bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-Wide Analysis of Light Sensing inProchlorococcus
Authors: Steglich Claudia , Futschik Matthias , Rector Trent , Steen Robert , Chisholm Sallie W. 
Published: November 2006

ABSTRACTProchlorococcusMED4 has, with a total of only 1,716 annotated protein-coding genes, the most compact genome of a free-living photoautotroph. Although light quality and quantity play an important role in regulating the growth rate of this organism in its natural habitat, the majority of known light-sensing proteins are absent from its genome. To explore the potential for light sensing in this phototroph, we measured its global gene expression pattern in response to different light qualities and quantities by using high-density Affymetrix microarrays. Though seven different conditions were tested, only blue light elicited a strong response. In addition, hierarchical clustering revealed that the responses to high white light and blue light were very similar and different from that of the lower-intensity white light, suggesting that the actual sensing of high light is mediated via a blue-light receptor. Bacterial cryptochromes seem to be good candidates for the blue-light sensors. The existence of a signaling pathway for the redox state of the photosynthetic electron transport chain was suggested by the presence of genes that responded similarly to red and blue light as well as genes that responded to the addition of DCMU [3-(3,4-dichlorophenyl)-1,1-N-N′-dimethylurea], a specific inhibitor of photosystem II-mediated electron transport.
Conservation and Variation between
Rhodobacter capsulatus
and
Escherichia coli
Tat Systems
Authors: Lindenstrauß Ute , Brüser Thomas 
Published: November 2006

ABSTRACT

The Tat system allows the translocation of folded and often cofactor-containing proteins across biological membranes. Here, we show by an interspecies transfer of a complete Tat translocon that Tat systems are largely, but not fully, interchangeable even between different classes of proteobacteria. The Tat apparatus from the α-proteobacterium
Rhodobacter capsulatus
was transferred to a Tat-deficient
Escherichia coli
strain, which is a γ-proteobacterium. Similar to that of
E. coli
, the
R. capsulatus
Tat system consists of three components, rc-TatA, rc-TatB, and rc-TatC. A fourth gene (
rc-tatF
) is present in the
rc-tatABCF
operon which has no apparent relevance for translocation. The translational starts of
rc-tatC and rc-tatF
overlap in four nucleotides (ATGA) with the preceding
tat
genes, pointing to efficient translational coupling of
rc
-
tatB
,
rc
-
tatC
, and
rc-tatF
. We show by a variety of physiological and biochemical assays that the
R. capsulatus
Tat system functionally targets the
E. coli
Tat substrates TorA, AmiA, AmiC, and formate dehydrogenase. Even a Tat substrate from a third organism is accepted, demonstrating that usually Tat systems and Tat substrates from different proteobacteria are compatible with each other. Only one exceptional Tat substrate of
E. coli
, a membrane-anchored dimethyl sulfoxide (DMSO) reductase, was not targeted by the
R. capsulatus
Tat system, resulting in a DMSO respiration deficiency. Although the general features of Tat substrates and translocons are similar between species, the data indicate that details in the targeting pathways can vary considerably.
Crl Facilitates RNA Polymerase Holoenzyme Formation
Authors: Gaal Tamas , Mandel Mark J. , Silhavy Thomas J. , Gourse Richard L. 
Published: November 2006

ABSTRACTTheEscherichia coliCrl protein has been described as a transcriptional coactivator for the stationary-phase sigma factor σS. In a transcription system with highly purified components, we demonstrate that Crl affects transcription not only by the EσSRNA polymerase holoenzyme but also by Eσ70and Eσ32. Crl increased transcription dramatically but only when the σ concentration was low and when Crl was added to σ prior to assembly with the core enzyme. Our results suggest that Crl facilitates holoenzyme formation, the first positive regulator identified with this mechanism of action.
Heteroduplex analysis for the three common HFE variants: methodology, reliablity and analysis of over 5000 requests for testing
Authors: Kingston Jeanne , Bowen Derrick , Sweeney Marion , Lawless Susan , Jackson Helen , Worwood Mark 
Published: November 2006

