bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYC stimulates EZH2 expression by repression of its negative regulator miR-26a
Authors: Sander Sandrine , Bullinger Lars , Klapproth Kay , Fiedler Katja , Kestler Hans A. , Barth Thomas F. E. , Möller Peter , Stilgenbauer Stephan , Pollack Jonathan R. , Wirth Thomas 
Published: August 2008

Abstract
The MYC oncogene, which is commonly mutated/amplified in tumors, represents an important regulator of cell growth because of its ability to induce both proliferation and apoptosis. Recent evidence links MYC to altered miRNA expression, thereby suggesting that MYC-regulated miRNAs might contribute to tumorigenesis. To further analyze the impact of MYC-regulated miRNAs, we investigated a murine lymphoma model harboring the MYC transgene in a Tet-off system to control its expression. Microarray-based miRNA expression profiling revealed both known and novel MYC targets. Among the miRNAs repressed by MYC, we identified the potential tumor suppressor miR-26a, which possessed the ability to attenuate proliferation in MYC-dependent cells. Interestingly, miR-26a was also found to be deregulated in primary human Burkitt lymphoma samples, thereby probably being of clinical relevance. Although today only few miRNA targets have been identified in human disease, we could show that ectopic expression of miR-26a influenced cell cycle progression by targeting the bona fide oncogene EZH2, a Polycomb protein and global regulator of gene expression yet unknown to be regulated by miRNAs. Thus, in addition to directly targeting protein-coding genes, MYC modulates genes important to oncogenesis via deregulation of miRNAs, thereby vitally contributing to MYC-induced lymphomagenesis.
Thalidomide and rituximab in Waldenstrom macroglobulinemia
Authors: Treon Steven P. , Soumerai Jacob D. , Branagan Andrew R. , Hunter Zachary R. , Patterson Christopher J. , Ioakimidis Leukothea , Briccetti Frederick M. , Pasmantier Mark , Zimbler Harvey , Cooper Robert B. , Moore Maria , Hill John , Rauch Alan , Garbo Lawrence , Chu Luis , Chua Cynthia , Nantel Stephen H. , Lovett David R. , Boedeker Hans , Sonneborn Henry , Howard John , Musto Paul , Ciccarelli Bryan T. , Hatjiharissi Evdoxia , Anderson Kenneth C. 
Published: August 2008

Abstract
Thalidomide enhances rituximab-mediated, antibody-dependent, cell-mediated cytotoxicity. We therefore conducted a phase 2 study using thalidomide and rituximab in symptomatic Waldenstrom macroglobulinemia (WM) patients naive to either agent. Intended therapy consisted of daily thalidomide (200 mg for 2 weeks, then 400 mg for 50 weeks) and rituximab (375 mg/m2 per week) dosed on weeks 2 to 5 and 13 to 16. Twenty-five patients were enrolled, 20 of whom were untreated. Responses were complete response (n = 1), partial response (n = 15), and major response (n = 2), for overall and major response rate of 72% and 64%, respectively, on an intent-to-treat basis. Median serum IgM decreased from 3670 to 1590 mg/dL (P < .001), whereas median hematocrit rose from 33.0% to 37.6% (P = .004) at best response. Median time to progression for responders was 38 months. Peripheral neuropathy to thalidomide was the most common adverse event. Among 11 patients experiencing grade 2 or greater neuropathy, 10 resolved to grade 1 or less at a median of 6.7 months. Thalidomide in combination with rituximab is active and produces long-term responses in WM. Lower doses of thalidomide (ie, ≤ 200 mg/day) should be considered given the high frequency of treatment-related neuropathy in this patient population. This trial is registered at www.clinicaltrials.gov as #NCT00142116.
Biologic properties and enucleation of red blood cells from human embryonic stem cells
Authors: Lu Shi-Jiang , Feng Qiang , Park Jennifer S. , Vida Loyda , Lee Bao-Shiang , Strausbauch Michael , Wettstein Peter J. , Honig George R. , Lanza Robert 
Published: August 2008

