bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and Function of Ferroportin 1 in O‐2A Progenitor Cells
Authors: Lin Qing , Feng Junsheng , Zhao Xiaozhen , Zhang Geng , Wang Wei 
Published: November 2012

AbstractIron plays a crucial role in the survival, differentiation, and myelin formation of oligodendrocyte lineages. However, the regulation mechanism of iron homeostasis in oligodendrocytes remains unclear. Recently, much research has focused on Ferroportin 1 (FPN1), an iron exporter protein. First, about 95% pure primary rat O‐2A progenitor cells were obtained by shaking methods in our laboratory. The expression of FPN1 mRNA and protein in O‐2A progenitor cells were determined by reverse transcription‐PCR and western blot. In addition, the localization of FPN1 at the cell membrane, in the cytoplasm and in processes was assayed by double‐labeling immunofluorescence. A time‐dependent increase of iron efflux from O‐2A progenitor cells was confirmed by the calcein‐indicated iron efflux assay. However, the same cells treated with FPN1 antibody showed no obvious change in iron release. For further confirmation, overexpression of FPN1 in O‐2A progenitor cells was transduced with lentivirus. The release of iron in O‐2A progenitor cells was dramatically increased by the overexpressed FPN1 when compared with that of the control group. Both ferritin (Ft) and transferrin receptor (TfR) are routinely used as indicators of labile iron pool. Cells pretreated with FPN1 antibody upregulated Ft and downregulated TfR protein level, while the opposite results occurred in the FPN1 overexpressing cells. Determination of Ft and TfR indirectly indicated that FPN1 might contribute to iron release from O‐2A progenitor cells. We suggested that expression of FPN1 in O‐2A progenitor cells might play a critical role in iron efflux from these cells. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.
Lysosome Dysfunction Enhances Oxidative Stress‐Induced Apoptosis through Ubiquitinated Protein Accumulation in Hela Cells
Authors: Yu Chunyan , Huang Xiaowei , Xu Ye , LI Hongyan , Su Jing , Zhong Jiateng , Kang Jinsong , Liu Yuhe , Sun Liankun 
Published: November 2012

AbstractThe role of lysosomal system in oxidative stress‐induced apoptosis in cancer cells is not fully understood. Menadione is frequently used as oxidative stress model. It is indicated that menadione could induce autophagy in Hela cells. In the present study, we examined whether the lysosomal inhibitor, ammonium chloride (NH4Cl) could prevent the autophagy flux by inhibiting the fusion of autophagosomes with lysosomes and enhance apoptosis induced by menadione via mitochondrial pathway. The results demonstrated generation and accumulation of reactive oxygen species and increased levels of ubiquitinated proteins and GRP78 in cells treated with both menadione and NH4Cl. Our data indicates that lysosomal system through autophagy plays an important role in preventing menadione‐induced apoptosis in Hela cells by clearing misfolded proteins, which alleviates endoplasmic reticulum stress. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.
Difference in subchondral cancellous bone between postmenopausal women with hip osteoarthritis and osteoporotic fracture: Implication for fatigue microdamage, bone microarchitecture, and biomechanical properties
Authors: Li Zhan‐Chun , Dai Li‐Yang , Jiang Lei‐Sheng , Qiu Shijing 
Published: November 2012

AbstractObjectiveOsteoarthritis (OA) and osteoporosis (OP) of the hip rarely occur in the same patient. The purpose of this study was to determine whether this difference might be attributable to the different quantity and quality of subchondral cancellous bone in the two conditions.MethodsSubchondral cancellous bone from the femoral head was obtained at the time of hip arthroplasty from 60 postmenopausal women, 30 with OA and 30 with OP. In each group, 10 specimens were subjected to compressive fatigue loading and 20 were left nonloaded. Specimens were examined by compressive mechanical testing, micro–computed tomography scanning, fluorescence microscopy, and nanoindentation techniques.ResultsBoth the ultimate stress and the elastic modulus of cancellous bone from OA patients were significantly higher than those of cancellous bone from OP patients (P < 0.05). Compared to cancellous bone from OP patients, the bone volume fraction and trabecular thickness were significantly increased, but bone matrix mineralization was significantly decreased, in cancellous bone from OA patients (P < 0.05 for each comparison). The microcrack density was significantly higher in OP cancellous bone than in OA cancellous bone (P < 0.001), irrespective of fatigue loading. In addition, fatigue loading resulted in a significant increase in microcrack density in both OA and OP cancellous bone (P < 0.001). There was no significant difference in nanoindentation elastic modulus and hardness between cancellous bone from OA and OP patients, as well as between bones with and without fatigue loading.ConclusionThe difference in mechanical properties between OA and OP cancellous bone is attributed to different bone mass and bone structure. OP cancellous bone is susceptible to fatigue damage due to insufficient structure. However, increased bone volume and plate‐like structure provide OA cancellous bone a superior capacity to resist fatigue damage.
Do radiographic disease and pain account for why people with or at high risk of knee osteoarthritis do not meet physical activity guidelines?
Authors: White Daniel K. , Tudor‐Locke Catrine , Felson David T. , Gross K. Douglas , Niu Jingbo , Nevitt Michael , Lewis Cora E. , Torner James , Neogi Tuhina 
Published: November 2012

