bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical evaluation of carcinoembryonic cell adhesion molecule (CEACAM) 6 as potential therapy target for pancreatic adenocarcinoma
Authors: Strickland Laura A , Ross Jed , Williams Simon , Ross Sarajane , Romero Maria , Spencer Susan , Erickson Rich , Sutcliffe Julie , Verbeke Caroline , Polakis Paul , van Bruggen Nicholas , Koeppen Hartmut 
Published: February 2009

AbstractDespite the availability of new targeted therapies, ductal pancreatic adenocarcinoma continues to carry a poor prognosis. Carcinoembryonic antigen‐related cell adhesion molecule (CEACAM)6 has been reported as a potential biomarker and therapy target for this malignancy. We have evaluated CEACAM6 as a potential therapy target, using an antibody–drug conjugate (ADC). Expression of CEACAM6 in pancreatic adenocarcinomas was determined using immunohistochemistry on tissue microarrays. The expression pattern in granulocytes and granulocytic precursors was measured by flow cytometry. Murine xenograft and non‐human primate models served to evaluate efficacy and safety, respectively. Robust expression of CEACAM6 was found in > 90% of invasive pancreatic adenocarcinomas as well as in intraepithelial neoplastic lesions. In the granulocytic lineage, CEACAM6 was expressed at all stages of granulocytic maturation except for the early lineage‐committed precursor cell. The anti‐CEACAM6 ADC showed efficacy against established CEACAM6‐expressing tumours. In non‐human primates, antigen‐dependent toxicity of the ADC consisted of dose‐dependent and reversible depletion of granulocytes and their precursors. This was associated with preferential and rapid localization of the antibody in bone marrow, as determined by sequential in vivo PET imaging of the radiolabelled anti‐CEACAM6. Localization of the radiolabelled tracer could be attenuated by predosing with unlabelled antibody confirming specific accumulation in this compartment. Based on the expression pattern in normal and malignant pancreatic tissues, efficacy against established tumours and limited and reversible bone marrow toxicity, we propose that CEACAM6 should be considered for an ADC‐based therapy approach against pancreatic adenocarcinomas and possibly other CEACAM6‐positive neoplasms. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Soluble endoglin and transforming growth factor‐β1 in women who subsequently developed preeclampsia
Authors: Lim Ji Hyae , Kim Shin Young , Park So Yeon , Lee Moon Hee , Yang Jae Hyug , Kim Moon Young , Chung Jin Hoon , Lee Si Won , Ryu Hyun Mee 
Published: February 2009

AbstractObjectiveThis study aimed to analyze the differences of soluble endoglin (sEng) and transforming growth factor‐beta1 (TGF‐β1) according to preeclamptic complications and to investigate the correlation between these factors and the clinical symptoms of preeclampsia.MethodWe estimated the levels of sEng and TGF‐β1 in plasma collected in the second trimester at the time of genetic amniocentesis from 60 women who subsequently developed preeclampsia and 124 contemporaneous normotensive women.ResultssEng levels were higher in cases than in controls, whereas TGF‐β1 levels were lower (P < 0.001). sEng levels, but not TGF‐β1 levels, were higher in cases with severe or preterm delivery than in cases with mild preeclampsia or term delivery (P < 0.001) and were increased in cases destined to deliver a small gestational age neonate (P < 0.001). Moreover, sEng levels, but not TGF‐β1 levels, showed a positive correlation with maximum diastolic and systolic blood pressure (r = 0.57, P < 0.001; and r = 0.33, P < 0.001, respectively) and proteinuria (r = 0.42, P < 0.001).ConclusionEarly midtrimester plasma levels of sEng are predictive of subsequence occurrence and severity of preeclampsia, in terms of severity of hypertension and proteinuria, prematurity, and association with small for gestational age neonates. Copyright © 2009 John Wiley & Sons, Ltd.
Validation of an LC‐MS based approach for profiling histones in chronic lymphocytic leukemia
Authors: Su Xiaodan , Lucas David M. , Zhang Liwen , Xu Hua , Zabrouskov Vlad , Davis Melanie E. , Knapp Amy R. , Young Donn C. , Payne Philip R. O. , Parthun Mark R. , Marcucci Guido , Grever Michael R. , Byrd John C. , Freitas Michael A. 
Published: February 2009

