bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel role for signal transducer and activator of transcription 5b (STAT5b) in β1-integrin-mediated human breast cancer cell migration
Authors: Bernaciak Teresa M , Zareno Jessica , Parsons J Thomas , Silva Corinne M 
Published: July 2009

Abstract
Introduction
Signal transducer and activator of transcription (STAT) 5b is a transcription factor involved in pro-proliferative and pro-survival signaling in a number of solid tumors, including breast cancer. The contribution of STAT5b to breast cancer cell motility has not been explored. This work aims to elucidate the role of STAT5b in breast cancer cell migration.

Methods
STAT5b was knocked down by using siRNA in two aggressive, highly migratory breast cancer cell lines (BT-549 and MDA-MB-231), and transwell migration assays were performed to determine the importance of STAT5b for their migration. Knockdown-rescue experiments were used to validate the specificity of STAT5b knockdown and to determine which regions/functions of STAT5b are necessary for its role in migration. Live-cell imaging of wound healing and spreading was carried out to examine cell morphology and motility after STAT5b knockdown.

Results
Knockdown of STAT5b, but not STAT5a, inhibited migration of BT-549 and MDA-MB-231 breast cancer cells to serum by 60% to 80%, and inhibited migration equally over a range of serum concentrations (0.1% to 10% serum). Migratory inhibition upon STAT5b knockdown could be rescued by reintroduction of wild-type STAT5b, as well as Y699F- and dominant-negative STAT5b mutants, but not an SH2 domain defective R618K-STAT5b mutant. β1- integrin-mediated migration of breast cancer cells to fibronectin was inhibited with STAT5b knockdown, and loss of STAT5b correlated with loss of directional migration and formation of multiple, highly contractile protrusions upon attachment to fibronectin.

Conclusions
The data presented here demonstrate that STAT5b is integral to breast cancer cell migration and identify a novel, SH2-dependent function of STAT5b in regulating β1-integrin-mediated migration of highly aggressive breast cancer cells.
Differential Endothelin Receptor Expression and Function in Rat Myometrial Cells and Leiomyoma ELT3 Cells
Authors: Raymond Marie-Noëlle , Robin Philippe , De Zen Federica , Vilain Ginette , Tanfin Zahra 
Published: July 2009

AbstractUterine leiomyoma are the most common benign tumors of the myometrium. We previously identified endothelin (ET)-1 as a proliferative and antiapoptotic factor in Eker rat-derived leiomyoma (ELT3) cells. A major role of ETB receptor in the prosurvival effect was revealed. Here we investigated, in ELT3 and myometrial cells, the respective contribution of ETA and ETB in the proliferative effect of ET-1. In myometrial cells, binding experiments show that ETA is almost exclusively expressed and stimulates phospholipase C (PLC) activity and ERK1/2 phosphorylation and proliferation. In ELT3 cells, ETB is expressed at about the same level as ETA, and the two receptors are differently coupled to Gi protein. The ETB agonist, sarafotoxin S6c, stimulates PLC activity 60% less than ET-1 but is as potent as ET-1 to increase ERK1/2 phosphorylation and induce proliferation. However, the ability of ETA to activate ERK1/2 is observed after ETB desensitization. Although ETA and ETB antagonists partially reduce ET-1 stimulated PLC activity, they are without effect on ET-1-induced ERK1/2 phosphorylation and proliferation. Only the simultaneous use of ETA and ETB antagonists reduces ET-1-triggered ERK1/2 activation. These unconventional properties of ETRs may reveal the existence of functional ETA-ETB heterodimers. Finally, treatment of ELT3 cells with ETB but not ETA-directed small interfering RNA reduces the proliferative effect of ET-1. All the data obtained in ELT3 cells strengthen the relation between ETB overexpression, which decreases the ETA to ETB ratio, and the ability of leiomyoma cells to highly proliferate and resist apoptosis.
Low- and High-Density Lipoproteins Modulate Function, Apoptosis, and Proliferation of Primary Human and Murine Pancreatic β-Cells
Authors: Rütti Sabine , Ehses Jan A. , Sibler Rahel A. , Prazak Richard , Rohrer Lucia , Georgopoulos Spiros , Meier Daniel T. , Niclauss Nadja , Berney Thierry , Donath Marc Y. , von Eckardstein Arnold 
Published: July 2009