Objective:To describe the analysis of over 5300 patient samples for theHFEgenotype.Methods:Blood samples received from hospitals in England, Wales and Ireland were analysed with a single, multiplex PCR using heteroduplex generators for the C282Y, H63D and S65C variants of theHFEgene. PCR products labelled with fluorescent dyes were analysed by capillary electrophoresis. Genotype frequencies were analysed according to the reasons given for testing.Results:Analysis of 400 samples sent in duplicate revealed one error that was associated with reporting rather than the methodology. Of 5327 samples received, 1122 were for family testing, 2470 for diagnostic testing and in 1735 cases no reason was given. Overall, homozygosity for C282Y was found in 14% of samples received for family testing and in 16% of the remaining samples. Clinical indications such as “liver disease” were of little predictive value for homozygosity for C282Y, but this increased if a raised serum ferritin concentration or transferrin saturation was indicated. When the diagnosis was iron overload, 39% of subjects tested were homozygous for C282Y. Compound heterozygosity (C282Y/H63D) was more frequent than in the general population but the frequency was not further increased in subjects for whom there was a diagnosis of iron overload. The frequencies of heterozygosity for H63D or S65C and homozygosity for H63D were not significantly increased in any group compared with the general population frequency.Conclusion:These results demonstrate the reliability of the methodology and confirm the difficulty of identifying genetic haemochromatosis purely on the basis of clinical suspicion that haemochromatosis may be responsible for liver disease, diabetes or arthritis.
Muscle, liver, and pancreas: Three Musketeers fighting to control glycemia
Authors: Klip Amira , Vranic Mladen 
Published: November 2006

This essay examines the historical significance of two APS classic papers that are freely available on line: Wall JS, Steele R, de Bodo RC, and Altszuler N. Effect of insulin on utilization and production of circulating glucose. Am J Physiol 189: 43–50, 1957. ( http://ajplegacy.physiology.org/cgi/reprint/189/1/43 ) DeFronzo RA, Tobin JD, and Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol Endocrinol Metab Gastroinstest Physiol 6: E214–E223, 1979. ( http://ajpgi.physiology.org/cgi/reprint/237/3/G214 )
Identification and Functional Characterization of a Novel Unspliced Transcript Variant of HIC-1 in Human Cancer Cells Exposed to Adverse Growth Conditions
Authors: Mondal Abdul Matin , Chinnadurai Sivasamy , Datta Kamal , Chauhan Shyam S. , Sinha Subrata , Chattopadhyay Parthaprasad 
Published: November 2006

Abstract
The wild-type p53 gene has been widely implicated in the regulation of hypermethylated in cancer-1 (HIC-1) transcription, a master growth regulatory gene with multiple promoters and, consequently, multiple alternatively spliced transcripts. We investigated the role of p53 (wild type and mutant, both endogenous and exogenous) in modulating the various HIC-1 transcripts. We discovered a novel unspliced HIC-1 transcript, identified as “f” in leukocytes and in the human cell lines U87MG (wild-type p53), U373MG (mutant p53), MCF-7 (wild-type p53), HeLa (p53 degraded by HPV18-E6 oncoprotein), and Saos-2 (p53 null). This transcript is initiated from a new transcription start site and has an intervening stop codon that would result in a possibly truncated 22-amino-acid polypeptide. When U87MG (wild-type p53) and MCF-7 cells (wild-type p53) were exposed to adverse growth conditions of serum starvation or treated with the chemotherapeutic agent cisplatin, cells underwent apoptosis and cell cycle arrest accompanied by increase in p53 and HIC-1 transcript levels. Although the increase of the HIC-1-spliced transcripts followed the increase of p53, increase in f transcript coincided with declining p53 and HIC-1 transcript and protein levels. Moreover, the levels of HIC-1 f transcript were not induced by exogenously transfected wild-type p53 in p53-mutated U373MG and p53-null Saos-2 cells, unlike the spliced transcripts that code for full-length HIC-1 protein. These findings suggest a working model wherein the status of f transcript, which is not under direct transcriptional control of wild-type p53, may influence the level of HIC-1 protein in cancer cells. (Cancer Res 2006; 66(21): 10466-77)
Androgens Modulate Expression of Transcription Intermediary Factor 2, an Androgen Receptor Coactivator whose Expression Level Correlates with Early Biochemical Recurrence in Prostate Cancer
Authors: Agoulnik Irina U. , Vaid Ajula , Nakka Manjula , Alvarado Misty , Bingman William E. , Erdem Halime , Frolov Anna , Smith Carolyn L. , Ayala Gustavo E. , Ittmann Michael M. , Weigel Nancy L. 
Published: November 2006

