Miracle-dz/UniFAR-FTUs huggingface dataset:
­­Role of Runx2 in Crosstalk Between Mek/Erk and PI3K/Akt Signaling in MCF‐10A Cells

Crosstalk among mitogen‐activated protein kinase (MAPK) and phosphatidyl inositol 3′ kinase (PI3K) signaling pathways integrates extracellular cues to regulate mammary epithelial cell growth, proliferation, differentiation, and survival. The runt‐related transcription factor, Runx2, is expressed in normal mammary epithelium and promotes differentiation, however, its function in regulation of the MAPK and PI3K signaling crosstalk is not known. We determined the function of Runx2 expression in growth factor‐mediated phosphorylation of Erk1/2 and Akt, key downstream kinases in MAPK and PI3K pathway crosstalk in MCF‐10A mammary epithelial cells. The Runx2‐mediated alterations in cell signaling and associated changes in phenotype were determined by real‐time quantitative PCR, Western blotting, immunofluorescence, and flow cytometry approaches. The results revealed that ectopic Runx2 expression differentially downregulates the growth factor (EGF vs. IGF or insulin)‐induced pErk1/2 and pAkt levels. Additionally, the ectopic Runx2 expression increases FOXO1 levels, cell cycle G1 stage and promotes survival of MCF‐10A cells. Furthermore, we demonstrate that Runx2 expression increases EGF‐induced phosphorylation of epidermal growth factor receptor (pEGFR) and relieves Mek/Erk‐mediated negative regulation of pEGFR and pAkt levels. Altogether, our results identify functions of Runx2 in MAPK and PI3K signaling crosstalk in MCF‐10A cells that could be critical in understanding the mammary epithelial cell growth and survival. J. Cell. Biochem. 115: 2208–2217, 2014. © 2014 Wiley Periodicals, Inc.
Endometrial adenocarcinoma with squamdus cell differentiation

In a histopathologic review of all cases of endometrial carcinoma diagnosed in Norway between 1970 and 1978, 255 cases of adenocarcinoma with squamous cell differentiation were found among the 1985 cases reviewed. One hundred eighty‐one (9.1%) were adenoacanthoma and 74 (3.7%) adenosquamous carcinoma. The mean age for patients with adenoacanthoma was 57.7 years (range, 32 to 85 years) and for adenosquamous carcinoma, 62.8 years (range, 43 to 84 years). Five‐year and 10‐year survival rates for all patients were 83.5% and 71.8%, respectively. For patients with adenosquamous carcinoma, corresponding figures were 64.9% and 52.7%, and for those with adenoacanthoma, the figures were 91.2% and 79.6%, respectively. When stratified for grade and depth of myometrial infiltration, there was no difference in survival rates between patients with adenoacanthoma and adenosquamous carcinoma, provided hysterectomy was part of the primary treatment. In patients who had surgery, myometrial infiltration was the most important single prognostic factor. It is recommended that the terms adenoacanthoma and adenosquamous carcinoma be replaced by the descriptive term adenocarcinoma with squamous cell differentiation.
MicroRNA Profile of Tumorigenic Cells During Carcinogenesis of Lung Adenocarcinoma

To obtain microRNA (miRNA) profile and clarify their biological function in tumorigenic Sca‐1+CD34+ cells during carcinogenesis of lung adenocarcinoma. After intranasal infection with recombinant Adeno‐Cre viruses (AdV‐Cre), lung adenocarcinoma was identified pathologically in Lox‐stop‐lox Kras (LSL‐Kras) G12D mice. Sca‐1+CD34+ cells were sorted by flow cytometry and tested for tumor‐initiating ability, self‐renewal and tumorigenicity. MiRNA profiles were obtained using microarray and further confirmed by real‐time RT‐PCR (qRT‐PCR). MiRNA functions were predicted bioinformatically, and miR‐294 function was verified to explore its role in tumor migration and invasion. Lung adenocarcinoma was induced in LSL‐Kras G12D mice within 30 days. In vivo, the tumorigenicity of Sca‐1+CD34+ cells was 25 times stronger than Sca‐1−CD34− cells. During tumorigenesis of lung adenocarcinoma, the expression of 145 miRNAs in Sca‐1+CD34+ cells increased and 72 miRNAs decreased (P < 0.01). Four successively up‐regulated miRNAs (miR‐15a*, miR‐203, miR‐294 and miR‐295*) and three successively down‐regulated ones (miR‐19b, miR‐483 and miR‐615–5p) were identified. Among them, miR‐294 could constitutively bind to 3'‐UTR of matrix metalloproteinase 3 (MMP3), and down‐regulate MMP3 protein expression. MiR‐294 also significantly inhibited migration and invasion of Lewis lung cancer cells. MiRNAs are characteristically expressed in tumor‐initiating Sca‐1+CD34+ cells of lung adenocarcinoma, and may play important roles during the carcinogenesis of lung adenocarcinoma. J. Cell. Biochem. 116: 458–466, 2015. © 2014 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.
Real‐Time Fluorescence Imaging of the DNA Damage Repair Response During Mitosis

