bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regaining the Woodward–Hoffmann rules for chelotropic reactions via conceptual DFT
Authors: Jaque Pablo , Correa José V. , De Proft Frank , Toro-Labbé Alejandro , Geerlings Paul 
Published: August 2010

In our continuous effort to retrieve the Woodward–Hoffmann rules from conceptual density functional theory (DFT), we have examined the last type of pericyclic reactions, i.e., chelotropic reactions. Both the initial hardness response and the dual descriptor have been investigated to predict the allowed and forbidden character for the addition of SO2to butadiene (4n system) and 1,3,5-hexatriene (4n + 2 system). It is shown that with both electronic descriptors, the conrotatory/disrotatory mode for the linear and nonlinear mechanisms are retrieved based on a density-only approach, free from consideration of orbital and (or) wave function symmetry. The dual descriptor moreover reveals that stabilizing interactions are presented only for the linear path, which can be considered as an overall favourable mechanism for a chelotropic reaction.
Contrasting effects of intervention with ETAand ETBreceptor antagonists in hypertension induced by angiotensin II and high-salt dietThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.
Authors: Boesen Erika I. , Pollock Jennifer S. , Pollock David M. 
Published: August 2010

Endothelin (ET) receptor antagonists are antihypertensive and renoprotective in angiotensin II (AngII)-induced hypertension if administered when AngII infusion commences, but their effects on established hypertension are poorly understood. We therefore tested the effects of intervening with an ETA(ABT-627) or ETB(A-192621) receptor antagonist after establishing hypertension with AngII (65 ng/min s.c.) plus 8% NaCl diet (AngII–HS) in rats. Prior to administration of ABT-627, AngII–HS and AngII–HS plus ABT-627 groups displayed robust hypertension (mean arterial pressure (MAP), 170 ± 5 and 165 ± 5 mm Hg versus 110 ± 3 mm Hg in normal salt control rats at day 7, P < 0.05). Administering ABT-627 from day 8 of AngII–HS treatment prevented further rises in MAP (168 ± 5 and 191 ± 3 mm Hg at day 13 in AngII–HS plus ABT-627 and AngII–HS, P < 0.001), without blunting the significant increases in urinary protein (19-fold), albumin (25-fold), or MCP-1 excretion (6- to 8-fold) or the reduction in creatinine clearance. Administering A-192621 from day 8 mildly exacerbated AngII–HS induced hypertension (P < 0.05 for AngII–HS versus AngII–HS plus A-192621 on days 11 and 12 only) and reduced plasma nitrite/nitrate concentration (P < 0.05), without affecting proteinuria, albuminuria, or creatinine clearance. These results confirm the importance of ETAreceptor signaling in maintaining AngII–HS hypertension and suggest that including ETBreceptor blockade in therapeutic approaches to treating hypertension would be ineffective or even counterproductive.
Chromatin Remodeling Is Required for Gene Reactivation after Decitabine-Mediated DNA Hypomethylation
Authors: Si Jiali , Boumber Yanis A. , Shu Jingmin , Qin Taichun , Ahmed Saira , He Rong , Jelinek Jaroslav , Issa Jean-Pierre J. 
Published: August 2010

