bluuebunny/crossref_metadata_2025_split huggingface dataset:
KLF1 directly coordinates almost all aspects of terminal erythroid differentiation
Authors: Tallack Michael R. , Perkins Andrew C. 
Published: December 2010

AbstractThe molecular events and transcriptional mechanisms that underlie erythropoiesis are of great interest to biologists and hematologists since disorders of erythrocytes are common and remain relatively poorly understood. Kruppel‐like factor 1 (KLF1) is a critical transcription factor for erythropoiesis in mice and man. Recently the use of chromatin immunoprecipitation (ChIP) coupled to next‐generation DNA sequencing (ChIP‐seq) has led to an updated understanding of how KLF1 functions in vivo. The full extent of KLF1 target genes have provided new insights into erythropoiesis, and have established that KLF1 controls almost all aspects of erythroid cell development and maturation. © 2010 IUBMB IUBMB Life, 62(12): 886–890
Naturally occurring organic osmolytes: From cell physiology to disease prevention
Authors: Khan Shagufta H. , Ahmad Nihal , Ahmad Faizan , Kumar Raj 
Published: December 2010

AbstractOsmolytes are naturally occurring organic compounds, which represent different chemical classes including amino acids, methylamines, and polyols. By accumulating high concentrations of osmolytes, organisms adapt to perturbations that can cause structural changes in their cellular proteins. Osmolytes shift equilibrium toward natively‐folded conformations by raising the free energy of the unfolded state. As osmolytes predominantly affect the protein backbone, the balance between osmolyte–backbone interactions and amino acid side chain–solvent interactions determines protein folding. Abnormal cell volume regulation significantly contributes to the pathophysiology of several disorders, and cells respond to these changes by importing, exporting, or synthesizing osmolytes to maintain volume homeostasis. In recent years, it has become quite evident that cells regulate many biological processes such as protein folding, protein disaggregation, and protein–protein interactions via accumulation of specific osmolytes. Many genetic diseases are attributed to the problems associated with protein misfolding/aggregation, and it has been shown that certain osmolytes can protect these proteins from misfolding. Thus, osmolytes can be utilized as therapeutic targets for such diseases. In this review article, we discuss the role of naturally occurring osmolytes in protein stability, underlying mechanisms, and their potential use as therapeutic molecules. © 2010 IUBMB IUBMB Life, 62(12): 891–895
Dynamic interaction between breast cancer cells and osteoblastic tissue: Comparison of Two‐ and Three‐dimensional cultures
Authors: Krishnan Venkatesh , Shuman Laurie A. , Sosnoski Donna M. , Dhurjati Ravi , Vogler Erwin A. , Mastro Andrea M. 
Published: December 2010

AbstractBreast cancer cell colonization of osteoblast monolayers grown in standard tissue culture (2D) is compared to colonization of a multi‐cell‐layer osteoblastic tissue (3D) grown in a specialized bioreactor. Colonization of 3D tissue recapitulates events observed in clinical samples including cancer penetration of tissue, growth of microcolonies, and formation of “Single cell file” commonly observed in end‐stage pathological bone tissue. By contrast, adherent cancer cell colonies did not penetrate 2D tissue and did not form cell files. Thus, it appears that 3D tissue is a more biologically (clinically) relevant model than 2D monolayers in which to study cancer cell interactions with osteoblastic tissue. This direct comparison of 2D and 3D formats is implemented using MC3T3‐E1 murine osteoblasts and MDA‐MB‐231 human metastatic breast cancer cells, or the metastasis‐suppressed line, MDA‐MB‐231BRMS1, for comparison. When osteoblasts were co‐cultured with metastatic cells, production of osteocalcin (a mineralization marker) decreased and secretion of the pro‐inflammatory cytokine IL‐6 increased in both 2D and 3D formats. Cancer cell penetration of the 3D tissue coincided with a changed osteoblast morphology from cuboidal to spindle‐shaped, and with osteoblasts alignment parallel to the cancer cells. Metastasis‐suppressed cells did not penetrate 3D tissue, did not cause a change in osteoblast morphology or align in rows. Moreover, they proliferated much less in the 3D culture than in the 2D culture in a manner similar to their growth in bone. In both systems, the cancer cells proliferated to a greater extent with immature osteoblasts compared to more mature osteoblasts. J. Cell. Physiol. 226: 2150–2158, 2011. © 2010 Wiley‐Liss, Inc.
PKCε promotes cardiac mitochondrial and metabolic adaptation to chronic hypobaric hypoxia by GSK3β inhibition
Authors: McCarthy Joy , Lochner Amanda , Opie Lionel H. , Sack Michael N. , Essop M. Faadiel 
Published: December 2010

