bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3‐only proteins Bim and Bmf
Authors: Labi Verena , Bertele Daniela , Woess Claudia , Tischner Denise , Bock Florian J. , Schwemmers Sven , Pahl Heike L. , Geley Stephan , Kunze Mirjam , Niemeyer Charlotte M. , Villunger Andreas , Erlacher Miriam 
Published: November 2012

AbstractAnti‐apoptotic Bcl‐2 family members are critical for the regulation of haematopoietic stem and progenitor cell (HSPC) survival. Little is known about the role of their pro‐apoptotic antagonists, i.e. ‘BH3‐only’ proteins, in this cell compartment. Based on the analysis of cytokine deprivation‐induced changes in mRNA expression levels of Bcl‐2 family proteins, we determined the consequences of BH3‐only protein depletion on HSPC survival in culture and, for selected candidates, on engraftment in vivo. Thereby, we revealed a critical role for Bim and Bmf as regulators of HSPC dynamics both during early engraftment and long‐term reconstitution. HSPCs derived from wild‐type donors were readily displaced by Bim‐ or Bmf‐deficient or Bcl‐2‐overexpressing HSPCs as early as 10 days after engraftment. Moreover, in the absence of Bim, significantly lower numbers of transplanted HSPCs were able to fully engraft radio‐depleted recipients. Finally, we provide proof of principle that RNAi‐based reduction of BIM or BMF, or overexpression of BCL‐2 in human CD34+ cord blood cells may be an attractive therapeutic option to increase stem cell survival and transplantation efficacy.
The orphan receptor TR3 participates in angiotensin II‐induced cardiac hypertrophy by controlling mTOR signalling
Authors: Wang Rong‐Hao , He Jian‐Ping , Su Mao‐Long , Luo Jie , Xu Ming , Du Xiao‐Dan , Chen Hang‐Zi , Wang Wei‐Jia , Wang Yuan , Zhang Nan , Zhao Bi‐Xing , Zhao Wen‐Xiu , Shan Zhong‐Gui , Han Jiahuai , Chang Chawnshang , Wu Qiao 
Published: November 2012

AbstractAngiotensin II (AngII) induces cardiac hypertrophy and increases the expression of TR3. To determine whether TR3 is involved in the regulation of the pathological cardiac hypertrophy induced by AngII, we established mouse and rat hypertrophy models using chronic AngII administration. Our results reveal that a deficiency of TR3 in mice or the knockdown of TR3 in the left ventricle of rats attenuated AngII‐induced cardiac hypertrophy compared with the respective controls. A mechanistic analysis demonstrates that the TR3‐mediated activation of mTORC1 is associated with AngII‐induced cardiac hypertrophy. TR3 was shown to form a trimer with the TSC1/TSC2 complex that specifically promoted TSC2 degradation via a proteasome/ubiquitination pathway. As a result, mTORC1, but not mTORC2, was activated; this was accompanied by increased protein synthesis, enhanced production of reactive oxygen species and enlarged cell size, thereby resulting in cardiac hypertrophy. This study demonstrates that TR3 positively regulates cardiac hypertrophy by influencing the effect of AngII on the mTOR pathway. The elimination or reduction of TR3 may reduce cardiac hypertrophy; therefore, TR3 is a potential target for clinical therapy.
Stability of pharmaceuticals and other polar organic compounds stored on polar organic chemical integrative samplers and solid-phase extraction cartridges
Authors: Carlson Jules C. , Challis Jonathan K. , Hanson Mark L. , Wong Charles S. 
Published: November 2012

Abstract
The stability of 24 chemicals, including pharmaceuticals and personal care products, and some agrochemicals on extraction media was evaluated by preloading them onto Oasis hydrophilic lipophilic balanced solid-phase extraction (SPE) cartridges and polar organic chemical integrative samplers (POCIS) followed by storage at –20°C over time. After 20 months, the average loss was 11% on POCIS, with only 2,4-dichlorophenoxyacetic acid, atrazine, chlorpyrifos, and gemfibrozil showing a statistically significant decline compared with initial concentrations. Losses on SPE cartridges were below 19%, with an average loss of 9%. In addition to laboratory spiked samples, multiple POCIS deployed in wastewater-impacted surface waters and SPE extracts of these waters were stored in their original coextracted matrix for nearly two years with minimal observed losses. Errors from typical sampling, handling, and concentration estimates from POCIS sampling rates were typically ± 15 to 30% relative standard deviation, so observed storage losses are minimal for most POCIS applications. While losses during storage on SPE cartridges for 20 months were small but statistically significant for many compounds, addition of labeled internal standards prior to freezing should correct for such losses. Thus, storage of processed water samples for analysis of polar organic pollutants is viable for archival purposes or studies for which samples cannot be analyzed in the short term. Environ. Toxicol. Chem. 2013;32:337–344. © 2012 SETAC
Bottom-up nutrient and top-down fish impacts on insect-mediated mercury flux from aquatic ecosystems
Authors: Jones Taylor A. , Chumchal Matthew M. , Drenner Ray W. , Timmins Gabrielle N. , Nowlin Weston H. 
Published: November 2012