AbstractObjectiveKnee osteoarthritis (OA) and pain are assumed to be barriers to meeting physical activity guidelines, but this has not been formally evaluated. The purpose of this study was to determine the proportions of people with and those without knee OA and knee pain who meet recommended physical activity levels through walking.MethodsWe performed a cross‐sectional analysis of community‐dwelling adults from the Multicenter Osteoarthritis Study who had or who were at high risk of knee OA. Participants wore a StepWatch activity monitor to record steps per day for 7 days. The proportion of participants who met the recommended physical activity levels was defined as those accumulating ≥150 minutes per week at ≥100 steps per minute in bouts lasting ≥10 minutes. These proportions were also determined for those with and those without knee OA, as classified by radiography and by severity of knee pain.ResultsOf the 1,788 study participants (mean ± SD age 67.2 ± 7.7 years, mean ± SD body mass index 30.7 ± 6.0 kg/m2, 60% women), lower overall percentages of participants with radiographic knee OA and knee pain met recommended physical activity levels. However, these differences were not statistically significant between those with and those without knee OA; 7.3% and 10.1% of men (P = 0.34) and 6.3% and 7.8% of women (P = 0.51), respectively, met recommended physical activity levels. Similarly, for those with moderate/severe knee pain and those with no knee pain, 12.9% and 10.9% of men (P = 0.74) and 6.7% and 11.0% of women (P = 0.40), respectively, met recommended physical activity levels.ConclusionDisease and pain have little impact on achieving recommended physical activity levels among people with or at high risk of knee OA.
Zone‐specific gene expression patterns in articular cartilage
Authors: Grogan Shawn P. , Duffy Stuart F. , Pauli Chantal , Koziol James A. , Su Andrew I. , D'Lima Darryl D. , Lotz Martin K. 
Published: November 2012

AbstractObjectiveTo identify novel genes and pathways specific to the superficial zone (SZ), middle zone (MZ), and deep zone (DZ) of normal articular cartilage.MethodsArticular cartilage was obtained from the knees of 4 normal human donors. The cartilage zones were dissected on a microtome. RNA was analyzed on human genome arrays. The zone‐specific DNA array data obtained from human tissue were compared to array data obtained from bovine cartilage. Genes differentially expressed between zones were evaluated using direct annotation for structural or functional features, and by enrichment analysis for integrated pathways or functions.ResultsThe greatest differences in genome‐wide RNA expression data were between the SZ and DZ in both human and bovine cartilage. The MZ, being a transitional zone between the SZ and DZ, thereby shared some of the same pathways as well as structural/functional features of the adjacent zones. Cellular functions and biologic processes that were enriched in the SZ relative to the DZ included, most prominently, extracellular matrix–receptor interactions, cell adhesion molecule functions, regulation of actin cytoskeleton, ribosome‐related functions, and signaling aspects such as the IFN, IL4, Cdc42/Rac, and JAK/STAT signaling pathways. Two pathways were enriched in the DZ relative to the SZ, including PPARG and EGFR/SMRTE.ConclusionThese differences in cartilage zonal gene expression identify new markers and pathways that govern the unique differentiation status of chondrocyte subpopulations.
Association of fibromyalgia with altered skeletal muscle characteristics which may contribute to postexertional fatigue in postmenopausal women
Authors: Srikuea Ratchakrit , Symons T. Brock , Long Douglas E. , Lee Jonah D. , Shang Yu , Chomentowski Peter J. , Yu Guoqiang , Crofford Leslie J. , Peterson Charlotte A. 
Published: November 2012