AbstractPKCε is central to cardioprotection. Sub‐proteome analysis demonstrated co‐localization of activated cardiac PKCε (aPKCε) with metabolic, mitochondrial, and cardioprotective modulators like hypoxia‐inducible factor 1α (HIF‐1α). aPKCε relocates to the mitochondrion, inactivating glycogen synthase kinase 3β (GSK3β) to modulate glycogen metabolism, hypertrophy and HIF‐1α. However, there is no established mechanistic link between PKCε, p‐GSK3β and HIF1‐α. Here we hypothesized that cardiac‐restricted aPKCε improves mitochondrial response to hypobaric hypoxia by altered substrate fuel selection via a GSK3β/HIF‐1α‐dependent mechanism. aPKCε and wild‐type (WT) mice were exposed to 14 days of hypobaric hypoxia (45 kPa, 11% O2) and cardiac metabolism, functional parameters, p‐GSK3β/HIF‐1α expression, mitochondrial function and ultrastructure analyzed versus normoxic controls. Mitochondrial ADP‐dependent respiration, ATP production and membrane potential were attenuated in hypoxic WT but maintained in hypoxic aPKCε mitochondria (P < 0.005, n = 8). Electron microscopy revealed a hypoxia‐associated increase in mitochondrial number with ultrastructural disarray in WT versus aPKCε hearts. Concordantly, left ventricular work was diminished in hypoxic WT but not aPKCε mice (glucose only perfusions). However, addition of palmitate abrogated this (P < 0.05 vs. WT). aPKCε hearts displayed increased glucose utilization at baseline and with hypoxia. In parallel, p‐GSK3β and HIF1‐α peptide levels were increased in hypoxic aPKCε hearts versus WT. Our study demonstrates that modest, sustained PKCε activation blunts cardiac pathophysiologic responses usually observed in response to chronic hypoxia. Moreover, we propose that preferential glucose utilization by PKCε hearts is orchestrated by a p‐GSK3β/HIF‐1α‐mediated mechanism, playing a crucial role to sustain contractile function in response to chronic hypobaric hypoxia. J. Cell. Physiol. 226: 2457–2468, 2011. © 2010 Wiley‐Liss, Inc.
Functional role of rho‐kinase in ameloblast differentiation
Authors: Otsu Keishi , Kishigami Ryota , Fujiwara Naoki , Ishizeki Kiyoto , Harada Hidemitsu 
Published: December 2010

AbstractDuring tooth development, inner enamel epithelial (IEE) cells differentiate into enamel‐secreting ameloblasts, a polarized and elongated cellular population. The molecular underpinnings of this morphogenesis and cytodifferentiation, however, are not well understood. Here, we show that Rho‐associated coiled‐coil‐containing protein kinase (ROCK) regulates ameloblast differentiation and enamel formation. In mouse incisor organ cultures, inhibition of ROCK, hindered IEE cell elongation and disrupted polarization of differentiated ameloblasts. Expression of enamel matrix proteins, such as amelogenin and ameloblastin, and formation of the terminal band structure of actin and E‐cadherin were also perturbed. Cultures of dental epithelial cells revealed that ROCK regulates cell morphology and cell adhesion through localization of actin bundles, E‐cadherin, and β‐catenin to cell membranes. Moreover, inhibition of ROCK promoted cell proliferation. Small interfering RNA specific for ROCK1 and ROCK2 demonstrated that the ROCK isoforms performed complementary functions in the regulation of actin organization and E‐cadherin‐mediated cell–cell adhesion. Thus, our results have uncovered a novel role for ROCK in amelogenesis. J. Cell. Physiol. 226: 2527–2534, 2011. © 2010 Wiley‐Liss, Inc.
Overexpression of gastrokine 1 in gastric cancer cells induces Fas‐mediated apoptosis
Authors: Rippa Emilia , La Monica Giovanna , Allocca Rosa , Romano Maria Fiammetta , De Palma Maurizio , Arcari Paolo 
Published: December 2010

