bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and functional characterization of cereblon as a binding protein for large‐conductance calcium‐activated potassium channel in rat brain
Authors: Jo Sooyeon , Lee Kwang‐Hee , Song Sungmin , Jung Yong‐Keun , Park Chul‐Seung 
Published: December 2005

AbstractLarge‐conductance Ca2+‐activated K+ (BKCa) channels are activated by membrane depolarization and modulated by intracellular Ca2+. Here, we report the direct interaction of cereblon (CRBN) with the cytosolic carboxy‐terminus of the BKCa channel α subunit (Slo). Rat CRBN contained the N‐terminal domain of the Lon protease, a ‘regulators of G protein‐signaling’ (RGS)‐like domain, a leucine zipper (LZ) motif, and four putative protein kinase C (PKC) phosphorylation sites. RNA messages of rat cereblon (rCRBN) were widely distributed in different tissues with especially high‐levels of expression in the brain. Direct association of rCRBN with the BKCa channel was confirmed by immunoprecipitation in brain lysate, and the two proteins were co‐localized in cultured rat hippocampal neurons. Ionic currents evoked by the rSlo channel were dramatically suppressed upon coexpression of rCRBN. rCRBN decreased the formation of the tetrameric rSlo complex thus reducing the surface expression of functional channels. Therefore, we suggest that CRBN may play an important role in assembly and surface expression of functional BKCa channels by direct interaction with the cytosolic C‐terminus of its α‐subunit.
Retailer's Response to Alternate Manufacturer's Incentives Under a Single‐Period, Price‐Dependent, Stochastic‐Demand Framework*
Authors: Arcelus F. J. , Kumar Satyendra , Srinivasan G. 
Published: December 2005

ABSTRACTThis article considers the joint development of the optimal pricing and ordering policies of a profit‐maximizing retailer, faced with (i) a manufacturer trade incentive in the form of a price discount for itself or a rebate directly to the end customer; (ii) a stochastic consumer demand dependent upon the magnitude of the selling price and of the trade incentive, that is contrasted with a riskless demand, which is the expected value of the stochastic demand; and (iii) a single‐period newsvendor‐type framework. Additional analysis includes the development of equal profit policies in either form of trade incentive, an assessment of the conditions under which a one‐dollar discount is more profitable than a one‐dollar rebate, and an evaluation of the impact upon the retailer‐expected profits of changes in either incentive or in the degree of demand uncertainty. A numerical example highlights the main features of the model. The analytical and numerical results clearly show that, as compared to the results for the riskless demand, dealing with uncertainty through a stochastic demand leads to (i) (lower) higher retail prices if additive (multiplicative) error, (ii) lower (higher) pass throughs if additive (multiplicative) error, (iii) higher claw backs in both error structures wherever applicable, and (iv) higher rebates to achieve equivalent profits in both error structures.
Still Worthy of Our Land?
Authors: Greenberg Joel 
Published: December 2005

Return to Wild America
. A Yearlong Search for the Continent's Natural Soul.
By Scott Weidensaul

North Point Press, New York, 2005. 422 pp. $26, C$36.50. ISBN 0-86547-688-8.
The author surveys the natural world of North America through a consideration of the gains and losses at sites Roger Tory Peterson and James Fisher visited on the 1953 tour described in their classic Wild America.
Crowing About Culture
Authors: Dally Joanna 
Published: December 2005

In the Company of Crows and Ravens
.
By John M. Marzluff and Tony Angell

Yale University Press, New Haven, CT, 2005. 404 pp. $30, £18.95. ISBN 0-300-10076-0.
Writing for a broad audience, Marzluff and Angell explore the interactions between people and crows and the influences each has had on the other.
Evolutionary Genetics of the Accessory Gene Regulator (
agr
) Locus in
Staphylococcus aureus
Authors: Robinson D. Ashley , Monk Alastair B. , Cooper Jessica E. , Feil Edward J. , Enright Mark C. 
Published: December 2005

