bluuebunny/crossref_metadata_2025_split huggingface dataset:
The microenvironment in hepatocyte regeneration and function in rats with advanced cirrhosis
Authors: Liu Liping , Yannam Govardhana Rao , Nishikawa Taichiro , Yamamoto Toshiyuki , Basma Hesham , Ito Ryotaro , Nagaya Masaki , Dutta-Moscato Joyeeta , Stolz Donna B. , Duan Fenghai , Kaestner Klaus H. , Vodovotz Yoram , Soto-Gutierrez Alejandro , Fox Ira J. 
Published: November 2011

Abstract

In advanced cirrhosis, impaired function is caused by intrinsic damage to the native liver cells and from the abnormal microenvironment in which the cells reside. The extent to which each plays a role in liver failure and regeneration is unknown. To examine this issue, hepatocytes from cirrhotic and age-matched control rats were isolated, characterized, and transplanted into the livers of noncirrhotic hosts whose livers permit extensive repopulation with donor cells. Primary hepatocytes derived from livers with advanced cirrhosis and compensated function maintained metabolic activity and the ability to secrete liver-specific proteins, whereas hepatocytes derived from cirrhotic livers with decompensated function failed to maintain metabolic or secretory activity. Telomere studies and transcriptomic analysis of hepatocytes recovered from progressively worsening cirrhotic livers suggest that hepatocytes from irreversibly failing livers show signs of replicative senescence and express genes that simultaneously drive both proliferation and apoptosis, with a later effect on metabolism, all under the control of a central cluster of regulatory genes, including nuclear factor κB and hepatocyte nuclear factor 4α. Cells from cirrhotic and control livers engrafted equally well, but those from animals with cirrhosis and failing livers showed little initial evidence of proliferative capacity or function. Both, however, recovered more than 2 months after transplantation, indicating that either mature hepatocytes or a subpopulation of adult stem cells are capable of full recovery in severe cirrhosis.

Conclusion :

Transplantation studies indicate that the state of the host microenvironment is critical to the regenerative potential of hepatocytes, and that a change in the extracellular matrix can lead to regeneration and restoration of function by cells derived from livers with end-stage organ failure. (Hepatology 2011)
Peer interaction in mergers: Evidence of collective rumination
Authors: Marmenout Katty 
Published: November 2011

AbstractFollowing abundant anecdotal evidence of low morale in mergers and its important detrimental effect on postmerger performance, the purpose of this multimethod experimental study was to find out how employee reactions to a merger evolve over time following peer interaction (i.e., discussion with colleagues). Using a scenario study, initial reactions to a merger announcement were compared with socially influenced reactions. As anticipated, an overall strong detrimental effect of peer interaction on employee reactions was observed. Next, findings indicate that deal characteristics (culture clash potential, announced degree of integration, and position in deal structure) play a moderating role. Indeed, how peer interaction affects outcomes depends on the position in the deal structure. Qualitative data analysis of the group discussions sheds light on how employee reactions become more detrimental. This process is conceptualized as “collective rumination,” defined as repetitively and passively discussing organizational problems and their negative consequences with a group of peers. The study concludes with implications for practice and identifies three powerful levers (active involvement, distraction, and positive leadership) to influence the way in which employees react to the event. © 2011 Wiley Periodicals, Inc.
Previous fractures at multiple sites increase the risk for subsequent fractures: The global longitudinal study of osteoporosis in women
Authors: Gehlbach Stephen , Saag Kenneth G , Adachi Jonathan D , Hooven Fred H , Flahive Julie , Boonen Steven , Chapurlat Roland D , Compston Juliet E , Cooper Cyrus , Díez-Perez Adolfo , Greenspan Susan L , LaCroix Andrea Z , Netelenbos J Coen , Pfeilschifter Johannes , Rossini Maurizio , Roux Christian , Sambrook Philip N , Silverman Stuart , Siris Ethel S , Watts Nelson B , Lindsay Robert 
Published: November 2011