Abstract
The DNA hypomethylating drug decitabine (DAC) reactivates silenced gene expression in cancer and is approved for the treatment of the myelodysplastic syndrome. Gene reactivation after DAC is variable and incompletely understood. Here, we established a cell line system (YB5) derived from the SW48 colon cancer cell line to study DAC-induced reactivation. YB5 contains a hypermethylated cytomegalovirus promoter driving green fluorescent protein (GFP), and the locus is transcriptionally silent. GFP reexpression can be achieved by DAC treatment, but the expression level of individual cells is heterogeneous. DAC-treated YB5 cells were separated into GFP-positive and GFP-negative subpopulations. By comparing DAC-treated sorted GFP-positive and GFP-negative cells, we found that their methylation levels were similarly decreased but that histone modifications and histone H3 densities were remarkably different. Despite a similar degree of (incomplete) DNA hypomethylation, GFP-positive cells reverted to an active chromatin structure marked by higher H3K9 acetylation, lower H3K27 trimethylation, and lower promoter nucleosome density. GFP-negative cells had histone modifications and promoter nucleosome density, similar to parental cells. On DAC withdrawal, gradual resilencing and remethylation occurred in both GFP-positive and GFP-negative cells, and the resilencing correlated with a gradual increase in nucleosome occupancy in GFP-positive cells. These data show that hypomethylation alone after DAC is insufficient for gene expression induction, and that chromatin resetting to an active state including nucleosome eviction is required for activation of protein expression. Our findings suggest that gene expression is the key in optimizing DAC treatment strategies in the clinic. Cancer Res; 70(17); 6968–77. ©2010 AACR.
miR-335 Directly Targets Rb1 (pRb/p105) in a Proximal Connection to p53-Dependent Stress Response
Authors: Scarola Michele , Schoeftner Stefan , Schneider Claudio , Benetti Roberta 
Published: August 2010

Abstract
Loss-of-function mutations of retinoblastoma family (Rb) proteins drive tumorigenesis by overcoming barriers to cellular proliferation. Consequently, factors modulating Rb function are of great clinical import. Here, we show that miR-335 is differentially expressed in human cancer cells and that it tightly regulates the expression of Rb1 (pRb/p105) by specifically targeting a conserved sequence motif in its 3′ untranslated region. We found that by altering Rb1 (pRb/p105) levels, miR-335 activates the p53 tumor suppressor pathway to limit cell proliferation and neoplastic cell transformation. DNA damage elicited an increase in miR-335 expression in a p53-dependent manner. miR-335 and p53 cooperated in a positive feedback loop to drive cell cycle arrest. Together, these results indicate that miR-335 helps control proliferation by balancing the activities of the Rb and p53 tumor suppressor pathways. Further, they establish that miR-335 activation plays an important role in the induction of p53-dependent cell cycle arrest after DNA damage. Cancer Res; 70(17); 6925–33. ©2010 AACR.
Recruitment of Phosphorylated NPM1 to Sites of DNA Damage through RNF8-Dependent Ubiquitin Conjugates
Authors: Koike Ayaka , Nishikawa Hiroyuki , Wu Wenwen , Okada Yukinori , Venkitaraman Ashok R. , Ohta Tomohiko 
Published: August 2010

Abstract
Protein accumulation at DNA double-strand breaks (DSB) is essential for genome stability; however, the mechanisms governing these events are not fully understood. Here, we report a new role for the nucleophosmin protein NPM1 in these mechanisms. Thr199-phosphorylated NPM1 (pT199-NPM1) is recruited to nuclear DNA damage foci induced by ionizing radiation (IR). Foci formation is impaired by depletion of the E3 ubiquitin ligases RNF8 and RNF168 or the E2 Ubc13, and pT199-NPM1 binds to Lys63-linked ubiquitin polymers in vitro. Thus, phosphorylated NPM1 may interact with RNF8-dependent ubiquitin conjugates at sites of DNA damage. The interaction was found to rely on T199 phosphorylation, an acidic tract, and an adjacent ubiquitin-interacting motif–like domain. Depletion of the breast cancer suppressor BRCA1 or its partner, RAP80, enhanced IR-induced NPM1 foci and prolonged persistence of the foci, possibly implicating BRCA1 in pT199-NPM1 action and dynamics. Replacement of endogenous NPM1 with its nonphosphorylable T199A mutant prolonged persistence of IR-induced RAD51 foci accompanied by unrepaired DNA damage. Collectively, our findings suggest that phosphorylated NPM1 is a novel component in DSB repair that is recruited by ubiquitin conjugates downstream of RNF8 and RNF168. Cancer Res; 70(17); 6746–56. ©2010 AACR.
Combination of Two Insulin-Like Growth Factor-I Receptor Inhibitory Antibodies Targeting Distinct Epitopes Leads to an Enhanced Antitumor Response
Authors: Dong Jianying , Demarest Stephen J. , Sereno Arlene , Tamraz Susan , Langley Emma , Doern Adam , Snipas Tracey , Perron Keli , Joseph Ingrid , Glaser Scott M. , Ho Steffan N. , Reff Mitchell E. , Hariharan Kandasamy 
Published: August 2010

