bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional and Posttranscriptional Regulation of ArabidopsisTCH4 Expression by Diverse Stimuli. Roles of cis Regions and Brassinosteroids
Authors: Iliev Emanuil A. , Xu Wei , Polisensky Diana H. , Oh Man-Ho , Torisky Rebecca S. , Clouse Steven D. , Braam Janet 
Published: October 2002

Abstract
The Arabidopsis TCH4 gene is up-regulated in expression by diverse environmental and hormonal stimuli. BecauseTCH4 encodes a xyloglucan endotransglucosylase/hydrolase, this change in expression may reflect a recruitment of cell wall-modifying activity in response to environmental stress and growth. How diverse stimuli lead to the common response of TCH4 expression regulation is not known. Here, we show that induction of expression by the diverse stimuli of touch, darkness, cold, heat, and brassinosteroids (BRs) is conferred to reporter genes by the same 102-bp 5′-untranscribed TCH4region; this result is consistent with the idea that shared regulatory elements are employed by diverse stimuli. Distal regions influence magnitude and kinetics of expression and likely harbor regulatory elements that are redundant with those located more proximal to the transcriptional start site. Substitution of the proximal regulatory region sequences in the context of distal elements does not disrupt inducible expression. TCH4 expression induction is transcriptional, at least in part because 5′-untranscribed sequences are sufficient to confer this regulation. However, 5′-untranslated sequences are necessary and sufficient to confer the marked transience of TCH4 expression, most likely through an effect on mRNA stability. Perception of BR is not necessary forTCH4::GUS induction by environmental stimuli because regulation is intact in the BR-insensitive mutant,bri1-2. The full response to auxin, however, requires the functioning of BRI1. Developmental expression ofTCH4 is unlikely to be meditated by BR becauseTCH4::GUS is expressed in BR perception and biosynthetic mutants bri1-2 and det2-1, respectively.
Hoganite and paceite, two new acetate minerals from the Potosi mine, Broken Hill, Australia
Authors: Hibbs D. E. , Kolitsch U. , Leverett P. , Sharpe J. L. , Williams P. A. 
Published: October 2002

AbstractHoganite, copper(II) acetate monohydrate, and paceite (pronounced ‘pace-ite’), calcium(II) copper(II) tetraacetate hexahydrate, occur as isolated crystals embedded in ferruginous gossan from the Potosi Pit, Broken Hill, New South Wales, Australia. They are associated with goethite, hematite, quartz, linarite, malachite, azurite, cerussite and cuprian smithsonite. Hoganite is bluish green with a pale blue streak and a Mohs hardness of 1½; it possesses perfect {001} and distinct {110} cleavages and has a conchoidal fracture. Chemical analysis of hoganite gave (wt.%) C 23.85; H 3.95; Cu 31.6; Fe 0.4; O (by difference) 40.2, yielding an empirical formula of C4H7.89O5.07Cu1.00Fe0.01. The simplified formula is C4H8O5Cu or Cu(CH3COO)2.H2O, the mineral being identical to the synthetic compound of the same formula. Single-crystal X-ray data for hoganite are: monoclinic, space group C2/c, a = 13.162(3), b = 8.555(2), c = 13.850(3)Å, β = 117.08(3)°, Z = 8. The density, calculated from single-crystal data, is 1.910 g cm−3. The strongest lines in the X-ray powder pattern are [dobs (Iobs) (hkl)] 6.921 (100) (011); 3.532 (28) (202); 6.176 (14) (200); 3.592 (11) (22); 5.382 (10) (11); 2.278 (10) (204); 5.872 (9) (002). Hoganite (orientation presently unknown) is biaxial positive with α = 1.533(2), β = 1.541(3), γ = 1.554(2), 2V(meas.) = 85(5)°, 2V(calc.) = 76.8°, dispersion is r < v, medium (white light); it is strongly pleochroic with X = blue, Y = pale bluish, Z = pale bluish green and absorption X > Y > Z. The mineral is named after Graham P. Hogan of Broken Hill, New South Wales, Australia, a miner and well-known collector of Broken Hill minerals.Paceite is dark blue with a pale blue streak and a Mohs hardness of 1½; it possesses perfect {100} and {110} cleavages and has an uneven fracture. Chemical analysis of paceite gave (wt.%) C 21.25; H 5.3; Ca 9.0; Cu 14.1; O (by difference) 50.35, yielding an empirical formula of C8H23.77O14.23Ca1.02-Cu1.00. The simplified formula is C8H24O14CaCu or CaCu(CH3COO)4.6H2O, the mineral being identical to the synthetic compound of the same formula. Unit-cell data (refined from X-ray powder diffraction data) for paceite are: tetragonal, space group I4/m, a = 11.155(4), c = 16.236(17)Å, Z = 4. The density, calculated from refined cell data, is 1.472 g cm−3. The strongest lines in the X-ray powder pattern are [dobs (Iobs) (hkl)] 7.896 (100) (110); 3.530 (20) (310); 5.586 (15) (200); 8.132 (8) (002); 9.297 (6) (101); 2.497 (4) (420); 3.042 (3) (321). Paceite is uniaxial positive with ω = 1.439(2) and ɛ = 1.482(3) (white light); pleochroism is bluish with a greenish tint (O), pale bluish with a greyish tint (E), and absorption O ⩾ E. The mineral is named after Frank L. Pace of Broken Hill, New South Wales, Australia, an ex-miner and well-known collector of Broken Hill minerals.
Single-cell analysis of CD30+ cells in lymphomatoid papulosis demonstrates a common clonal T-cell origin
Authors: Steinhoff Matthias , Hummel Michael , Anagnostopoulos Ioannis , Kaudewitz Peter , Seitz Volkhard , Assaf Chalid , Sander Christian , Stein Harald 
Published: October 2002

