bluuebunny/crossref_metadata_2025_split huggingface dataset:
Luteinizing Hormone–Induced Up-Regulation of ErbB-2 Is Insufficient Stimulant of Growth and Invasion in Ovarian Cancer Cells
Authors: Warrenfeltz Susanne W. , Lott Stephen A. , Palmer Travis M. , Gray Judy C. , Puett David 
Published: November 2008

Abstract
The effects of luteinizing hormone (LH), a gonadotropic hormone implicated in the development of ovarian cancer, are mediated by specific binding to its G protein–coupled receptor, the LH receptor (LHR). Activated LHR initiates second messenger responses, including cyclic AMP (cAMP) and inositol phosphate. Because cAMP increases expression of ErbB-2, a receptor tyrosine kinase whose overexpression in cancers correlates with poor survival, we hypothesized that LH may regulate ErbB-2 expression. Cell surface LHR expression in stable transformants of the ErbB-2–overexpressing ovarian cancer cell line SKOV3 was confirmed by PCR and whole-cell ligand binding studies. Second messenger accumulation in the LHR-expressing cells confirmed signaling through Gs and Gq. Western blots of total protein revealed that LHR introduction up-regulated ErbB-2 protein expression 2-fold and this was further up-regulated in a time- and dose-dependent manner in response to LH. Forskolin and 8Br-cAMP also up-regulated ErbB-2 in both LHR-expressing and mock-transfected cells, indicating that regulation of ErbB-2 is a cAMP-mediated event. Kinase inhibitor studies indicated the involvement of protein kinase A–mediated, protein kinase C–mediated, epidermal growth factor receptor–mediated, and ErbB-2–mediated mechanisms. The LH-induced up-regulation of ErbB-2 was insufficient to overcome the negative effects of LH on proliferation, invasion, and migration. A molecular signature for this nonaggressive phenotype was determined by Taqman array to include increased and decreased expression of genes encoding adhesion proteins and metalloproteinases, respectively. These data establish a role for LH and LHR in the regulation of ErbB-2 expression and suggest that, in some systems, ErbB-2 up-regulation alone is insufficient in producing a more aggressive phenotype. (Mol Cancer Res 2008;6(11):1775–85)
An insulator with barrier-element activity promotes α-spectrin gene expression in erythroid cells
Authors: Gallagher Patrick G. , Nilson Douglas G. , Steiner Laurie A. , Maksimova Yelena D. , Lin Jolinta Y. , Bodine David M. 
Published: November 2008

AbstractUnderstanding mechanisms controlling expression of the α-spectrin gene is important for understanding erythropoiesis, membrane biogenesis, and spectrin-linked hemolytic anemia. We showed previously that a minimal α-spectrin promoter directed low levels of expression only in early erythroid development, indicating elements outside the promoter are required for expression in adult erythrocytes. Addition of noncoding exon 1′ and intron 1′ conferred a 10-fold increase in activity in reporter gene assays. In this report, we used a transgenic mouse model to show that addition of exon 1′ and intron 1′ to the α-spectrin promoter conferred tissue-specific expression of a linked Aγ-globin gene in erythroid cells at all developmental stages. Expression was nearly position-independent, as 21 of 23 lines expressed the transgene, and γ-globin protein was present in 100% of erythrocytes, indicating uniform expression. Additional in vivo studies revealed that exon 1′ functions as an insulator with barrier-element activity. Chromatin immunoprecipitation assays demonstrated that this region was occupied by the upstream stimulatory factors 1/2 (USF1/USF2), similar to the well-characterized chicken HS4 insulator. These data identify the first barrier element described in an erythrocyte membrane protein gene and indicate that exon 1′ and intron 1′ are excellent candidate regions for mutations in patients with spectrin-linked hemolytic anemia.
IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner
Authors: Azevedo Rita I. , Soares Maria Vieira D. , Barata João T. , Tendeiro Rita , Serra-Caetano Ana , Victorino Rui M. M. , Sousa Ana E. 
Published: November 2008