ABSTRACT

The accessory gene regulator (
agr
) locus influences the expression of many virulence genes in the human pathogen
Staphylococcus aureus
. Four allelic groups of
agr
, which generally inhibit the regulatory activity of each other, have been identified within the species. Interference in virulence gene expression caused by different
agr
groups has been suggested to be a mechanism for isolating bacterial populations and a fundamental basis for subdividing the species. To test the hypothesis that the species is phylogenetically structured according to
agr
groups, we mapped
agr
groups onto a clone phylogeny inferred from partial sequences of 14 genes from 27 genetically diverse strains. Shimodaira-Hasegawa and parametric bootstrap tests rejected the hypotheses that the species is subdivided into three or five monophyletic
agr
groups but failed to reject the hypothesis that the species is subdivided into two groups that each consist of multiple clonal complexes and multiple
agr
groups. Additional evidence for
agr
recombination is found from clustered polymorphisms in complete
agr
sequences. However,
agr
recombination has not occurred frequently or randomly through time, because the topology and branch lengths of the clone phylogeny are reflected within each
agr
group. To account for these observations, we propose a new evolutionary model that involves a genetically polymorphic ancestral population of
S. aureus
that horizontally transferred
agr
groups between two subspecies groups near the time that these subspecies groups diverged.
The Maltodextrin System ofEscherichia coli: Glycogen-Derived Endogenous Induction and Osmoregulation
Authors: Dippel Renate , Bergmiller Tobias , Böhm Alex , Boos Winfried 
Published: December 2005

ABSTRACTStrains ofEscherichia colilacking MalQ (maltodextrin glucanotransferase or amylomaltase) are endogenously induced for the maltose regulon by maltotriose that is derived from the degradation of glycogen (glycogen-dependent endogenous induction). A high level of induction was dependent on the presence of MalP, maltodextrin phosphorylase, while expression was counteracted by MalZ, maltodextrin glucosidase. Glycogen-derived endogenous induction was sensitive to high osmolarity. This osmodependence was caused by MalZ.malZ, the gene encoding this enzyme, was found to be induced by high osmolarity even in the absence of MalT, the central regulator of allmalgenes. The osmodependent expression ofmalZwas neither RpoS nor OmpR dependent. In contrast, themalPQoperon, whose expression was also increased at a high osmolarity, was partially dependent on RpoS. In the absence of glycogen, residual endogenous induction of themalgenes that is sensitive to increasing osmolarity can still be observed. This glycogen-independent endogenous induction is not understood, and it is not affected by altering the expression of MalP, MalQ, and MalZ. In particular, its independence from MalZ suggests that the responsible inducer is not maltotriose.
A Relative-Entropy Algorithm for Genomic Fingerprinting Captures Host-Phage Similarities
Authors: Robins Harlan , Krasnitz Michael , Barak Hagar , Levine Arnold J. 
Published: December 2005

ABSTRACTThe degeneracy of codons allows a multitude of possible sequences to code for the same protein. Hidden within the particular choice of sequence for each organism are over 100 previously undiscovered biologically significant, short oligonucleotides (length, 2 to 7 nucleotides). We present an information-theoretic algorithm that finds these novel signals. Applying this algorithm to the 209 sequenced bacterial genomes in the NCBI database, we determine a set of oligonucleotides for each bacterium which uniquely characterizes the organism. Some of these signals have known biological functions, like restriction enzyme binding sites, but most are new. An accompanying scoring algorithm is introduced that accurately (92%) places sequences of 100 kb with their correct species among the choice of hundreds. This algorithm also does far better than previous methods at relating phage genomes to their bacterial hosts, suggesting that the lists of oligonucleotides are “genomic fingerprints” that encode information about the effects of the cellular environment on DNA sequence. Our approach provides a novel basis for phylogeny and is potentially ideally suited for classifying the short DNA fragments obtained by environmental shotgun sequencing. The methods developed here can be readily extended to other problems in bioinformatics.
1-Deoxy-
d
-Xylulose 5-Phosphate Reductoisomerase (IspC) from
Mycobacterium tuberculosis
: towards Understanding Mycobacterial Resistance to Fosmidomycin
Authors: Dhiman Rakesh K. , Schaeffer Merrill L. , Bailey Ann Marie , Testa Charles A. , Scherman Hataichanok , Crick Dean C. 
Published: December 2005

ABSTRACT

1-Deoxy-
d
-xylulose 5-phosphate reductoisomerase (IspC) catalyzes the first committed step in the mevalonate-independent isopentenyl diphosphate biosynthetic pathway and is a potential drug target in some pathogenic bacteria. The antibiotic fosmidomycin has been shown to inhibit IspC in a number of organisms and is active against most gram-negative bacteria but not gram positives, including
Mycobacterium tuberculosis
, even though the mevalonate-independent pathway is the sole isopentenyl diphosphate biosynthetic pathway in this organism. Therefore, the enzymatic properties of recombinant IspC from
M. tuberculosis
were characterized. Rv2870c from
M. tuberculosis
converts 1-deoxy-
d
-xylulose 5-phosphate to 2-
C
-methyl-
d
-erythritol 4-phosphate in the presence of NADPH. The enzymatic activity is dependent on the presence of Mg
2+
ions and exhibits optimal activity between pH 7.5 and 7.9; the

