bluuebunny/crossref_metadata_2025_split huggingface dataset:
CEBPD Reverses RB/E2F1-Mediated Gene Repression and Participates in HMDB-Induced Apoptosis of Cancer Cells
Authors: Pan Yen-Chun , Li Chien-Feng , Ko Chiung-Yuan , Pan Min-Hsiung , Chen Pei-Jung , Tseng Joseph T. , Wu Wen-Chun , Chang Wen-Chang , Huang A-Mei , Sterneck Esta , Wang Ju-Ming 
Published: October 2010

Abstract
Purpose: Recent evidence indicates that a tumor suppressor gene CEBPD (CCAAT/enhancer-binding protein delta) is downregulated in many cancers including cervical cancer, which provides a therapeutic potential associated with its reactivation. However, little is known for CEBPD activators and the effect of reactivation of CEBPD transcription upon anticancer drug treatment. In this study, we identified a novel CEBPD activator, 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB). The purpose of this study is to characterize the mechanism of HMDB-induced CEBPD activation and its potential effect in cancer therapy.
Experimental Design: Methylation-specific PCR assay, reporter assay, and chromatin immunoprecipitation (ChIP) assay were performed to dissect the signaling pathway of HMDB-induced CEBPD transcription. Furthermore, a consequence of HMDB-induced CEBPD expression was linked with E2F1 and retinoblastoma (RB), which discloses the scenario of CEBPD, E2F1, and RB bindings and transcriptional regulation on the promoters of proapoptotic genes, PPARG2 and GADD153. Finally, the anticancer effect of HMDB was examined in xenograft mice.
Results: We demonstrate that CEBPD plays an essential role in HMDB-mediated apoptosis of cancer cells. HMDB up-regulates CEBPD transcription through the p38/CREB pathway, thus leading to transcriptional activation of PPARG2 and GADD153. Furthermore, increased level of CEBPD attenuates E2F1-induced cancer cell proliferation and partially rescues RB/E2F1-mediated repression of PPARG2 and GADD153 transcription. Moreover, HMDB treatment attenuates the growth of A431 xenografts in severe combined immunodeficient mice mice.
Conclusions: These results clearly demonstrate that HMDB kills cancer cells through activation of CEBPD pathways and suggest that HMDB can serve as a superior chemotherapeutic agent with limited potential for adverse side effects. Clin Cancer Res; 16(23); 5770–80. ©2010 AACR.
Modulation of 4E-BP1 Function as a Critical Determinant of Enzastaurin-Induced Apoptosis
Authors: Dumstorf Chad A. , Konicek Bruce W. , McNulty Ann M. , Parsons Stephen H. , Furic Luc , Sonenberg Nahum , Graff Jeremy R. 
Published: October 2010

Abstract
Enzastaurin (LY317615.HCl) is currently in a phase III registration trial for diffuse large B-Cell lymphoma and numerous phase II clinical trials. Enzastaurin suppresses angiogenesis and induces apoptosis in multiple human tumor cell lines by inhibiting protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K)/AKT pathway signaling. PI3K/AKT pathway signaling liberates eukaryotic translation initiation factor 4E (eIF4E) through the hierarchical phosphorylation of eIF4E binding proteins (4E-BP). When hypophosphorylated, 4E-BPs associate with eIF4E, preventing eIF4E from binding eIF4G, blocking the formation of the eIF4F translation initiation complex. Herein, we show that enzastaurin treatment impacts signaling throughout the AKT/mTOR pathway leading to hypophosphorylation of 4E-BP1 in cancer cells of diverse lineages (glioblastoma, colon carcinoma, and B-cell lymphoma). Accordingly, enzastaurin treatment increases the amount of eIF4E bound to 4E-BP1 and decreases association of eIF4E with eIF4G, thereby reducing eIF4F translation initiation complex levels. We therefore chose to evaluate whether this effect on 4E-BP1 was involved in enzastaurin-induced apoptosis. Remarkably, enzastaurin-induced apoptosis was blocked in cancer cells depleted of 4E-BP1 by siRNAs, or in 4EBP1/2 knockout murine embryonic fibroblasts cells. Furthermore, eIF4E expression was increased and 4E-BP1 expression was decreased in cancer cells selected for reduced sensitivity to enzastaurin-induced apoptosis. These data highlight the importance of modulating 4E-BP1 function, and eIF4F complex levels, in the direct antitumor effect of enzastaurin and suggest that 4E-BP1 function may serve as a promising determinant of enzastaurin activity. Mol Cancer Ther; 9(12); 3158–63. ©2010 AACR.
Notch Signaling Pathway as a Therapeutic Target in Breast Cancer
Authors: Al-Hussaini Hamed , Subramanyam Deepa , Reedijk Michael , Sridhar Srikala S. 
Published: October 2010