AbstractHuman erythropoiesis is a complex multistep process that involves the differentiation of early erythroid progenitors to mature erythrocytes. Here we show that it is feasible to differentiate and mature human embryonic stem cells (hESCs) into functional oxygen-carrying erythrocytes on a large scale (1010-1011 cells/6-well plate hESCs). We also show for the first time that the oxygen equilibrium curves of the hESC-derived cells are comparable with normal red blood cells and respond to changes in pH and 2,3-diphosphoglyerate. Although these cells mainly expressed fetal and embryonic globins, they also possessed the capacity to express the adult β-globin chain on further maturation in vitro. Polymerase chain reaction and globin chain specific immunofluorescent analysis showed that the cells increased expression of β-globin (from 0% to > 16%) after in vitro culture. Importantly, the cells underwent multiple maturation events, including a progressive decrease in size, increase in glycophorin A expression, and chromatin and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to more than 60% of the cells generating red blood cells with a diameter of approximately 6 to 8 μm. The results show that it is feasible to differentiate and mature hESCs into functional oxygen-carrying erythrocytes on a large scale.
Transhiatal esophagectomy in a high volume institution
Authors: Davies Andrew R , Forshaw Matthew J , Khan Aadil A , Noorani Alia S , Patel Vanash M , Strauss Dirk C , Mason Robert C 
Published: August 2008

Abstract

Background
The optimal operative approach for carcinoma at the lower esophagus and esophagogastric junction remains controversial. The aim of this study was to assess a single unit experience of transhiatal esophagectomy in an era when the use of systemic oncological therapies has increased dramatically.

Study Design
Between January 2000 and November 2006, 215 consecutive patients (182 males, 33 females, median age = 65 years) underwent transhiatal esophagectomy; invasive malignancy was detected preoperatively in 188 patients. 90 patients (42%) received neoadjuvant chemotherapy. Prospective data was obtained for these patients and cross-referenced with cancer registry survival data.

Results
There were 2 in-hospital deaths (0.9%). Major complications included: respiratory complications in 65 patients (30%), cardiovascular complications in 31 patients (14%) and clinically apparent anastomotic leak in 12 patients (6%). Median length of hospital stay was 14 days. The radicality of resection was inversely related to T stage: an R0 resection was achieved in 98–100% of T0/1 tumors and only 14% of T4 tumors. With a median follow up of 26 months, one and five year survival rates were estimated at 81% and 48% respectively.

Conclusion
Transhiatal esophagectomy is an effective operative approach for tumors of the infracarinal esophagus and the esophagogastric junction. It is associated with low mortality and morbidity and a five survival rate of nearly 50% when combined with neoadjuvant chemotherapy.
Nanoscience and nanotechnology: The bottom-up construction of molecular devices and machines
Authors: Balzani Vincenzo 
Published: August 2008

AbstractThe bottom-up approach to miniaturization, which starts from molecules to build up nanostructures, enables the extension of the macroscopic concepts of a device and a machine to molecular level. Molecular-level devices and machines operate via electronic and/or nuclear rearrangements and, like macroscopic devices and machines, need energy to operate and signals to communicate with the operator. Examples of molecular-level photonic wires, plug/socket systems, light-harvesting antennas, artificial muscles, molecular lifts, and light-powered linear and rotary motors are illustrated. The extension of the concepts of a device and a machine to the molecular level is of interest not only for basic research, but also for the growth of nanoscience and the development of nanotechnology.
Chemoselective reactions: Toward the synthesis of biologically active natural products with anticancer activities
Authors: Reymond Sébastien , Ferrié Laurent , Guérinot Amandine , Capdevielle Patrice , Cossy Janine 
Published: August 2008

Abstract
Leucascandrolide A and migrastatin were synthesized efficiently by using chemoselective reactions such as olefin metatheses. The use of an iron-catalyzed cross-coupling reaction overcame difficulties encountered with palladium-catalyzed processes in our synthetic approach toward spirangien A.
Multitarget drugs: Focus on the NO-donor hybrid drugs
Authors: Gasco Alberto , Boschi Donatella , Chegaev Konstantin , Cena Clara , Di Stilo Antonella , Fruttero Roberta , Lazzarato Loretta , Rolando Barbara , Tosco Paolo 
Published: August 2008

Abstract
The article addresses the design of multitarget drugs, namely, compounds capable of interacting with more than one target simultaneously. These agents could be useful tools in the therapy of complex diseases such as cardiovascular and inflammatory diseases. An interesting case of multitarget compounds are nitric oxide (NO)-donor hybrids, structures which combine the physiological properties of NO with those of a lead drug. In particular, the authors discuss the symbiotic approach used to design NO-donor nonsteroidal anti-inflammatory drugs (NO-NSAIDs) and NO-donor antioxidants. The former could be useful agents in the treatment of anti-inflammatory diseases being devoid of gastro- and cardiotoxicity, the latter could be a valid approach to the treatment of many cardiovascular diseases.
Oxidation-responsiveness of nanomaterials for targeting inflammatory reactions
Authors: Khutoryanskiy Vitaliy V. , Tirelli Nicola 
Published: August 2008