Abstract
The insulin-like growth factor-I receptor (IGF-IR) is a cell surface receptor tyrosine kinase that mediates cell survival signaling and supports tumor progression in multiple tumor types. We identified a spectrum of inhibitory IGF-IR antibodies with diverse binding epitopes and ligand-blocking properties. By binding distinct inhibitory epitopes, two of these antibodies, BIIB4 and BIIB5, block both IGF-I and IGF-II binding to IGF-IR using competitive and allosteric mechanisms, respectively. Here, we explored the inhibitory effects of combining BIIB4 and BIIB5. In biochemical assays, the combination of BIIB4 and BIIB5 improved both the potency and extent of IGF-I and IGF-II blockade compared with either antibody alone. In tumor cells, the combination of BIIB4 and BIIB5 accelerated IGF-IR downregulation and more efficiently inhibited IGF-IR activation as well as downstream signaling, particularly AKT phosphorylation. In several carcinoma cell lines, the antibody combination more effectively inhibited ligand-driven cell growth than either BIIB4 or BIIB5 alone. Notably, the enhanced tumor growth–inhibitory activity of the BIIB4 and BIIB5 combination was much more pronounced at high ligand concentrations, where the individual antibodies exhibited substantially reduced activity. Compared with single antibodies, the BIIB4 and BIIB5 combination also significantly further enhanced the antitumor activity of the epidermal growth factor receptor inhibitor erlotinib and the mTOR inhibitor rapamycin. Moreover, in osteosarcoma and hepatocellular carcinoma xenograft models, the BIIB4 and BIIB5 combination significantly reduced tumor growth to a greater degree than each single antibody. Taken together, our results suggest that targeting multiple distinct inhibitory epitopes on IGF-IR may be a more effective strategy of affecting the IGF-IR pathway in cancer. Mol Cancer Ther; 9(9); 2593–604. ©2010 AACR.
Association of Human Cytochrome P450 1A1 (CYP1A1) and Sulfotransferase 1A1 (SULT1A1) Polymorphisms with Differential Metabolism and Cytotoxicity of Aminoflavone
Authors: Zheng Qiang , Sha Xianyi , Liu Jiansheng , Heath Elisabeth , LoRusso Patricia , Li Jing 
Published: August 2010

AbstractAminoflavone (AF), a clinically investigational novel anticancer agent, requires sequential metabolic activation by CYP1A1 and SULT1A1 to exert its antitumor activities. The purpose of this study was to determine the functional significance of common polymorphisms of human CYP1A1 and SULT1A1 on the metabolism and cytotoxicity of AF. To this end, Chinese Hamster V79 cells were genetically engineered to stably express human CYP1A1*1 (wild-type), CYP1A1*2C (I462V), or CYP1A1*4 (T461N) and coexpress human CYP1A1*1 with human SULT1A1*1 (wild-type), SULT1A1*2 (R213H), or SULT1A1*3 (M223V). The metabolism and cytotoxicity of AF were evaluated in these cellular models. All common variants of CYP1A1 and SULT1A1 were actively involved in the metabolic activation of AF, but with a varying degree of activity. Whereas CYP1A1 I462V variant exhibited a superior activity (mainly caused by a significantly higher Vmax) for hydroxylations of AF, expression of different CYP1A1 variants did not confer cell differential sensitivity to AF. The cells coexpressing CYP1A1*1 with SULT1A1*1, SULT1A1*2, or SULT1A1*3 displayed SULT1A1 allele-specific sensitivity to AF: SULT1A1*3 exhibited the highest sensitivity (IC50, 0.01 μmol/L), followed by SULT1A1*1 (IC50, 0.5 μmol/L), and SULT1A1*2 showed the lowest sensitivity (IC50, 4.4 μmol/L). These data suggest that the presence of low-activity SULT1A1*2 may predict poor response to AF, whereas the presence of high-activity CYP1A1/SULT1A1 alleles, especially combination of CYP1A1*2C and SULT1A1*3 or SULT1A1*1, may be beneficial to patients receiving AF. The present study provides a foundation for future clinical investigations of potential genetic biomarkers that may enable selection of patients for the greatest potential benefit from AF treatment. Mol Cancer Ther; 9(10); 2803–13. ©2010 AACR.
Vascular Reactivity and Flow Characteristics of Radial Artery and Long Saphenous Vein Coronary Bypass Grafts
Authors: Webb Carolyn M. , Moat Neil E. , Chong Chee F. , Collins Peter 
Published: August 2010