The response to DNA damage during mitosis was visualized using real‐time fluorescence imaging of focus formation by the DNA‐damage repair (DDR) response protein 53BP1 linked to green fluorescent protein (GFP) (53BP1‐GFP) in the MiaPaCa‐2Tet‐On pancreatic cancer cell line. To observe 53BP1‐GFP foci during mitosis, MiaPaCa‐2Tet‐On 53BP1‐GFP cells were imaged every 30 min by confocal microscopy. Time‐lapse imaging demonstrated that 11.4 ± 2.1% of the mitotic MiaPaCa‐2Tet‐On 53BP1‐GFP cells had increased focus formation over time. Non‐mitotic cells did not have an increase in 53BP1‐GFP focus formation over time. Some of the mitotic MiaPaCa‐2Tet‐On 53BP1‐GFP cells with focus formation became apoptotic. The results of the present report suggest that DNA strand breaks occur during mitosis and undergo repair, which may cause some of the mitotic cells to enter apoptosis in a phenomenon possibly related to mitotic catastrophe. J. Cell. Biochem. 116: 661–666, 2015. © 2014 Wiley Periodicals, Inc.
Protonation Behavior of Histidine during HSF1 Activation by Physiological Acidification

The expression of eukaryotic molecular chaperones (heat shock proteins, HSPs) is triggered in response to a wide range of environmental stresses, including: heat shock, hydrogen peroxide, heavy metal, low‐pH, or virus infection. Biochemical and genetic studies have clearly shown the fundamental roles of heat shock factor 1 (HSF1) in stress‐inducible HSP gene expression, resistance to stress‐induced cell death, carcinogenesis, and other biological phenomena. Previous studies show that acidic pH changes within the physiological range directly activate the HSF1 function in vitro. However, the detailed mechanism is unclear. Though computational pKa‐predications of the amino acid side‐chain, acidic‐pH induced protonation of a histidine residue was found to be most‐likely involved in this process. The histidine 83 (His83) residue, which could be protonated by mild decrease in pH, causes mild acidic‐induced HSF1 activation (including in‐vitro trimerization, DNA binding, in‐vivo nuclear accumulation, and HSPs expression). His83, which is located in the loop region of the HSF1 DNA binding domain, was suggested to enhance the intermolecular force with Arginine 79, which helps HSF1 form a DNA‐binding competent. Therefore, low‐pH‐induced activation of HSF1 by the protonation of histidine can help us better to understand the HSF1 mechanism and develop more therapeutic applications (particularly in cancer therapy). J. Cell. Biochem. 116: 977–984, 2015. © 2015 Wiley Periodicals, Inc.
Litwak and Longino’s Developmental Model of Later-Life Migration: Evidence From the American Community Survey, 2005–2007

The present study revisits Litwak and Longino’s seminal article, “Migration Patterns among the Elderly: A Developmental Perspective. ” Data from the American Community Survey, 2005—2007 are exploited to partially replicate and build on the original study. Findings indicate that Florida later-life migrant exchanges with selected states in the Northeast and Midwest appear to be characterized by positively selected in-bound streams and negatively selected out-bound streams, consistent with the results reported by Litwak and Longino. The “amenity in-migrant, assistance out-migrant” pattern is also evident in the exchange of older migrants between Florida and other regions, excepting the West. Older in-migrants to Arizona from the Midwest and West similarly appear to be positively selected compared to their out-bound counterparts leaving Arizona for destinations in those same regions. Implications of these results are discussed together with study limitations and directions for further research.
Functional and Clinical Evidence That TAZ is a Candidate Oncogene in Hepatocellular Carcinoma