Abstract
Oxidation is an almost ubiquitous feature of inflammatory reactions. We discuss the development of nanocarriers that respond to the presence of oxidants with profound physical reorganization, which could in perspective allow their use for delivering anti-inflammatory principles in an inflammation-responsive fashion. We also present a study demonstrating that the response of polysulfide nanoparticles has a bulk character, i.e., the odixation reactions happen homogeneously throughout the nanoparticles, and not interfacially.
Synthesis of substituted conjugated polymers: Tuning properties by functionalization
Authors: Farinola Gianluca M. , Babudri Francesco , Cardone Antonio , Hassan Omar Omar , Naso Francesco 
Published: August 2008

AbstractThe review addresses features of special interest concerning two classes of functionalized semiconducting polymers: poly(aryleneethynylene)s (PAEs) bearing biomolecules as chiral nonracemic pendant groups and poly(phenylenevinylene)s (PPVs), which are fluorinated in various positions of the repeating units. Molecular design and choice of specific substituents, synthetic protocols, and the effect of functionalization on properties of the polymers both in solution and in the solid state are discussed.
Total synthesis of cytotoxic marine macrolides: Callipeltoside A, aurisides A and B, and dolastatin 19
Authors: Paterson Ian , Findlay Alison D. 
Published: August 2008

Abstract
Synthetic studies pertaining to a novel class of structurally related glycosidic 14-membered macrolides of marine origin are reported. The evolution of a versatile aldol-based strategy that culminated in the total syntheses of callipeltoside A and aurisides A and B is detailed. Using a combination of biogenetic considerations and conformational analysis, a revised stereochemical assignment for the related polyketide dolastatin 19 was proposed and validated by total synthesis.
Discovery of leishmanicidal agents from medicinal plants
Authors: Atta-ur-Rahman  , Samreen  , Atia-tul-Wahab  , Choudhary M. Iqbal 
Published: August 2008

Abstract
Antileishmanial activity of several classes of natural compounds was evaluated by using an in vitro parasitic assay model. This has led to the discovery of new antileishmanial agents with potential to be useful in the treatment of visceral and cutaneous leishmaniasis.
Chemical wizardry? The generation of diversity in terpenoid biosynthesis
Authors: Allemann Rudolf K. 
Published: August 2008

Abstract
Terpene synthases catalyze the conversion of linear prenyl-diphosphates to a multitude of hydrocarbon skeletons with often high regio- and stereoselectivity. These remarkable enzymes all rely on a shared fold for activity, namely, the class I terpene cyclase fold. Recent work has illuminated the catalytic strategy used by these enzymes to catalyze the arguably most complex chemical reactions found in Nature. Terpene synthases catalyze the formation of a reactive carbocation and provide a template for the cyclization reactions while at the same time providing the necessary stability of the carbocationic reaction intermediates as well as strictly controlling water access.
Catalytic metallodrugs
Authors: Cowan James A. 
Published: August 2008

Abstract
Drug discovery remains a top priority in medical science. The phenomenon of drug resistance has heightened the need for both new classes of pharmaceutical, as well as novel modes of action. A new paradigm for drug activity is presented, which includes both recognition and subsequent irreversible inactivation of therapeutic targets. Application to both RNA and enzyme therapeutic targets has been demonstrated, while incorporation of both binding and catalytic centers provides a double-filter mechanism for improved target selectivity and lower dosing. In contrast to RNA targets that are subject to strand scission chemistry mediated by ribose H-atom abstraction, proteins appear to be inactivated through oxidative damage to amino acid side chains around the enzyme active site. Methods to monitor both intracellular delivery and activity against RNA targets have been developed based on plasmid expression of the green fluorescent protein (GFP). Herein, the activity of representative metallodrugs is described in the context of both in vitro and cellular assays, and the mechanism of action is discussed. Studies with scavengers of reactive oxygen species (ROS) confirmed hydrogen peroxide to be an obligatory diffusible intermediate, prior to formation of a Cu-bound hydroxyl radical species generated from Fenton-type chemistry.
Adenine-based calcium signal pathway messengers: Synthesis and agonistic properties of cyclic ADP-ribose analogs
Authors: Zhang Liangren , Yang Zhenjun , Guse Andreas H. , Zhang Lihe 
Published: August 2008