Background—Radial artery (RA) aortocoronary bypass grafts anastomosed to a branch of the circumflex coronary artery have significantly better patency rates than saphenous vein (SV) grafts at 5 years, but the physiological characteristics and mechanisms involved are not clearly defined. We compared RA and SV graft vasomotor and flow responses to endothelium-dependent and -independent stimuli 5 years after surgery in a subgroup of patients enrolled in the Radial artery versus Saphenous Vein Patency (RSVP) trial.Methods and Results—Twenty-seven patients were included in the study (RA, n=15; SV, n=12). Graft blood flow was calculated from flow velocity, measured by intracoronary Doppler, and luminal diameter, measured by quantitative coronary angiography, before and after intragraft infusions of adenosine, acetylcholine, and isosorbide dinitrate. At rest, RA luminal diameters were significantly smaller than SV luminal diameters (P=0.029), blood flow velocity was greater in RA than SV (P=0.008), and volume blood flows were similar. RA but not SV dilated in response to adenosine and isosorbide dinitrate (allP<0.05, RA versus SV, percent change from baseline), and there were no significant differences in the diameter responses to acetylcholine. Volume blood flow responses to adenosine, acetylcholine, and isosorbide dinitrate were comparable.Conclusions—Five years after surgery, RA coronary bypass conduits grafted to a single coronary territory demonstrated preserved flow-mediated vasodilatation, whereas SV grafts did not. Our results may provide insight into the more favorable patency of RA grafts over SV grafts.Clinical Trial Registration—http://www.clinicaltrials.gov. Unique identifier: NCT00139399.
Effects of disinhibitory transcutaneous electrical nerve stimulation and therapeutic exercise on sagittal plane peak knee kinematics and kinetics in people with knee osteoarthritis during gait: a randomized controlled trial
Authors: Pietrosimone Brian G , Saliba Susan A , Hart Joseph M , Hertel Jay , Kerrigan D. Casey , Ingersoll Christopher D 
Published: August 2010