Abstract
The highly conserved Notch signaling pathway is involved in regulating a number of key cellular processes. This pathway has been implicated in both the development and progression of breast cancer and has emerged as a possible therapeutic target. Several clinical trials are currently underway to determine if targeting the Notch pathway with drugs such as the γ-secretase inhibitors may be an effective therapeutic strategy that improves outcomes in this disease. Mol Cancer Ther; 10(1); 9–15. ©2010 AACR.
New Criteria During Right Ventricular Pacing to Determine the Mechanism of Supraventricular Tachycardia
Authors: AlMahameed Soufian T. , Buxton Alfred E. , Michaud Gregory F. 
Published: October 2010

Background—
Right ventricular pacing (RVP) during supraventricular tachycardia produces progressive QRS fusion before the QRS morphology becomes stable. This transition zone (TZ) may provide useful information for differentiating orthodromic reciprocating tachycardia (ORT) from atrioventricular nodal reentrant tachycardia and atrial tachycardia independent of entrainment success.

Methods and Results—
We studied the effect of properly timed RVP on atrial timing during the TZ in 92 patients with supraventricular tachycardia who had RVP within 40 ms of the tachycardia cycle length. The TZ during RVP includes progressively fused QRS complexes and the first paced complex with a stable QRS morphology based on analysis of the 12-lead ECG. We also measured the stimulus-atrial interval from the end of the TZ and with each QRS complex thereafter until pacing was terminated or ventriculo-atrial block occurred. A fixed stimulus-atrial interval was defined as variation <10 ms during RVP. Atrial preexcitation, postexcitation, or supraventricular tachycardia termination with abrupt ventriculo-atrial block was observed within the TZ in 32 of 34 patients with ORT. A fixed stimulus-atrial interval was established within the TZ in 33 of 34 patients with ORT. At least 1 of these 2 responses was observed in all patients with ORT. None of the patients with atrioventricular nodal reentrant tachycardia or atrial tachycardia had atrial timing perturbed or a fixed stimulus-atrial interval established within the TZ.

Conclusions—
During RVP within 40 ms of the tachycardia cycle length, ORT is the likely mechanism when atrial timing is perturbed or a fixed stimulus-atrial interval is established within the TZ.
Ginseng Inhibits Cardiomyocyte Hypertrophy and Heart Failure via NHE-1 Inhibition and Attenuation of Calcineurin Activation
Authors: Guo Juan , Gan Xiaohong Tracey , Haist James V , Rajapurohitam Venkatesh , Zeidan Asad , Faruq Nazo Said , Karmazyn Morris 
Published: October 2010

Background—
Ginseng is a medicinal plant used widely in Asia that has gained popularity in the West during the past decade. Increasing evidence suggests a therapeutic role for ginseng in the cardiovascular system. The pharmacological properties of ginseng are mainly attributed to ginsenosides, the principal bioactive constituents in ginseng. The present study was carried out to determine whether ginseng exerts a direct antihypertrophic effect in cultured cardiomyocytes and whether it modifies the heart failure process in vivo. Moreover, we determined the potential underlying mechanisms for these actions.

Methods and Results—

Experiments were performed on cultured neonatal rat ventricular myocytes as well as adult rats subjected to coronary artery ligation (CAL). Treatment of cardiomyocytes with the α
1
adrenoceptor agonist phenylephrine (PE) for 24 hours produced a marked hypertrophic effect as evidenced by significantly increased cell surface area and ANP gene expression. These effects were attenuated by ginseng in a concentration-dependent manner with a complete inhibition of hypertrophy at a concentration of 10 μg/mL. Phenylephrine-induced hypertrophy was associated with increased gene and protein expression of the Na
+
-H
+
exchanger 1 (NHE-1), increased NHE-1 activity, increased intracellular concentrations of Na
+
and Ca
2+
, enhanced calcineurin activity, increased translocation of NFAT3 into nuclei, and GATA-4 activation, all of which were significantly inhibited by ginseng. Upregulation of these systems was also evident in rats subjected to 4 weeks of CAL. However, animals treated with ginseng demonstrated markedly reduced hemodynamic and hypertrophic responses, which were accompanied by attenuation of upregulation of NHE-1 and calcineurin activity.