Abstract
Prostate cancer is an androgen-dependent disease; metastatic prostate cancer is typically treated by androgen receptor (AR) blockade. Recurrence after androgen ablation and evidence that AR continues to play a role in many prostate cancers has led to an examination of other factors that potentiate AR activity. AR is a ligand-activated transcription factor whose activity is regulated not only by hormone but also by the levels of coactivators recruited by AR to facilitate transcription. We sought to assess the consequences of reducing expression of the transcription intermediary factor 2 (TIF2) coactivator on prostate cancer cell growth and AR action in cell lines to examine TIF2 expression in prostate cancer and to correlate expression with clinical outcome. Depletion of TIF2 reduced expression of AR-induced target genes and slowed proliferation of AR-dependent and AR-independent prostate cancer cells. Remarkably, we found that TIF2 expression is directly repressed by high levels of androgens in multiple AR-expressing cell lines. Expression of a reporter containing 5′-flanking region of the TIF2 was repressed both by androgens and by the antagonist, Casodex. Expression of TIF2 correlates with biochemical (prostate-specific antigen) recurrence (P = 0.0136). In agreement with our in vitro findings, the highest expression of TIF2 was found in patients whose cancer relapsed after androgen ablation therapy, supporting the idea that AR blockade might activate pathways that lead to stimulation of AR-dependent and AR-independent proliferation of prostate epithelium. The elevated expression of TIF2 at low hormone levels likely aids in inducing AR activity under these conditions; treatment with Casodex has the potential to counteract this induction. (Cancer Res 2006; 66(21): 10594-602)
Loss of Nkx2.8 Deregulates Progenitor Cells in the Large Airways and Leads to Dysplasia
Authors: Tian Jianmin , Mahmood Radma , Hnasko Robert , Locker Joseph 
Published: November 2006

Abstract
Nkx2.8, a homeodomain transcription factor, has been characterized in liver cancer and in the developing central nervous system. We now show that this factor is also expressed in the lung, where it localizes in adults to a discrete population of tracheobronchial basal cells. To target the mouse gene, the first exon was replaced by a LacZ marker gene joined to the intact 5′-untranslated region. Marker expression was observed throughout the lower respiratory tract, beginning on E11 in a few cells of the distal lung buds. The region of expression then spread upward. By neonatal day 1, expression was greatest in the large airways and the Nkx2.8−/− mice exhibited generalized tracheobronchial hyperplasia. Bromodeoxyuridine (BrdUrd) labeling studies showed that a higher rate of bronchial cell proliferation persisted at 6 to 8 months. In adults, Nkx2.8 marker expression decreased with progressive differentiation into ciliated and secretory cells. The cell localizations and patterns of coexpression with BrdUrd and differentiation markers suggest a progenitor relationship: the cells that most strongly express Nkx2.8 seem to function as tracheobronchial stem cells. Moreover, Nkx2.8 acts to limit the number of these progenitor cells because the marker-expressing population was greatly expanded in Nkx2.8−/− mice. Increased proliferation and an altered progenitor relationship caused progressive bronchial pathology, which manifested as widespread dysplasia in the large airways of 1-year-old Nkx2.8−/− mice. (Cancer Res 2006; 66(21): 10399-407)
Activation of CDCA1-KNTC2, Members of Centromere Protein Complex, Involved in Pulmonary Carcinogenesis
Authors: Hayama Satoshi , Daigo Yataro , Kato Tatsuya , Ishikawa Nobuhisa , Yamabuki Takumi , Miyamoto Masaki , Ito Tomoo , Tsuchiya Eiju , Kondo Satoshi , Nakamura Yusuke 
Published: November 2006