Abstract
A series of cyclic ADP-ribose (cADPR) analogs, in which modifications mainly focused on riboses, was synthesized in order to explore the molecular mechanism of calcium release regulated by cADPR. Biological activities investigated in intact T-lymphocytes showed that the structurally simplified analogs, N1-ethoxymethyl-substituted cyclic inosine diphosphoribose (cIDPRE), N1,N9-diethoxymethyl-substituted cyclic inosine diphosphoribose (cIDPDE), and N1-ethoxymethyl-substituted cyclic adenosine diphosphoribose (cADPRE) in which the northern ribose or both northern and southern riboses were replaced by ether linkages are membrane-permeant and induce calcium release from intracellular stores. This research has provided novel molecules to probe cADPR-mediated calcium signaling and enlarges our knowledge of the structure-activity relationships of cADPR analogs.
On the role of aromatic-sugar interactions in the molecular recognition of carbohydrates: A 3D view by using NMR
Authors: Díaz M. Dolores , Fernández-Alonso María del Carmen , Cuevas Gabriel , Cañada F. Javier , Jiménez-Barbero Jesús 
Published: August 2008

AbstractThis revision describes an up-to-date review of our efforts to investigate the interaction of carbohydrates with aromatic moieties at different levels of complexity. Protein-sugar interactions have been studied using NMR experiments on a variety of hevein/chitooligosaccharide systems. In addition, NMR and computational methods have also been used to evaluate the interaction of simple aromatic entities with simple monosaccharides. In between, the stacking features of aromatic-containing glycomolecules have also been described by using an analogous experimental-theoretical approach.
Antibody-catalyzed water-oxidation pathway
Authors: Wentworth Paul , Witter Daniel P. 
Published: August 2008

Abstract
The intrinsic ability of all antibodies to generate hydrogen peroxide (H2O2) from singlet dioxygen (1O2*) via the antibody-catalyzed water-oxidation pathway (ACWOP) has triggered a rethink of the potential role of antibodies both in immune defense, inflammation, and disease. It has been shown that photochemical activation of this pathway is highly bactericidal. More recently, cholesterol oxidation by-products that may arise from the ACWOP have been discovered in vivo and are receiving a great deal of attention as possible key players in atherosclerosis and diseases of protein misfolding, such as Alzheimer's disease and Parkinson's disease.
Bisphosphonate Therapy Ameliorates Hearing Loss in Mice Lacking Osteoprotegerin
Authors: Kanzaki Sho , Takada Yasunari , Ogawa Kaoru , Matsuo Koichi 
Published: August 2008

Abstract
Three auditory ossicles including the malleus, incus, and stapes conduct sound in the middle ear from the tympanic membrane to the inner ear. Auditory ossicles are massively resorbed by osteoclasts in Opg−/− mice, which lack osteoprotegerin (OPG), a soluble decoy receptor for the osteoclastogenic cytokine RANKL. Opg−/− mice exhibit progressive hearing loss and are a model for juvenile Paget's disease. However, effects of antiresorptive treatment on auditory ossicles and on hearing function in Opg−/− mice are unknown. We intraperitoneally injected Opg−/− mice with bisphosphonate risedronate 5 d/wk for 9 wk. Morphology of auditory ossicles was examined microscopically, radiographically, and histologically. Hearing function was monitored by measuring the auditory brain stem response (ABR). Control Opg−/− mice exhibited thinning of all three ossicles and tibia. In contrast, risedronate treatment significantly inhibited bone loss in auditory ossicles as well as in long bones of Opg−/− mice. Bony fusion of the junction between the stapes and the otic capsule was reduced after treatment. Moreover, ABR measurement showed that hearing in Opg−/− mice was significantly improved by risedronate treatment. These data suggest that hearing loss in pathologies characterized by excessive resorption of the auditory ossicles may be prevented by bisphosphonates.
Successful Skeletal Aging: A Marker of Low Fracture Risk and Longevity. The Study of Osteoporotic Fractures (SOF)
Authors: Cauley Jane A , Lui Li-Yung , Barnes Deborah , Ensrud Kristine E , Zmuda Joseph M , Hillier Teresa A , Hochberg Marc C , Schwartz Ann V , Yaffe Kristine , Cummings Steven R , Newman Anne B 
Published: August 2008