Conclusions—
Taken together, our results demonstrate a robust antihypertrophic and antiremodeling effect of ginseng, which is mediated by inhibition of NHE-1–dependent calcineurin activation.
Blind outcome assessment: the development and use of procedures to maintain and describe blinding in a pragmatic physiotherapy rehabilitation trial
Authors: Lowe CJ Minns , Wilson MS , Sackley CM , Barker KL 
Published: October 2010

Objectives: (1) To develop trial protocols which promote the achievement of blind outcome assessment. (2) To report outcome assessor beliefs regarding group allocation at follow-up assessments. (3) To document and describe instances of unblinding occurring during the trial to assist and inform rehabilitation researchers and clinicians. Design: Prospective longitudinal observational study. Setting: An NHS Hospital Trust specializing in orthopaedic surgery. Subjects: One hundred and seven patients participating in a prospective pragmatic randomized controlled trial investigating physiotherapy rehabilitation following total knee arthroplasty, plus three outcome assessors. Interventions: A protocol was developed using available research and designed to minimize instances of unblinding during a physiotherapy rehabilitation trial. Administrative, office, patient and research staff procedures were included. Main measures: Trial questionnaires measured blind outcome assessment responses at 3 and 12 months post surgery. The outcome assessor kept a field diary recording the events surrounding instances of unblinding. Data underwent descriptive and content analysis. Results: Blind outcome assessment was believed successful for n = 74 (81.32%) assessments at 3-month follow-up, and n = 83 (91.21%) at 12 months. Forty instances ( n = 28 participants) of unblinding were described in the field diary. While the main cause of unblinding was participants telling the outcome assessor, in 12.5% of events the assessor drew the wrong conclusion regarding group allocation. Not all unblinding events were remembered at subsequent assessments, even in this relatively small trial. Conclusions: Blind outcome assessment was considered achievable in this trial. Specific trial protocols enabled blinding beliefs to be reported and instances of unblinding to be described.
Characterization of an Ex vivo Femoral Head Model Assessed by Markers of Bone and Cartilage Turnover
Authors: Madsen Suzi Hoegh , Goettrup Anne Sofie , Thomsen Gedske , Christensen Søren Tvorup , Schultz Nikolaj , Henriksen Kim , Bay-Jensen Anne-Christine , Karsdal Morten Asser 
Published: October 2010

Objective: The pathophysiology of osteoarthritis involves the whole joint and is characterized by cartilage degradation and altered subchondral bone turnover. At present, there is a need for biological models that allow investigation of the interactions between the key cellular players in bone/cartilage: osteoblasts, osteoclasts, and chondrocytes. Methods: Femoral heads from 3-, 6-, 9-, and 12-week-old female mice were isolated and cultured for 10 days in serum-free media in the absence or presence of IGF-I (100 nM) (anabolic stimulation) or OSM (10 ng/mL) + TNF-α (20 ng/mL) (catabolic stimulation). Histology on femoral heads before and after culture was performed, and the growth plate size was examined to evaluate the effects on cell metabolism. The conditioned medium was examined for biochemical markers of bone and cartilage degradation/formation. Results: Each age group represented a unique system regarding the interest of bone or cartilage metabolism. Stimulation over 10 days with OSM + TNF-α resulted in depletion of proteoglycans from the cartilage surface in all ages. Furthermore, OSM + TNF-α decreased growth plate size, whereas IGF-I increased the size. Measurements from the conditioned media showed that OSM + TNF-α increased the number of osteoclasts by approximately 80% and induced bone and cartilage degradation by approximately 1200% and approximately 2600%, respectively. Stimulation with IGF-I decreased the osteoclast number and increased cartilage formation by approximately 30%. Conclusion: Biochemical markers and histology together showed that the catabolic stimulation induced degradation and the anabolic stimulation induced formation in the femoral heads. We propose that we have established an explant whole-tissue model for investigating cell-cell interactions, reflecting parts of the processes in the pathogenesis of joint degenerative diseases.
Primary and secondary phases in copper-cobalt smelting slags from the Copperbelt Province, Zambia
Authors: Vítková M. , Ettler V. , Johan Z. , Kříbek B. , Šebek O. , Mihaljevič M. 
Published: October 2010