Abstract
We found cotransactivation of cell division associated 1 (CDCA1) and kinetochore associated 2 (KNTC2), members of the evolutionarily conserved centromere protein complex, in non–small cell lung carcinomas (NSCLC). Immunohistochemical analysis using lung cancer tissue microarray confirmed high levels of CDCA1 and KNTC2 proteins in the great majority of lung cancers of various histologic types. Their elevated expressions were associated with poorer prognosis of NSCLC patients. Knockdown of either CDCA1 or KNTC2 expression with small interfering RNA significantly suppressed growth of NSCLC cells. Furthermore, inhibition of their binding by a cell-permeable peptide carrying the CDCA1-derived 19-amino-acid peptide (11R-CDCA1398-416) that correspond to the binding domain to KNTC2 effectively suppressed growth of NSCLC cells. As our data imply that human CDCA1 and KNTC2 seem to fall in the category of cancer-testis antigens, and that their simultaneous up-regulation is a frequent and important feature of cell growth/survival of lung cancer, selective suppression of CDCA1 or KNTC2 activity and/or inhibition of the CDCA1-KNTC2 complex formation could be a promising therapeutic target for treatment of lung cancers. (Cancer Res 2006; 66(21): 10339-48)
Lysyl Oxidase Mediates Hypoxic Control of Metastasis
Authors: Erler Janine T. , Giaccia Amato J. 
Published: November 2006

Abstract
Hypoxic cancer cells pose a great challenge to the oncologist because they are especially aggressive, metastatic, and resistant to therapy. Recently, we showed that elevation of the extracellular matrix protein lysyl oxidase (LOX) correlates with metastatic disease and is essential for hypoxia-induced metastasis. In an orthotopic rodent model of breast cancer, a small-molecule or antibody inhibitor of LOX abolished metastasis, offering preclinical validation of this enzyme as a therapeutic target. (Cancer Res 2006; 66(21): 10238-41)
Adaptation and tradition in the pursuit of good health
Authors: Yu Wai-kam Sam 
Published: November 2006

English By examining the health strategies used by Chinese people in Britain and the responses of traditional Chinese societies to foreign medical practices, this article shows the significance of the studies of the ethnic minority groups' traditional values and/or practices to the development of ethnic-sensitive social work. French En examinant les stratégies sanitaires des Chinois en Grande-Bretagne et la position des sociétés chinoises à l'égard des pratiques médicales étrangères, cette recherche démontre l'importance d'étudier les valeurs traditionnelles des groupes ethniques minoritaires et de développer des pratiques de travail social qui tiennent compte de l'ethnicité. Spanish Mediante el examen de las estrategias de salud utilizadas por la población China en Gran Bretaña y las respuestas de las sociedades Chinas frente a las prácticas médicas extranjeras, este artículo muestra la importancia del estudio de los valores tradicionales y/o prácticas de los grupos étnicos minoritarios para el desarrollo de un trabajo social étnicamente sensible.
IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo
Authors: Fröhlich Anja , Marsland Benjamin J. , Sonderegger Ivo , Kurrer Michael , Hodge Martin R. , Harris Nicola L. , Kopf Manfred 
Published: November 2006

AbstractInterleukin 21 (IL-21) is a member of the common γ-chain family of cytokines, which influence a broad spectrum of immunologic responses. A number of studies have examined the function of IL-21, but its specific role in Th1/Th2-cell differentiation and related effector responses remains to be clarified. Thus, we generated IL-21R–deficient mice and have investigated the role of IL-21R signaling using a series of in vivo experimentally induced disease models. We first addressed the role of IL-21R signaling in Th2 immune responses by examining allergic airway inflammation, and Nippostrongylus brasiliensis and Heligmosomoides polygyrus antihelminth responses. In each of these systems, IL-21R signaling played a clear role in the development of Th2 responses. Comparatively, IL-21R signaling was not required for the containment of Leishmania major infection or the development of experimental autoimmune myocarditis, indicative of competent Th1 and Th17 responses, respectively. Adoptive transfer of T cells and analysis of IL-21R+/+/IL-21R−/− chimera mice revealed that IL-21R–signaling was central to Th2-cell survival or migration to peripheral tissues. Overall, our data show IL-21 plays a crucial role in supporting polarized Th2 responses in vivo, while appearing superfluous for Th1 and Th17 responses.
Endolyn (CD164) modulates the CXCL12-mediated migration of umbilical cord blood CD133+ cells
Authors: Forde Sinead , Tye Britt Jorgensen , Newey Sarah E. , Roubelakis Maria , Smythe Jon , McGuckin Colin P. , Pettengell Ruth , Watt Suzanne M. 
Published: November 2006