AbstractThe in vitro evaluation of histones and their PTMs has drawn substantial interest in the development of epigenetic therapies. The differential expression of histone isoforms may serve as a potential marker in the classification of diseases affected by chromatin abnormalities. In this study, protein profiling by LC and MS was used to explore differences in histone composition in primary chronic lymphocytic leukemia (CLL) cells. Extensive method validations were performed to determine the experimental variances that would impact histone relative abundance. The resulting data demonstrated that the proposed methodology was suitable for the analysis of histone profiles. In 4 normal individuals and 40 CLL patients, a significant decrease in the relative abundance of histone H2A variants (H2AFL and H2AFA/M*) was observed in primary CLL cells as compared to normal B cells. Protein identities were determined using high mass accuracy MS and shotgun proteomics.
Role of translation by mitochondrial‐type ribosomes during sperm capacitation: An analysis based on a proteomic approach
Authors: Zhao Chun , Guo Xue‐Jiang , Shi Zhong‐Hua , Wang Fu‐Qiang , Huang Xiao‐Yan , Huo Ran , Zhu Hui , Wang Xin‐Ru , Liu Jia‐Yin , Zhou Zuo‐Min , Sha Jia‐Hao 
Published: February 2009

AbstractMammalian spermatozoa contain a complex population of mRNAs, some of which have been demonstrated to be translated de novo by mitochondrial‐type ribosomes using D‐chloramphenicol (CP), a specific inhibitor of mitochondrial translation. However, little is known about the functions of these mRNAs in mature sperm. In the present study, differential proteomic approaches were applied to study sperm protein profiles translated by mitochondrial‐type ribosomes using the inhibitor CP and 44 proteins were identified with lower expression in CP‐treated sperm in comparison to capacitated sperm (ratio ≥ 1.5, p<0.05). Results of Western blot and real‐time PCR suggest that four proteins were translated by mitochondrial‐type ribosomes. Bioinformatics analysis indicated that 26 of 44 proteins were involved in some critical processes correlated to sperm–egg interaction event. In addition, Mups, whose functions in reproduction have never been studied, were chosen for further study. Our results showed that Mups proteins were localized to the acrosome and flagellum of precapacitated sperm, and were also expressed in the equatorial segment of capacitated sperm. The depletion of Mups using neutralizing antibodies significantly inhibited capacitation in a dose‐dependent manner, subsequently inhibited acrosome reaction and sperm–egg fusion. In summary, mitochondrial translation during capacitation can store proteins beneficial for sperm–egg interaction.
Preliminary quantitative profile of differential protein expression between rat L6 myoblasts and myotubes by stable isotope labeling with amino acids in cell culture
Authors: Cui Ziyou , Chen Xiulan , Lu Bingwen , Park Sung Kyu , Xu Tao , Xie Zhensheng , Xue Peng , Hou Junjie , Hang Haiying , Yates John R. , Yang Fuquan 
Published: February 2009

AbstractDefining the mechanisms governing myogenesis has advanced in recent years. Skeletal‐muscle differentiation is a multi‐step process controlled spatially and temporally by various factors at the transcription level. To explore those factors involved in myogenesis, stable isotope labeling with amino acids in cell culture (SILAC), coupled with high‐accuracy mass spectrometry (LTQ‐Orbitrap), was applied successfully. Rat L6 cell line is an excellent model system for studying muscle myogenesis in vitro. When mononucleate L6 myoblast cells reach confluence in culture plate, they could transform into multinucleate myotubes by serum starvation. By comparing protein expression of L6 myoblasts and terminally differentiated multinucleated myotubes, 1170 proteins were quantified and 379 proteins changed significantly in fully differentiated myotubes in contrast to myoblasts. These differentially expressed proteins are mainly involved in inter‐or intracellular signaling, protein synthesis and degradation, protein folding, cell adhesion and extracelluar matrix, cell structure and motility, metabolism, substance transportation, etc. These findings were supported by many previous studies on myogenic differentiation, of which many up‐regulated proteins were found to be involved in promoting skeletal muscle differentiation for the first time in our study. In summary, our results provide new clues for understanding the mechanism of myogenesis.
Development of novel mass spectrometric methods for identifying HOCl‐induced modifications to proteins
Authors: Mouls Laetitia , Silajdzic Edina , Haroune Nicolas , Spickett Corinne M. , Pitt Andrew R. 
Published: February 2009