Transcriptional co‐activator with PDZ‐binding motif (TAZ) has been reported to be associated with carcinogenesis. However, the cellular function of TAZ in human hepatocellular carcinoma (HCC) remains elusive. In this study, an immunohistochemistry analysis revealed that the expression of TAZ in cancer tissue samples from 180 HCC patients was significantly higher than that in adjacent normal tissues. In addition, TAZ overexpression was significantly correlated with aggressive tumor characteristics such as tumor size, TNM stage, lymph node or distant metastasis, histological differentiation, and recurrent HCC (P < 0.05). The Kaplan–Meier test showed that TAZ‐positive expression was related to a poor prognosis compared to TAZ‐negative expression (P < 0.05). Furthermore, the expression level of TAZ was generally correlated with the invasiveness of cancer cells. The overexpression of TAZ in the Huh7 cell line, which endogenously expresses TAZ at low levels, significantly promoted cell proliferation, migration and invasion and inhibited apoptosis, whereas RNA interference‐mediated knockdown of TAZ in the highly invasive cell line MHCC‐97H significantly suppressed cell proliferation, migration and invasion in vitro and tumor formation in vivo. J. Cell. Biochem. 116: 2465–2475, 2015. © 2015 Wiley Periodicals, Inc.
A Prospective and Randomized Comparison of Limited Versus Extensive Atrial Substrate Modification After Circumferential Pulmonary Vein Isolation in Nonparoxysmal Atrial Fibrillation

The optimal substrate ablation approach in patients with persistent atrial fibrillation (Per AF) remains unclear. This was a prospective randomized study comparing the efficacy of limited (continuous complex fractionated atrial electrogram, CFAE: <60 milliseconds) versus extensive (continuous CFAE plus variable CFAE: <120 milliseconds) atrial substrate modification in Per AF patients.
Chondroitin Sulfate‐E Binds to Both Osteoactivin and Integrin αVβ3 and Inhibits Osteoclast Differentiation

Integrins and their ligands have been suggested to be associated with osteoclast‐mediated bone resorption. The present study was designed to investigate whether chondroitin sulfate E (CS‐E), which is one of the sulfated glycosaminoglycans (GAGs), is involved in osteoactivin (OA) activity, and osteoclast differentiation. The binding affinity of sulfated GAGs to integrin and its ligand was measured using biotin‐labeled CS‐E, and the osteoclast differentiation was evaluated by tartrate‐resistant acid phosphatase staining and a pit formation assay. CS‐E as well as CS‐B, synthetic chondroitin polysulfate, and heparin inhibited osteoclast differentiation of bone marrow‐derived macrophages. Pre‐coating of OA to synthetic calcium phosphate‐coated plates enhanced the osteoclastic differentiation of RAW264 cells, and addition of a neutralizing antibody to OA inhibited its differentiation. CS‐E bound not only to OA, fibronectin, and vitronectin, but also to its receptor integrin αVβ3, and inhibited the direct binding of OA to integrin αVβ3. Furthermore, CS‐E blocked the binding of OA to cells and inhibited OA‐induced osteoclastic differentiation. On the other hand, heparinase treatment of RAW264 cells inhibited osteoclastic differentiation. Since binding of OA to the cells was inhibited by the presence of heparan sulfate or heparinase treatment of cells, heparan sulfate proteoglycan (HSPG) was also considered to be an OA receptor. Taken together, the present results suggest that CS‐E is capable of inhibiting OA‐induced osteoclast differentiation by blocking the interaction of OA to integrin αVβ3 and HSPG. J. Cell. Biochem. 116: 2247–2257, 2015. © 2015 Wiley Periodicals, Inc.
Comprehensive data on ionising radiation from Fukushima Daiichi nuclear power plant in the town of Miharu, Fukushima prefecture: The Misho Project

Data related to radioactivity released from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident on 15 March 2011 gathered by residents of Miharu, Fukushima Prefecture, and by Tohoku University are presented. These data sets consist of (1) the earliest radiation monitoring by a Geiger counter in the town, (2) ratios of radioactivity between 132Te and 137Cs for a wide area between Fukushima and Tokyo, (3) radiation measurement of soil samples collected from 18 school grounds, and (4) external radiation exposure of 1400 students using OSL badges. By combining and analysing these various data sets, a curve for the cumulative total external exposure as a function of time, with 16 : 00 h on 15 March 2011 being time zero, is obtained. The average cumulative external dosage is estimated to be 10 mSv (σ = 4.2 mSv) over 10 years. In addition, the initiative that the residents of Miharu took in response to the FDNPP accident, which became known as The Misho Project (MP), is documented; in particular, the time at which the municipality instructed the immediate ingestion of iodine tablets by those under the age of 40, 13 : 00 h on 15 March 2011, is assessed.
PRDM1, a Tumor‐Suppressor Gene, is Induced by Genkwadaphnin in Human Colon Cancer SW620 Cells