AbstractThe CD31+ subset of human naive CD4+ T cells is thought to contain the population of cells that have recently emigrated from the thymus, while their CD31− counterparts have been proposed to originate from CD31+ cells after homeostatic cell division. Naive T-cell maintenance is known to involve homeostatic cytokines such as interleukin-7 (IL-7). It remains to be investigated what role this cytokine has in the homeostasis of naive CD4+ T-cell subsets defined by CD31 expression. We provide evidence that IL-7 exerts a preferential proliferative effect on CD31+ naive CD4+ T cells from adult peripheral blood compared with the CD31− subset. IL-7–driven proliferation did not result in loss of CD31 expression, suggesting that CD31+ naive CD4+ T cells can undergo cytokine-driven homeostatic proliferation while preserving CD31. Furthermore, IL-7 sustained or increased CD31 expression even in nonproliferating cells. Both proliferation and CD31 maintenance were dependent on the activation of phosphoinositide 3-kinase (PI3K) signaling. Taken together, our data suggest that during adulthood CD31+ naive CD4+ T cells are maintained by IL-7 and that IL-7–based therapies may exert a preferential effect on this population.
Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry
Authors: Juliusson Gunnar , Antunovic Petar , Derolf Åsa , Lehmann Sören , Möllgård Lars , Stockelberg Dick , Tidefelt Ulf , Wahlin Anders , Höglund Martin 
Published: November 2008

AbstractAcute myeloid leukemia (AML) is most common in the elderly, and most elderly are thought to be unfit for intensive treatment because of the risk of fatal toxicity. The Swedish Acute Leukemia Registry covers 98% of all patients with AML (nonacute promyelocytic leukemia) diagnosed in 1997 to 2005 (n = 2767), with a median follow-up of 5 years, and reports eligibility for intensive therapy, performance status (PS), complete remission rates, and survival. Outcomes were strongly age and PS dependent. Early death rates were always lower with intensive therapy than with palliation only. Long-term survivors were found among elderly given intensive treatment despite poor initial PS. Total survival of elderly AML patients was better in the geographic regions where most of them were given standard intensive therapy. This analysis provides unique real world data from a large, complete, and unselected AML population, both treated and untreated, and gives background to treatment decisions for the elderly. Standard intensive treatment improves early death rates and long-term survival compared with palliation. Most AML patients up to 80 years of age should be considered fit for intensive therapy, and new therapies must be compared with standard induction.
Differential impact ofl-arginine deprivation on the activation and effector functions of T cells and macrophages
Authors: Choi B-S , Martinez-Falero I Clara , Corset C , Munder M , Modolell M , Müller I , Kropf P 
Published: November 2008

AbstractThe metabolism of the amino acid l-arginine is emerging as a crucial mechanism for the regulation of immune responses. Here, we characterized the impact of l-arginine deprivation on T cell and macrophage (MΦ) effector functions: We show that whereas l-arginine is required unconditionally for T cell activation, MΦ can up-regulate activation markers and produce cytokines and chemokines in the absence of l-arginine. Furthermore, we show that l-arginine deprivation does not affect the capacity of activated MΦ to up-regulate l-arginine-metabolizing enzymes such as inducible NO synthase and arginase 1. Thus, our results show that to exert their effector functions, T cells and MΦ have different requirements for l-arginine.
Orexin-A Hyperphagia: Hindbrain Participation in Consummatory Feeding Responses
Authors: Baird John-Paul , Choe Angela , Loveland Jasmine L. , Beck Janine , Mahoney Carrie E. , Lord Julia S. , Grigg Lindsay A. 
Published: November 2008