Abstract
Methyl mercury (MeHg) is one of the most hazardous contaminants in the environment, adversely affecting the health of wildlife and humans. Recent studies have demonstrated that aquatic insects biotransport MeHg and other contaminants to terrestrial consumers, but the factors that regulate the flux of MeHg out of aquatic ecosystems via emergent insects have not been studied. The authors used experimental mesocosms to test the hypothesis that insect emergence and the associated flux of MeHg from aquatic to terrestrial ecosystems is affected by both bottom-up nutrient effects and top-down fish consumer effects. In the present study, nutrient addition led to an increase in MeHg flux primarily by enhancing the biomass of emerging insects whose tissues were contaminated with MeHg, whereas fish decreased MeHg flux primarily by reducing the biomass of emerging insects. Furthermore, the authors found that these factors are interdependent such that the effects of nutrients are more pronounced when fish are absent, and the effects of fish are more pronounced when nutrient concentrations are high. The present study is the first to demonstrate that the flux of MeHg from aquatic to terrestrial ecosystems is strongly enhanced by bottom-up nutrient effects and diminished by top-down consumer effects. Environ. Toxicol. Chem. 2013;32:612–618. © 2012 SETAC
Pragmatism: A practical philosophy for environmental scientists
Authors: Suter Glenn W , Cormier Susan M 
Published: November 2012

Abstract
Challenges to the credibility of the scientific community make it particularly important for environmental scientists to understand the bases for the authority of their science. We argue that pragmatism provides a defensible and effective scientific philosophy. It provides a transparent basis for justifying belief and a set of practices and concepts for inference. It makes the scientific community the author of scientific truth, which has implications for the opening of science in the age of social media and the communication of consensus positions on important issues. We describe how pragmatism acknowledges the social aspect of science without losing the scientific tradition of critical thinking. Integr Environ Assess Manag 2013; 9: 181–184. © 2012 SETAC
Identification of carbapenem‐resistant Acinetobacter baumannii clones using infrared spectroscopy
Authors: Sousa Clara , Grosso Filipa , Meirinhos‐Soares Luís , Peixe Luísa , Lopes João 
Published: November 2012

AbstractIn this work we assessed the discriminatory ability of Fourier‐transform Infrared Spectroscopy (FTIR) in 22 representative isolates from a collection of 318 carbapenem‐hydrolyzing class D β ‐lactamases (CHDL)‐producing Acinetobacter spp. (5 hospitals; 2001–2008) previously characterized by DNA‐based typing methods. FTIR spectra were acquired with a Bruker spectrometer and analyzed with support of several chemometric tools. The results showed that FTIR spectroscopy was able to distinguish the main CHDL‐producing Acinetobacter baumannii lineages causing infection in Portugal, the ST103 carrying blaOXA‐58, ST98 carrying blaOXA‐24/40and ST92 carrying blaOXA‐23. Moreover, this study revealed distinctive phenotypic features of A. baumannii lineages causing infections that might justify different epidemic potential. Spectroscopy may arise as a low cost and easily to perform alternative for typing A. baumannii isolates. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Gefitinib inhibits the cross‐talk between mesenchymal stem cells and prostate cancer cells leading to tumor cell proliferation and inhibition of docetaxel activity
Authors: Borghese Cinzia , Cattaruzza Lara , Pivetta Eliana , Normanno Nicola , De Luca Antonella , Mazzucato Mario , Celegato Marta , Colombatti Alfonso , Aldinucci Donatella 
Published: November 2012