AbstractObjectiveTo identify muscle physiologic properties that may contribute to postexertional fatigue and malaise in women with fibromyalgia (FM).MethodsHealthy postmenopausal women with (n = 11) and without (n = 11) FM, ages 51–70 years, participated in this study. Physical characteristics and responses to self‐reported questionnaires were evaluated. Strength loss and tissue oxygenation in response to a fatiguing exercise protocol were used to quantify fatigability and the local muscle hemodynamic profile. Muscle biopsies were performed to assess between‐group differences in baseline muscle properties using histochemical, immunohistochemical, and electron microscopic analyses.ResultsThere was no significant difference between healthy controls and FM patients in muscle fatigue in response to exercise. However, self‐reported fatigue and pain were correlated with prolonged loss of strength following 12 minutes of recovery in patients with FM. Although there was no difference in percent succinate dehydrogenase (SDH)–positive (type I) and SDH‐negative (type II) fibers or in mean fiber cross‐sectional area between groups, FM patients exhibited greater variability in fiber size and altered fiber size distribution. In healthy controls only, fatigue resistance was strongly correlated with the size of SDH‐positive fibers and hemoglobin oxygenation. In contrast, FM patients with the highest percentage of SDH‐positive fibers recovered strength most effectively, and this was correlated with capillary density. However, overall, capillary density was lower in the FM group.ConclusionPeripheral mechanisms, i.e., altered muscle fiber size distribution and decreased capillary density, may contribute to postexertional fatigue in FM. Understanding of these defects in fibromyalgic muscle may provide valuable insight with regard to treatment.
Quantitative imaging of murine osteoarthritic cartilage by phase‐contrast micro–computed tomography
Authors: Ruan Merry Z. C. , Dawson Brian , Jiang Ming‐Ming , Gannon Francis , Heggeness Michael , Lee Brendan H. L. 
Published: November 2012

AbstractObjectiveThe mouse is an optimal model organism in which gene–environment interactions can be used to study the pathogenesis of osteoarthritis (OA). The gold standard for arthritis research in mice is based on histopathology and immunohistochemistry, which are labor‐intensive, prone to sampling bias and technical variability, and limited in throughput. The aim of this study was to develop a new technique that assesses mouse cartilage by integrating quantitative volumetric imaging techniques.MethodsA novel mouse model of OA was generated by cruciate ligament transection (CLT) and evaluated by histopathology and immunohistochemistry. Knee joint specimens were then imaged using a new technique that combines high‐resolution micro–computed tomography (micro‐CT) and phase‐contrast optics followed by quantitative analyses. A comparative analysis was also performed in a previously established mouse model of OA generated by destabilization of the medial meniscus (DMM).ResultsPhase‐contrast micro‐CT achieved cellular resolution of chondrocytes and quantitative assessment of parameters such as articular cartilage volume and surface area. In mouse models of OA generated by either CLT or DMM, we showed that phase‐contrast micro‐CT distinguished control and OA cartilage by providing quantitative measures with high reproducibility and minimal variability. Features of OA at the cellular or tissue level could also be observed in images generated by phase‐contrast micro‐CT.ConclusionWe established an imaging technology that comprehensively assessed and quantified the 2‐dimensional and 3‐dimensional changes of articular cartilage. Application of this technology will facilitate the rapid and high‐throughput assessment of genetic and therapeutic models of OA in mice.
Stimulation of superficial zone protein accumulation by hedgehog and Wnt signaling in surface zone bovine articular chondrocytes
Authors: Iwakura Takashi , Inui Atsuyuki , Reddi A. Hari 
Published: November 2012

