bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Intracellular Delivery of a Recombinant Peptide Derived from the Acidic Domain of PIAS3 Inhibits STAT3 Transactivation and Induces Tumor Cell Death
Authors: Borghouts Corina , Tittmann Hanna , Delis Natalia , Kirchenbauer Marisa , Brill Boris , Groner Bernd 
Published: April 2010

Abstract
Signaling components, which confer an “addiction” phenotype on cancer cells, represent promising drug targets. The transcription factor signal transducers and activators of transcription 3 (STAT3) is constitutively activated in many different types of tumor cells and its activity is indispensible in a large fraction. We found that the expression of the endogenous inhibitor of STAT3, protein inhibitor of activated STAT3 (PIAS3), positively correlates with STAT3 activation in normal cells. This suggests that PIAS3 controls the extent and the duration of STAT3 activity in normal cells and thus prevents its oncogenic function. In cancer cells, however, the expression of PIAS3 is posttranscriptionally suppressed, possibly enhancing the oncogenic effects of activated STAT3. We delimited the interacting domains of STAT3 and PIAS3 and identified a short fragment of the COOH-terminal acidic region of PIAS3, which binds strongly to the coiled-coil domain of STAT3. This PIAS3 fragment was used to derive the recombinant STAT3-specific inhibitor rPP-C8. The addition of a protein transduction domain allowed the efficient internalization of rPP-C8 into cancer cells. This resulted in the suppression of STAT3 target gene expression, in the inhibition of migration and proliferation, and in the induction of apoptosis at low concentrations [half maximal effective concentration (EC50), &lt;3 μmol/L]. rPP-C8 did not affect normal fibroblasts and represents an interesting lead for the development of novel cancer drugs targeting the coiled-coil domain of STAT3. Mol Cancer Res; 8(4); 539–53. ©2010 AACR.
"How Can a Daughter Glorify the Family Name?" Filiality and Women's Rights in the Late Qing
Authors: Ying Hu 
Published: April 2010

AbstractThis paper examines married daughters' filiality toward their natal families through three case studies. The protagonists are Qiu Jin (1875?-1907), Wu Zhiying (1868-1934) and Xu Zihua (1873-1935). Using the lens of filiality, we are able to observe the finer nuances of their gendered self-conception within the context of the rapidly changing world at the end of China's imperial era. I argue that the language and sentiment of filiality facilitated a substantial broadening of women's rights: in expanding what a literati daughter can claim as her intellectual inheritance, in providing the basis of a legal argument for a daughter's inheritance rights, and in offering a conduit for the experience of women's participation in political changes.
Correction ou corruption? La critique du texte de Valerius Flaccus
Authors: Liberman Gauthier 
Published: April 2010

AbstractThe author tries to show through close examination of four characteristic passages of Valerius Flaccus’ Argonautica (5.614, 6.709, 7.55-6, 7.162-3) that strained exegesis or quotation of dubious parallels, to be met with in Valerian studies, may be wrong solutions of problems better dealt with if one admits textual corruption.
Adult Starvation and Disease‐Related Malnutrition
Authors: Jensen Gordon L. , Mirtallo Jay , Compher Charlene , Dhaliwal Rupinder , Forbes Alastair , Grijalba Rafael Figueredo , Hardy Gil , Kondrup Jens , Labadarios Demetre , Nyulasi Ibolya , Castillo Pineda Juan Carlos , Waitzberg Dan 
Published: April 2010