AbstractIncreasing evidence suggests that bone marrow derived mesenchymal stem cells (BM‐MSCs) are recruited into the stroma of developing tumors where they contribute to progression by enhancing tumor growth and metastasis, or by inducing anticancer‐drug resistance. Prostate cancer cells secrete ligands of epidermal growth factor receptor (EGFR) and EGFR signaling could play an important role in the cross‐talk between mesenchymal stem cells and prostate cancer cells. In this study, we showed that treatment of human primary MSCs with conditioned medium (CM) derived from the bone metastatic PC3 carcinoma cells (PC3‐CM) resulted in: a significant activation of EGFR; increased proliferation; increased osteoblastic but decreased adipocitic differentiation; inhibition of senescence induced by serum starvation; increased CCL5 secretion. These activities were significantly inhibited in the presence of the EGFR tyrosine kinase inhibitor gefitinib. PC3‐CM directly inhibited osteoclastogenesis as well as the ability of osteoblasts to induce osteoclast differentiation. The increased MSCs migration by PC3‐CM and PC3 cells was partially mediated by CCL5. MSC‐CM increased the formation of colonies by PC3 cells and inhibited the anti‐proliferative activity of Docetaxel. Activation of EGFR expressed on MSCs by PC3‐CM enhanced their capability to increase PC3 cells proliferation and to inhibit Docetaxel activity. These findings, by showing that the tumor‐promoting interactions between PC3 cells and MSCs are mediated, at least in part, by EGFR, suggest a novel application of the EGFR‐tyrosine kinase inhibitors in the treatment of prostate cancer. J. Cell. Biochem. 114: 1135–1144, 2013. © 2012 Wiley Periodicals, Inc.
Target network analysis of adiponectin, a multifaceted adipokine
Authors: Chen Xiuping 
Published: November 2012

AbstractApplication of network analysis to dissect the potential molecular mechanisms of biological processes and complicated diseases has been the new trend in biology and medicine in recent years. Among which, the protein–protein interactions (PPI) networks attract interests of most researchers. Adiponectin, a cytokine secreted from adipose tissue, participates in a number of metabolic processes, including glucose regulation and fatty acid metabolism and involves in a series of complicated diseases from head to toe. Hundreds of proteins including many identified and potential drug targets have been reported to be involved in adiponectin related signaling pathways, which comprised a complicated regulation network. Therapeutic target database (TTD) provides extensive information about the known and explored therapeutic protein targets and the signaling pathway information. In this study, adiponectin associated drug targets based PPI was constructed and its topological properties were analyzed, which might provide some insight into the dissection of adiponectin action mechanisms and promote adiponectin signaling based drug target identification and drug discovery. J. Cell. Biochem. 114: 1145–1152, 2013. © 2012 Wiley Periodicals, Inc.
BRAF mutation and RASSF1A expression in thyroid carcinoma of southern Italy
Authors: Santoro Angela , Pannone Giuseppe , Carosi Maria Antonia , Francesconi Arianna , Pescarmona Edoardo , Russo Giuseppe Maria , Feola Antonia , Losito Simona , Franco Renato , Nappi Luigi , Aquino Gabriella , De Rosa Gaetano , Di Domenico Marina , Bufo Pantaleo 
Published: November 2012

AbstractAim of this work is to provide a detailed comparison of clinical‐pathologic features between well‐differentiated and poorly differentiated tumors according to their BRAF and RASSF1A status. We analyzed RASSF1A methylation by MSP and BRAF mutation by LCRT‐PCR with LightMix® kit BRAF V600E in neoplastic thyroid tissues. Immunohistochemical evaluation of RASSF1A expression was also performed by standard automated LSAB‐HRP technique. An overall higher degree of RASSF1A over‐expression than normal thyroid parenchyma surrounding tumors (P < 0.05) has been found in all malignant well‐differentiated lesions. Moreover, statistically significant higher levels of RASSF1A expression were observed in differentiated cancers associated to an inflammatory autoimmune background (P = 0.01). Amplifiable DNA for LC PCR with LightMix® kit BRAF V600E was obtained in nine PTCs, four FVPTCs, five ATCs, and one control. The V600E mutation was found in 13 of 18 (72%) tumors. BRAF was mutated in 6 of 9 (66%) classical PTC, in 2 of 4 (50%) follicular variant PTC and in all ACs (100%). The overall frequency of RASSF1A promoter methylation observed was 20.5% (9 cases out 44). Hypermethylation of RASSF1A in primary tumors was variable according to histotypes ranging from100% (5/5) in ACs to only 12.5% (4/32) in PTCs. We show a correlation between RASSF1A methylation status and RASSF1A protein expression. Finally, we conclude that BRAF V600E mutation and RASSF1A methylation were pathogenetic event restricted to a subgroup of PTC/FVPTCs in early stage and to clinically aggressive ATCs. J. Cell. Biochem. 114: 1174–1182, 2013. © 2012 Wiley Periodicals, Inc.
mTOR inhibitors radiosensitize PTEN‐deficient non‐small‐cell lung cancer cells harboring an EGFR activating mutation by inducing autophagy
Authors: Kim Eun Ju , Jeong Jae‐Hoon , Bae Sangwoo , Kang Seongman , Kim Cheol Hyeon , Lim Young‐Bin 
Published: November 2012

