tbuckley/cabot-search huggingface dataset:
Calycosin-7-O-β-d-glucopyranoside stimulates osteoblast differentiation through regulating the BMP/WNT signaling pathways
Authors: Jing Jian, Lijuan Sun, Xun Cheng, Xiaofang Hu, Jichao Liang, Yong Chen
Journal: Acta Pharmaceutica Sinica B (2015)

The isoflavone calycosin-7-O-β-d-glucopyranoside (CG) is a principal constituent of Astragalus membranaceus (AR) and has been reported to inhibit osteoclast development in vitro and bone loss in vivo. The aim of this study was to investigate the osteogenic effects of CG and its underlying mechanism in ST2 cells. The results show that exposure of cells to CG in osteogenic differentiation medium increases ALP activity, osteocalcin (Ocal) mRNA expression and the osteoblastic mineralization process. Mechanistically, CG treatment increased the expression of bone morphogenetic protein 2 (BMP-2), p-Smad 1/5/8, β-catenin and Runx2, all of which are regulators of the BMP- or wingless-type MMTV integration site family (WNT)/β-catenin-signaling pathways. Moreover, the osteogenic effects of CG were inhibited by Noggin and DKK-1 which are classical inhibitors of the BMP and WNT/β-catenin-signaling pathways, respectively. Taken together, the results indicate that CG promotes the osteoblastic differentiation of ST2 cells through regulating the BMP/WNT signaling pathways. On this basis, CG may be a useful lead compound for improving the treatment of bone-decreasing diseases and enhancing bone regeneration.
Abstract 10591: Changes in Mitral Annular Geometry Following Percutaneous Edge-to-Edge Mitral Valve Repair Using the Mitraclip Device - New Insights in a High-Risk Patient Cohort
Authors: Jason Dungu, Gabriela C Campos, Rizniya Jaffarulla, Sueli Gomes-Pereira, Nilesh Sutaria, Christopher S Baker, Petros Nihoyannopoulos, Michael Bellamy
Journal: Circulation (2011)

Background:  Percutaneous edge-to-edge mitral valve repair (Mitraclip) is an evolving therapy for patients with symptomatic severe mitral regurgitation (MR). Whether this leads to secondary changes in the mitral annulus is unknown.   Methods:  We studied changes in mitral annular geometry before and immediately after Mitraclip implant in a cohort of high-risk patients (n=20) with symptomatic MR (more than or equal to grade 3+). Mitral valve quantification software (MVQ) and 3D transesophageal echocardiography were used to measure the following mitral annular parameters, (1) anterior-posterior diameter (DAP, mm), (2) intercommissural diameter (DAlPm, mm), (3) 3D circumference (C3D, mm), (4) 3D area (A3D, mm2) (5) height (H, mm) and (6) sphericity index (DAP/DAlPm ratio) in both functional and degenerative MR etiology.   Results:  Eleven patients (52%) had a 2-grade reduction in MR and 6 patients (29%) 1-grade reduction (p    Conclusions:  Mitraclip implant leads to acute changes in mitral annular geometry, in particular, a significant reduction in AP diameter that differs according to MR etiology. The impact of these acute changes on longer-term success rates, durability of MR reduction and adverse events remains largely unknown.
Abstract 710: Notch1 Receptor Enhances Myocyte Differentiation of Cardiac Progenitor Cells and Myocardial Regeneration After Infarction
Authors: Alessandro Boni, Angelo Nascimbene, Robert Siggins, Konrad Urbanek, Katsuya Amano, Francesca Delucchi, Saori Yasuzawa-Amano, Nicole LeCapitaine, Irina Trofimova, Andrea Di Marco, Serena Vitale, Narissa Small, Federico Mosna, Arantxa Gonzalez, Ornella Rimoldi, Jan Kajstura, Piero Anversa, Annarosa Leri
Journal: Circulation (2007)