Orexin-A (ORXA) is an orexigenic neuropeptide produced by the lateral hypothalamus that increases food intake when injected into the brain ventricles or forebrain nuclei. We used a licking microstructure analysis to evaluate hindbrain and forebrain ORXA effects in intact and hindbrain-lesioned rats, to identify the motivational and anatomical bases of ORXA hyperphagia. Intact rats with cannulas in the fourth brain ventricle (4V) received vehicle (artificial cerebrospinal fluid) or ORXA (0.1, 0.4, 1, or 10 nm) injections before 90 min access to 0.1 m sucrose. Meal size and frequency were increased in a double-dissociated manner by the 1 and 10 nm doses, respectively. In experiment 2, 4V 1 nm ORXA was applied to rats offered solutions varied in caloric and gustatory intensity (water and 0.1 and 1 m sucrose). ORXA increased meal frequency for all tastants. ORXA increased meal size only for 0.1 m sucrose, by prolonging the meal without affecting early ingestion rate or lick burst size, suggesting that 4V ORXA influenced inhibitory postingestive feedback rather than taste evaluation. In experiment 3, rats with cannulas in the third ventricle (3V) received dorsal medullary lesions centered on the area postrema (APX group) or sham procedures, and licking for water and 0.1 and 1 m sucrose was evaluated after 1 nm 3V ORXA/artificial cerebrospinal fluid injections. The 3V ORXA increased 0.1 m sucrose meal size and meal frequency for all tastants in the sham group, as observed after 4V ORXA in experiment 2. In the APX group, 3V ORXA injections influenced meal frequency, but they no longer increased meal size. However, the APX rats increased meal size for 0.1 m sucrose after food and water deprivation and after 3V angiotensin II injection. They also showed meal size suppression after 3V injection of the melanocortin-3/4 receptor agonist melanotan II (1 nm). These findings suggest that the area postrema and subjacent nucleus of the solitary tract are necessary for increases in consummatory (meal size) but not appetitive (meal frequency) responses to 3V ORXA. The meal size increases may be due to reduced postingestive feedback inhibition induced by ORXA delivered to either the hindbrain or forebrain ventricles.
Orexin-A increases meal size via gut feedback disinhibition, not enhanced gustatory evaluation. Medullary lesions abolish meal size but not frequency increases, indicating dissociable sites for orexin-A feeding actions.
The Glucagon-Like Peptide-1 Receptor Regulates Endogenous Glucose Production and Muscle Glucose Uptake Independent of Its Incretin Action
Authors: Ayala Julio E. , Bracy Deanna P. , James Freyja D. , Julien Brianna M. , Wasserman David H. , Drucker Daniel J. 
Published: November 2008

Glucagon-like peptide-1 (GLP-1) diminishes postmeal glucose excursions by enhancing insulin secretion via activation of the β-cell GLP-1 receptor (Glp1r). GLP-1 may also control glucose levels through mechanisms that are independent of this incretin effect. The hyperinsulinemic-euglycemic clamp (insulin clamp) and exercise were used to examine the incretin-independent glucoregulatory properties of the Glp1r because both perturbations stimulate glucose flux independent of insulin secretion. Chow-fed mice with a functional disruption of the Glp1r (Glp1r−/−) were compared with wild-type littermates (Glp1r+/+). Studies were performed on 5-h-fasted mice implanted with arterial and venous catheters for sampling and infusions, respectively. During insulin clamps, [3-3H]glucose and 2[14C]deoxyglucose were used to determine whole-body glucose turnover and glucose metabolic index (Rg), an indicator of glucose uptake. Rg in sedentary and treadmill exercised mice was determined using 2[3H]deoxyglucose. Glp1r−/− mice exhibited increased glucose disappearance, muscle Rg, and muscle glycogen levels during insulin clamps. This was not associated with enhanced muscle insulin signaling. Glp1r−/− mice exhibited impaired suppression of endogenous glucose production and hepatic glycogen accumulation during insulin clamps. This was associated with impaired liver insulin signaling. Glp1r−/− mice became significantly hyperglycemic during exercise. Muscle Rg was normal in exercised Glp1r−/− mice, suggesting that hyperglycemia resulted from an added drive to stimulate glucose production. Muscle AMP-activated protein kinase phosphorylation was higher in exercised Glp1r−/− mice. This was associated with increased relative exercise intensity and decreased exercise endurance. In conclusion, these results show that the endogenous Glp1r regulates hepatic and muscle glucose flux independent of its ability to enhance insulin secretion.
During increased glucose flux, the glucagon-like peptide-1 receptor regulates endogenous glucose production and muscle glucose uptake independent of its ability to stimulate insulin secretion.
Differential Neuroendocrine Expression of Multiple Brain-Derived Neurotrophic Factor Transcripts
Authors: Kidane Adhanet H. , Heinrich Gerhard , Dirks Ron P. H. , de Ruyck Brechje A. , Lubsen Nicolette H. , Roubos Eric W. , Jenks Bruce G. 
Published: November 2008