AbstractHematopoietic stem cell/hematopoietic progenitor cell (HSC/HPC) homing to specific microenvironmental niches involves interactions between multiple receptor ligand pairs. Although CXCL12/CXCR4 plays a central role in these events, CXCR4 regulators that provide the specificity for such cells to lodge and be retained in particular niches are poorly defined. Here, we provide evidence that the sialomucin endolyn (CD164), an adhesion receptor that regulates the adhesion of CD34+ cells to bone marrow stroma and the recruitment of CD34+CD38lo/− cells into cycle, associates with CXCR4. The class II 103B2 monoclonal antibody, which binds the CD164 N-linked glycan-dependent epitope or CD164 knockdown by RNA interference, significantly inhibits the migration of CD133+ HPCs toward CXCL12 in vitro. On presentation of CXCL12 on fibronectin, CD164 associates with CXCR4, an interaction that temporally follows the association of CXCR4 with the integrins VLA-4 and VLA-5. This coincides with PKC-ζ and Akt signaling through the CXCR4 receptor, which was disrupted on the loss of CD164 though MAPK signaling was unaffected. We therefore demonstrate a novel association among 3 distinct families of cell-surface receptors that regulate cell migratory responses and identify a new role for CD164. We propose that this lends specificity to the homing and lodgment of these cells within the bone marrow niche.
MEK blockade converts AML differentiating response to retinoids into extensive apoptosis
Authors: Milella Michele , Konopleva Marina , Precupanu Cristina M. , Tabe Yoko , Ricciardi Maria Rosaria , Gregorj Chiara , Collins Steven J. , Carter Bing Z. , D'Angelo Carmen , Petrucci Maria Teresa , Foà Robin , Cognetti Francesco , Tafuri Agostino , Andreeff Michael 
Published: November 2006

AbstractThe aberrant function of transcription factors and/or kinase-based signaling pathways that regulate the ability of hematopoietic cells to proliferate, differentiate, and escape apoptosis accounts for the leukemic transformation of myeloid progenitors. Here, we demonstrate that simultaneous retinoid receptor ligation and blockade of the MEK/ERK signaling module, using the small-molecule inhibitor CI-1040, result in a strikingly synergistic induction of apoptosis in both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells with constitutive ERK activation. This proapoptotic synergism requires functional RAR and RXR retinoid receptors, as demonstrated using RAR- and RXR-selective ligands and RAR-defective cells. In the presence of MEK inhibitors, however, retinoid-induced chromatin remodeling, target-gene transcription, and granulocytic differentiation are strikingly inhibited and apoptosis induction becomes independent of death-inducing ligand/receptor pairs; this suggests that apoptosis induction by combined retinoids and MEK inhibitors is entirely distinct from the classical “postmaturation” apoptosis induced by retinoids alone. Finally, we identify disruption of Bcl-2–dependent mitochondrial homeostasis as a possible point of convergence for the proapoptotic synergism observed with retinoids and MEK inhibitors. Taken together, these results indicate that combined retinoid treatment and MEK blockade exert powerful antileukemic effects and could be developed into a novel therapeutic strategy for both AML and APL.
Naphthoquinone enhances antigen-related airway inflammation in mice
Authors: Inoue K. , Takano H. , Hiyoshi K. , Ichinose T. , Sadakane K. , Yanagisawa R. , Tomura S. , Kumagai Y. 
Published: November 2006

The current authors have previously demonstrated that diesel exhaust particles (DEP) enhance antigen-related airway inflammation in mice. Furthermore, a recent study has shown that organic chemicals in DEP, rather than their carbonaceous nuclei, are important contributors to the aggravating effects of airway inflammation. However, the components in DEP responsible for the enhancing effects on the model remain to be identified.The current authors investigated the effects of naphthoquinone (NQ), one of the extractable chemical compounds of DEP, on antigen-related airway inflammation, local expression of cytokine proteins, and antigen-specific immunoglobulin (Ig) production in mice. Pulmonary exposure to NQ dose-dependently aggravated antigen-related airway inflammation, as characterised by infiltration of eosinophils and lymphocytes around the airways and an increase in goblet cells in the bronchial epithelium. Combined exposure to NQ and antigen enhanced the local expression of interleukin (IL)-4, IL-5, eotaxin, macrophage chemoattractant protein-1 and keratinocyte chemoattractant, compared with exposure to antigen or NQ alone. Also, NQ exhibited adjuvant activity for the antigen-specific production of IgG1and IgG2a.These results provide the first experimental evidence that naphthoquinone can enhance antigen-related airway inflammationin vivo, and that naphthoquinone can, to some extent, partly play a role in the pathogenesis of diesel exhaust particle toxicity on the condition.