Genkwadaphnin (GD‐1) is isolated from the flower buds of Daphne genkwa Siebold et Zuccarini (Thymelaeaceae), and it has been used as a traditional Korean and Chinese medicine. In this study, the authors observe that GD‐1 inhibits the growth of the colon cancer cell line, SW620, through the up‐regulation of p21 expression in a PRDM1‐dependent manner. After treatment with GD‐1, the transcriptional repressor PRDM1 is prominently induced in SW620 cells. Furthermore, GD‐1 induce the phosphorylation of PKD1 and MEK and subsequently provide PRDM1 enhancement, resulting in the suppression of c‐Myc expression and the up‐regulation of p21. PKD1 knockdown using siRNA abrogates PRDM1 expression by GD‐1 and subsequently disrupts the regulation of c‐Myc and p21 expression. Treating SW620 cells with GD‐1 inhibits cell‐cycle progression and is characterized by the down‐regulation of c‐Myc followed by the up‐regulation of p21 expression. The up‐regulation of p21 by GD‐1 induces the growth arrest of the SW620 colon cancer cell line. Based on these data, the authors propose that GD‐1 has tumor‐suppressor activity that may contribute to the anti‐tumor effects of PRDM1 in colon cancer. J. Cell. Biochem. 117: 172–179, 2016. © 2015 Wiley Periodicals, Inc.
Managing Funding Constraints in Frontline HIV/AIDS Social Services in Canada

ABSTRACT The need for HIV/AIDS social services continues to grow; workers confront increasingly complex client needs, and changes to government funding policies present new challenges to frontline social workers. Drawing on a qualitative study involving 59 social service practitioners in Ontario, Canada, this paper explores how frontline workers experience policy changes that restrict government funding. Respondents report that many of their clients are focused on immediate needs, such as food or shelter, rather than their HIV infection. They describe how funding cuts can introduce uncertainty into their work, and they note that their work now feels more bureaucratic and less caring. More organizational work is required to access resources and workers often find themselves playing a gate-keeping role. The paper describes how workers try to minimize the negative policy changes they perceive, but some of their ways of managing increased demand can actually end up increasing barriers to clients. Findings suggest that changing policies can undermine efforts to involve people with HIV in service delivery and to advocate for changing the social context of the epidemic.
Parent attitudes toward various behaviour management techniques used in pediatric dentistry in Southern Thailand

Abstract The purpose of this study was to evaluate parents' attitudes toward various behaviour management techniques. One hundred and eighty-five parents participated in the study. Nine techniques were presented to parents prior to rating acceptance. The explanation included a written description, pictures and rationale for each technique. The results showed that the ‘tell-show-do’ technique was accepted by all parents (100%), followed by positive reinforcement (94%) and distraction (83%). Almost half of the parents (49%) accepted papoose board with 29 (16%) of them rating this technique as totally acceptable. Parent-child separation was accepted by 47% of the parents with 18% rating it as totally acceptable. Techniques judged least acceptable were general anesthesia (62%), hand-over-mouth (58%), voice control (56%), and sedation (55%). We concluded that in different communities, implied consent should not be assumed for individual behaviour management and every case should be considered on an individual basis for informed consent.
Diagnosis and Management of Hyponatremia

Appropriate treatment of hyponatremic disorders is de pendent on an understanding of the mechanisms that cause these abnormalities. This article offers a patho physiological approach to hypoosmolar syndromes. Common causes of hyponatremia are reviewed with particular emphasis on congestive heart failure, ad vanced liver disease, diuretic use, and the syndrome of inappropriate antidiuretic hormone secretion. New con cepts in treatment are discussed with the aid of clinical examples that emphasize critical information. A number of recent studies have questioned the safety of rapidly correcting hyponatremia; recommendations based on our current understanding of these risks are proposed. Pitfalls in the diagnosis and management of patients with hyponatremic disorders are also discussed.
C‐Mpl Is Expressed on Osteoblasts and Osteoclasts and Is Important in Regulating Skeletal Homeostasis