AbstractLymphomatoid papulosis (LyP) represents an intriguing cutaneous T-cell lymphoproliferative disorder with a histologic appearance resembling malignant lymphoma. This finding strongly contrasts with the benign clinical course of the disease. However, in 10% to 20% of cases, LyP can precede, coexist with, or follow malignant lymphoma. In these cases, the same T-cell population has been shown to be present in the LyP as well as in the associated lymphoma. In most LyP cases, there is—despite the sometimes extremely long course of the disease—no evolution of a secondary lymphoma. The investigation of these uncomplicated LyP cases for the presence of clonal T-cell receptor rearrangements has produced heterogeneous results. This might be explained by biologic or technical reasons arising from analyzing whole tissue DNA extracts. To definitively clarify whether the large atypical CD30+ cells in LyP without associated lymphoma all belong to the same clone or represent individually rearranged T cells, we analyzed the T-cell receptor–γ rearrangements of single CD30+ as well as of single CD30− cells isolated from 14 LyP lesions of 11 patients. By using this approach we could demonstrate that the CD30+ cells represent members of a single T-cell clone in all LyP cases. Moreover, in 3 patients the same CD30+ cell clone was found in anatomically and temporally separate lesions. In contrast, with only a few exceptions, the CD30− cells were polyclonal in all instances and unrelated to the CD30+ cell clone. Our results demonstrate that LyP unequivocally represents a monoclonal T-cell disorder of CD30+ cells in all instances.
Role of GITR in activation response of T lymphocytes
Authors: Ronchetti Simona , Nocentini Giuseppe , Riccardi Carlo , Pandolfi Pier Paolo 
Published: October 2002

AbstractIn this study, we describe the generation and characterization of mice in which GITR gene (TNFRSF18 [tumor necrosis factor receptor superfamily 18]), a member of the TNFRSF expressed mainly on T lymphocytes, has been ablated (GITR−/− mice). Results indicate that GITR inactivation does not impair the normal development of the lymphoid organs but modulates T-cell activation. In fact, whenGITR−/− T lymphocytes are activated by treatment with an anti-CD3 monoclonal antibody they proliferate more than wild-type cells. Moreover, activatedGITR−/− T lymphocytes express higher levels of interleukin-2 receptor, produce larger amounts of interleukin-2, and are more sensitive to activation-induced cell death than controls. These results suggest that GITR is involved in the regulation of T-cell receptor/CD3–driven T-cell activation and programmed cell death.
Bismuth 213–labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts
Authors: Sandmaier Brenda M. , Bethge Wolfgang A. , Wilbur D. Scott , Hamlin Donald K. , Santos Erlinda B. , Brechbiel Martin W. , Fisher Darrell R. , Storb Rainer 
Published: October 2002