AbstractA low high-density lipoprotein (HDL) plasma concentration and the abundance of small dense low-density lipoproteins (LDL) are risk factors for developing type 2 diabetes. We therefore investigated whether HDL and LDL play a role in the regulation of pancreatic islet cell apoptosis, proliferation, and secretory function. Isolated mouse and human islets were exposed to plasma lipoproteins of healthy human donors. In murine and human β-cells, LDL decreased both proliferation and maximal glucose-stimulated insulin secretion. The comparative analysis of β-cells from wild-type and LDL receptor-deficient mice revealed that the inhibitory effect of LDL on insulin secretion but not proliferation requires the LDL receptor. HDL was found to modulate the survival of both human and murine islets by decreasing basal as well as IL-1β and glucose-induced apoptosis. IL-1β-induced β-cell apoptosis was also inhibited in the presence of either the delipidated protein or the deproteinated lipid moieties of HDL, apolipoprotein A1 (the main protein component of HDL), or sphingosine-1-phosphate (a bioactive sphingolipid mostly carried by HDL). In murine β-cells, the protective effect of HDL against IL-1β-induced apoptosis was also observed in the absence of the HDL receptor scavenger receptor class B type 1. Our data show that both LDL and HDL affect function or survival of β-cells and raise the question whether dyslipidemia contributes to β-cell failure and hence the manifestation and progression of type 2 diabetes mellitus.
Complex Regulation of Mammalian Target of Rapamycin Complex 1 in the Basomedial Hypothalamus by Leptin and Nutritional Status
Authors: Villanueva Eneida C. , Münzberg Heike , Cota Daniela , Leshan Rebecca L. , Kopp Keely , Ishida-Takahashi Ryoko , Jones Justin C. , Fingar Diane C. , Seeley Randy J. , Myers Martin G. 
Published: July 2009

Abstract
The medial basal hypothalamus, including the arcuate nucleus (ARC) and the ventromedial hypothalamic nucleus (VMH), integrates signals of energy status to modulate metabolism and energy balance. Leptin and feeding regulate the mammalian target of rapamycin complex 1 (mTORC1) in the hypothalamus, and hypothalamic mTORC1 contributes to the control of feeding and energy balance. To determine the mechanisms by which leptin modulates mTORC1 in specific hypothalamic neurons, we immunohistochemically assessed the mTORC1-dependent phosphorylation of ribosomal protein S6 (pS6). In addition to confirming the modulation of ARC mTORC1 activity by acute leptin treatment, this analysis revealed the robust activation of mTORC1-dependent ARC pS6 in response to fasting and leptin deficiency in leptin receptor-expressing Agouti-related protein neurons. In contrast, fasting and leptin deficiency suppress VMH mTORC1 signaling. The appropriate regulation of ARC mTORC1 by mutant leptin receptor isoforms correlated with their ability to suppress the activity of Agouti-related protein neurons, suggesting the potential stimulation of mTORC1 by the neuronal activity. Indeed, fasting- and leptin deficiency-induced pS6-immunoreactivity (IR) extensively colocalized with c-Fos-IR in ARC and VMH neurons. Furthermore, ghrelin, which activates orexigenic ARC neurons, increased ARC mTORC1 activity and induced colocalized pS6- and c-Fos-IR. Thus, neuronal activity promotes mTORC1/pS6 in response to signals of energy deficit. In contrast, insulin, which activates mTORC1 via the phosphatidylinositol 3-kinase pathway, increased ARC and VMH pS6-IR in the absence of neuronal activation. The regulation of mTORC1 in the basomedial hypothalamus thus varies by cell and stimulus type, as opposed to responding in a uniform manner to nutritional and hormonal perturbations.
Lower Zinc-α2-Glycoprotein Production by Adipose Tissue and Liver in Obese Patients Unrelated to Insulin Resistance
Authors: Selva David M. , Lecube Albert , Hernández Cristina , Baena Juan A. , Fort José M. , Simó Rafael 
Published: July 2009