Abstract
Successful aging is multidimensional, and many phenotypes have been proposed. We examined a biomarker of aging based on repeated measures of BMD for up to 15 yr and hypothesized that maintenance of BMD will be associated with low fracture risk and disability and improved survival. We studied 9704 women recruited at four U.S. clinical centers and enrolled in the Study of Osteoporotic Fractures, a longitudinal cohort study. Of these, 8224 women had at least one hip BMD measurement. Hip BMD was measured a maximum of five times over 15 yr. Random effects regression was used to determine a BMD slope for each subject. Three groups were formed—“maintained” BMD: slope ≥0, n = 724 (9%); “expected” BMD loss: slope &lt;0 to &lt;1 SD below mean, n = 6478 (79%); and “accelerated” BMD loss: slope ≥1 SD below mean, n = 1022 (12%). Cox proportional hazards models were used to compare the relative hazard (RH; 95% CI) of fracture, incident mobility disability, and mortality in the maintained and accelerated groups compared with the expected. A 1 SD decrease in the BMD slope was associated with an increased risk of all outcomes. In multivariate models, the RH of nonspine fracture was 0.81 (0.71–0.93) and of hip fracture was 0.36 (0.25–0.53) for women in the maintained compared with the expected group. The incidence of mobility disability was lower in the maintained versus expected group (RH = 0.70; 95% CI = 0.59–0.83), but this was largely explained by other factors. Women who experienced accelerated bone loss were more likely to develop disability (RH = 1.56; 95% CI: 1.33–1.84). Mortality risks were lower in the maintained compared with the expected group (RH = 0.49; 95% CI: 0.42–0.58). In conclusion, a subset of older women maintained their BMD up to 15 yr, suggesting that bone loss is not an inevitable consequence of aging. These women experienced a lower risk of fractures, disability, and mortality, suggesting that this phenotype may be a marker of successful aging.
Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism Is Associated With Spinal BMD in 9-Year-Old Children
Authors: Steer Colin D , Emmett Pauline M , Lewis Sarah J , Smith George Davey , Tobias Jon H 
Published: August 2008

AbstractThe C677T MTHFR polymorphism has been associated with lumbar spine and hip BMD. In older adults, the genetic effect has been reported in women only. However, in younger adults, this influence may only be present in men. This study is the first to investigate associations between the C677T MTHFR polymorphism and bone phenotypes in children. Regression analyses were used to study the relationship between MTHFR genotype and bone phenotypes derived from total body DXA scans in children 9.9 yr of age from the Avon Longitudinal Study of Parents and Children (ALSPAC). A total of 5816 children had both genetic and DXA data for the total body less head region (TBLH) and 3196 for the spine. A strong association was observed between the C677T MTHFR genotype and spine BMD (p &lt; 0.001; 0.10 SD decrease per T allele). There was some evidence that this genetic effect was stronger in boys compared with girls (p = 0.04 for sex interaction). In contrast, there was no association between the C677T MTHFR genotype and TBLH BMD. The association between MTHFR genotype and spine BMD was attenuated particularly in girls by high maternal dietary intakes of vitamin B6 and folate during pregnancy but not by child dietary intakes at 7 yr. To the extent that these findings reflect known influences of C677T MTHFR genotype on plasma homocysteine levels, our results suggest that the latter is an important regulator of spinal BMD in childhood.
Functional Characterization of Genetic Variation in the Frizzled 1 (FZD1) Promoter and Association With Bone Phenotypes: More to the LRP5 Story?
Authors: Yerges Laura M , Zhang Yingze , Cauley Jane A , Kammerer Candace M , Nestlerode Cara S , Wheeler Victor W , Patrick Alan L , Bunker Clareann H , Moffett Susan P , Ferrell Robert E , Zmuda Joseph M 
Published: August 2008

Abstract
WNT signaling is an important determinant of bone formation. The WNT co-receptor, Frizzled homolog 1 (FZD1), initiates WNT signal transduction. To study the influence of FZD1 genetic variation on measures of bone health, we first sequenced a 6.8-kb region surrounding FZD1 in 48 samples of African ancestry. We genotyped all common polymorphisms and performed association analysis with bone phenotypes in a larger sample. Only 3 of 35 SNPs identified were present in ≥5% of the sample and assayed further in 1084 men of African ancestry. Two of these SNPs were in the FZD1 promoter (rs2232157, rs2232158) and were associated with femoral neck areal BMD (p = 0.041 and 0.009, respectively). The minor alleles of these two SNPs were also associated with larger bone size at the radius (p &lt; 0.05 for both), and rs2232158 was associated with greater strength-strain index, an indicator of bone's ability to withstand torsion. Functional experiments were completed to assess the influence of the rs2232158 promoter polymorphism on transcriptional regulation of FZD1. The minor C allele in rs2232158 creates a binding site for the transcription factor Egr1, has higher Egr1 binding affinity, and has greater FZD1 promoter activity in MG63 and SaOS-2 cells, providing a plausible molecular mechanism for the population associations. This study indicates that a cis-regulatory polymorphism in the FZD1 promoter region may have a functional role in determining bone structural geometry.