AbstractGastrokine 1 (GKN1) is involved in the replenishment of the surface lumen epithelial cell layer, in maintaining the mucosal integrity, and could play a role in cell proliferation and differentiation. In fact, after injury of the gastric mucosa, restoration may occur very rapidly in the presence of GKN1. In contrast, if the protein is downregulated, the repair process may be hampered; however, application of GKN1 to gastrointestinal cells promoted epithelial restoration. Because GKN1 possesses some mitogenic effects on intestinal epithelial cells (IEC‐6) whereas this protein was also capable of inhibiting proliferation in gastric cancer cells (MKN28), we decided to study its involvement in apoptosis to understand the role of GKN1 in the modulation of inflammatory damage or tumorigenesis in gastric mucosa. We found by cytofluorimetry, Western blot and RT‐PCR that the overexpression of GKN1 in gastric cancer cell lines (AGS and MKN28) stimulated the expression of Fas receptor. Moreover, compared to control cells, a significant increase of apoptosis, evaluated by TUNEL, was observed when GKN1 transfected cells were treated with a monoclonal antibody (IgM) anti‐Fas. The activation of Fas expression was also observed by the overexpression of GKN1 in other cancer cell lines. Moreover, in GKN1‐overexpressing gastric cancer cells exposed to FasL, the activation of caspase‐3 was also observed by Western blot and fluorescence assays. Our data represent the first report for GKN1 as modulator of apoptotic signals and suggest that GKN1 might play an important role for tissue repair during the early stages of neoplastic transformation. J. Cell. Physiol. 226: 2571–2578, 2011. © 2010 Wiley‐Liss, Inc.
The effect of endothelin‐1 on Src‐family tyrosine kinases and Na,K‐ATPase activity in porcine lens epithelium
Authors: Mandal A. , Shahidullah M. , Beimgraben C. , Delamere N.A. 
Published: December 2010

AbstractPrevious studies show Src family kinase (SFK) activation is involved in a response that stimulates Na,K‐ATPase. Here, we tested whether SFK activation is involved in the Na,K‐ATPase response to endothelin‐1 (ET‐1). Intact porcine lenses were exposed to 100 nM ET‐1 for 5–30 min. Then, the epithelium was removed and used for Na,K‐ATPase activity measurement and Western blot analysis of SFK activation. Na,K‐ATPase activity was reduced by ∼30% in lenses exposed to ET‐1 for 15 min. The response was abolished by the SFK inhibitor PP2 or the ET receptor antagonist, PD145065. Activation of a ∼61 kDa SFK was evident from an increase in Y416 phosphorylation, which reached a maximum at 15 min ET‐1 treatment, and a decrease in Y527 phosphorylation. PP2 prevented SFK activation. Since Fyn, Src, Hck, and Yes may contribute to the observed 61 kDa band, these SFKs were isolated by immunoprecipitation and analyzed. Based on Y416 phosphorylation, ET‐1 appeared to activate Fyn, while Src and Hck were inhibited and Yes was unaltered. ET‐1 requires SFK activation to cause Na,K‐ATPase inhibition. ET‐1 elicits a different pattern of SFK activation from that reported earlier for purinergic agonists that stimulate Na,K‐ATPase activity and activate Src. In the ET‐1 response Src is inhibited and Fyn is activated. The findings suggest SFK phosphorylation is involved in a regulatory mechanism for Na,K‐ATPase. Knowing this may help us understand drug actions on Na,K‐ATPase. Faulty regulation of Na,K‐ATPase in the lens could contribute to cataract formation since an abnormal sodium content is associated with lens opacification. J. Cell. Physiol. 226: 2555–2561, 2011. © 2010 Wiley‐Liss, Inc.
The requirement for proteomics to unravel stem cell regulatory mechanisms
Authors: Williamson Andrew J.K. , Whetton Anthony D. 
Published: December 2010

AbstractStem cells are defined by their ability to self‐renew and to differentiate, the processes whereby these events are achieved is the subject of much investigation. These studies include cancer stem cell populations, where eradication of this specific population is the ultimate goal of treatment. Whilst cellular signalling events and transcription factor complex‐mediated changes in gene expression have been analysed in some detail within stem cells, full systematic understanding of the events promoting self‐renewal or the commitment process leading to formation of a specific cell type require a systems biology approach. This in turn demands a need for proteomic analysis of post‐translational regulation of protein levels, protein interactions, protein post‐translational modification (e.g. ubiquitination, methylation, acetylation, phosphorylation) to identify networks for stem cell regulation. Furthermore, the phenomenon of induced pluripotency via cellular reprogramming also can be understood optimally using combined molecular biology and proteomics approaches; here we describe current research employing proteomics and mass spectrometry to dissect stem cell regulatory mechanisms. J. Cell. Physiol. 226: 2478–2483, 2011. © 2010 Wiley‐Liss, Inc.
Neutral sphingomyelinase, NADPH oxidase and reactive oxygen species. Role in acute hypoxic pulmonary vasoconstriction
Authors: Frazziano Giovanna , Moreno Laura , Moral‐Sanz Javier , Menendez Carmen , Escolano Lucía , Gonzalez Constancio , Villamor Eduardo , Alvarez‐Sala Jose Luis , Cogolludo Angel L. , Perez‐Vizcaino Francisco 
Published: December 2010