AbstractTo lower treatment-related mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for postgrafting immunosuppression was developed. To circumvent possible toxic effects of external-beam γ irradiation, strategies for targeted radiation therapy were investigated. We tested whether the short-lived (half-life, 46 minutes) α-emitter bismuth 213 (213Bi) conjugated to an anti-CD45 monoclonal antibody (mAb) could replace 200 cGy TBI and selectively target hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow transplantation. Biodistribution studies using iodine 123–labeled anti-CD45 mAb showed uptake in blood, marrow, lymph nodes, spleen, and liver. In a dose-escalation study, 7 dogs treated with the 213Bi–anti-CD45 conjugate (213Bi dose, 0.1-5.9 mCi/kg [3.7-218 MBq/kg]) without marrow grafts had no toxic effects other than a mild, reversible suppression of blood counts. On the basis of these studies, 3 dogs were treated with 0.5 mg/kg 213Bi-labeled anti-CD45 mAb (213Bi doses, 3.6, 4.6, and 8.8 mCi/kg [133, 170, and 326 MBq/kg]) given in 6 injections 3 and 2 days before grafting of marrow from DLA-identical littermates. The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the day before transplantation until 35 days afterward). The therapy was well tolerated except for transient elevations in levels of transaminases in 3 dogs, followed by, in one dog, ascites. All dogs had prompt engraftment and achieved stable mixed hematopoietic chimerism, with donor contributions ranging from 30% to 70% after more than 27 weeks of follow-up. These results will form the basis for additional studies in animals and later the design of clinical trials using213Bi as a nonmyeloablative conditioning regimen with minimal toxicity.
Nondisjunction of chromosomes leading to hyperdiploid childhood B-cell precursor acute lymphoblastic leukemia is an early event during leukemogenesis
Authors: Panzer-Grümayer E. Renate , Fasching Karin , Panzer Simon , Hettinger Klaudia , Schmitt Klaus , Stöckler-Ipsiroglu Sylvia , Haas Oskar A. 
Published: October 2002

Abstract
A hyperdiploid karyotype is found in 30% of B-cell precursor acute lymphoblastic leukemias in childhood. The time of nondisjunction of chromosomes leading to hyperdiploidy during leukemogenesis is unknown. We used the 3 clonotypic immunoglobulin heavy chain (IgH) gene rearrangements as molecular markers for each of the 3 chromosomes 14 in a case with hyperdiploid acute lymphoblastic leukemia to define the order of events—namely, somatic recombination and nondisjunction of chromosomes—during leukemia development. A partial sequence homology of the incomplete DJH rearrangement with 1 of the 2 nonfunctional VDJH rearrangements suggests that the doubling of chromosomes had occurred after this DJHrearrangement and thus during early B-cell differentiation. The occurrence of the nondisjunction of chromosomes as well as ongoing rearrangement processes in utero were confirmed by the presence of all 3 IgH rearrangements in neonatal blood spots, providing the first evidence that hyperdiploidy formation is an early event in leukemogenesis in these leukemias.
A 2-kb c-mpl promoter fragment is sufficient to direct expression to the megakaryocytic lineage and sites of embryonic hematopoiesis in transgenic mice
Authors: Ziegler Sandra , Bürki Kurt , Skoda Radek C. 
Published: October 2002

Abstract
Thrombopoietin receptor c-mpl is expressed on hematopoietic progenitors and cells of the megakaryocytic lineage. The c-mpl promoter may, therefore, be useful for directing the expression of transgenes. We tested whether a 2-kb genomic DNA fragment comprising the putative c-mpl regulatory elements and most of the 5′-untranslated region of mouse c-mpl is able to direct the expression of a reporter gene to hematopoietic cells in transgenic mice. As a reporter gene we used the human placental alkaline phosphatase (PLAP). In adult transgenic mice, PLAP expression was specifically detected in megakaryocytes and platelets. Embryos showed PLAP reporter gene expression already in the yolk sac at embryonic day 6.5 (E6.5) and in blood islands at E7.5. At E9.5, expression was found in blood vessels of the yolk sac and the embryo proper, followed by high levels of expression in the fetal liver at E11.5. Expression in E6.5 yolk sac is compatible with a function of c-mpl and its ligand, thrombopoietin, in the earliest stages of embryonic hematopoiesis.
The DAU allele cluster of the RHDgene
Authors: Wagner Franz F. , Ladewig Birgit , Angert Katharina S. , Heymann Guido A. , Eicher Nicole I. , Flegel Willy A. 
Published: October 2002