Context: Zinc-α2 glycoprotein (ZAG) has been proposed as a new candidate in the pathogenesis of obesity, but most of the information stems from studies performed in rodents and in vitro assays.
Objective: The main aim of the study was to compare serum levels of ZAG and its expression (mRNA levels and protein) in adipose tissue and the liver between obese and nonobese subjects. The relationship between ZAG and insulin resistance was also explored.
Design: This was a case-control study.
Setting: The study was conducted at a university referral center.
Patients and Methods: Samples of serum, sc adipose tissue (SAT), visceral adipose tissue (VAT), and liver were obtained from 20 obese subjects during bariatric surgery. Samples from 10 nonobese patients matched by age and gender were used as a control group. Serum ZAG levels were determined by ELISA. ZAG mRNA levels were measured by real-time PCR and protein content by Western blot. The effect of insulin on liver production of ZAG was assessed using HepG2 cultures.
Results: Serum concentration of ZAG (micrograms per milliliter) was significantly lower in obese subjects (40.87 ± 10.45 vs. 63.26 ± 16.40; P = 0.002). ZAG expression was significantly lower in the adipose tissue (SAT and VAT) and liver of obese patients than in control subjects. Significant negative correlations between body mass index and circulating ZAG (r = −0.65, P &lt; 0.001) as well as between body mass index and mRNA ZAG levels in SAT (r = −0.68, P &lt; 0.001) and VAT were detected (r = −0.64, P &lt; 0.001). No relationship was found between ZAG and homeostasis model assessment for insulin resistance and insulin had no effect on ZAG production in vitro.
Conclusion: A down-regulation of ZAG in SAT, VAT, and liver exists in obese patients but seems unrelated to insulin resistance.
A downregulation of zinc-α2 glycoprotein in adipose tissue and liver exists in obese patients, and it is unrelated to insulin resistance.
Rhenium-catalyzed Regio- and Stereoselective Dimerization and Cyclotrimerization of Terminal Alkynes
Authors: Kawata Atsushi , Kuninobu Yoichiro , Takai Kazuhiko 
Published: July 2009

Abstract
A combination of catalytic amounts of [ReBr(CO)3(thf)]2 and tetrabutylammonium fluoride (TBAF) promoted the dimerization of aryl- and alkenyl-substituted alkynes with high regio- and stereoselectivities, and gave only (E)-enynes. When terminal alkynes having a carbonyl group were employed as substrates, regioselective cyclotrimerization of the alkynes occurred to give 1,3,5-trisubstituted aromatic compounds.
A Case of Resistant Hypercalcemia of Malignancy with a Proposed Treatment Algorithm
Authors: McMahan Jonathan , Linneman Travis 
Published: July 2009

Objective: To report and describe a case of refractory hypercalcemia of malignancy (HCM) associated with metastatic, transitional-cell carcinoma of the left ureter. Case Summary: A 71-year-old male complaining of generalized weakness and night sweats for the past 3 months was sent to the emergency department when routine laboratory tests revealed a corrected serum calcium concentration of 14.4 mg/dL. Intravenous crystalloid fluids and pamidronate were administered with achievement of normocalcemia, and the patient was discharged. Computed tomography scan and liver biopsy revealed recurrent transitional-cell carcinoma with extensive liver metastasis. The patient returned approximately 1 week after discharge with a serum calcium level of 13.9 mg/dL. An initial decrease in serum calcium was observed with intravenous fluids, pamidronate, and calcitonin, but the normalization slowed and reversed within 3 days. Normocalcemia was achieved upon administration of zoledronic acid and the patient was discharged on day 14. The patient died 1 week after discharge from complications unrelated to hypercalcemia. Discussion: Hypercalcemia is common in patients with malignancy and is associated with potentially life-threatening sequelae. Four mechanisms of HCM have been recognized thus far, with ectopic tumor production of parathyroid hormone—related protein (PTHrP) being the leading cause. Treatment of HCM revolves around 2 principles; treatment of the underlying malignancy along with reduction of the serum calcium level. Evidence-based therapies for management include: intravenous crystalloid fluids with or without loop diuretics, bisphosphonates, calcitonin, gallium nitrate, and corticosteroids. Therapies used for this patient included aggressive hydration, calcitonin, and 3 distinct treatment courses of intravenous bisphosphonates with varying success. Other potential agents were explored for use in the event of continued hypercalcemia. These therapies remain viable options based on individual patient factors. To our knowledge, no published guidelines or algorithms exist for choosing between additional modalities in the treatment of refractory HCM. Conclusions: For patients with HCM who do not achieve a response from bisphosphonates, or for those who need repeated dosing more often than expected, changing to a different drug class could be an alternative. The specific mechanism of hypercalcemia should be considered when developing a treatment regimen for patients who have had a suboptimal response to initial therapy with bisphosphonates. Multiple treatment modalities exist for the treatment of hypercalcemia, each with a different mechanism of action. As with the treatment of other disease states, we can use this knowledge to more specifically target the mechanism of the patient's disease.
Denosumab in Osteoporosis and Oncology
Authors: Burkiewicz Jill S , Scarpace Sarah L , Bruce Susan P 
Published: July 2009