Brain-derived neurotrophic factor (BDNF) is a neurotrophin with important growth-promoting properties. We report here the first characterization of a BDNF gene in an amphibian, Xenopus laevis, and demonstrate that environmental factors can activate this gene in a promoter-specific fashion. The Xenopus BDNF gene contains six promoter-specific 5′-exons and one 3′-protein-encoding exon. We examined the expression of promoter-specific transcripts in Xenopus neuroendocrine melanotrope cells. These cells make a good model to study how environmental factors control gene expression. In animals placed on a black background melanotrope cells more actively produce and release αMSH than in animals on a white background. BDNF is cosequestered and coreleased with αMSH and stimulates biosynthesis of proopiomelanocortin (POMC), the precursor protein for αMSH. Our analysis of the expression of the BDNF transcripts revealed that there is differential use of some BDNF promoters in melanotrope cells, depending on the adaptation state of the frog. During black-background adaptation, stimulation of expression of BDNF transcript IV preceded that of the POMC transcript, suggesting the BDNF gene is an effector gene for POMC expression. The possible mechanisms regulating expression of the various transcripts are discussed on the basis of the potential calcium- and cAMP-responsive elements in the promoter region of exon IV. Finally, we show that the upstream open reading frames of BDNF transcripts I and IV markedly decrease BDNF translation efficiency, giving the first indication for a functional role of untranslated BDNF exons.We show promoter-specific expression of BDNF transcripts in neuroendocrine melanotrope cells and provide evidence that upstream open reading frames of BDNF transcripts decrease translation efficiency.
Cells Expressing RFamide-Related Peptide-1/3, the Mammalian Gonadotropin-Inhibitory Hormone Orthologs, Are Not Hypophysiotropic Neuroendocrine Neurons in the Rat
Authors: Rizwan Mohammed Z. , Porteous Robert , Herbison Allan E. , Anderson Greg M. 
Published: November 2008

An RFamide peptide named gonadotropin-inhibitory hormone, which directly inhibits gonadotropin synthesis and secretion from the anterior pituitary gland, has recently been discovered in the avian hypothalamus. It is not known whether the mammalian orthologs of gonadotropin-inhibitory hormone and RFamide-related peptide (RFRP)-1 and -3 act in the same way. We used a newly generated antibody against the rat RFRP precursor combined with retrograde tract tracing to characterize the cell body distribution and fiber projections of RFRP-1 and -3 neurons in rats. RFRP-1/3-immunoreactive cell bodies were found exclusively within the dorsomedial hypothalamus. Immunoreactive fibers were observed in the septal-preoptic area, hypothalamus, midbrain, brainstem, and hippocampus but not in the external zone of the median eminence. Intraperitoneal injection of the retrograde tracer Fluoro-Gold in rats resulted in the labeling of the majority of GnRH neurons but essentially no RFRP-1/3 neurons. In contrast, intracerebral injections of Fluoro-Gold into the rostral preoptic area and CA2/CA3 hippocampus resulted in the labeling of 75 ± 5% and 21 ± 8% of RFRP-1/3 cell bodies, respectively. To assess actions at the pituitary in vivo, RFRP-3 was administered as an iv bolus to ovariectomized rats and plasma LH concentration measured at 0, 2.5, 5, 10, and 30 min. RFRP-3 had no effects on basal secretion, but GnRH-stimulated LH release was reduced by about 25% at 5 min. Together these observations suggest that RFRP-3 is not a hypophysiotropic neuroendocrine hormone in rats.
Hypothalamic RFRP-1/3 neurons project to the preoptic area and hippocampus but not the median eminence, suggesting that RFRP-1/3 is not a hypophysiotropic gonadotropin inhibitor in the rat.
Blockade of Estrogen Receptor Signaling Inhibits Growth and Migration of Medulloblastoma
Authors: Belcher Scott M. , Ma Xiaolan , Le Hoa H. 
Published: November 2008