K
m

for 1-deoxyxylulose 5-phosphate was calculated to be 47.1 μM, and the

K
m

for NADPH was 29.7 μM. The specificity constant of Rv2780c in the forward direction is 1.5 × 10
6
M
−1
min
−1
, and the reaction is inhibited by fosmidomycin, with a 50% inhibitory concentration of 310 nM. In addition,
Rv2870c
complements an inactivated chromosomal copy of
IspC
in
Salmonella enterica
, and the complemented strain is sensitive to fosmidomycin. Thus,
M. tuberculosis
resistance to fosmidomycin is not due to intrinsic properties of Rv2870c, and the enzyme appears to be a valid drug target in this pathogen.
The Shiga Toxin 1-Converting Bacteriophage BP-4795 Encodes an NleA-Like Type III Effector Protein
Authors: Creuzburg Kristina , Recktenwald Jürgen , Kuhle Volker , Herold Sylvia , Hensel Michael , Schmidt Herbert 
Published: December 2005

ABSTRACT

In this study, the complete DNA sequence of Shiga toxin 1-converting bacteriophage BP-4795 was determined. The genome of BP-4795 consists of 85 open reading frames, including two complete IS
629
elements and three morons at the end of its late regulatory region. One of these morons encodes a type III effector that is translocated by the locus of enterocyte effacement-encoded type III secretion system into HeLa cells, where it localizes with the Golgi apparatus.
An α/β-Fold C—C Bond Hydrolase Is Involved in a Central Step of Nicotine Catabolism by
Arthrobacter nicotinovorans
Authors: Sachelaru Paula , Schiltz Emile , Igloi Gabor L. , Brandsch Roderich 
Published: December 2005

ABSTRACT

The enzyme catalyzing the hydrolytic cleavage of 2,6-dihydroxypseudooxynicotine to 2,6-dihydroxypyridine and γ-
N
-methylaminobutyrate was found to be encoded on pAO1 of
Arthrobacter nicotinovorans
. The new enzyme answers an old question about nicotine catabolism and may be the first C—C bond hydrolase that is involved in the biodegradation of a heterocyclic compound.
Characterization of the DNA Gyrase from the Thermoacidophilic Archaeon
Thermoplasma acidophilum
Authors: Yamashiro Kan , Yamagishi Akihiko 
Published: December 2005

ABSTRACT

Thermoplasma acidophilum
is sensitive to the antibiotic drug novobiocin, which inhibits DNA gyrase. We characterized DNA gyrases from
T. acidophilum
strains in vitro. The DNA gyrase from a novobiocin-resistant strain and an engineered mutant were less sensitive to novobiocin. The novobiocin-resistant gyrase genes might serve as
T. acidophilum
genetic markers.
Survivin Expression Is Regulated by Coexpression of Human Epidermal Growth Factor Receptor 2 and Epidermal Growth Factor Receptor via Phosphatidylinositol 3-Kinase/AKT Signaling Pathway in Breast Cancer Cells
Authors: Asanuma Hiroko , Torigoe Toshihiko , Kamiguchi Kenjiro , Hirohashi Yoshihiko , Ohmura Tousei , Hirata Koichi , Sato Masaaki , Sato Noriyuki 
Published: December 2005

Abstract
Survivin, a member of the inhibitor of apoptosis protein family, is widely expressed in a variety of human cancer tissues. Survivin inhibits activation of caspases, and its overexpression can lead to resistance to apoptotic stimuli. In this study, survivin protein expression was assessed by immunohistochemical staining of 195 invasive breast cancer specimens. Overall, 79.5% of the tumors were positive for survivin. The expression of epidermal growth factor receptor (EGFR) family, human epidermal growth factor receptor 2 (HER2) and EGFR, was also examined in 53 cases, and consequently, it was indicated that survivin positivity might be correlated with the coexpression of HER2 and EGFR. To clarify the regulatory mechanism of survivin expression in breast cancer cells, the effect of HER2 and/or EGFR expression on the survivin levels was examined. It was revealed that the survivin protein level was up-regulated by the coexpression of HER2 and EGFR, leading to the increased resistance against etoposide-induced apoptosis in breast cancer cells. Conversely, survivin levels and apoptosis resistance were decreased when cells were treated with HER2-specific inhibitor, Herceptin. Although Herceptin could down-regulate both phosphatidylinositol 3-kinase (PI3K)/AKT signal and mitogen-activated protein/extracellular signal-related kinase (ERK) kinase 1 (MEK1)/ERK signal in HER2-positive breast cancer cells, PI3K-specific inhibitor but not MEK1-specific inhibitor could decrease the survivin levels. The present study clarified the regulatory mechanism of HER2 in the expression of survivin protein in breast cancer cells.
CD24 Expression Causes the Acquisition of Multiple Cellular Properties Associated with Tumor Growth and Metastasis
Authors: Baumann Petra , Cremers Natascha , Kroese Frans , Orend Gertraud , Chiquet-Ehrismann Ruth , Uede Toshi , Yagita Hideo , Sleeman Jonathan P. 
Published: December 2005