Objective: To review the pharmacology, pharmacokinetics, pharmacodynamics, safety, efficacy, and use of denosumab in osteoporosis, breast cancer, prostate cancer, and multiple myeloma. Data Sources: Studies and abstracts were identified through MEDLINE and International Pharmaceutical Abstracts (1966–July 2009). Key search terms include denosumab, AMG-162, and receptor activator of nuclear factor-κB ligand system. Information available in abstract form was retrieved from major oncology and bone metabolism meetings. Additional data were obtained from the manufacturer. Study Selection and Data Extraction: All available studies in humans were included except for studies in rheumatoid arthritis and giant cell tumor of the bone. Data Synthesis: In patients with osteoporosis, denosumab significantly reduces bone resorption and fractures. Studies of denosumab in the prevention and treatment of osteoporosis have demonstrated significantly increased bone mineral density and reduced bone turnover markers. Studies of denosumab versus placebo in the treatment of osteoporosis have demonstrated reductions in vertebral, hip, and nonvertebral fractures. In oncology, positive results from clinical trials in patients receiving endocrine therapy for breast and prostate cancer demonstrated decreases in bone loss and skeletal-related events. Denosumab seems to be at least as effective in reducing bone turnover markers as intravenous bisphosphonates in the oncology setting. The most common adverse effects in patients with osteoporosis were arthralgia, nasopharyngitis, back pain, and headache. The most common adverse effects in patients with cancer were infection, pain in the extremities, arthralgia, bone pain, fatigue, and pain. Serious adverse effects include infections requiring hospitalization. Conclusions: Denosumab has documented efficacy and safety in patients with osteoporosis, breast cancer, and prostate cancer. Additional clinical trial data are needed to more completely establish the effectiveness of denosumab in the treatment of osteoporosis and neoplastic disease as well as its cost-effectiveness and long-term safety.
Associations Among Therapist Beliefs, Personal Resources and Burnout in Clinical Psychologists
Authors: Emery Sally , Wade Tracey D. , McLean Sara 
Published: July 2009

AbstractThere were two aims of the research with 190 Australian clinical psychologists: (1) to investigate the construct validity of the Therapist Belief Scale (TBS), and (2) to examine the relative contribution of demographics, workplace variables, and individual factors to burnout. Construct validity was examined using exploratory and confirmatory factor analyses and associations between the variables. Multivariate regressions were used to examine the relative contributions to burnout. The TBS showed three factors related to distress, inflexibility, and control, all of which were significantly associated with lower levels of personal accomplishment. Multivariate analyses showed emotional exhaustion to be associated being a woman, working for the government, having less personal resources, and endorsing more therapist beliefs related to control. Higher levels of personal accomplishment were significantly associated with a lower annual income, not having a mixed caseload, having more personal resources, and endorsing lower levels of therapist beliefs related to inflexibility and control.
Synthesis of a lignin polymer model consisting of only phenolic β-O-4 linkages and testing its reactivity under alkaline conditions 10th EWLP, Stockholm, Sweden, August 25–28, 2008
Authors: Megiatto Jackson D. , Cazeils Emmanuel , Grelier Stéphane , Gardrat Christian , Ham-Pichavant Frédérique , Castellan Alain 
Published: July 2009