Medulloblastoma (MD) is the most common malignant brain tumor in children. These invasive neuroectodermal tumors arise from cerebellar granule cell-like precursors. In the developing cerebellum, estrogen influences growth and viability of granule cell precursors that transiently express elevated levels estrogen receptor-β (ERβ) during differentiation. Immunoanalysis revealed that ERβ was expressed in the maturing human cerebellum, in all 22 primary MD tumors analyzed, and in two MD-derived cell lines (D283Med and Daoy). Very low levels of ERα-like proteins were detected in each cell line and 41% of tumor samples. Physiological concentrations of the 17β-estradiol- or the ERβ-selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile diarylpropionitrile dose-dependently increased MD growth and cellular migration. In contrast, the ERα-selective agonist (4-propyl-[1H]pyrazole-1,3,5-triyl) trisphenol did not influence MD growth. Similar to previous studies in normal cerebellar granule cell precursors, these studies demonstrate that the physiological actions of estrogens in MD are mediated by ERβ. Preclinical studies assessing the therapeutic efficacy of antiestrogen chemotherapeutics for treating human MD were performed. It was found that pharmacological inhibition of ER-mediated signaling with the ER antagonist drug Faslodex (ICI182,780) blocked all estrogen-mediated effects in both cell culture and xenograft models of human MD. These studies have revealed that functional ERβ expression is a fundamental aspect of MD biology and has defined antiestrogen therapy as a potentially efficacious clinical approach to improve the long-term outcomes for MD patients.Estrogens, via ERβ, stimulate growth of medulloblastoma. ICI182,780 and the antiestrogen drug Faslodex block estrogen-stimulated tumor growth in vitro and in xenograft models of medulloblastoma.
Honeybees can learn the relationship between the solar ephemeris and a newly-experienced landscape
Authors: Towne William F. 
Published: November 2008

SUMMARY
Many species learn the sun's daily pattern of azimuthal movement (the solar ephemeris function) for use in sun-compass orientation. In honeybees, this learning is accomplished with much innate guidance and yields stubborn,imprinting-like retention of certain aspects of the stored information. One such case involves the failure of transplanted bees to update their memories of the relationship between the solar ephemeris and a new landscape, even after many days' experience at the new site. In the present study, I ask whether the bees in previous transplantation experiments failed to update their memories of the relationship between the sun and landscape because the source and recipient landscapes were (rotated) panoramic twins of each other,each dominated by a conspicuous treeline. To test this hypothesis, I transplanted bees from their natal site at the bottom of a valley to a panoramically different, treelined site and later tested the bees' knowledge of the sun's course in relation to the treeline. The test involved observing the bees' communicative dances under overcast skies at a second treeline that was a mirror image of the first. The cloudy-day dances show that the bees had indeed learned the relationship between sun's pattern of movement and the(panoramically novel) treelined site, indicating that the bees' memory of the relationship between the ephemeris function and the landscape is not incapable of revision as the earlier results had suggested. I discuss these results in the context of a brief summary of our current understanding of solar ephemeris learning in bees.
Branchial FXYD protein expression in response to salinity change and its interaction with Na+/K+-ATPase of the euryhaline teleost Tetraodon nigroviridis
Authors: Wang Pei-Jen , Lin Chia-Hao , Hwang Hau-Hsuan , Lee Tsung-Han 
Published: November 2008

SUMMARY
Na+/K+-ATPase (NKA) is a ubiquitous membrane-bound protein crucial for teleost osmoregulation. The enzyme is composed of two essential subunits, a catalytic α subunit and a glycosylated βsubunit which is responsible for membrane targeting of the enzyme. In mammals,seven FXYD members have been found. FXYD proteins have been identified as the regulatory protein of NKA in mammals and elasmobranchs, it is thus interesting to examine the expression and functions of FXYD protein in the euryhaline teleosts with salinity-dependent changes of gill NKA activity. The present study investigated the expression and distribution of the FXYD protein in gills of seawater (SW)- or freshwater (FW)-acclimated euryhaline pufferfish(Tetraodon nigroviridis). The full-length pufferfish FXYD gene(pFXYD) was confirmed by RT-PCR. pFXYD was found to be expressed in many organs including gills of both SW and FW pufferfish. pFXYD mRNA abundance in gills, determined by real-time PCR, was significantly higher in FW fish than in SW fish. An antiserum raised against a partial amino acid sequence of pFXYD was used for the immunoblots of gill homogenates and a major band at 13 kDa was detected. The relative amounts of pFXYD protein and mRNA in gills of SW and FW pufferfish were identical, but opposite to the expression levels of NKA. Immunofluorescent staining of frozen sections demonstrated that pFXYD was colocalized to NKA-immunoreactive cells in the gill filaments. In addition, interaction between pFXYD and NKA was demonstrated by co-immunoprecipitation. Taken together, salinity-dependent expression of pFXYD protein and NKA, as well as the evidence for their colocalization and interaction in pufferfish gills suggested that pFXYD regulates NKA activity in gills of euryhaline teleosts upon salinity challenge.