Objective: To determine whether sensory transcutaneous electrical nerve stimulation (TENS) augmented with therapeutic exercise and worn for daily activities for four weeks would alter peak gait kinetics and kinematics, compared with placebo electrical stimulation and exercise, and exercise only. Design: Randomized controlled trial. Setting: Motion analysis laboratory. Subjects: Thirty-six participants with radiographically assessed knee osteoarthritis and volitional quadriceps activation below 90% were randomly assigned to electrical stimulation, placebo and comparison (exercise-only) groups. Interventions: Participants in all three groups completed a four-week quadriceps strengthening programme directed by an experienced rehabilitation clinician. Active electrical stimulation units and placebo units were worn in the electrical stimulation and placebo groups throughout the rehabilitation sessions as well as during all activities of daily living. Main measures: Peak external knee flexion moment and angle during stance phase were analysed at a comfortable walking speed before and after the intervention. Findings: Comfortable walking speed increased for all groups over time (TENS 1.16 ± 0.15 versus 1.32 ± 0.16 m/s; placebo 1.21 ± 0.34 versus 1.3 ± 0.24 m/s; comparison 1.27 ± 0.18 versus 1.5 ± 0.14 m/s), yet no group differences in speed were found. No differences were found for peak flexion moment or angle between groups overtime. Conclusions: TENS in conjunction with therapeutic exercise does not seem to affect peak flexion moment and angle during stance over a four-week period in participants with tibiofemoral osteoarthritis.
LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis
Authors: Sumida Hayakazu , Noguchi Kyoko , Kihara Yasuyuki , Abe Manabu , Yanagida Keisuke , Hamano Fumie , Sato Shinichi , Tamaki Kunihiko , Morishita Yasuyuki , Kano Mitsunobu R. , Iwata Caname , Miyazono Kohei , Sakimura Kenji , Shimizu Takao , Ishii Satoshi 
Published: August 2010

AbstractLysophosphatidic acid (LPA) is a potent lipid mediator with a wide variety of biological actions mediated through G protein-coupled receptors (LPA1-6). LPA4 has been identified as a G13 protein-coupled receptor, but its physiological role is unknown. Here we show that a subset of LPA4-deficient embryos did not survive gestation and displayed hemorrhages and/or edema in many organs at multiple embryonic stages. The blood vessels of bleeding LPA4-deficient embryos were often dilated. The recruitment of mural cells, namely smooth muscle cells and pericytes, was impaired. Consistently, Matrigel plug assays showed decreased mural cell coverage of endothelial cells in the neovessels of LPA4-deficient adult mice. In situ hybridization detected Lpa4 mRNA in the endothelium of some vasculatures. Similarly, the lymphatic vessels of edematous embryos were dilated. These results suggest that LPA4 regulates establishment of the structure and function of blood and lymphatic vessels during mouse embryogenesis. Considering the critical role of autotaxin (an enzyme involved in LPA production) and Gα13 in vascular development, we suggest that LPA4 provides a link between these 2 molecules.
FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells
Authors: Liu Fei , Lee Jae Y. , Wei Huijun , Tanabe Osamu , Engel James D. , Morrison Sean J. , Guan Jun-Lin 
Published: August 2010

Abstract
Little is known about whether autophagic mechanisms are active in hematopoietic stem cells (HSCs) or how they are regulated. FIP200 (200-kDa FAK-family interacting protein) plays important roles in mammalian autophagy and other cellular functions, but its role in hematopoietic cells has not been examined. Here we show that conditional deletion of FIP200 in hematopoietic cells leads to perinatal lethality and severe anemia. FIP200 was cell-autonomously required for the maintenance and function of fetal HSCs. FIP200-deficient HSC were unable to reconstitute lethally irradiated recipients. FIP200 ablation did not result in increased HSC apoptosis, but it did increase the rate of HSC proliferation. Consistent with an essential role for FIP200 in autophagy, FIP200-null fetal HSCs exhibited both increased mitochondrial mass and reactive oxygen species. These data identify FIP200 as a key intrinsic regulator of fetal HSCs and implicate a potential role for autophagy in the maintenance of fetal hematopoiesis and HSCs.
Characterization and functional analysis of seven flagellin genes in Rhizobium leguminosarum bv. viciae. Characterization of R. leguminosarum flagellins
Authors: Tambalo Dinah D , Bustard Denise E , Del Bel Kate L , Koval Susan F , Khan Morgan F , Hynes Michael F 
Published: August 2010

Abstract

Background

Rhizobium leguminosarum bv. viciae establishes symbiotic nitrogen fixing partnerships with plant species belonging to the Tribe Vicieae, which includes the genera Vicia, Lathyrus, Pisum and Lens. Motility and chemotaxis are important in the ecology of R. leguminosarum to provide a competitive advantage during the early steps of nodulation, but the mechanisms of motility and flagellar assembly remain poorly studied. This paper addresses the role of the seven flagellin genes in producing a functional flagellum.