AbstractThe molecular mechanisms underlying hypoxic pulmonary vasoconstriction (HPV) are not yet properly understood. Mitochondrial electron transport chain (ETC) and NADPH oxidase have been proposed as possible oxygen sensors, with derived reactive oxygen species (ROS) playing key roles in coupling the sensor(s) to the contractile machinery. We have recently reported that activation of neutral sphingomyelinase (nSMase) and protein kinase C ζ (PKCζ) participate in the signalling cascade of HPV. Herein, we studied the significance of nSMase in controlling ROS production rate in rat pulmonary artery (PA) smooth muscle cells and thereby HPV in rat PA. ROS production (analyzed by dichlorofluorescein and dihydroethidium fluorescence) was increased by hypoxia in endothelium‐denuded PA segments and their inhibition prevented hypoxia‐induced voltage‐gated potassium channel (KV) inhibition and pulmonary vasoconstriction. Consistently, H2O2, or its analogue t‐BHP, decreased KV currents and induced a contractile response, mimicking the effects of hypoxia. Inhibitors of mitochondrial ETC (rotenone) and NADPH oxidase (apocynin) prevented hypoxia‐induced ROS production, KV channel inhibition and vasoconstriction. Hypoxia induced p47phox phosphorylation and its interaction with caveolin‐1. Inhibition of nSMase (GW4869) or PKCζ prevented p47phox phosphorylation and ROS production. The increase in ceramide induced by hypoxia (analyzed by immunocytochemistry) was inhibited by rotenone. Exogenous ceramide increased ROS production in a PKCζ sensitive manner. We propose an integrated signalling pathway for HPV which includes nSMase‐PKCζ‐NADPH oxidase as a necessary step required for ROS production and vasoconstriction. J. Cell. Physiol. 226: 2633–2640, 2011. © 2010 Wiley‐Liss, Inc.
Proteomic and functional analysis of human sperm detergent resistant membranes
Authors: Nixon Brett , Mitchell Lisa A. , Anderson Amanda L. , Mclaughlin Eileen A. , O'bryan Moira K. , Aitken R. John 
Published: December 2010

AbstractMammalian spermatozoa attain the ability to fertilize an oocyte as they negotiate the female reproductive tract. This acquisition of functional competence is preceded by an intricate cascade of biochemical and functional changes collectively known as “capacitation.” Among the universal correlates of the capacitation process is a remarkable remodeling of the lipid and protein architecture of the sperm plasma membrane. While the mechanisms that underpin this dynamic reorganization remain enigmatic, emerging evidence has raised the prospect that it may be coordinated, in part, by specialized membrane microdomains, or rafts. In the present study we have demonstrated that human spermatozoa express recognized markers of membrane rafts. Further, upon depletion of membrane cholesterol through either physiological (capacitation) or pharmacological (methyl‐β‐cyclodextrin) intervention, these membrane rafts appear to undergo a polarized redistribution to the peri‐acrosomal region of the sperm head. This finding encourages speculation that membrane rafts represent platforms for the organization of proteins involved in sperm–oocyte interactions. Support for this notion rests with the demonstration that membrane rafts isolated on the basis of their biochemical composition in the form of detergent resistant membranes (DRMs), possess the ability to adhere to homologous zona pellucidae. Furthermore a comprehensive proteomic analysis of the DRMs identified a number of proteins known for their affinity for the zona pellucida in addition to other candidates putatively involved in the mediation of downstream binding and/or fusion with the oolemma. Collectively these data afford novel insights into the subcellular localization and potential functions of membrane rafts in human spermatozoa. J. Cell. Physiol. 226: 2651–2665, 2011. © 2010 Wiley‐Liss, Inc.
Role of Doppler sonography in the diagnosis of pulmonary sequestration in an elderly patient: A case report
Authors: Huang Li‐Kuo , Tsai Ming‐Ji , Chao Heng‐Sheng , Chen Chun‐Ku , Chang Shi‐Chuan 
Published: December 2010

AbstractAn 83‐year‐old man presented with an asymptomatic mass‐like lesion in left lower lobe on chest radiograph and CT, with no change over the past 7 years. Because of discrepancy between clinical and radiological manifestations, chest color Doppler sonography was done and identified a large tortuous pulsating vessel with systemic arterial waveform flowing toward the probe and entering the lesion at its apex. Subsequent contrast‐enhanced reconstructed CT scans of the chest with angiography confirmed the diagnosis of intralobar pulmonary sequestration. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2011
Does obesity limit the sonographic diagnosis of appendicitis in children?
Authors: Yiğiter Murat , Kantarcı Mecit , Yalçin Onur , Yalçin Ahmet , Salman Ahmet Bedii 
Published: December 2010