AbstractObjectiveTo determine the roles of the hedgehog and Wnt signaling pathways in accumulation of superficial zone protein (SZP) in surface zone articular chondrocytes.MethodsExplant cultures of disks of surface zone cartilage or isolated chondrocytes from the surface zone of articular cartilage of bovine stifle joints were cultured in serum‐free chemically defined medium. Accumulation of SZP in the culture medium, in response to hedgehog proteins (sonic hedgehog [SHH] and Indian hedgehog [IHH]), Wnt proteins (Wnt‐3a, Wnt‐5a, and Wnt‐11), agonists of the Wnt/β‐catenin pathway (glycogen synthase kinase 3β [GSK‐3β] inhibitors), and antagonists of the Wnt/β‐catenin pathway, was investigated. The interaction between transforming growth factor β1 (TGFβ1) and hedgehog proteins or antagonists of the Wnt/β‐catenin pathway was also investigated.ResultsHedgehog proteins stimulated SZP accumulation. Activation of the Wnt/β‐catenin pathway by Wnt‐3a and GSK‐3β inhibitors led to inhibition of SZP accumulation; however, Wnt‐5a and Wnt‐11 had no influence on SZP accumulation. Conversely, antagonists of the Wnt/β‐catenin pathway stimulated SZP accumulation. In addition, there were combinatorial effects of TGFβ1 and hedgehog proteins or antagonists of the Wnt/β‐catenin pathway on SZP accumulation.ConclusionSHH and IHH signaling has a stimulatory effect on SZP accumulation in surface zone cartilage and isolated articular chondrocytes. These findings provide insight into the regulatory mechanisms of articular cartilage homeostasis and maintenance by morphogens.
Clinical significance of organic anion transporting polypeptides (OATPs) in drug disposition: their roles in hepatic clearance and intestinal absorption
Authors: Shitara Yoshihisa , Maeda Kazuya , Ikejiri Kazuaki , Yoshida Kenta , Horie Toshiharu , Sugiyama Yuichi 
Published: November 2012

ABSTRACTOrganic anion transporting polypeptide (OATP) family transporters accept a number of drugs and are increasingly being recognized as important factors in governing drug and metabolite pharmacokinetics. OATP1B1 and OATP1B3 play an important role in hepatic drug uptake while OATP2B1 and OATP1A2 might be key players in intestinal absorption and transport across blood–brain barrier of drugs, respectively. To understand the importance of OATPs in the hepatic clearance of drugs, the rate‐determining process for elimination should be considered; for some drugs, hepatic uptake clearance rather than metabolic intrinsic clearance is the more important determinant of hepatic clearances. The importance of the unbound concentration ratio (liver/blood), Kp,uu, of drugs, which is partly governed by OATPs, is exemplified in interpreting the difference in the IC50 of statins between the hepatocyte and microsome systems for the inhibition of HMG‐CoA reductase activity. The intrinsic activity and/or expression level of OATPs are affected by genetic polymorphisms and drug–drug interactions. Their effects on the elimination rate or intestinal absorption rate of drugs may sometimes depend on the substrate drug. This is partly because of the different contribution of OATP isoforms to clearance or intestinal absorption. When the contribution of the OATP‐mediated pathway is substantial, the pharmacokinetics of substrate drugs should be greatly affected. This review describes the estimation of the contribution of OATP1B1 to the total hepatic uptake of drugs from the data of fold‐increases in the plasma concentration of substrate drugs by the genetic polymorphism of this transporter. To understand the importance of the OATP family transporters, modeling and simulation with a physiologically based pharmacokinetic model are helpful. Copyright © 2012 John Wiley & Sons, Ltd.
Modulation of the shape and speed of a chemical wave in an unstirred Belousov–Zhabotinsky reaction by a rotating magnet
Authors: Okano Hideyuki , Kitahata Hiroyuki 
Published: November 2012

AbstractThe objective of this study was to observe whether a rotating magnetic field (RMF) could change the anomalous chemical wave propagation induced by a moderate‐intensity gradient static magnetic field (SMF) in an unstirred Belousov–Zhabotinsky (BZ) reaction. The application of the SMF (maximum magnetic flux density = 0.22 T, maximum magnetic flux density gradient = 25.5 T/m, and peak magnetic force product (flux density × gradient) = 4 T2/m) accelerated the propagation velocity in a two‐dimensional pattern. Characteristic anomalous patterns of the wavefront shape were generated and the patterns were dependent on the SMF distribution. The deformation and increase in the propagation velocity were diminished by the application of an RMF at a rotation rate of 1 rpm for a few minutes. Numerical simulation by means of the time‐averaged value of the magnetic flux density gradient or the MF gradient force over one rotation partially supported the experimental observations. These considerations suggest that RMF exposure modulates the chemical wave propagation and that the degree of modulation could be, at least in part, dependent on the time‐averaged MF distribution over one rotation. Bioelectromagnetics 34:220–230, 2013. © 2012 Wiley Periodicals, Inc.
Co‐hydrolysis of lignocellulosic biomass for microbial lipid accumulation
Authors: Ruan Zhenhua , Zanotti Michael , Zhong Yuan , Liao Wei , Ducey Chad , Liu Yan 
Published: November 2012