Background & Aims:Multiple definitions for malnutrition syndromes are found in the literature resulting in confusion. Recent evidence suggests that varying degrees of acute or chronic inflammation are key contributing factors in the pathophysiology of malnutrition that is associated with disease or injury.Methods:An International Guideline Committee was constituted to develop a consensus approach to defining malnutrition syndromes for adults in the clinical setting. Consensus was achieved through a series of meetings held at the A.S.P.E.N. and ESPEN Congresses.Results:It was agreed that an etiology‐based approach that incorporates a current understanding of inflammatory response would be most appropriate. The Committee proposes the following nomenclature for nutrition diagnosis in adults in the clinical practice setting. “Starvation‐related malnutrition”, when there is chronic starvation without inflammation, “chronic disease‐related malnutrition”, when inflammation is chronic and of mild to moderate degree, and “acute disease or injury‐related malnutrition”, when inflammation is acute and of severe degree.Conclusions:This commentary is intended to present a simple etiology‐based construct for the diagnosis of adult malnutrition in the clinical setting. Development of associated laboratory, functional, food intake, and body weight criteria and their application to routine clinical practice will require validation.
Canonical BMP signaling is dispensable for hematopoietic stem cell function in both adult and fetal liver hematopoiesis, but essential to preserve colon architecture
Authors: Singbrant Sofie , Karlsson Göran , Ehinger Mats , Olsson Karin , Jaako Pekka , Miharada Ken-ichi , Stadtfeld Matthias , Graf Thomas , Karlsson Stefan 
Published: April 2010

AbstractNumerous publications have described the importance of bone morphogenetic protein (BMP) signaling in the specification of hematopoietic tissue in developing embryos. Here we investigate the full role of canonical BMP signaling in both adult and fetal liver hematopoiesis using conditional knockout strategies because conventional disruption of components of the BMP signaling pathway result in early death of the embryo. By targeting both Smad1 and Smad5, we have generated a double-knockout mouse with complete disruption of canonical BMP signaling. Interestingly, concurrent deletion of Smad1 and Smad5 results in death because of extrahematopoietic pathologic changes in the colon. However, Smad1/Smad5-deficient bone marrow cells can compete normally with wild-type cells and display unaffected self-renewal and differentiation capacity when transplanted into lethally irradiated recipients. Moreover, although BMP receptor expression is increased in fetal liver, fetal liver cells deficient in both Smad1 and Smad5 remain competent to long-term reconstitute lethally irradiated recipients in a multilineage manner. In conclusion, canonical BMP signaling is not required to maintain either adult or fetal liver hematopoiesis, despite its crucial role in the initial patterning of hematopoiesis in early embryonic development.
An evolutionarily conserved PTEN-C/EBPα-CTNNA1 axis controls myeloid development and transformation
Authors: Fu Chun-Tang , Zhu Kang-Yong , Mi Jian-Qing , Liu Yuan-Fang , Murray Susan T. , Fu Yan-Fang , Ren Chun-Guang , Dong Zhi-Wei , Liu Yi-Jie , Dong Mei , Jin Yi , Chen Yi , Deng Min , Zhang Wu , Chen Bin , Breslin Peter , Chen Sai-Juan , Chen Zhu , Becker Michael W. , Zhu Jiang , Zhang Ji-Wang , Liu Ting Xi 
Published: April 2010

AbstractLoss of function of tumor suppressor genes, such as PTEN, CEBPΑ, and CTNNA1 (encoding the α-catenin protein), has been found to play an essential role in leukemogenesis. However, whether these genes genetically interact remains largely unknown. Here, we show that PTEN-mammalian target of rapamycin signaling acts upstream to dictate the ratio of wild-type p42 C/EBPα to its dominant-negative p30 isoform, which critically determines whether p30 C/EBPα (lower p42/p30 ratio) or p42 C/EBPα (higher p42/p30 ratio) binds to the proximal promoter of the retained CTNNA1 allele. Binding of p30 C/EBPα recruits the polycomb repressive complex 2 to suppress CTNNA1 transcription through repressive H3K27me3 modification, whereas binding of p42 C/EBPα relieves this repression and promotes CTNNA1 expression through activating H3K4me3 modification. Loss of Pten function in mice and zebrafish induces myelodysplasia with abnormal invasiveness of myeloid progenitors accompanied by significant reductions in both wild-type C/EBPα and α-catenin protein. Importantly, frame-shift mutations in either PTEN or CEBPA were detected exclusively in the primary LICs with low CTNNA1 expression. This study uncovers a novel molecular pathway, PTEN-C/EBPα-CTNNA1, which is evolutionarily conserved and might be therapeutically targeted to eradicate LICs with low CTNNA1 expression.
DNIC-mediated analgesia produced by a supramaximal electrical or a high-dose formalin conditioning stimulus: roles of opioid and α2-adrenergic receptors
Authors: Wen Yeong-Ray , Wang Chia-Chuan , Yeh Geng-Chang , Hsu Sheng-Feng , Huang Yung-Jen , Li Yen-Li , Sun Wei-Zen 
Published: April 2010