AbstractProtein oxidation is thought to contribute to a number of inflammatory diseases, hence the development of sensitive and specific analytical techniques to detect oxidative PTMs (oxPTMs) in biological samples is highly desirable. Precursor ion scanning for fragment ions of oxidized amino acid residues was investigated as a label‐free MS approach to mapping specific oxPTMs in a complex mixture of proteins. Using HOCl‐oxidized lysozyme as a model system, it was found that the immonium ions of oxidized tyrosine and tryptophan formed in MS2 analysis could not be used as diagnostic ions, owing to the occurrence of isobaric fragment ions from unmodified peptides. Using a double quadrupole linear ion trap mass spectrometer, precursor ion scanning was combined with detection of MS3 fragment ions from the immonium ions and collisionally‐activated decomposition peptide sequencing to achieve selectivity for the oxPTMs. For chlorotyrosine, the immonium ion at 170.1 m/z fragmented to yield diagnostic ions at 153.1, 134.1, and 125.1 m/z, and the hydroxytyrosine immonium ion at 152.1 m/z gave diagnostic ions at 135.1 and 107.1 m/z. Selective MS3 fragment ions were also identified for 2‐hydroxytryptophan and 5‐hydroxytryptophan. The method was used successfully to map these oxPTMs in a mixture of nine proteins that had been treated with HOCl, thereby demonstrating its potential for application to complex biological samples.
Two‐dimensional proteome reference maps for the human pathogenic filamentous fungus Aspergillus fumigatus
Authors: Vödisch Martin , Albrecht Daniela , Leßing Franziska , Schmidt André D. , Winkler Robert , Guthke Reinhard , Brakhage Axel A. , Kniemeyer Olaf 
Published: February 2009

AbstractThe filamentous fungus Aspergillus fumigatus has become the most important airborne fungal pathogen causing life‐threatening infections in immunosuppressed patients. We established a 2‐D reference map for A. fumigatus. Using MALDI‐TOF‐MS/MS, we identified 381 spots representing 334 proteins. Proteins involved in cellular metabolism, protein synthesis, transport processes and cell cycle were most abundant. Furthermore, we established a protocol for the isolation of mitochondria of A. fumigatus and developed a mitochondrial proteome reference map. 147 proteins represented by 234 spots were identified.
NSOM‐ and AFM‐based nanotechnology elucidates nano‐structural and atomic‐force features of a Y. pestis V immunogen‐containing particle vaccine capable of eliciting robust response
Authors: Zeng Gucheng , Chen Jianbo , Zhong Liyun , Wang Richard , Jiang Lifang , Cai Jiye , Yan Lin , Huang Dan , Chen Crystal Y. , Chen Zheng W. 
Published: February 2009

AbstractIt is postulated that unique nanoscale proteomic features of immunogen on vaccine particles may determine immunogen‐packing density, stability, specificity, and pH‐sensitivity on the vaccine particle surface and thus impact the vaccine‐elicited immune responses. To test this presumption, we employed near‐filed scanning optical microscopy (NSOM)‐ and atomic force microscopy (AFM)‐based nanotechnology to study nano‐structural and single‐molecule force bases of Yersinia pestis (Y. pestis) V immunogen fused with protein anchor (V‐PA) loaded on gram positive enhancer matrix (GEM) vaccine particles. Surprisingly, the single‐molecule sensitive NSOM revealed that ∼90% of V‐PA immunogen molecules were packed as high‐density nanoclusters on GEM particle. AFM‐based single‐molecule force analyses indicated a highly stable and specific binding between V‐PA and GEM at the physiological pH. In contrast, this specific binding was mostly abrogated at the acidic pH equivalent to the biochemical pH in phagolysosomes of antigen‐presenting‐cells in which immunogen protein is processed for antigen presentation. Intranasal mucosal vaccination of mice with such immunogen loaded on vaccine particles elicited robust antigen‐specific immune response. This study indicated that high‐density, high‐stability, specific, and immunological pH‐responsive loading of immunogen nanoclusters on vaccine particles could readily be presented to the immune system for induction of strong antigen‐specific immune responses.
Identification of miR‐21 targets in breast cancer cells using a quantitative proteomic approach
Authors: Yang Yi , Chaerkady Raghothama , Beer Michael A. , Mendell Joshua T. , Pandey Akhilesh 
Published: February 2009