AbstractPurpose:The purpose of this study is to evaluate whether obesity has a negative impact on the ultrasound (US) visualization of the appendix in children clinically diagnosed with appendicitis.Methods:The medical records and US examinations of 122 children who underwent surgery due to acute or perforated appendicitis between February 2007 and January 2010 were reviewed. The body mass index (BMI) of each child was calculated and children were placed in one of three categories: group 1, underweight (BMI <10th percentile); group 2, normal weight (BMI between 10th and 85th percentiles); and group 3, overweight (BMI >85th percentile). US findings were classified as nonvisualized, normal, or inflamed appendix. The visualization rates of the appendix were compared between the three groups and the diagnostic accuracy of the US examination was calculated based on the histopathological results for each group.Results:There was no statistical difference between the three groups with regard to the visualization of the appendix by US. Diagnostic accuracy of US was 90.4%, 80.5%, and 80% in group 1, group 2, and group 3, respectively.Conclusion:The findings of our study, in contrast to the findings of other reported studies, demonstrate that obesity does not affect the success rate of US in the visualization of the inflamed appendix in children. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2011
Prognostic significance of HLA class I expression in Ewing's sarcoma family of tumors
Authors: Yabe Hiroki , Tsukahara Tomohide , Kawaguchi Satoshi , Wada Takuro , Torigoe Toshihiko , Sato Noriyuki , Terai Chihiro , Aoki Masaya , Hirose Shigemichi , Morioka Hideo , Yabe Hiroo 
Published: December 2010

AbstractBackgroundEwing's sarcoma family of tumors (ESFT) is one of the most malignant groups of tumors in young people. Human leukocyte antigen (HLA) class I displays endogenously processed peptides to CD8+ T lymphocytes and has a key role for host immune surveillance. In ESFT, the investigation concerning both HLA class I expression and T‐cell infiltration has yet to be reported.MethodsBiopsy specimens from 28 ESFT patients were evaluated by immunohistochemistry with the anti‐HLA class I monoclonal antibody (mAb) EMR8‐5 and anti‐CD8 mAb, respectively.ResultsExpression of HLA class I was negative in 10 tumors and down‐regulated in 22 tumors. The status of CD8+ T cell infiltration was closely associated with the expression levels of HLA class I. ESFT patients with down‐regulated or negative expression of HLA class I showed significantly poorer survival than the rest of the patients.ConclusionsOur results suggested that CD8+ T cell‐mediated immune response restricted by HLA class I might play an important role in immune surveillance of ESFT, and we revealed for the first time that the status of HLA class I expression affects the survival of the patients with ESFT. J. Surg. Oncol. J. Surg. Oncol. 2011; 103:380–385. © 2010 Wiley‐Liss, Inc.
Invasive melanoma of the face: Management, outcomes, and the role of sentinel lymph node biopsy in 260 patients at a single institution
Authors: Chambers Anthony J. , Murynka Tania , Arlette John P. , Mckinnon J. Gregory 
Published: December 2010

AbstractBackground and ObjectivesThe face is a common site of melanoma occurrence. The purpose of this study was to examine the management and outcomes of patients with invasive melanoma of the face.MethodsPatients with invasive melanoma of the face managed at our institution from 1997 to 2008 were retrospectively reviewed. Details of sentinel lymph node biopsy (SNB), disease recurrence, and deaths were recorded.ResultsTwo hundred sixty patients were reviewed (mean age 68, mean tumor thickness 0.87 mm). Of 100 patients eligible for SNB (tumor thickness ≥ 1 mm, Clark level ≥ IV, or ulceration) this was performed in only 29 (29%), and those who underwent SNB were younger than those who did not (mean age 59 vs. 79 years, P < 0.0001). SNB was successful in 28 (97%), and no complications occurred. SNB was positive in 3 (11%). After mean follow‐up of 30 months, nodal recurrence occurred in 9 (3.5%) and distant recurrence in 20 (7.7%). There were 60 deaths (overall mortality 23%); attributed to melanoma in only 16 cases (disease specific mortality 6.2%).ConclusionsFacial melanoma is associated with low rates of regional recurrence despite underutilization of SNB. Older patients are less likely to undergo SNB. Due to the advanced age of patients with facial melanoma, most deaths occurring are from unrelated causes. J. Surg. Oncol. 2011; 103:426–430. © 2010 Wiley‐Liss, Inc.