AbstractBackgroundDiffuse noxious inhibitory controls (DNIC) can be produced by different types of conditioning stimuli, but the analgesic properties and underlying mechanisms remain unclear. The aim of this study was to differentiate the induction of DNIC analgesia between noxious electrical and inflammatory conditioning stimuli.MethodsFirst, rats subjected to either a supramaximal electrical stimulation or an injection of high-dose formalin in the hind limb were identified to have pain responses with behavioral evidence and spinal Fos-immunoreactive profiles. Second, suppression of tail-flick latencies by the two noxious stimuli was assessed to confirm the presence of DNIC. Third, an opioid receptor antagonist (naloxone) and an α2-adrenoreceptor antagonist (yohimbine) were injected, intraperitoneally and intrathecally respectively, before conditioning noxious stimuli to test the involvement of descending inhibitory pathways in DNIC-mediated analgesia.ResultsAn intramuscular injection of 100 μl of 5% formalin produced noxious behaviors with cumulative pain scores similar to those of 50 μl of 2% formalin in the paw. Both electrical and chemical stimulation significantly increased Fos expression in the superficial dorsal horns, but possessed characteristic distribution patterns individually. Both conditioning stimuli prolonged the tail-flick latencies indicating a DNIC response. However, the electrical stimulation-induced DNIC was reversed by yohimbine, but not by naloxone; whereas noxious formalin-induced analgesia was both naloxone- and yohimbine-reversible.ConclusionsIt is demonstrated that DNIC produced by different types of conditioning stimuli can be mediated by different descending inhibitory controls, indicating the organization within the central nervous circuit is complex and possibly exhibits particular clinical manifestations.
Response network analysis of differential gene expression in human epithelial lung cells during avian influenza infections
Authors: Tatebe Ken , Zeytun Ahmet , Ribeiro Ruy M , Hoffmann Robert , Harrod Kevin S , Forst Christian V 
Published: April 2010

AbstractBackgroundThe recent emergence of the H5N1 influenza virus from avian reservoirs has raised concern about future influenza strains of high virulence emerging that could easily infect humans. We analyzed differential gene expression of lung epithelial cells to compare the response to H5N1 infection with a more benign infection with Respiratory Syncytial Virus (RSV). These gene expression data are then used as seeds to find important nodes by using a novel combination of the Gene Ontology database and the Human Network of gene interactions. Additional analysis of the data is conducted by training support vector machines (SVM) with the data and examining the orientations of the optimal hyperplanes generated.ResultsAnalysis of gene clustering in the Gene Ontology shows no significant clustering of genes unique to H5N1 response at 8 hours post infection. At 24 hours post infection, however, a number of significant gene clusters are found for nodes representing "immune response" and "response to virus" terms. There were no significant clusters of genes in the Gene Ontology for the control (Mock) or RSV experiments that were unique relative to the H5N1 response. The genes found to be most important in distinguishing H5N1 infected cells from the controls using SVM showed a large degree of overlap with the list of significantly regulated genes. However, though none of these genes were members of the GO clusters found to be significant.ConclusionsCharacteristics of H5N1 infection compared to RSV infection show several immune response factors that are specific for each of these infections. These include faster timescales within the cell as well as a more focused activation of immunity factors. Many of the genes that are found to be significantly expressed in H5N1 response relative to the control experiments are not found to cluster significantly in the Gene Ontology. These genes are, however, often closely linked to the clustered genes through the Human Network. This may suggest the need for more diverse annotations of these genes and verification of their action in immune response.
Directionality in protein fold prediction
Authors: Ellis Jonathan J , Huard Fabien PE , Deane Charlotte M , Srivastava Sheenal , Wood Graham R 
Published: April 2010