Cardiac progenitor cells (CPCs) have been identified in the adult heart. However, the molecular mechanisms involved in the commitment of CPCs to the myocyte lineage remain to be determined. Notch-1 is a transmembrane receptor activated by the DSL family of ligands which include Jagged1 and Delta-4. Upon ligand binding, the activated receptor undergoes cleavage by γ-secretase, and its intracellular portion (Notch intracellular domain, NICD) is released, translocates to the nucleus and exerts its function as a transcriptional regulator. The objective of this study was to determine whether the components of the Notch pathway are present in the CPCs of the adult mammalian heart and whether activation of the Notch-1 receptor promotes the differentiation of CPCs into myocytes. For this purpose, c-kit-positive CPCs were isolated from the mouse heart and analyzed by FACS and immunocytochemistry. Notch-1 receptor was detected in ~50% of c-kit-positive CPCs. CPCs were then plated on culture dishes coated with immobilized Jagged1 or Delta-4 and maintained in low-serum medium. Additional groups of cells were similarly exposed to the ligands but were also treated with γ-secretase inhibitor. After 5 days in culture, the number of CPCs was markedly lower in the presence of the Notch ligands and significantly higher in the presence of the γ-secretase inhibitor. After 8 days in culture, cells became confluent and did not express any longer c-kit. With respect to cells treated with the γ-secretase inhibitor, exposure to Jagged1 and Delta-4 resulted respectively in a 10-fold and 20-fold increase in the fraction of CPCs positive for Nkx2.5. These findings were consistent with a positive effect of Notch on CPC differentiation and Nkx2.5 upregulation. To establish whether Notch influenced cardiomyogenesis in vivo, infarcted mice were treated for 11 days with the γ-secretase inhibitor. The regenerative response of the infarcted heart, defined by the percentage of BrdU-positive myocytes distributed in the border zone, was 50% lower in animals that received the γ-secretase inhibitor. Thus, Notch1 modulates CPC differentiation in vitro and myocardial regeneration in vivo after infarction.
Abstract 244: The Relationship of Left Ventricular Untwisting to Diastology in Type 1 Diabetes
Authors: Ganesh Nallur Shivu, Khalid Abozguia, Thanh Phan, Ibrar Ahmed, Parth Narendran, Martin Stevens, Michael Frenneaux
Journal: Circulation (2009)

BACKGROUND: Left ventricular (LV) torsion followed by untwisting during diastole is an important component that affects LV filling. We used speckle tracking echocardiography to study the early chan...
Abstract 4208: Hemodynamic Relevance of Calcified Coronary Artery Lesions -Non-Invasive Assessment Using Dual-Source CT and Magnetic Resonance Stress Imaging
Authors: Johannes Rixe, Guido Conradi, Andreas Rolf, Holger Steiger, Helge Moellmann, Holger Nef, Christian W. Hamm, Thorsten Dill
Journal: Circulation (2008)
Abstract 1099: Adiponectin Enhances De Novo Hepatic HDL Synthesis Through LXR Alpha-and COUP-TFII-Dependent Pathways
Authors: Kazumi Tsubakio-Yamamoto, Shizuya Yamashita, Tohru Ohama, Daisaku Masuda, Jose C Sandoval, Miwako Inagaki, Kazuhiro Nakatani, Miyako Yuasa-Kawase, Ryota Kawase, Hajime Nakaoka, Yumiko Nakagawa-Toyama, Makoto Nishida, Makoto Ishigami, Shinji Kihara, Iichiro Shimomura, Issei Komuro
Journal: Circulation (2009)
The integrated memory model: A new framework for understanding the mechanisms of change in psychotherapy
Authors: Richard D. Lane, Lynn Nadel, Leslie Greenberg, Lee Ryan
Journal: Behavioral and Brain Sciences (2015)