Abstract
The glycosylphosphatidylinositol-anchored membrane protein CD24 functions as an adhesion molecule for P-selectin and L1 and plays a role in B-cell development and neurogenesis. Over the last few years, a large body of literature has also implicated CD24 expression in tumorigenesis and progression. Here, we show that ectopic CD24 expression can be sufficient to promote tumor metastasis in experimental animals. By developing a doxycycline-inducible system for the expression of CD24 in breast cancer cells, we have also analyzed the cellular properties that CD24 expression influences. We found that CD24 expression increased tumor cell proliferation. Furthermore, in addition to promoting binding to P-selectin, CD24 expression also indirectly stimulated cell adhesion to fibronectin, collagens I and IV, and laminin through the activation of α3β1 and α4β1 integrin activity. Moreover, CD24 expression supported rapid cell spreading and strongly induced cell motility and invasion. CD24-induced proliferation and motility were integrin independent. Together, these observations implicate CD24 in the regulation of multiple cell properties of direct relevance to tumor growth and metastasis.
Interleukin-6, Secreted by Human Ovarian Carcinoma Cells, Is a Potent Proangiogenic Cytokine
Authors: Nilsson Monique B. , Langley Robert R. , Fidler Isaiah J. 
Published: December 2005

AbstractAngiogenesis, a key rate-limiting step in the growth and dissemination of malignant tumors, is regulated by the balance between positive and negative effectors. Recent studies indicate that the pleiotropic cytokine interleukin-6 (IL-6) may contribute to the vascularization of some tumors by disrupting the equilibrium between positive and negative angiogenic regulatory molecules. We determined whether IL-6 participates in the angiogenesis observed during the progression of ovarian carcinoma. We measured IL-6 production by human ovarian cancer cell lines in vitro and in vivo. Not all cell lines secreted IL-6 in vitro; however, when the cell lines were implanted into the peritoneal cavity of female nude mice, every line secreted IL-6. Most human ovarian carcinoma cell lines tested secreted significant levels of the soluble IL-6 receptor (sIL-6R). Endothelial cell lines established from the ovary and mesentery of female H-2Kb-tsA58 mice were tested for response to IL-6. Both endothelial cell lines expressed the IL-6R and their stimulation with the exogenous ligand significantly enhanced cell migration and activated the downstream signaling molecule signal transducers and activators of transcription 3. Dual immunohistochemical staining for IL-6R and CD31 revealed IL-6R expression on human endothelial cells within normal ovary and carcinoma specimens. Gelfoam sponges containing 0.4% agarose and IL-6 or basic fibroblast growth factor and implanted into the subcutis of BALB/c mice were vascularized to the same extent. Collectively, the data indicate that ovarian tumor cells secreted IL-6, a highly angiogenic cytokine that supports progression of disease.
Induction of Aromatase Expression in Cervical Carcinomas: Effects of Endogenous Estrogen on Cervical Cancer Cell Proliferation
Authors: Nair Hareesh B. , Luthra Roopa , Kirma Nameer , Liu Ya-Guang , Flowers Lisa , Evans Dean , Tekmal Rajeshwar Rao 
Published: December 2005