AbstractPyrometallurgical slags from three Cu-Co smelters (Nkana, Mufulira, Chambishi) in the Copperbelt Province, Zambia, were studied from mineralogical and chemical points of view. The slags were enriched in metals and metalloids, mainly Cu (up to 35 wt.%), Co (up to 2.4 wt.%) and As (up to 3650 ppm). The following primary phases were observed in slags: Ca-Fe silicates (clinopyroxene, olivine) and leucite, oxides (spinel-series phases), ubiquitous silicate glass and sulphide/metallic droplets of various sizes. The presence of glass and skeletal/dendritic crystal shapes indicated rapid cooling of the slag melt. Copper and cobalt were found in low concentrations in the majority of silicates (olivine, clinopyroxene) and oxides, substituting for Fe in their structures (up to 7.15 wt.% CoO in olivine, 4.11 wt.% CuO in spinel). Similarly, up to 0.91 wt.% CoO and 6.90 wt.% CuO were observed in the interstitial glass. Nevertheless, the main carriers of these metals in the slags studied were Cu sulphides (digenite, chalcocite, bornite, chalcopyrite), Co-Fe sulphides (cobaltpentlandite), Co-bearing intermetallic phases ((Fe,Co)2As) and alloys. Weathering features corresponding to the presence of secondary metal-bearing phases, such as malachite (Cu2(CO3)(OH)2), brochantite (Cu4SO4(OH)6) and sphaerocobaltite (CoCO3), were observed on the slag surfaces. They indicate that the slags studied are reactive on contact with water/atmosphere and that their environmental stability and release of potentially harmful metals and metalloids must be evaluated further.
The Mull Palaeogene dyke swarm: insights into the evolution of the Mull igneous centre and dyke-emplacement mechanisms
Authors: MacDonald R. , Bagiński B. , Upton B. G. J. , Pinkerton H. , MacInnes D. A. , MacGillivray J. C. 
Published: October 2010

AbstractGeochemical data are presented for five large Palaeogene dykes, members of the Mull swarm in southern Scotland and northern England (the Moneyacres, Hawick-Acklington, Barrmill, Muirkirk- Hartfell and Dalraith-Linburn dykes). The rock types range from basalt through andesite to dacite, although the range in individual intrusions is more restricted. The dykes are divisible into two groups; those where the compositional variation was generated by fractional crystallization of basaltic magmas, and those where it resulted from variable degrees of mixing of basaltic and silicic magmas. Several dykes are composite; the marginal facies can be more or less evolved than the central facies. The dyke magmas are thought to have originated from stratified magma chambers beneath the Mull centre and models are presented to show how the different components were derived from the chambers. Some dykes appear to have been terminated at or near the Southern Upland Fault, perhaps as a result of the chilling of early magma pulses by water in the fault. The Palaeogene dyke swarm is considerably more complex than previously recognized and has a significant input to models of the evolution of the Mull magmatic system.
Carlhintzeite, Ca2AlF7·H2O, from the Gigante granitic pegmatite, Córdoba province, Argentina: description and crystal structure
Authors: Kampf A. R. , Colombo F. , González del Tánago J. 
Published: October 2010

AbstractCarlhintzeite, Ca2AlF7·H2O, has been found at the Gigante pegmatite, Punilla Department, Córdoba Province, Argentina. It occurs as colourless prismatic crystals up to 0.8 mm long, ubiquitously twinned on {001}. Electron microprobe analyses provided the empirical formula Ca1.98Al1.02F6.24(OH)0.76·H1.62O. A crystal fragment used for the collection of structure data provided the triclinic, C1̄ cell: a = 9.4227(4), b = 6.9670(5), c = 9.2671(7) Å, α = 90.974(6), β = 104.802(5), γ = 90.026(6)°, V = 558.08(7) Å3 and Z = 4. The crystal structure, solved by direct methods and refined to R1 = 0.0322 for 723 Fo > 4σF reflections, is made up of linkages of AlF6 octahedra, CaF8 polyhedra and CaF6(H2O)2 polyhedra. The AlF6 octahedra are isolated from one another, but share polyhedral elements with Ca polyhedra. Most notably, the Al1 octahedron shares trans faces with two CaF8 polyhedra and the Al2 octahedron shares trans edges with two CaF6(H2O)2 polyhedra. The linkage of the Ca polyhedra alone can be described as a framework in which edge-sharing chains along b are cross-linked by edge-sharing. Edge-sharing chains of Ca polyhedra along b in the carlhintzeite structure are similar to those along c in the structures of gearksutite, CaAlF4(OH)·(H2O), and prosopite, CaAl2F4(OH)4.
The experimental replacement of ilmenite by rutile in HCl solutions
Authors: Janssen A. , Putnis A. , Geisler T. , Putnis C. V. 
Published: October 2010