AbstractClinical resistance to gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), in patients with lung cancer has been linked to acquisition of the T790M resistance mutation in activated EGFR or amplification of MET. Phosphatase and tensin homolog (PTEN) loss has been recently reported as a gefitinib resistance mechanism in lung cancer. The aim of this study was to evaluate the efficacy of radiotherapy in non‐small‐cell lung cancer (NSCLC) with acquired gefitinib resistance caused by PTEN deficiency to suggest radiotherapy as an alternative to EGFR TKIs. PTEN deficient‐mediated gefitinib resistance was generated in HCC827 cells, an EGFR TKI sensitive NSCLC cell line, by PTEN knockdown with a lentiviral vector expressing short hairpin RNA‐targeting PTEN. The impact of PTEN knockdown on sensitivity to radiation in the presence or absence of PTEN downstream signaling inhibitors was investigated. PTEN knockdown conferred acquired resistance not only to gefitinib but also to radiation on HCC827 cells. mTOR inhibitors alone failed to reduce HCC827 cell viability, regardless of PTEN expression, but ameliorated PTEN knockdown‐induced radioresistance. PTEN knockdown‐mediated radioresistance was accompanied by repression of radiation‐induced cytotoxic autophagy, and treatment with mTOR inhibitors released the repression of cytotoxic autophagy to overcome PTEN knockdown‐induced radioresistance in HCC827 cells. These results suggest that inhibiting mTOR signaling could be an effective strategy to radiosensitize NSCLC harboring the EGFR activating mutation that acquires resistance to both TKIs and radiotherapy due to PTEN loss or inactivation mutations. J. Cell. Biochem. 114: 1248–1256, 2013. © 2012 Wiley Periodicals, Inc.
(Ala)4‐X‐(Ala)4 as a model system for the optimization of the χ1 and χ2 amino acid side‐chain dihedral empirical force field parameters
Authors: Shim Jihyun , Zhu Xiao , Best Robert B. , MacKerell Alexander D. 
Published: November 2012

AbstractAmino acid side‐chain fluctuations play an essential role in the structure and function of proteins. Accordingly, in theoretical studies of proteins, it is important to have an accurate description of their conformational properties. Recently, new side‐chain torsion parameters were introduced into the CHARMM and Amber additive force fields and evaluated based on the conformational properties of the individual side‐chains using protein simulations in explicit solvent. While effective for validation, molecular dynamics simulations of proteins must be extended into the microsecond regime to obtain full convergence of the side‐chain conformations, limiting their use for force field optimization. To address this, we systematically test the utility of explicit solvent simulations of (Ala)4‐X‐(Ala)4 peptides, where X represents the amino acids, as model systems for the optimization of χ1 and χ2 side‐chain parameters. The effect of (Ala)4‐X‐(Ala)4 backbone conformation was tested by constraining the backbone in the α‐helical, C5, C7eq, and PPII conformations and performing exhaustive sampling using Hamiltonian replica exchange simulations. Rotamer distributions from protein and the (Ala)4‐X‐(Ala)4 simulations showed the highest correlation for the C7eq and PPII conformations, although agreement was the best for the α‐helical conformation for Asn. Hydrogen bond analysis indicates the utility of the C7eq and PPII conformations to be due to specific side‐chain‐backbone hydrogen bonds not being oversampled, thereby allowing sampling of a range of side‐chain conformations consistent with the distributions occurring in full proteins. It is anticipated that the (Ala)4‐X‐(Ala)4 model system will allow for iterative force field optimization targeting condensed‐phase conformational distributions of side‐chains. © 2012 Wiley Periodicals, Inc.
Observations on variation in the ultrastructure of the proximal testicular ducts of the ground skink, scincella lateralis (reptilia: Squamata)
Authors: Sever David M. , Rheubert Justin L. , Hill Toren A. , Siegel Dustin S. 
Published: November 2012