AbstractVariant D occurs frequently in Africans. However, considerably lessRHD alleles have been described in this population compared with Europeans. We characterized 5 new RHD alleles, dubbedDAU-0 to DAU-4, that shared a T379M substitution and occurred in a cDe haplotype.DAU-1 to DAU-4 were detected in Africans with partial D phenotypes. They harbored one and 2 additional missense mutations, respectively, dispersed throughout the RhD protein. An anti-D immunization was found in DAU-3. DAU-0carrying T379M only was detected by screening European blood donors and expressed a normal D phenotype. Within the phylogeny of theRHD alleles, DAU formed an independent allele cluster, separate from the DIVa, weak D type 4, and Eurasian D clusters. The characterization of the RH phylogeny provided a framework for future studies on RH alleles. The identification of theDAU alleles increased the number of known partial D alleles in Africans considerably. DAU alleles may be a major cause of antigen D variability and anti-D immunization in patients of African descent.
Functional involvement of Akt signaling downstream of Jak1 in v-Abl–induced activation of hematopoietic cells
Authors: Oki Shinji , Limnander Andre , Danial Nika N. , Rothman Paul B. 
Published: October 2002

AbstractActivation of intracellular signaling pathways is important for cellular transformation and tumorigenesis. The nonreceptor tyrosine kinases Jak1 and Jak3, which bind to the v-Abl oncoprotein, are constitutively activated in cells transformed with the Abelson murine leukemia virus. A mutant of p160 v-Abl lacking the Jak1-binding region (v-Abl Δ858-1080) has a significant defect in Jak/STAT (signal transducers and activators of transcription) activation, cytokine-independent cell growth/survival, and tumorigenesis. To identify the pathways downstream of Jak kinases in v-Abl–mediated signaling, we examined the activation of several signaling molecules by p160 v-Abl or the v-Abl Δ858-1080 mutant. We demonstrate that, in addition to the decreased Ras activation, signaling through phosphatidylinositol-3 kinase and Akt are impaired in cells expressing mutant v-Abl. The proliferative defect of v-Abl Δ858-1080 was rescued by activated v-Akt and was also moderately rescued by activated v-H-Ras. However, constitutive active phosphatidylinositol-3 kinase (p110CAAX) did not complement this effect. Cells expressing v-Abl Δ858-1080 demonstrated reduced tumor formation in nude mice. In contrast, cells coexpressing v-Akt with v-Abl Δ858-1080 demonstrated reduced latency and increased frequency of tumor formation in nude nice compared with cells expressing v-Abl Δ858-1080 alone, whereas v-H-Ras or p110CAAX had minimum effects on tumor formation. These results suggest that Jak1–dependent Akt activation is important in v-Abl–mediated transformation.
Sustained phenotypic correction of hemophilia B dogs with a factor IX null mutation by liver-directed gene therapy
Authors: Mount Jane D. , Herzog Roland W. , Tillson D. Michael , Goodman Susan A. , Robinson Nancy , McCleland Mark L. , Bellinger Dwight , Nichols Timothy C. , Arruda Valder R. , Lothrop Clinton D. , High Katherine A. 
Published: October 2002

Abstract
Hemophilia B is an X-linked coagulopathy caused by absence of functional coagulation factor IX (FIX). Using adeno-associated virus (AAV)–mediated, liver-directed gene therapy, we achieved long-term (&gt; 17 months) substantial correction of canine hemophilia B in 3 of 4 animals, including 2 dogs with an FIX null mutation. This was accomplished with a comparatively low dose of 1 × 1012 vector genomes/kg. Canine FIX (cFIX) levels rose to 5% to 12% of normal, high enough to result in nearly complete phenotypic correction of the disease. Activated clotting times and whole blood clotting times were normalized, activated partial thromboplastin times were substantially reduced, and anti-cFIX was not detected. The fourth animal, also a null mutation dog, showed transient expression (4 weeks), but subsequently developed neutralizing anti-cFIX (inhibitor). Previous work in the canine null mutation model has invariably resulted in inhibitor formation following treatment by either gene or protein replacement therapies. This study demonstrates that hepatic AAV gene transfer can result in sustained therapeutic expression in a large animal model characterized by increased risk of a neutralizing anti-FIX response.
Extensive in vivo self-renewal, long-term reconstitution capacity, and hematopoietic multipotency of Pax5-deficient precursor B-cell clones
Authors: Schaniel Christoph , Gottar Marie , Roosnek Eddy , Melchers Fritz , Rolink Antonius G. 
Published: October 2002

