrogate for this study.ResultsThere were 190 MRA‐PE exams performed with 97.4% (185/190) of diagnostic quality. There were 148 patients (120 F: 28 M) that had both a diagnostic MRA‐PE exam and 1 complete year of EMR follow‐up. There were 167 patients (137 F: 30 M) with 3 months or greater follow‐up. We found 83% (139/167) and 81% (120/148) MRA‐PE exams negative for PE at 3 months and 1 year, respectively. Positive exams for PE were seen in 14% (23/167). During the 1‐year follow‐up period, five patients (false negative) were diagnosed with DVT (5/148 = 3.4 %), and one of these patients also experienced a non–life‐threatening PE. The negative predictive value (NPV) for MRA‐PE was 97% (92–99; 95% CI) at 3 months and 96% (90–98; 95% CI) with 1 year of follow‐up.ConclusionThe NPV of MRA‐PE, when used for the primary diagnosis of pulmonary embolism in symptomatic patients, were found to be similar to the published values for CTA‐PE. In addition, the technical success rate and safety of MRA‐PE were excellent. J. Magn. Reson. Imaging 2013;38:914–925. © 2013 Wiley Periodicals, Inc.
Noninvasive automated motion assessment of intestinal motility by continuously tagged MR imaging
Authors: van der Paardt Marije P. , Sprengers André M.J. , Zijta Frank M. , Lamerichs Rolf , Nederveen Aart J. , Stoker Jaap 
Published: April 2013

PurposeTo evaluate continuously tagged 3 Tesla MRI for monitoring glucagon‐induced bowel motility changes in healthy volunteers.Materials and MethodsAfter standardized oral bowel preparation, 10 healthy volunteers underwent a free‐breathing, continuously tagged three‐dimensional (3D) dynamic fast‐field‐echo (FFE), at a 3.36 Hz sampling frequency. One milligram of glucagon was administered intravenously during data acquisition. Each dataset was divided into four temporal sets of 2 min (period 1 to 4). Taglines were tracked automatically using a scale spaced based algorithm. Assessment of global spectral resolution was performed for three frequency intervals: 0.008–0.300 Hz (motility), 0.300–0.400 Hz (breathing motion), and 0.400–0.533 Hz (higher order motion). Additional analyses were performed at fine spectral resolution in frequency bands of 0.033 Hz. Glucagon‐induced motility changes were investigated by means of a motility index (spectral power normalized to the maximal spectral power per‐volunteer), resulting in a range of 0 to 1 (no motion to maximal motion). Statistical comparison was done for period 1 and 4 (Wilcoxon‐signed rank test).ResultsAfter glucagon administration, a significant decrease in the motility index was found for the low‐ (0.008–0.300 Hz) (P < 0.0001) and high‐frequency interval (0.400–0.533 Hz) (P < 0.0001). Around breathing motion frequencies, no decrease in motility index was detected.ConclusionFree‐breathing, continuously tagged MR imaging is a noninvasive method for automated bowel motility assessment and allows for detection of drug‐induced changes. J. Magn. Reson. Imaging 2014;39:9–16. © 2013 Wiley Periodicals, Inc.
Diffusion tensor imaging of extraocular muscle using two‐dimensional single‐shot interleaved multiple inner volume imaging diffusion‐weighted EPI at 3 tesla
Authors: Seo Hyung Suk , Kim Seong‐Eun , Rose John , Hadley J. Rock , Parker Dennis L. , Jeong Eun‐Kee 
Published: April 2013

PurposeTo evaluate the feasibility of diffusion tensor imaging (DTI) for the medial and lateral rectus extraocular muscle (EOM) evaluation, to investigate the normal DTI parameters of the medial and lateral rectus EOM, and to compare with other skeletal muscle.Materials and MethodsSeven multiple sclerosis patients and five normal subjects (M:F = 5:7, mean age = 31.6 ± 9.2) without EOM disorder were included. The orbital DTIs using 2D‐ss‐IMVI‐DWEPI were scanned with b = 500 s/mm2 and 12 directions. The mean diffusivity (MD) and fractional anisotrophy (FA) of medial and lateral rectus EOMs in both orbits, and temporalis muscles were measured in regions of interest on two consecutive axial slices. Student t‐test was performed to compare the mean apparent diffusion coefficient and FA values between medial and lateral rectus EOMs, and between EOMs and temporalis muscles.ResultsThe MDs in medial (0.58 ± 0.18 × 10−3mm2/s) and lateral rectus EOMs (0.71 ± 0.18 × 10−3mm2/s) were significantly lower than temporalis muscle (0.84 ± 0.14 × 10−3 mm2/s) (P < 0.001, respectively). The MD in medial rectus EOM was significantly lower than lateral rectus EOM (P = 0.001). The FAs in medial (0.40 ± 0.05) and lateral rectus EOMs (0.40 ± 0.05) were significantly higher than temporalis muscle (0.25 ± 0.05) (P < 0.001, respectively). There was no significant difference between the FAs in medial and lateral rectus EOMs (P > 0.05).ConclusionThe MDs of EOMs were lower and the FAs were higher than those of skeletal muscle. These are well correlated to the unique characteristics of EOMs. J. Magn. Reson. Imaging 2013;38:1162–1168. © 2013 Wiley Periodicals, Inc.
Software‐assisted small bowel motility analysis using free‐breathing MRI: Feasibility study
Authors: Bickelhaupt Sebastian , Froehlich Johannes M. , Cattin Roger , Raible Stephan , Bouquet Hanspeter , Bill Urs , Patak Michael A. 
Published: April 2013

PurposeTo validate a software prototype allowing for small bowel motility analysis in free breathing by comparing it to manual measurements.Materials and MethodsIn all, 25 patients (15 male, 10 female; mean age 39 years) were included in this Institutional Review Board‐approved, retrospective study. Magnetic resonance imaging (MRI) was performed on a 1.5T system after standardized preparation acquiring motility sequences in free breathing over 69–84 seconds. Small bowel motility was analyzed manually and with the software. Functional parameters, measurement time, and reproducibility were compared using the coefficient of variance and paired Student's t‐test. Correlation was analyzed using Pearson's correlation coefficient and linear regression.ResultsThe 25 segments were analyzed twice both by hand and using the software with automatic breathing correction. All assessed parameters significantly correlated between the methods (P < 0.01), but the scattering of repeated measurements was significantly (P < 0.01) lower using the software (3.90%, standard deviation [SD] ± 5.69) than manual examinations (9.77%, SD ± 11.08). The time needed was significantly less (P < 0.001) with the software (4.52 minutes, SD ± 1.58) compared to manual measurement, lasting 17.48 minutes for manual (SD ± 1.75 minutes).ConclusionThe use of the software proves reliable and faster small bowel motility measurements in free‐breathing MRI compared to manual analyses. The new technique allows for analyses of prolonged sequences acquired in free breathing, improving the informative value of the examinations by amplifying the evaluable data. J. Magn. Reson. Imaging 2014;39:17–23. © 2013 Wiley Periodicals, Inc.