Abstract
Previous fractures of the hip, spine, or wrist are well-recognized predictors of future fracture, but the role of other fracture sites is less clear. We sought to assess the relationship between prior fracture at 10 skeletal locations and incident fracture. The Global Longitudinal Study of Osteoporosis in Women (GLOW) is an observational cohort study being conducted in 17 physician practices in 10 countries. Women aged ≥55 years answered questionnaires at baseline and at 1 and/or 2 years (fractures in previous year). Of 60,393 women enrolled, follow-up data were available for 51,762. Of these, 17.6%, 4.0%, and 1.6% had suffered 1, 2, or ≥3 fractures, respectively, since age 45 years. During the first 2 years of follow-up, 3149 women suffered 3683 incident fractures. Compared with women with no previous fractures, women with 1, 2, or ≥3 prior fractures were 1.8-, 3.0-, and 4.8-fold more likely to have any incident fracture; those with ≥3 prior fractures were 9.1-fold more likely to sustain a new vertebral fracture. Nine of 10 prior fracture locations were associated with an incident fracture. The strongest predictors of incident spine and hip fractures were prior spine fracture (hazard ratio [HR] = 7.3) and hip (HR = 3.5). Prior rib fractures were associated with a 2.3-fold risk of subsequent vertebral fracture, and previous upper leg fracture predicted a 2.2-fold increased risk of hip fracture. Women with a history of ankle fracture were at 1.8-fold risk of future fracture of a weight-bearing bone. Our findings suggest that a broad range of prior fracture sites are associated with an increased risk of incident fractures, with important implications for clinical assessments and risk model development. © 2012 American Society for Bone and Mineral Research
Esophageal and gastric cancer incidence and mortality in alendronate users
Authors: Abrahamsen Bo , Pazianas Michael , Eiken Pia , Russell R Graham G , Eastell Richard 
Published: November 2011

Abstract
Recent studies have reached conflicting conclusions regarding the risk of esophageal cancer with oral bisphosphonates. Prior studies did not record the number of cancer deaths or endoscopy rates, which could be higher in bisphosphonate users and lead to more cancers being diagnosed at a stage when their esophageal or gastric location could be accurately distinguished. We conducted a register-based, open cohort study using national healthcare data for Denmark. Upper endoscopy frequency, cancer incidence and mortality was examined in 30,606 alendronate users (female, age 50+) and 122,424 matched controls. Primary outcomes were esophageal cancer incidence and death because of esophageal cancer. The analysis showed that alendronate users were more likely to have undergone recent upper endoscopy (4.1 versus 1.7%, p &lt; 0.001). Alendronate users had a lower risk of incident gastric cancer [odds ratio (OR) 0.61; 95% confidence interval (CI): 0.39–0.97) and no increased risk of esophageal cancer (OR 0.71; 95% CI: 0.43–1.19). Risk reductions were greater in users with 10+ prescriptions. The risk of dying of esophageal cancer was significantly reduced in alendronate users after 3 years OR 0.45 (95% CI: 0.22–0.92) but not after 9 years (OR 1.01; 95% CI: 0.52–1.95). An additional comparison with etidronate users revealed no statistically significant difference in outcomes. In conclusion, we found no excess in esophageal cancer deaths or incidence. The early decrease in esophageal cancer rates may relate to the greater use of endoscopy before starting alendronate. Longer term observations also indicated no excess risk of esophageal cancer death and a significantly decreased risk of gastric cancer death. © 2012 American Society for Bone and Mineral Research
Variability of the paracrine‐induced osteoclastogenesis by human breast cancer cell lines
Authors: Costa‐Rodrigues João , Moniz Karen A. , Teixeira Manuel R. , Fernandes Maria H. 
Published: November 2011