Abstract
Self-renewal, pluripotency, and long-term reconstitution are defining characteristics of single hematopoietic stem cells.Pax5−/− precursor B cells apparently possess similar characteristics. Here, using serial transplantations, with in vitro recloning and growth of the bone marrow–homed donor cells occurring after all transplantations, we analyzed the extent of self-renewal and hematopoietic multipotency ofPax5−/− precursor B-cell clones. Moreover, telomere length and telomerase activity in these clones was analyzed at various time points. Thus far, 5 successive transplantations have been performed. Clones transplanted for the fifth time, which have proliferated for more than 150 cell divisions in vitro, still repopulate the bone marrow with precursor B cells and reconstitute these recipients with lymphoid and myeloid cells. During this extensive proliferation, Pax5−/− precursor B cells shorten their telomeres at 70 to 90 base pairs per division. Their telomerase activity remains at 3% of that of HEK293 cancer cells during all serial in vivo transplantations/in vitro expansions. Together, these data show thatPax5−/− precursor B-cell clones possess extensive in vivo self-renewal capacity, long-term reconstitution capacity, and hematopoietic multipotency, with their telomeres shortening at the normal rate.
Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation
Authors: Sévigny Jean , Sundberg Christian , Braun Norbert , Guckelberger Olaf , Csizmadia Eva , Qawi Imrana , Imai Masato , Zimmermann Herbert , Robson Simon C. 
Published: October 2002

AbstractNucleoside triphosphate diphosphohydrolases (NTPDases) are a recently described family of ectonucleotidases that differentially hydrolyze the γ and β phosphate residues of extracellular nucleotides. Expression of this enzymatic activity has the potential to influence nucleotide P2 receptor signaling within the vasculature. We and others have documented that NTPDase1 (CD39, 78 kd) hydrolyzes both triphosphonucleosides and diphosphonucleosides and thereby terminates platelet aggregation responses to adenosine diphosphate (ADP). In contrast, we now show that NTPDase2 (CD39L1, 75 kd), a preferential nucleoside triphosphatase, activates platelet aggregation by converting adenosine triphosphate (ATP) to ADP, the specific agonist of P2Y1 and P2Y12 receptors. We developed specific antibodies to murine NTPDase1 and NTPDase2 and observed that both enzymes are present in the cardiac vasculature; NTPDase1 is expressed by endothelium, endocardium, and to a lesser extent by vascular smooth muscle, while NTPDase2 is associated with the adventitia of muscularized vessels, microvascular pericytes, and other cell populations in the subendocardial space. Moreover, NTPDase2 represents a novel marker for microvascular pericytes. Differential expression of NTPDases in the vasculature suggests spatial regulation of nucleotide-mediated signaling. In this context, NTPDase1 should abrogate platelet aggregation and recruitment in intact vessels by the conversion of ADP to adenosine monophosphate, while NTPDase2 expression would promote platelet microthrombus formation at sites of extravasation following vessel injury. Our data suggest that specific NTPDases, in tandem with ecto-5′-nucleotidase, not only terminate P2 receptor activation and trigger adenosine receptors but may also allow preferential activation of specific subsets of P2 receptors sensitive to ADP (eg, P2Y1, P2Y3, P2Y12) and uridine diphosphate (P2Y6).
Agonist-induced aggregation of Chinese hamster ovary cells coexpressing the human receptors for fibrinogen (integrin αIIbβ3) and the platelet-activating factor: dissociation between adhesion and aggregation
Authors: Larrucea Susana , González-Manchón Consuelo , Butta Nora , Arias-Salgado Elena G. , Shen Linnan , Ayuso Matilde S. , Parrilla Roberto 
Published: October 2002

AbstractThis work reports the establishment of a Chinese hamster ovary (CHO) cell line stably coexpressing the human αIIbβ3 integrin and the platelet-activating factor receptor (PAFR). These cells aggregate in response to PAF in a Ca++, αIIbβ3, and soluble fibrinogen (Fg)–dependent manner that is prevented by PAF antagonists or αIIbβ3 blockade. The aggregating response is accompanied by enhanced binding of fibrinogen and the activation-dependent IgM PAC1. This model has permitted us to identify, for the first time, intracellular signals distinctly associated with either αIIbβ3-mediated adhesion or aggregation. Nonreceptor activation of protein kinase C (PKC) by phorbol ester produced cellular adhesion and spreading onto immobilized Fg, but it was not a sufficient signal to provoke cellular aggregation. Moreover, inhibition of PKC impeded the PAF stimulation of cellular adhesion, whereas the aggregation was not prevented. The PAF-induced cellular aggregation was distinctly associated with signaling events arising from the liganded Fg receptor and the agonist-induced stimulation of a calcium/calmodulin-dependent signaling pathway. Sustained tyrosine phosphorylation of both mitogen-activated protein kinase (MAPK) and an approximately 100-kd protein was associated with the PAF-induced aggregation, whereas phosphorylation of focal adhesion kinase (FAK) was preferably associated with cellular adherence and spreading onto immobilized Fg.