AbstractMicroRNA (miRNA) play essential roles in biological processes ranging from cellular proliferation to apoptosis. Recently, miRNA have also been implicated in a number of diseases including cancers. However, the targets of most miRNA remain unknown. The majority of reports describing identification of miRNA targets are based on computational approaches or detection of altered mRNA levels despite the fact that most miRNA are thought to regulate their targets primarily at the level of translational inhibition in animals. miR‐21 is a miRNA with oncogenic activity that is involved in various cancer‐related processes such as invasion and migration. Given the importance of miR‐21 in tumorigenesis, we employed a quantitative proteomic strategy to systematically identify potential targets of miR‐21. By knocking down the expression of endogenous miR‐21 in MCF‐7 breast cancer cells, we observed an increase in the abundance of 58 proteins, implying that they could be potential targets of miR‐21. Validation of 12 of these candidate targets in luciferase assays showed that 6 of them were likely direct targets of miR‐21. Importantly, the mRNA of the majority of the candidate targets tested did not show a concomitant increase in abundance. Overall, our results demonstrate that miR‐21 affects the expression of many of its targets through translational inhibition and highlights the utility of proteomic approaches for identifying miRNA targets.
Staphylococcus aureus ClpC ATPase is a late growth phase effector of metabolism and persistence
Authors: Chatterjee Indranil , Schmitt Sigrid , Batzilla Christoph F. , Engelmann Susanne , Keller Andreas , Ring Michael W. , Kautenburger Ralf , Ziebuhr Wilma , Hecker Michael , Preissner Klaus T. , Bischoff Markus , Proctor Richard A. , Beck Horst P. , Lenhof Hans‐Peter , Somerville Greg A. , Herrmann Mathias 
Published: February 2009

AbstractStaphylococcus aureus Clp ATPases (molecular chaperones) alter normal physiological functions including an aconitase‐mediated effect on post‐stationary growth, acetate catabolism, and entry into death phase (Chatterjee et al., J. Bacteriol. 2005, 187, 4488–4496). In the present study, the global function of ClpC in physiology, metabolism, and late‐stationary phase survival was examined using DNA microarrays and 2‐D PAGE followed by MALDI‐TOF MS. The results suggest that ClpC is involved in regulating the expression of genes and/or proteins of gluconeogenesis, the pentose‐phosphate pathway, pyruvate metabolism, the electron transport chain, nucleotide metabolism, oxidative stress, metal ion homeostasis, stringent response, and programmed cell death. Thus, one major function of ClpC is balancing late growth phase carbon metabolism. Furthermore, these changes in carbon metabolism result in alterations of the intracellular concentration of free NADH, the amount of cell‐associated iron, and fatty acid metabolism. This study provides strong evidence for ClpC as a critical factor in staphylococcal energy metabolism, stress regulation, and late‐stationary phase survival; therefore, these data provide important insight into the adaptation of S. aureus toward a persister state in chronic infections.
Secretome analysis of differentially induced proteins in rice suspension‐cultured cells triggered by rice blast fungus and elicitor
Authors: Kim Sun Tae , Kang Young Hyun , Wang Yiming , Wu Jingni , Park Zee Yong , Rakwal Randeep , Agrawal Ganesh Kumar , Lee Sang Yeol , Kang Kyu Young 
Published: February 2009

AbstractSecreted proteins were investigated in rice suspension‐cultured cells treated with rice blast fungus Magnaporthe grisea and its elicitor using biochemical and 2‐DE coupled with MS analyses followed by their in planta mRNA expression analysis. M. grisea and elicitor successfully interacted with suspension‐cultured cells and prepared secreted proteins from these cultures were essentially intracellular proteins free. Comparative 2‐D gel analyses identified 21 differential protein spots due to M. grisea and/or elicitor over control. MALDI‐TOF‐MS and μLC‐ESI‐MS/MS analyses of these protein spots revealed that most of assigned proteins were involved in defense such as nine chitinases, two germin A/oxalate oxidases, five domain unknown function 26 (DUF 26) secretory proteins, and β‐expansin. One chitin binding chitinase protein was isolated using chitin binding beads and strong enzymatic activity was identified in an in‐gel assay. Interestingly, their protein abundance correlated well at transcript levels in elicitor‐treated cultures as judged by semi‐quantitative RT‐PCR. Each identified differentially expressed protein group was compared at transcript levels in rice leaves inoculated with incompatible (KJ401) and compatible (KJ301) races of M. grisea. Time‐course profiling revealed their inductions were stronger and earlier in incompatible than compatible interactions. Identified secreted proteins and their expression correlation at transcript level in suspension‐cultured cells and also in planta suggest that suspension‐cultured cells can be useful to investigate the secretome of rice blast–pathogen interactions.
Evaluation of a type 1 diabetes serum cohort by SELDI‐TOF MS protein profiling
Authors: Albrethsen Jakob , Kaas Anne , Schönle Eugen , Swift Peter , Kocova Mirjana , Gammeltoft Steen , Hansen Lars , Mortensen Henrik Bindesbøl 
Published: February 2009