AbstractBreast cancer frequently metastasizes to the bone, often leading to the formation of osteolytic lesions. This work compares the paracrine‐induced osteoclastogenesis mediated by four human breast cancer cell lines, the estrogen‐receptor positive T47D and MCF‐7 and the estrogen‐negative SK‐BR‐3 and Hs‐578T cell lines. Human osteoclast precursor cells were cultured in the presence of conditioned media from the breast cancer cell lines (10% and 20%), collected at different culture periods (48 h, 7 days, and 14 days). Cultures performed in the absence or the presence of M‐CSF and RANKL served as negative and positive control, respectively. Results showed that the cell lines differentially expressed several osteoclastogenic genes. All cell lines exhibited a significant osteoclastogenic potential, evidenced by a high TRAP activity and number of osteoclastic cells, expression of several osteoclast‐related genes, and, particularly, a high calcium phosphate resorption activity. Differences among the osteoclastogenic potential of the cell lines were noted. T47D and MCF‐7 cell lines displayed the highest and the lowest osteoclastogenic response, respectively. Despite the variability observed, MEK and NF‐κB signaling pathways, and, at a lesser extent, PGE2 production, seemed to have a central role on the observed osteoclastogenic response. In conclusion, the tested breast cancer cell lines exhibited a high osteoclastogenic potential, although with some variability on the cell response profile, a factor to be considered in the development of new therapeutic approaches for breast cancer‐induced bone metastasis. J. Cell. Biochem. 113: 1069–1079, 2012. © 2011 Wiley Periodicals, Inc.
Helicobacter pylori CagA inhibits the expression of Runx3 via Src/MEK/ERK and p38 MAPK pathways in gastric epithelial cell
Authors: Liu Zhifang , Xu Xia , Chen Long , Li Wenjuan , Sun Yundong , Zeng Jiping , Yu Han , Chen Chunyan , Jia Jihui 
Published: November 2011

AbstractInfection with CagA‐positive Helicobacter pylori is the strongest risk factor for gastric carcinoma. Upon delivery into gastric epithelial cells, CagA disturbs cellular functions by physically interacting with and deregulating intracellular signaling molecules via both tyrosine phosphorylation‐dependent and ‐independent mechanisms. Runx3 was suggested to be a tumor suppressor and closely associated with tumorigenesis and progression of gastric cancer. The aim of our study is to verify the effect of H. pylori virulence factor CagA on Runx3 expression level and investigate the corresponding molecular mechanisms and signaling pathways influencing Runx3 expression. Human gastric epithelial immortalized GES‐1 cells were transfected with CagA‐expression vector or control vector with FuGENE HD transfection reagent. Runx3 expression levels were determined by QRT‐PCR and immunoblotting. Then we constructed a 1,150 bp Runx3 promoter luciferase reporter plasmid, pGL3‐1150 bp, which was co‐transfected into GES‐1 cell with CagA‐expression vector or control vector. Luciferase reporter assay was used to determine the effects of CagA on the 1,150 bp promoter activity of Runx3. Signal inhibitors were used to detect the signal pathway(s) through which CagA affects Runx3. Our results showed that CagA can reduce the expression level of Runx3 at both mRNA and protein levels significantly. Importantly, the 1,150 bp Runx3 promoter activity was decreased in cells transfected with CagA‐expression vector comparing with cells transfected with control vector. And this inhibition is dependent on the phosphorylation of CagA. Signal pathways Src/MEK/ERK and p38 MAPK are involved in this regulation. Our findings provide new insights for understanding the mechanism of H. pylori carcinogenesis. J. Cell. Biochem. 113: 1080–1086, 2012. © 2011 Wiley Periodicals, Inc.
Ins and outs of Mycobacterium tuberculosis PPE family in pathogenesis and implications for novel measures against tuberculosis
Authors: Deng Wanyan , Xie Jianping 
Published: November 2011

AbstractMycobacterium tuberculosis is the most successful pathogen with multiple mechanisms to subvert host immune response, resulting in insidious disease. A unique Mycobacterium antigen family termed PPE (Pro‐Pro‐Glu) has long been widely speculated as “molecular mantra” to escape host immunity. Members of this family are characterized by a conserved N terminal and a variable C terminal. This family associated closely with ESAT‐6(ESX) secretion system and largely located in cell wall or cell membrane. The expression of PPE protein is temporally regulated, and highly expressed during M. tuberculosis persistence. Importantly, the distribution of PPE family is so far limited to Mycobacterium genus, prevalent among pathogenic Mycobacterium species. It is tempting to explore this family due to its potential in the latency and reactivation of M. tuberculosis. The evolution, structure, and functions of most PPE proteins remain elusive. The understanding of these questions will deepen our appreciation of the pathogenesis of M. tuberculosis and accelerate novel anti‐TB measures discovery. J. Cell. Biochem. 113: 1087–1095, 2012. © 2011 Wiley Periodicals, Inc.
Fluid pressure induces osteoclast differentiation comparably to titanium particles but through a molecular pathway only partly involving TNFα
Authors: Nilsson Anna , Norgård Maria , Andersson Göran , Fahlgren Anna 
Published: November 2011