AbstractThe North American Ground Skink, Scincella lateralis, is a member of the most speciose family of lizards, the Scincidae. The only descriptions of the testicular ducts of skinks concern the light microscopy of 13 species in eight other genera. We combine histological observations with results from transmission electron microscopy on a sample of skinks collected throughout the active season. The single rete testis has squamous epithelium with a large, indented nucleus and no junctional complexes between cells or conspicuous organelles. Nuclei of sperm in the rete testis area are associated with cytoplasmic bodies that are lost in the ductuli efferentes. The ductuli efferentes have both ciliated and nonciliated cells and show little seasonal variation except for the narrowing of intercellular canaliculi when sperm are absent. When the ductus epididymis contains sperm, the anterior one‐third lacks copious secretory material around luminal sperm, whereas in the posterior two‐thirds sperm are embedded in a dense matrix of secretory material. Light and dark principal cells exist and both contain saccular, often distended rough endoplasmic reticula, and widened intercellular canaliculi that bridge intracellular spaces. Junctional complexes are lacking between principal cells except for apical tight junctions. Electron‐dense secretory granules coalesce at the luminal border for apocrine release. The cranial end of the ductus deferens is similar in cytology to the posterior ductus epididymis. Each of the nine squamates in which the proximal testicular ducts have been studied with electron microscopy has some unique characters, but no synapomorphies for squamates as a group are recognized. J. Morphol., 2013. © 2012Wiley Periodicals, Inc.
Experimentally induced cam impingement in the sheep hip
Authors: Siebenrock Klaus A. , Fiechter Ruth , Tannast Moritz , Mamisch Tallal C. , von Rechenberg Brigitte 
Published: November 2012

AbstractSheep hips have a natural non‐spherical femoral head similar to a cam‐type deformity in human beings. By performing an intertrochanteric varus osteotomy, cam‐type femoro‐acetabular impingement (FAI) during flexion can be created. We tested the hypotheses that macroscopic lesions of the articular cartilage and an increased Mankin score (MS) can be reproduced by an experimentally induced cam‐type FAI in this ovine in vivo model. Furthermore, we hypothesized that the MS increases with longer ambulatory periods. Sixteen sheep underwent unilateral intertrochanteric varus osteotomy of the hip with the non‐operated hip as a control. Four sheep were sacrificed after 14, 22, 30, and 38‐weeks postoperatively. We evaluated macroscopic chondrolabral alterations, and recorded the MS, based on histochemical staining, for each ambulatory period. A significantly higher prevalence of macroscopic chondrolabral lesions was found in the impingement zone of the operated hips. The MS was significantly higher in the acetabular/femoral cartilage of the operated hips. Furthermore, these scores increased as the length of the ambulatory period increased. Cam‐type FAI can be induced in an ovine in vivo model. Localized chondrolabral degeneration of the hip, similar to that seen in humans (Tannast et al., Clin Orthop Relat Res 2008; 466: 273–280; Beck et al., J Bone Joint Surg Br 2005; 87: 1012–1018), can be reproduced. This experimental sheep model can be used to study cam‐type FAI. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 580–587, 2013
Toward an understanding of the short bone phenotype associated with multiple osteochondromas
Authors: Jones Kevin B. , Datar Manasi , Ravichandran Sandhya , Jin Huifeng , Jurrus Elizabeth , Whitaker Ross , Capecchi Mario R. 
Published: November 2012

AbstractIndividuals with multiple osteochondromas (MO) demonstrate shortened long bones. Ext1 or Ext2 haploinsufficiency cannot recapitulate the phenotype in mice. Loss of heterozygosity for Ext1 may induce shortening by steal of longitudinal growth into osteochondromas or by a general derangement of physeal signaling. We induced osteochondromagenesis at different time points during skeletal growth in a mouse genetic model, then analyzed femora and tibiae at 12 weeks using micro‐CT and a point‐distribution‐based shape analysis. Bone lengths and volumes were compared. Metaphyseal volume deviations from normal, as a measure of phenotypic widening, were tested for correlation with length deviations. Mice with osteochondromas had shorter femora and tibiae than controls, more consistently when osteochondromagenesis was induced earlier during skeletal growth. Volumetric metaphyseal widening did not correlate with longitudinal shortening, although some of the most severe shortening was in bones with abundant osteochondromas. Loss of heterozygosity for Ext1 was sufficient to drive bone shortening in a mouse model of MO, but shortening did not correlate with osteochondroma volumetric growth. While a steal phenomenon seems apparent in individual cases, some other mechanism must also be capable of contributing to the short bone phenotype, independent of osteochondroma formation. Clones of chondrocytes lacking functional heparan sulfate must blunt physeal signaling generally, rather than stealing growth potential focally. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 651–657, 2013