AbstractTo determine the mechanism of acid-leaching of ilmenite to ultimately forming rutile, we have carried out an experimental study of ilmenite alteration in autoclaves at 150ºC in HCl solutions. The resulting products were studied by X-ray diffraction, scanning electron microscopy, electron microprobe and Raman spectroscopy. In some experiments the solution was initially enriched in 18O and the distribution of the isotope in the alteration products mapped from the frequency shift of cation oxygen stretching bands in the Raman spectra. The alteration begins at the original ilmenite crystal surface and has also taken place along an intricate branching network of fractures in the ilmenite, generated by the reaction. Element-distribution maps and chemical analyses of the reaction product within the fractures show marked depletion in Fe and Mn and a relative enrichment of Ti. Chemical analyses however, do not correspond to any stoichiometric composition, and may represent mixtures of TiO2 and Fe2O3. The fracturing is possibly driven by volume changes associated with dissolution of ilmenite and simultaneous reprecipitation of the product phases (including rutile) from an interfacial solution along an inward moving dissolution-reprecipitation front. Raman spectroscopy shows that the 18O is incorporated in the rutile structure during the recrystallization. Throughout the alteration process, the original morphology of the ilmenite is preserved although the product is highly porous. The rutile inherits crystallographic information from the parent ilmenite, resulting in a triply-twinned rutile microstructure. The results indicate that the ilmenite is replaced directly by rutile without the formation of any intermediate reaction products. The reaction is described in terms of an interface-coupled dissolution-precipitation mechanism.
Major- and trace-element composition of REE-rich turkestanite from peralkaline granites of the Morro Redondo Complex, Graciosa Province, south Brazil
Authors: Vilalva F. C. J. , Vlach S. R. F. 
Published: October 2010

AbstractTurkestanite, a rare Th- and REE-bearing cyclosilicate in the ekanite–steacyite group was found in evolved peralkaline granitesfrom the Morro Redondo Complex, south Brazil. It occurswith quartz, alkali feldspar and an unnamed Y-bearing silicate. Electron microprobe analysis indicates relatively homogeneous compositions with maximum ThO2, Na2O and K2O contentsof 22.4%, 2.93% and 3.15 wt.%, respectively, and significant REE2O3 abundances(5.21 to 11.04 wt.%). The REE patterns show enrichment of LREE over HREE, a strong negative Eu anomaly and positive Ce anomaly, the latter in the most transformed crystals. Laser ablation inductively coupled plasma mass spectrometry trace element patterns display considerable depletions in Nb, Zr, Hf, Ti and Li relative to whole-rock sample compositions. Observed compositional variations suggest the influence of coupled substitution mechanisms involving steacyite, a Na-dominant analogue of turkestanite, iraqite, a REE-bearing end-member in the ekanite–steacyite group, ekanite and some theoretical end-members. Turkestanite crystals were interpreted as having precipitated during post-magmatic stages in the presence of residual HFSE-rich fluidscarrying Ca, the circulation of which wasenhanced by deformational events.
Fluid-mineral interactions and constraints on monazite alteration during metamorphism
Authors: Budzyń B. , Hetherington C. J. , Williams M. L. , Jercinovic M. J. , Michalik M. 
Published: October 2010

AbstractClasts of metamorphosed Cadomian granites from the ∼50—60 Ma Carpathian flysch in Gródek near the Rożnowskie Lake (Silesian Unit, SE Poland) are studied. They are considered to represent the Silesian Ridge, one of the hypothetical, currently unexposed source areas that supplied Carpathian sedimentary basins with clastic material. The gneisses preserve several examples of corona textures that include cores of primary monazite surrounded by polygonal grains of secondary apatite with thorianite inclusions, with intermediate zones of lamellar grains of secondary monazite and outermost rims of clay minerals, or various combinations thereof. Preservation of the complete textures is rare with polygonal apatite with thorianite inclusions, lamellar grains of monazite and clay minerals being particularly prevalent. Locally, polygonal apatite with thorianite inclusions surrounded by allanite and REE-epidote corona with a bastnasite-synchysite phase occurs also. The textures observed developed during primary monazite breakdown and replacement by secondary minerals. The variation in reaction products indicates that alteration was strictly dependent on the local chemical system.