Abstract
A trimeric β-O-4 lignin model bearing a styrene unit was polymerized in the presence of azobisisobutyronitrile as an initiator of free radical polymerization. The polymer analysis achieved by size exclusion chromatography (SEC), 1H, 13C, 31P NMR, matrix-assisted laser desorption ionization combined with time-of-flight mass spectrometry (MALDI-ToF MS), differential scanning calorimetry, and thermogravimetry indicated its well-defined structure with good thermal stability at temperatures usually applied for alkaline pulping. SEC analysis proved a high degree of polymerization despite the size of the phenolic β-O-4 units in the polymer structure. MALDI-ToF spectrometry indicated that the polymer is composed of phenolic β-O-4 elements only. The chemical reactivity under alkaline conditions of the polymer was studied by both HPLC and 31P NMR. These two methods revealed two main concurrent processes, which include an oxidation of the phenol part followed by Cα-Cβ bond cleavage, and a formation of a quinone methide followed by its β-O-4 bond cleavage.
Material Variability and Repetitive Member Factors for the Allowable Properties of Engineered Wood Products
Authors: Verrill Steve , Kretschmann David E. 
Published: July 2009

Abstract
It has been argued that repetitive member allowable property adjustments should be larger for high-variability materials than for low-variability materials. We report analytic calculations and simulations that suggest that the order of such adjustments should be reversed, that is, given the manner in which allowable properties are currently calculated, as the coefficient of variation of the strength distribution of individual elements increases, the upward repetitive member adjustments (if any) of assemblies constructed from these elements should decrease.
Analyzing Settling of Fine-Grained Soil by Electrical Resistance Measurements
Authors: Verástegui Flores R. D. , Di Emidio G. , Van Impe W. F. 
Published: July 2009

Abstract
The industry and construction sector face an increasing problem of how to dispose of its voluminous residues. Much of these residues are constituted of large amounts of liquid phase and fine-grained solids in suspension, for example mine tailings and dredged materials. Therefore, there is a need to develop technologies that aim at reducing the volume of these residues for economical disposal or treatment. Depending on the type of solid and liquid phase, a number of additives are currently used to speed up the sedimentation and reduce the volume of these suspensions. In order to investigate the impact of different additives, a laboratory setup was designed to monitor the sedimentation process. This setup consists of a transparent plastic tube provided with electrodes. This paper focuses on the evaluation and performance of electrical resistance measurement as a means to monitor the sedimentation of a fine-grained soil. Experimental work was carried out on suspensions of kaolin clay in deionized water and electrolyte solutions. The results showed that electrical resistance measurements can provide valuable information related to densification and fabric of the soft sediment.
Associations Between Dietary Fiber and Inflammation, Hepatic Function, and Risk of Type 2 Diabetes in Older Men
Authors: Wannamethee S. Goya , Whincup Peter H. , Thomas Mary C. , Sattar Naveed 
Published: July 2009

OBJECTIVE
To examine the relationship between dietary fiber and the risk of type 2 diabetes in older men and the role of hepatic and inflammatory markers.

RESEARCH DESIGN AND METHODS
The study was performed prospectively and included 3,428 nondiabetic men (age 60–79 years) followed up for 7 years, during which there were 162 incident cases of type 2 diabetes.

RESULTS
Low total dietary fiber (lowest quartile ≤20 g/day) was associated with increased risk of diabetes after adjustment for total calorie intake and potential confounders (relative risk −1.47 [95% CI 1.03–2.11]). This increased risk was seen separately for both low cereal and low vegetable fiber intake. Dietary fiber was inversely associated with inflammatory markers (C-reactive protein, interleukin-6) and with tissue plasminogen activator and γ-glutamyl transferase. Adjustment for these markers attenuated the increased risk (1.28 [0.88–1.86]).

CONCLUSIONS
Dietary fiber is associated with reduced diabetes risk, which may be partly explained by inflammatory markers and hepatic fat deposition.