AbstractIn contrast to the well‐understood inflammatory pathway driven by TNFα, by which implant‐derived particles induce bone resorption, little is known about the process in which loosening is generated as a result of force‐induced mechanical stimulus at the bone–implant interface. Specifically, there is no knowledge as to what cells or signaling pathways couple mechanical stimuli to bone resorption in context of loosening. We hypothesized that different stimuli, i.e., fluid flow versus wear particles, act through different cytokine networks for activation and localization of osteoclasts. By using an animal model in which osteoclasts and bone resorption were induced by fluid pressure or particles, we were able to detect distinct differences in osteoclast localization and inflammatory gene expression between fluid pressure and titanium particles. Fluid pressure recruits and activates osteoclasts with bone marrow contact away from the fluid pressure exposure zone, whereas titanium particles recruit and activate osteoclasts in areas in direct contact to particles. Fluid pressure induced weaker expression of the selected inflammatory related genes, although the eventual degree of osteoclast induction was similar in both models. Using TNFαRa (4 mg/kg) (Enbrel) and dexamethasone (2 mg/kg) as specific and more general suppressors of inflammation we showed that the TNFαRa failed to generate statistically impaired osteoclast generation while dexamethasone was much more potent. These results demonstrate that fluid pressure induces osteoclasts at a different localization than titanium particles by a molecular pathway less associated with TNFα and the innate system, which open up for other pathways controlling pressure induced osteoclastogenesis. J. Cell. Biochem. 113: 1224–1234, 2012. © 2011 Wiley Periodicals, Inc.
M‐Ras induces Ral and JNK activation to regulate MEK/ERK‐independent gene expression in MCF‐7 breast cancer cells
Authors: Castro Ariel F. , Campos Tania , Babcock Justin T. , Armijo Marisol E. , Martínez‐Conde Alfonso , Pincheira Roxana , Quilliam Lawrence A. 
Published: November 2011

AbstractConstitutive activation of M‐Ras has previously been reported to cause morphologic and growth transformation of murine cells, suggesting that M‐Ras plays a role in tumorigenesis. Cell transformation by M‐Ras correlated with weak activation of the Raf/MEK/ERK pathway, although contributions from other downstream effectors were suggested. Recent studies indicate that signaling events distinct from the Raf/MEK/ERK cascade are critical for human tumorigenesis. However, it is unknown what signaling events M‐Ras triggers in human cells. Using constitutively active M‐Ras (Q71L) containing additional mutations within its effector‐binding loop, we found that M‐Ras induces MEK/ERK‐dependent and ‐independent Elk1 activation as well as phosphatidylinositol 3 kinase (PI3K)/Akt and JNK/cJun activation in human MCF‐7 breast cancer cells. Among several human cell lines examined, M‐Ras‐induced MEK/ERK‐independent Elk1 activation was only detected in MCF‐7 cells, and correlated with Rlf/M‐Ras interaction and Ral/JNK activation. Supporting a role for M‐Ras signaling in breast cancer, EGF activated M‐Ras and promoted its interaction with endogenous Rlf. In addition, constitutive activation of M‐Ras induced estrogen‐independent growth of MCF‐7 cells that was dependent on PI3K/Akt, MEK/ERK, and JNK activation. Thus, our studies demonstrate that M‐Ras signaling activity differs between human cells, highlighting the importance of defining Ras protein signaling within each cell type, especially when designing treatments for Ras‐induced cancer. These findings also demonstrate that M‐Ras activity may be important for progression of EGFR‐dependent tumors. J. Cell. Biochem. 113: 1253–1264, 2012. © 2011 Wiley Periodicals, Inc.
Convergence and error estimation in free energy calculations using the weighted histogram analysis method
Authors: Zhu Fangqiang , Hummer Gerhard 
Published: November 2011