Results

R. leguminosarum strains 3841 and VF39SM have seven flagellin genes (flaA, flaB, flaC, flaD, flaE, flaH, and flaG), which are transcribed separately. The predicted flagellins of 3841 are highly similar or identical to the corresponding flagellins in VF39SM. flaA, flaB, flaC, and flaD are in tandem array and are located in the main flagellar gene cluster. flaH and flaG are located outside of the flagellar/motility region while flaE is plasmid-borne. Five flagellin subunits (FlaA, FlaB, FlaC, FlaE, and FlaG) are highly similar to each other, whereas FlaD and FlaH are more distantly related. All flagellins exhibit conserved amino acid residues at the N- and C-terminal ends and are variable in the central regions. Strain 3841 has 1-3 plain subpolar flagella while strain VF39SM exhibits 4-7 plain peritrichous flagella. Three flagellins (FlaA/B/C) and five flagellins (FlaA/B/C/E/G) were detected by mass spectrometry in the flagellar filaments of strains 3841 and VF39SM, respectively. Mutation of flaA resulted in non-motile VF39SM and extremely reduced motility in 3841. Individual mutations of flaB and flaC resulted in shorter flagellar filaments and consequently reduced swimming and swarming motility for both strains. Mutant VF39SM strains carrying individual mutations in flaD, flaE, flaH, and flaG were not significantly affected in motility and filament morphology. The flagellar filament and the motility of 3841 strains with mutations in flaD and flaG were not significantly affected while flaE and flaH mutants exhibited shortened filaments and reduced swimming motility.

Conclusion
The results obtained from this study demonstrate that FlaA, FlaB, and FlaC are major components of the flagellar filament while FlaD and FlaG are minor components for R. leguminosarum strains 3841 and VF39SM. We also observed differences between the two strains, wherein FlaE and FlaH appear to be minor components of the flagellar filaments in VF39SM but these flagellin subunits may play more important roles in 3841. This paper also demonstrates that the flagellins of 3841 and VF39SM are possibly glycosylated.
Determination of reference genes for circadian studies in different tissues and mouse strains
Authors: Kosir Rok , Acimovic Jure , Golicnik Marko , Perse Martina , Majdic Gregor , Fink Martina , Rozman Damjana 
Published: August 2010

Abstract

Background
Circadian rhythms have a profound effect on human health. Their disruption can lead to serious pathologies, such as cancer and obesity. Gene expression studies in these pathologies are often studied in different mouse strains by quantitative real time polymerase chain reaction (qPCR). Selection of reference genes is a crucial step of qPCR experiments. Recent studies show that reference gene stability can vary between species and tissues, but none has taken circadian experiments into consideration.

Results
In the present study the expression of ten candidate reference genes (Actb, Eif2a, Gapdh, Hmbs, Hprt1, Ppib, Rn18s, Rplp0, Tbcc and Utp6c) was measured in 131 liver and 97 adrenal gland samples taken from three mouse strains (C57BL/6JOlaHsd, 129Pas plus C57BL/6J and Crem KO on 129Pas plus C57BL/6J background) every 4 h in a 24 h period. Expression stability was evaluated by geNorm and NormFinder programs. Differences in ranking of the most stable reference genes were observed both between individual mouse strains as well as between tissues within each mouse strain. We show that selection of reference gene (Actb) that is often used for analyses in individual mouse strains leads to errors if used for normalization when different mouse strains are compared. We identified alternative reference genes that are stable in these comparisons.

Conclusions
Genetic background and circadian time influence the expression stability of reference genes. Differences between mouse strains and tissues should be taken into consideration to avoid false interpretations. We show that the use of a single reference gene can lead to false biological conclusions. This manuscript provides a useful reference point for researchers that search for stable reference genes in the field of circadian biology.