AbstractProteomics analysis of serum from patients with type 1 diabetes (T1D) may lead to novel biomarkers for prediction of disease and for patient monitoring. However, the serum proteome is highly sensitive to sample processing and before proteomics biomarker research serum cohorts should preferably be examined for potential bias between sample groups.SELDI‐TOF MS protein profiling was used for preliminary evaluation of a biological‐bank with 766 serum samples from 270 patients with T1D, collected at 18 different paediatric centers representing 15 countries in Europe and Japan over 2 years (2000–2002). Samples collected 1 (n = 270), 6 (n = 248), and 12 (n = 248) months after T1D diagnosis were grouped across centers and compared. The serum protein profiles varied with collection site and day of analysis; however, markers of sample processing were not systematically different between samples collected at different times after diagnosis. Three members of the apolipoprotein family increased with time in patient serum collected 1, 6, and 12 months after diagnosis (ANOVA, p<0.001). These results support the use of this serum cohort for further proteomic studies and illustrate the potential of high‐throughput MALDI/SELDI‐TOF MS protein profiling for evaluation of serum cohorts before proteomics biomarker research.
Direct insight into insulin aggregation by 2D NMR complemented by PFGSE NMR
Authors: Bocian Wojciech , Sitkowski Jerzy , Tarnowska Anna , Bednarek Elżbieta , Kawȩcki Robert , Koźmiński Wiktor , Kozerski Lech 
Published: February 2009

AbstractThe aggregation of Zn(II)‐bound and zinc‐free human insulin was studied in solution using the Hβ∼CH3 crosspeaks of threonine residues in 2D COSY, TOCSY, and NOESY NMR spectra which allow viewing of the oligomers in equilibrium. This is complemented by PFGSE measurements of the translational diffusion coefficient, Di, used for monitoring the changes in equilibrium composition of aggregates on dilution of both insulins in physiological medium. The back calculation of the dilution isotherm allows establishing the association constants for oligomeric equilibria in solution and discussion of the models of association. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Traditional Chinese medicine: balancing the gut ecosystem
Authors: Li Houkai , Zhou Mingmei , Zhao Aihua , Jia Wei 
Published: February 2009

AbstractGut microflora has become a topic of interest in life sciences in the context of global systems biology, in which human biological system is viewed as ‘superorganisms’ involving an internal ecosystem of diverse microbiome. We conceive that multi‐pathway modulations of the human gut microbial system exerted by traditional Chinese medicines (TCMs) to restore the balance of the gut ecology may account for a large portion of their effectiveness in host during treatment. Such a concept is evidenced by series of studies which have revealed an interactive relationship between gut microflora and TCM, involving the two important aspects: gut microflora‐dependent drug metabolism in TCM and gut microflora‐targeted modulation of physiological conditions, both of which highlight the significance of gut microflora involvement in the future TCM investigation. Copyright © 2009 John Wiley & Sons, Ltd.
Reprogramming Retinal Pigment Epithelium to Differentiate Toward Retinal Neurons with Sox2
Authors: Ma Wenxin , Yan Run-Tao , Li Xiumei , Wang Shu-Zhen 
Published: February 2009

Abstract
Guiding non-neural, retinal pigment epithelium (RPE) to produce retinal neurons may offer a source of developing neurons for cell-replacement. Sox2 plays important roles in maintaining neural progenitor/stem cell properties and in converting fibroblasts into pluripotent stem cells. This study tests the possibility of using Sox2 to reprogram RPE to differentiate toward retinal neurons in vivo and in vitro. Expression of Sox2 in the chick retina was detected in progenitor cells, in cells at a discrete location in the layers of amacrine and ganglion cells, and in Műller glia. Overexpression of Sox2 in the developing eye resulted in hypopigmentation of the RPE. In the affected regions, expression of retinal ganglion cell markers became apparent in the RPE layer. In RPE cell culture, Sox2 promoted the expression of retinal ganglion and amacrine markers, and suppressed the expression of genes associated with RPE properties. Mechanistic investigation using the developing retina revealed a coexpression of Sox2 and basic fibroblast growth factor (bFGF), a growth factor commonly used in stem cell culture and capable of inducing RPE-to-retina transdifferentiation (or reprogramming) during early development. Similar patterns of changes in Sox2 expression and in bFGF expression were observed in atrophic retina and in injured retina. In RPE cell culture, Sox2 and bFGF mutually enhanced one another's expression. Upregulation of bFGF expression by Sox2 also occurred in the retina. These results suggest that Sox2 can initiate a reprogramming of RPE cells to differentiate toward retinal neurons and may engage bFGF during the process.
Disclosure of potential conflicts of interest is found at the end of this article.