Abstract In this response to commentaries on our target article, we highlight and clarify a variety of issues and respond to several comments, challenges, and misconceptions. Topics covered include the mechanisms of enduring change, the nature of memory, the conditions in which memories are updated, the role of emotional arousal in change, and current limitations in our understanding of the neural basis of change in psychotherapy. It is our hope that through research stimulated by this exchange the latter may be advanced.
Whole genome chromatin interaction analysis using paired end diTags
Authors: Melissa Fullwood, Jun Liu, Hong-Sain Ooi, You Fu Pan, Senali Abayratna, Yan Quan Luo, Pramila Ariyaratne, Han Xu, Vega Vinsensius, Bing Zhao, Tze Howe Charn, Ken Sung, Chia-Lin Wei, Edwin Cheung, Yijun Ruan
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

A51 

The human genome is organized into high level structures, and DNA elements separated by long genomic distances could functionally interact. We developed a method for whole genome chromatin interaction analysis using paired end ditag sequencing (ChIA-PET) to reveal long-range interactions mediated by transcription factors. In this method, chromatin is cross-linked and sonicated; the resulting protein/DNA complexes are ligated to a specific linker containing two type IIs restriction enzyme recognition sites, and digested to release paired end ditags (PETs) for high throughput sequencing. The sequences are mapped to the reference genome and clustered to identify transcription factor binding sites (TFBS) as well as long-range interactions between the TFBS. We validated this approach by mapping whole genome chromatin interactions mediated by estrogen receptor α (ERα) in human breast cancer cells. We identified 472 high-confidence and 1,910 medium-confidence intrachromosomal long-range interactions between ERα binding sites. Many long-range interactions involve multiple ERα binding sites, suggesting complex regulation by ERα. ChIP-3C was successfully used to validate 15 interactions present near 10 genes. Our results demonstrate that ChIA-PET is an unbiased approach for whole genome high-throughput analysis of long-range chromatin interactions, and that intrachromosomal long-range interactions between TFBS constitute a primary mechanism for ERα-mediated function.
Tuberculosis in a child – search for the infected adult nearby; case report, Portugal, 2007
Authors: R Duarte, E Tavares, A Miranda, A Carvalho
Journal: Eurosurveillance (2009)

Tuberculosis (TB) transmission in a non-household setting is difficult to detect, because contact with the source case is often not obvious. Here, we report on a case of a four-year-old child who got infected through sporadic non-household exposure at a coffee shop. The source case was a woman who had suffered from weight loss, productive cough and fatigue for two months before being diagnosed with TB. Screening the child s contacts revealed two active TB cases within its family. Overall 148 contacts were screened for both cases and 18 cases of latent TB infection detected. The connection between the child and the source case, who were not aware of their contact, was confirmed by molecular fingerprinting. Our case report illustrates the difficulty in detecting non-household transmission between individuals that do not have significant contact, and draws attention to the need to look for the infected adult whenever a child falls ill with TB. This report is a reminder of the importance to consider possibly neglected ways of TB transmission and highlights once again the need of early diagnosis of TB.
Contribution of enhanced ADCC to superior in vivo efficacy of a novel type II humanized, third generation CD20 antibody (GA101) in NHL xenograft models
Authors: Adam Nopora, Susanne Preiss, Valeria Nicolini, Michaela Rommele, Erwin van Puijenbroek, Olivier Freytag, Monika Patre, Sabine Bauer, Christian Klein, Pablo Umana, Christian Gerdes
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3991 