AbstractThe herbaceous perennial energy crops miscanthus, giant reed, and switchgrass, along with the annual crop residue corn stover, were evaluated for their bioconversion potential. A co‐hydrolysis process, which applied dilute acid pretreatment, directly followed by enzymatic saccharification without detoxification and liquid–solid separation between these two steps was implemented to convert lignocellulose into monomeric sugars (glucose and xylose). A factorial experiment in a randomized block design was employed to optimize the co‐hydrolysis process. Under the optimal reaction conditions, corn stover exhibited the greatest total sugar yield (glucose + xylose) at 0.545 g g−1 dry biomass at 83.3% of the theoretical yield, followed by switch grass (0.44 g g−1 dry biomass, 65.8% of theoretical yield), giant reed (0.355 g g−1 dry biomass, 64.7% of theoretical yield), and miscanthus (0.349 g g−1 dry biomass, 58.1% of theoretical yield). The influence of combined severity factor on the susceptibility of pretreated substrates to enzymatic hydrolysis was clearly discernible, showing that co‐hydrolysis is a technically feasible approach to release sugars from lignocellulosic biomass. The oleaginous fungus Mortierella isabellina was selected and applied to the co‐hydrolysate mediums to accumulate fungal lipids due to its capability of utilizing both C5 and C6 sugars. Fungal cultivations grown on the co‐hydrolysates exhibited comparable cell mass and lipid production to the synthetic medium with pure glucose and xylose. These results elucidated that combining fungal fermentation and co‐hydrolysis to accumulate lipids could have the potential to enhance the utilization efficiency of lignocellulosic biomass for advanced biofuels production. Biotechnol. Bioeng. 2013; 110: 1039–1049. © 2012 Wiley Periodicals, Inc.
Balancing redox cofactor generation and ATP synthesis: Key microaerobic responses in thermophilic fermentations
Authors: Loftie‐Eaton Wesley , Taylor Mark , Horne Kerry , Tuffin Marla I. , Burton Stephanie G. , Cowan Don A. 
Published: November 2012

AbstractGeobacillus thermoglucosidasius is a Gram‐positive, thermophilic bacterium capable of ethanologenic fermentation of both C5 and C6 sugars and may have possible use for commercial bioethanol production [Tang et al., 2009; Taylor et al. (2009) Trends Biotechnol 27(7): 398–405]. Little is known about the physiological changes that accompany a switch from aerobic (high redox) to microaerobic/fermentative (low redox) conditions in thermophilic organisms. The changes in the central metabolic pathways in response to a switch in redox potential were analyzed using quantitative real‐time PCR and proteomics. During low redox (fermentative) states, results indicated that glycolysis was uniformly up‐regulated, the Krebs (tricarboxylic acid or TCA) cycle non‐uniformly down‐regulated and that there was little to no change in the pentose phosphate pathway. Acetate accumulation was accounted for by strong down‐regulation of the acetate CoA ligase gene (acs) in addition to up‐regulation of the pta and ackA genes (involved in acetate production), thus conserving ATP while reducing flux through the TCA cycle. Substitution of an NADH dehydrogenase (down‐regulated) by an up‐regulated NADH:FAD oxidoreductase and up‐regulation of an ATP synthase subunit, alongside the observed shifts in the TCA cycle, suggested that an oxygen‐scavenging electron transport chain likely remained active during low redox conditions. Together with the observed up‐regulation of a glyoxalase and down‐regulation of superoxide dismutase, thought to provide protection against the accumulation of toxic phosphorylated glycolytic intermediates and reactive oxygen species, respectively, the changes observed in G. thermoglucosidasius NCIMB 11955 under conditions of aerobic‐to‐microaerobic switching were consistent with responses to low pO2 stress. Biotechnol. Bioeng. 2013; 110: 1057–1065. © 2012 Wiley Periodicals, Inc.