C‐Mpl is the receptor for thrombopoietin (TPO), the main megakaryocyte (MK) growth factor, and c‐Mpl is believed to be expressed on cells of the hematopoietic lineage. As MKs have been shown to enhance bone formation, it may be expected that mice in which c‐Mpl was globally knocked out (c‐Mpl−/− mice) would have decreased bone mass because they have fewer MKs. Instead, c‐Mpl−/− mice have a higher bone mass than WT controls. Using c‐Mpl−/− mice we investigated the basis for this discrepancy and discovered that c‐Mpl is expressed on both osteoblasts (OBs) and osteoclasts (OCs), an unexpected finding that prompted us to examine further how c‐Mpl regulates bone. Static and dynamic bone histomorphometry parameters suggest that c‐Mpl deficiency results in a net gain in bone volume with increases in OBs and OCs. In vitro, a higher percentage of c‐Mpl−/− OBs were in active phases of the cell cycle, leading to an increased number of OBs. No difference in OB differentiation was observed in vitro as examined by real‐time PCR and functional assays. In co‐culture systems, which allow for the interaction between OBs and OC progenitors, c‐Mpl−/− OBs enhanced osteoclastogenesis. Two of the major signaling pathways by which OBs regulate osteoclastogenesis, MCSF/OPG/RANKL and EphrinB2‐EphB2/B4, were unaffected in c‐Mpl−/− OBs. These data provide new findings for the role of MKs and c‐Mpl expression in bone and may provide insight into the homeostatic regulation of bone mass as well as bone loss diseases such as osteoporosis. J. Cell. Biochem. 117: 959–969, 2016. © 2015 Wiley Periodicals, Inc.
Regulation of the Expression of Heparan Sulfate 3‐O‐Sulfotransferase 3B (HS3ST3B) by Inflammatory Stimuli in Human Monocytes

Heparan sulfate (HS) is recognized as an important player in a wide range of dynamic steps of inflammatory reactions. Thereby, structural HS remodeling is likely to play an important role in the regulation of inflammatory and immune responses; however, little is known about underlying mechanism. In this study, we analyzed the regulation of expression of HS 3‐O‐sulfotransferases (HS3STs) in response to inflammatory stimuli. We found that among the seven HS3ST isoenzymes, only the expression of HS3ST3B was markedly up‐regulated in human primary monocytes and the related cell line THP1 after exposure to TLR agonists. TNF‐α was also efficient, to a lesser extent, to increase HS3ST3B expression, while IL‐6, IL‐4, and IFN‐γ were poor inducers. We then analyzed the molecular mechanisms that regulate the high expression of HS3ST3B in response to LPS. Based on the expression of HS3ST3B transcripts and on the response of a reporter gene containing the HS3ST3B1 promoter, we provide evidence that LPS induces a rapid and strong transcription of HS3ST3B1 gene, which was mainly dependent on the activation of NF‐κB and JNK signaling pathways. Additionally, active p38 MAPK and de novo synthesized proteins are involved in post‐transcriptional mechanisms to maintain a high level of HS3ST3B mRNA to a steady state. Altogether, our findings indicate that HS3ST3B1 gene behaves as a primary response gene, suggesting that it may play an important role in making 3‐O‐sulfated HS with specific functions in the regulation of inflammatory and immune responses. J. Cell. Biochem. 117: 1529–1542, 2016. © 2015 Wiley Periodicals, Inc.
Electrophysiologic and Clinical Consequences of Left Atrial Anterior Wall Linear Ablation in Patients With Persistent Atrial Fibrillation

As an alternative to the mitral isthmus line (MIL), the left atrial anterior wall line (LAAWL) is effective for the treatment of perimitral flutter. This study evaluated the electrophysiologic and clinical outcomes of LAAWL versus MIL in patients with persistent atrial fibrillation (AF).
A Computational Protein Phenotype Prediction Approach to Analyze the Deleterious Mutations of Human MED12 Gene

Genetic mutations in MED12, a subunit of Mediator complex are seen in a broad spectrum of human diseases. However, the underlying basis of how these pathogenic mutations elicit protein phenotype changes in terms of 3D structure, stability and protein binding sites remains unknown. Therefore, we aimed to investigate the structural and functional impacts of MED12 mutations, using computational methods as an alternate to traditional in vivo and in vitro approaches. The MED12 gene mutations details and their corresponding clinical associations were collected from different databases and by text‐mining. Initially, diverse computational approaches were applied to categorize the different classes of mutations based on their deleterious impact to MED12. Then, protein structures for wild and mutant types built by integrative modeling were analyzed for structural divergence, solvent accessibility, stability, and functional interaction deformities. Finally, this study was able to identify that genetic mutations mapped to exon‐2 region, highly conserved LCEWAV and Catenin domains induce biochemically severe amino acid changes which alters the protein phenotype as well as the stability of MED12‐CYCC interactions. To better understand the deleterious nature of FS‐IDs and Indels, this study asserts the utility of computational screening based on their propensity towards non‐sense mediated decay. Current study findings may help to narrow down the number of MED12 mutations to be screened for mediator complex dysfunction associated genetic diseases. This study supports computational methods as a primary filter to verify the plausible impact of pathogenic mutations based on the perspective of evolution, expression and phenotype of proteins. J. Cell. Biochem. 117: 2023–2035, 2016. © 2016 Wiley Periodicals, Inc.