GA101 is the first humanized type II CD20 antibody in clinical development for the treatment of B-cell malignancies. It was derived by humanization of the murine B-Ly1 antibody, introducing a modification of its elbow hinge sequence, and glycoengineering of the human IgG1 Fc region. By virtue of its Type II mode of binding to CD20, a property enhanced by the elbow hinge sequence modification, GA101 induces superior, Fc-independent direct target cell death as compared to Type I CD20 antibodies like rituximab. In addition, the glycoengineered Fc region of GA101 binds with higher affinity to FcgRIIIa on immune effector cells (e.g., NK cells and macrophages), leading to significantly enhanced ADCC relative to rituximab and other standard IgG1 antibodies.    The affinity of the Fc-FcgRIIIa interaction has previously been correlated with response to rituximab monotherapy of fNHL. Treatment of patients homozygous for the less common, high affinity variant of FcgRIIIa (158V) was associated with a higher response rate and longer progression-free survival, relative to patients carrying the low affinity form of this receptor (FcgRIIIa-158F) (Cartron et al., 2002). Glycoengineering of GA101 increased its binding affinity affinity to both FcgRIIIa variants and, importantly, led to higher binding affinity to the more common FcgRIIIa-158F form, as compared to rituximab binding to FcgRIIIa-158V. In mouse models, the homologue receptor of hFcgRIIIa (mFcgRIV) is expressed in monocytes, macrophages and granulocytes, but not on NK cells. In order to dissect the contribution of Fc glycoengineering to the in vivo efficacy of GA101, we compared it to its non-glycoengineered counterpart, and to rituximab, in human subcutaneous and orthotopic NHL xenograft models in Scid-beige mice. Of note, this is a mouse strain with disabled NK cells and granulocytes but with functional monocytes and macrophages. We showed that glycoengineering of GA101 led to significantly enhanced in vivo efficacy and that both both GA101 and its non-glycoengineered counterpart have dramatically superior in vivo efficacy as compared to the rituximab. Furthermore, a comparison of s.c. and orthotopic xenograft models indicated that the contribution of monocytes and macrophages to efficacy in orthotopic models is stronger. In humans, an additional contribution of enhanced ADCC mediated by NK cells may be expected as compared with that seen in murine models.
Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 2011
Authors: J E Afset, K W Larssen, K Bergh, A Sjödin, A Lärkeryd, A Johansson, M Forsman
Journal: Eurosurveillance (2015)

In 2011, a nationwide outbreak of tularaemia occurred in Norway with 180 recorded cases. It was associated with the largest peak in lemming density seen in 40 years. Francisella tularensis was isolated from 18 patients. To study the geographical distribution of F.tularensis genotypes in Norway and correlate genotype with epidemiology and clinical presentation,we performed whole genome sequencing of patient isolates. All 18 genomes from the outbreak carried genetic signatures of F. tularensis subsp. holarctica and were assigned to genetic clades using canonical single nucleotide polymorphisms. Ten isolates were assigned to major genetic clade B.6 (subclade B.7),seven to clade B.12, and one to clade B.4. The B.6 subclade B.7 was most common in southern and central Norway, while clade B.12 was evenly distributed between the southern, central and northern parts of the country. There was no association between genotype and clinical presentation of tularaemia, time of year or specimen type. We found extensive sequence similarity with F. tularensis subsp. holarctica genomes from high-endemic tularaemia areas in Sweden.Finding nearly identical genomes across large geographical distances in Norway and Sweden imply a life cycle of the bacterium without replication between the outbreaks and raise new questions about long-range migration mechanisms.
Abstract 4660: Death Due to Pacemaker or ICD Device Failure is Rare: Implications for the Management of Recalls
Authors: Robert G Hauser, David L Hayes, David S Cannom, Andrew E Epstein, Stephen C Vlay, G. Frank O Tyers, Susan L Song, Linda Kallinen
Journal: Circulation (2008)