Abstract

Background
Ever since the ground-breaking work of Anfinsen et al. in which a denatured protein was found to refold to its native state, it has been frequently stated by the protein fold prediction community that all the information required for protein folding lies in the amino acid sequence. Recent in vitro experiments and in silico computational studies, however, have shown that cotranslation may affect the folding pathway of some proteins, especially those of ancient folds. In this paper aspects of cotranslational folding have been incorporated into a protein structure prediction algorithm by adapting the Rosetta program to fold proteins as the nascent chain elongates. This makes it possible to conduct a pairwise comparison of folding accuracy, by comparing folds created sequentially from each end of the protein.

Results
A single main result emerged: in 94% of proteins analyzed, following the sense of translation, from N-terminus to C-terminus, produced better predictions than following the reverse sense of translation, from the C-terminus to N-terminus. Two secondary results emerged. First, this superiority of N-terminus to C-terminus folding was more marked for proteins showing stronger evidence of cotranslation and second, an algorithm following the sense of translation produced predictions comparable to, and occasionally better than, Rosetta.

Conclusions
There is a directionality effect in protein fold prediction. At present, prediction methods appear to be too noisy to take advantage of this effect; as techniques refine, it may be possible to draw benefit from a sequential approach to protein fold prediction.
CC3/TIP30 affects DNA damage repair
Authors: Fong Sylvia , King Frank , Shtivelman Emma 
Published: April 2010

Abstract

Background
The pro-apoptotic protein CC3/TIP30 has an unusual cellular function as an inhibitor of nucleocytoplasmic transport. This function is likely to be activated under conditions of stress. A number of studies support the notion that CC3 acts as a tumor and metastasis suppressor in various types of cancer. The yeast homolog of CC3 is likely to be involved in responses to DNA damage. Here we examined the potential role of CC3 in regulation of cellular responses to genotoxic stress.

Results
We found that forced expression of CC3 in CC3-negative cells strongly delays the repair of UV-induced DNA damage. Exogenously introduced CC3 negatively affects expression levels of DDB2/XPE and p21CIP1, and inhibits induction of c-FOS after UV exposure. In addition, exogenous CC3 prevents the nuclear accumulation of P21CIP in response to UV. These changes in the levels/localization of relevant proteins resulting from the enforced expression of CC3 are likely to contribute to the observed delay in DNA damage repair. Silencing of CC3 in CC3-positive cells has a modest delaying effect on repair of the UV induced damage, but has a much more significant negative affect on the translesion DNA synthesis after UV exposure. This could be related to the higher expression levels and increased nuclear localization of p21CIP1 in cells where expression of CC3 is silenced. Expression of CC3 also inhibits repair of oxidative DNA damage and leads to a decrease in levels of nucleoredoxin, that could contribute to the reduced viability of CC3 expressing cells after oxidative insult.

Conclusions
Manipulation of the cellular levels of CC3 alters expression levels and/or subcellular localization of proteins that exhibit nucleocytoplasmic shuttling. This results in altered responses to genotoxic stress and adversely affects DNA damage repair by affecting the recruitment of adequate amounts of required proteins to proper cellular compartments. Excess of cellular CC3 has a significant negative effect on DNA repair after UV and oxidant exposure, while silencing of endogenous CC3 slightly delays repair of UV-induced damage.
The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer
Authors: Calaluce Robert , Gubin Matthew M , Davis J Wade , Magee Joseph D , Chen Jing , Kuwano Yuki , Gorospe Myriam , Atasoy Ulus 
Published: April 2010