AbstractThe weighted histogram analysis method (WHAM) has become the standard technique for the analysis of umbrella sampling simulations. In this article, we address the challenges (1) of obtaining fast and accurate solutions of the coupled nonlinear WHAM equations, (2) of quantifying the statistical errors of the resulting free energies, (3) of diagnosing possible systematic errors, and (4) of optimally allocating of the computational resources. Traditionally, the WHAM equations are solved by a fixed‐point direct iteration method, despite poor convergence and possible numerical inaccuracies in the solutions. Here, we instead solve the mathematically equivalent problem of maximizing a target likelihood function, by using superlinear numerical optimization algorithms with a significantly faster convergence rate. To estimate the statistical errors in one‐dimensional free energy profiles obtained from WHAM, we note that for densely spaced umbrella windows with harmonic biasing potentials, the WHAM free energy profile can be approximated by a coarse‐grained free energy obtained by integrating the mean restraining forces. The statistical errors of the coarse‐grained free energies can be estimated straightforwardly and then used for the WHAM results. A generalization to multidimensional WHAM is described. We also propose two simple statistical criteria to test the consistency between the histograms of adjacent umbrella windows, which help identify inadequate sampling and hysteresis in the degrees of freedom orthogonal to the reaction coordinate. Together, the estimates of the statistical errors and the diagnostics of inconsistencies in the potentials of mean force provide a basis for the efficient allocation of computational resources in free energy simulations. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2012
Degeneration in the ventral cochlear nucleus after severe noise damage in mice
Authors: Feng J. , Bendiske J. , Morest D.K. 
Published: November 2011

AbstractTo study the mechanisms of noise‐induced hearing loss and the phantom noise, or tinnitus, often associated with it, we used a mouse model of noise damage designed for reproducible and quantitative structural analyses. We selected the posteroventral cochlear nucleus, which has shown considerable plasticity in past studies, and correlated its changes with the distribution of neurotrophin 3 (NT3). We used volume change, optical density analysis, and microscopic cluster analysis to measure the degeneration after noise exposure. There was a fluctuation pattern in the reorganization of nerve terminals. The data suggest that the source and size of the nerve terminals affect their capacity for regeneration. We hypothesize that the deafferentation of ventral cochlear nucleus is the structural basis of noise‐induced tinnitus. In addition, the immunofluorescent data show a possible connection between NT3 and astrocytes. There appears to be a compensatory process in the supporting glial cells during this degeneration. Glia may play a role in the mechanisms of noise‐induced hearing loss. © 2011 Wiley Periodicals, Inc.
A Novel Approach to Prepare Uniaxially Aligned Nanofibers and Longitudinally Aligned Seamless Tubes Through Electrospinning
Authors: Yang Libin , Yuan Wangzhang , Zhao Junhong , Ai Fei , Chen Xiaoyong , Zhang Yongming 
Published: November 2011

AbstractA novel method to produce uniaxially aligned nanofibers is described, in which a pair of parallel auxiliary electrodes at a positive potential is placed between the needle and the collector electrodes. Charged nanofibers ejecting from the polymer solution are pre‐aligned by the electrostatic repulsion originating from the auxiliary electrodes and deposited on the collector electrodes, forming a narrow mat with the fiber segments strongly curved. By adjusting the conductivity and shape profile of the collector, the curved segments can be straightened longitudinally. A seamless tube composed of longitudinally aligned nanofibers can be obtained. Such seamless tubes may be useful as biomaterials in tissue engineering.magnified image
Combined spin‐ and gradient‐echo perfusion‐weighted imaging
Authors: Schmiedeskamp Heiko , Straka Matus , Newbould Rexford D. , Zaharchuk Greg , Andre Jalal B. , Olivot Jean‐Marc , Moseley Michael E. , Albers Gregory W. , Bammer Roland 
Published: November 2011

AbstractIn this study, a spin‐ and gradient‐echo echo‐planar imaging (SAGE EPI) MRI pulse sequence is presented that allows simultaneous measurements of gradient‐echo and spin‐echo dynamic susceptibility‐contrast perfusion‐weighted imaging data. Following signal excitation, five readout trains were acquired using spin‐ and gradient‐echo echo‐planar imaging, all of them with echo times of less than 100 ms. Contrast agent concentrations in brain tissue were determined based on absolute R and R2 estimates rather than relative changes in the signals of individual echo trains, producing T1‐independent dynamic susceptibility‐contrast perfusion‐weighted imaging data. Moreover, this acquisition technique enabled vessel size imaging through the simultaneous quantification of R and R2, without an increase in acquisition time. In this work, the concepts of SAGE EPI pulse sequence and results in stroke and tumor imaging are presented. Overall, SAGE EPI combined the advantages of higher sensitivity to contrast agent passage of gradient‐echo perfusion‐weighted imaging with better microvascular selectivity of spin‐echo perfusion‐weighted imaging. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.