Knowledge of major adverse clinical events (MACE) associated with ICD and pacemaker (PM) pulse generator (PG) and lead performance may be important for managing patients who have these devices. The aim of our study was to assess MACE in our Multicenter Registry. Participating centers prospectively reported ICD and PM PG and lead failures, and PG replaced for normal battery depletion (NBD). Data included dates of implant and removal, failure signs including the elective replacement indicator (ERI), clinical consequences, and reason for removal. MACE were death, inappropriate shocks (IAS), syncope, heart failure, ischemia, sustained tachyarrhythmias, and replacement of a normally functioning PG or lead due to a manufacturers recall. Since 1998, 6,291 ICD and PM PG and leads were removed from service. Of 5,212 ICD and PM PGs, 4,562 (88%) were removed for NBD, 346 (7%) for a recall, and 304 (5%) for component defects. MACE are shown in the Table . The deaths (n=2) were due to component defects causing an ICD PG to short-circuit and a PM PG to deliver high rate pacing. Thus, of the 304 component defects in our database, 2 resulted in death (0.7%). No deaths were associated with ICD or PM lead failure, but 2 deaths occurred following PM lead extraction. The ERI, signifying NBD, resulted in 48 MACE, primarily syncope (67%). Most MACE are due to replacement of normally functioning recalled devices. However, our experience suggests that death due to ICD and PM PG component or lead failure is rare; this finding may be important for managing patients who have recalled devices. Overall, MACE may be substantially reduced by improving high voltage lead reliability, and by providing physiologic ERIs.
Abstract 15258: Reaching AHA 2020 Impact Goal for Cholesterol - Effect of Lifestyle Modification Counselling
Authors: Saurabh Aggarwal, Navdeep Gupta, Rohit S Loomba, Daniela Kovacs, Sandeep Khosla, Rohit R Arora
Journal: Circulation (2013)

The 2020 Strategic Impact Goal laid down by American Heart Association (AHA) aims to achieve a 20% reduction in cardiovascular and stroke deaths and a 20% improvement in cardiovascular health (CVH)...
BH3 Profiling Identifies Bcl-2 Dependency in Multiple Myeloma and Predicts Sensitivity to BH3 Mimetics
Authors: Cyrille Touzeau, Jeremy Ryan, Philippe Moreau, Triona Ni Chonghaile, Steven Le Gouill, Paul G. Richardson, Kenneth C. Anderson, Martine Amiot, Anthony G. Letai
Journal: Blood (2014)
Abstract 19671: Percutaneous Coronary Interventions with Drug-Eluting Stents for Unprotected Left Main Coronary Artery Stenosis are Associated with Reduced Stroke and Increased Repeat Revascularization Risk Compared with Coronary Artery Bypass Graft Surgery: Results from a Contemporary Aggregate Data Meta-Analysis
Authors: Mahboob Alam, Salim S Virani, Anita Deswal, Henry D Huang, David Paniagua, Biswajit Kar, Biykem Bozkurt, Hani Jneid
Journal: Circulation (2010)
Abstract 18591: Identifying “At-Risk” Elderly Persons for New Onset Heart Failure: Implications for Assessment of High-Sensitive Troponin T.
Authors: Christopher Defilippi, John Gottdiener, Willem Kop, Robert Christenson, Stephen Seliger
Journal: Circulation (2010)

Aims: In elderly persons, traditional risk factors have limited accuracy to predict cardiovascular (CV) outcomes. We hypothesized that utilizing a high sensitive troponin T (hsTnT) assay, as a meas...
Near-infrared Raman microspectroscopic analysis of the effect of etoposide on C6 glioma cell division cycle
Authors: Amharref nadia, Wenner thomas, Dukic sylvain, Manfait michel, Abdelilah beljebbar
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3235 