AbstractBackgroundThe discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs).MethodsThe ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip), provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE) of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established.ResultsWe used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+) and MDA-MB-231 (estrogen receptor negative, ER-) breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets,CD9andCALM2mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis.ConclusionThis is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular environment.
Validation of a Farsi version of the Early Childhood Oral Health Impact Scale (F-ECOHIS)
Authors: Jabarifar Seyed-Ebrahim , Golkari Ali , IJadi Mohammad H , Jafarzadeh Mehdi , Khadem Parvin 
Published: April 2010

Abstract

Background
The Early Childhood Oral Health Impact Scale (ECOHIS) has recently been developed to assess oral health-related quality of life (OHRQoL) of pre-school children in English speaking communities. This study aimed to translate the ECOHIS into Farsi and test its psychometric properties for use on 2- to 5-year-old children of Farsi speaking Iranian families.

Methods
EHOHIS questionnaire was translated into Farsi using a standardized forward-backward linguistic translation method. Its face and content validity was tested in two small pilot studies. In the main study, a convenience sample of 260 parents of 2- to 5-year-old children in Isfahan and Tehran were invited to complete the final Farsi version of the ECOHIS (F-ECOHIS) and answer two global self-rating questions about their children's dental appearance and oral health. Association between F-ECOHIS scores and answers to the two self-rating questions, and the correlation between child (9 items) and family (4 items) sections of the F-ECOHIS were used to assess the concurrent and convergent validity of the questionnaire. Internal consistency reliability of the F-ECOHIS was tested using Cronbach's alpha coefficient test and item total and inter-item correlations. One third of participants were invited to complete the F-ECOHIS again after 2 weeks to evaluate the test-retest reliability of the questionnaire.

Results
Two hundred and forty six parents were included in the main study. The association between the F-ECOHIS scores and the two self-rating questions and the correlation between its child and family sections were significant (P < 0.001). Cronbach's alpha coefficient of the F-ECOHIS and its child and family sections were 0.93, 0.89, and 0.85 respectively. Coefficients did not increase by deleting any item. The corrected item total correlation coefficient ranged from 0.52 to 0.74. The inter-item correlation coefficient ranged between 0.30 and 0.73. Seventy three parents participated in the follow up study for re-testing the questionnaire. Comparison of their test and re-test scores had a weighted kappa of 0.81 and inter-class correlation (ICC) of 0.82.

Conclusion
The F-ECOHIS questionnaire was valid and reliable for assessing the OHRQoL of 2- to 5-year-old pre-school children of Farsi speaking parents.
Measurement of intrinsic optical backscattering characteristics of cells using fiber-guided near infrared light
Authors: Hsu Ching-Huang , Chang Gwo-Ching , Li En-Ting , Lin Yu-Jing , Chen Jia-Jin Jason 
Published: April 2010

Abstract

Background
Intrinsic optical signals (IOS), which reflect changes in transmittance and scattering light, have been applied to characterize the physiological conditions of target biological tissues. Backscattering approaches allow mounting of the source and detector on the same side of a sample which creates a more compact physical layout of device. This study presents a compact backscattering design using fiber-optic guided near-infrared (NIR) light to measure the amplitude and phase changes of IOS under different osmotic challenges.

Methods
High-frequency intensity-modulated light was guided via optic fiber, which was controlled by micromanipulator to closely aim at a minimum cluster of cortical neurons. Several factors including the probe design, wavelength selection, optimal measuring distance between the fiber-optical probe and cells were considered. Our experimental setup was tested in cultured cells to observe the relationship between the changes in backscattered NIR light and cellular IOS, which is believed mainly caused by cell volume changes in hypo/hyperosmotic solutions (± 20, ± 40 and ± 60 mOsm).

Results
The critical parameters of the current setup including the optimal measuring distance from fiber-optical probe to target tissue and the linear relationship between backscattering intensity and cell volume were determined. The backscattering intensity was found to be inversely proportional to osmotic changes. However, the phase shift exhibited a nonlinear feature and reached a plateau at hyperosmotic solution.

Conclusions
Our study indicated that the backscattering NIR light guided by fiber-optical probe makes it a potential alternative for continuous observation of intrinsic optical properties of cell culture under varied physical or chemical challenges.