Abstract
Epidemiologic studies have implicated estrogenic exposure as well as human papilloma virus (HPV) infection in cervical carcinogenesis, and some studies have suggested that estrogen and HPV may play synergistic roles in cervical tumorigenesis. In this study, we report a novel finding that ∼35% of cervical carcinomas tested (n = 19) express aromatase, the enzyme responsible for converting androgen to estrogen, the rate-limiting and final step in estrogen biosynthesis. On the other hand, no aromatase expression was detected in precancerous (n = 42) or normal cervical (n = 17) tissue samples. Increased aromatase was associated with increases in estrogen receptors (ER-α and ER-β) and a decrease in progesterone receptor levels, suggesting that in situ estrogen signaling via ER may be involved in tumor growth. Stable overexpression of aromatase in HPV+ cervical cancer cells resulted in increased cellular proliferation, anchorage-independent growth, and ER expression and activity. In contrast, little change in ER was observed in HPV− cells. Steroid hormone receptor expression observed in vitro paralleled that seen in cervical carcinomas expressing aromatase. Aromatase overexpression also induced the expression of cyclin D1, proliferating cell nuclear antigen, and the HPV oncogenes, E6 and E7. Furthermore, the data underscores the importance of steroid receptor (estrogen and progesterone receptors) regulation in cervical carcinogenesis. To our knowledge, this is the first report demonstrating the induction of aromatase expression in cervical carcinomas, and opens the possibility that aromatase inhibitors may be potential therapeutic agents in cervical carcinomas expressing aromatase.
Cloning and Characterization of a p53 and DNA Damage Down-regulated Gene PIQ that Codes for a Novel Calmodulin-Binding IQ Motif Protein and Is Up-regulated in Gastrointestinal Cancers
Authors: Luo Xiuquan , He Qin , Huang Ying , Sheikh M. Saeed 
Published: December 2005

Abstract
We have identified a p53 and DNA damage–regulated gene that encodes a novel IQ motif protein, which we have named p53 and DNA damage–regulated IQ motif protein (PIQ). PIQ has two isoforms, long (PIQ-L) and short (PIQ-S), and both bind to calmodulin in the presence and absence of calcium. PIQ expression is down-regulated by p53 and DNA damage–inducing agents, whereas PIQ itself represses the expression of p53 up-regulated modulator of apoptosis that is a key mediator of p53-induced apoptosis. Thus, PIQ is a novel protein that may function to bridge a crosstalk between p53 and calmodulin-regulated cellular processes. We further show that PIQ expression is up-regulated in a number of primary colorectal and gastric tumors when compared with matching normal tissues, suggesting that PIQ may be involved in tumorigenesis and could serve as a valuable diagnostic/prognostic marker for gastrointestinal tumors.
Stromelysin-3 Is a Potent Negative Regulator of Adipogenesis Participating to Cancer Cell-Adipocyte Interaction/Crosstalk at the Tumor Invasive Front
Authors: Andarawewa Kumari L. , Motrescu Elena R. , Chenard Marie-Pierre , Gansmuller Anne , Stoll Isabelle , Tomasetto Catherine , Rio Marie-Christine 
Published: December 2005

Abstract
The initial invasive processes during cancer development remain largely unknown. Stromelysin-3/matrix metalloproteinase 11 (ST3/MMP11) is associated with tumor invasion and poor prognosis. We present novel evidence that adipocytes present at human breast tumor invasive front are induced by cancer cells to express ST3. Using mouse syngeneic model, light and electron microscopy showed that in ST3-deficient mice but not in wild-type mice, forced cancer cell-adipocyte interaction/crosstalk results in adipocyte membrane alteration, allowing cancer cell fat infiltration and death. Thus, adipocytes are involved in initial cancer cell survival into connective tissue, and this effect is ST3 mediated. This suggested that ST3 might play a role in adipocyte metabolism. Accordingly, ST3-deficient mice exhibited fat excess and increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and adipocyte protein 2 (aP2) adipogenic markers, indicating that, in vivo, ST3 negatively regulates fat homeostasis. Moreover, ST3-deficient mouse embryonic fibroblasts exhibited a dramatic enhanced potential to differentiate into adipocytes associated with increased PPARγ and aP2 expression, and recombinant ST3 treatment reverted their differentiation. Thus, in vitro, ST3 reduces adipocyte differentiation in an autocrine manner. High fibroblasts/adipocytes ratio is a stroma feature, and peritumoral fibroblast origin remains debated. Our results support the concept that invading cancer cells aberrantly restore the negative ST3 function on adipogenesis into proximal adipocytes/preadipocytes, leading to the accumulation/maintenance of a particular peritumoral fibroblast subpopulation. Accordingly, in human breast tumors, we observed that ST3-expressing peritumoral fibroblasts are distinct from α-smooth muscle actin-expressing myofibroblasts. This constitutes the first report of implication of a MMP in cancer cell-adipocyte interaction/crosstalk during early steps of connective tissue invasion.