Near-infrared Raman microspectroscopy and Fluorescence-Activated cell sorting (FACS) were used to investigate the effect of etoposide on C6 glioma cells. Cells were incubated at different drug concentrations (0, 0.2, 2, and 20 µM) over 1, 2, and 3 days. After drug treatment, cells were harvested, and two cell pellets prepared: one pellet was analysed by FACS to investigate the effect of etoposide on cell cycle. The other was analysed by Raman microspectroscopy to identify spectroscopic markers linked to changes during the cell cycle. To correlate these changes with the cell cycle, Raman spectra were measured at GG1, G2-M, and S phases obtained after fetal bovine serum starvation, nocodazol incubation, and thymidine exposure, respectively. These treatments lead to a maximum of 94% cells in GG1 phase, 97% in G2-M and 78% in S phase. Multivariate statistics were used to analyze changes in cellular spectra as a function of cell cycle phase. Our results demonstrate that all data measured on cells can be classified in one out of two groups: i) one group contains spectra recorded on untreated cells, cells blocked in GG1 phase and cells treated with 0.2 µM of etoposide during 24, 48 and 72 hours, ii) the second group includes spectra recorded on cells blocked in S and G2-M cell division cycle, and cells treated with 2 µM and 20 µM of etoposide. We are not able to discriminate between cells treated with 2 and 20 µM of etoposide, G2-M and S phase. In fact, cells accumulated in S and G2-M in response to those etoposide concentrations. FACS analysis revealed that treatment with 0.2, 2, and 20 µM of etoposide caused cells to accumulate mostly in GG1, G2-M and S phases, respectively. These results are in agreement with the spectroscopic analysis where cells accumulated in GG1 phase and cells treated with 0.2 µM of etoposide were pooled in the same class. Qualitative changes in cellular components associated with the different phases of cell cycle and with drug effect were also investigated. Our results show that Raman spectra are very sensitive to cell cycle phase due to drug treatment and are associated to molecular changes in protein, DNA and/or RNA content. These results may prove to be useful in the future to evaluate the effect and efficacy of chemotherapeutic treatment.
Abstract #2312: Curcumin inhibits low-dose radiation-induced NF\#954;B dependant adaptive response in bystander lung carcinoma cells
Authors: Jamunarani Veeraraghavan, Rakhesh Madhusoodhanan, Mohan Natarajan, Terence Herman, Natarajan Aravindan
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Studies have shown that signals produced by irradiated cells can induce radioprotection and survival advantage in bystander cells. To that end, NF\#954;B has been causally linked to the low-dose radiation induced adaptive response. We recently reported that curcumin inhibits radiation induced NF\#954;B activity and survival signaling response. Accordingly, in this study, in human lung bystander cells we investigated (1) influence of NF\#954;B in low-dose radiation induced adaptive response and (2) effect of curcumin in inhibiting radiation induced NF\#954;B dependent radioadaptation. Human lung adenocarcinoma (A549) cells either exposed to radiation (2 or 10 cGy) conditioned medium (RCM) or pre-treated with 200nM curcumin and exposed to RCM were harvested after 1, 3, 6, 24, 48 and 72 h. NF\#954;B-dependent regulation was investigated by examining the levels of NF\#954;B DNA-binding activity, and blocking NF\#954;B activity using cells transiently transfected with dn-I\#954;B\#945; (I\#954;B\#945;S32A/S36A) mutant. Transcriptional responses of 89 NF\#954;B signaling pathway molecules were analyzed using real time QPCR profiling. Expression of NF\#954;B dependent downstream pro-survival IAP1, IAP2 and Survivin were analyzed using immunoblotting. Cell survival was measured using MTT and clonogenic assays. QPCR profiling showed upregulation of 62 and 55 NF\#954;B pathway genes in 2cGy and 10cGy RCM exposed cells, respectively. Forty-four genes were commonly upregulated in both conditions. EMSA analysis showed a significant induction of NF\#954;B DNA binding activity in RCM treated cells. This RCM induced induction was sustained at least up to 72 h. Conversely, curcumin pre-treatment profoundly inhibited the induced NF\#954;B DNA-binding activity and markedly inhibited IAP1, IAP2 and Survivin in RCM treated cells. Furthermore, curcumin evidently inhibited clonogenic expansion in RCM treated cells. These results strongly suggest that curcumin inhibits low-dose radiation induced NF\#954;B dependent adaptive response in lung bystander cells.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2312.