bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the Alternative Oxidase Promoters from Soybean
Authors: Thirkettle-Watts David , McCabe Tulene C. , Clifton Rachel , Moore Carolyn , Finnegan Patrick M. , Day David A. , Whelan James 
Published: November 2003

Abstract
Alternative oxidase (Aox) is a nuclear-encoded mitochondrial protein. In soybean (Glycine max), the three members of the gene family have been shown to be differentially expressed during normal plant development and in response to stresses. To examine the function of the Aox promoters, genomic fragments were obtained for all three soybean genes: Aox1, Aox2a, and Aox2b. The regions of these fragments immediately upstream of the coding regions were used to drive β-glucuronidase (GUS) expression during transient transformation of soybean suspension culture cells and stable transformation of Arabidopsis. The expression patterns of the GUS reporter genes in soybean cells were in agreement with the presence or absence of the various endogenous Aox proteins, determined by immunoblotting. Deletion of different portions of the upstream regions identified sequences responsible for both positive and negative regulation of Aox gene expression in soybean cells. Reporter gene analysis in Arabidopsis plants showed differential tissue expression patterns driven by the three upstream regions, similar to those reported for the endogenous proteins in soybean. The expression profiles of all five members of the Arabidopsis Aox gene family were examined also, to compare with GUS expression driven by the soybean upstream fragments. Even though the promoter activity of the upstream fragments from soybean Aox2a and Aox2b displayed the same tissue specificity in Arabidopsis as they do in soybean, the most prominently expressed endogenous genes in all tissues of Arabidopsis were of the Aox1 type. Thus although regulation of Aox expression generally appears to involve the same signals in different species, different orthologs of Aox may respond variously to these signals. A comparison of upstream sequences between soybean Aox genes and similarly expressed Arabidopsis Aox genes identified common motifs.
Microspore Separation in thequartet 3Mutants of Arabidopsis Is Impaired by a Defect in a Developmentally Regulated Polygalacturonase Required for Pollen Mother Cell Wall Degradation
Authors: Rhee Seung Y. , Osborne Erin , Poindexter Patricia D. , Somerville Chris R. 
Published: November 2003

AbstractMutations in the QUARTET loci in Arabidopsis result in failure of microspore separation during pollen development due to a defect in degradation of the pollen mother cell wall during late stages of pollen development. Mutations in a new locus required for microspore separation, QRT3, were isolated, and the corresponding gene was cloned by T-DNA tagging. QRT3 encodes a protein that is approximately 30% similar to an endopolygalacturonase from peach (Prunus persica). The QRT3 protein was expressed in yeast (Saccharomyces cerevisiae) and found to exhibit polygalacturonase activity. In situ hybridization experiments showed that QRT3 is specifically and transiently expressed in the tapetum during the phase when microspores separate from their meiotic siblings. Immunohistochemical localization of QRT3 indicated that the protein is secreted from tapetal cells during the early microspore stage. Thus, QRT3 plays a direct role in degrading the pollen mother cell wall during microspore development.
Future of primary healthcare education: current problems and potential solutions
Authors: Lord J 
Published: November 2003

Abstract
This review examines the origins of primary care and the pressures currently faced in terms of patient expectation, regulation, accountability, and work force shortages. It recognises the appropriateness of adding to the burden in primary care further by the shift both of more services and more medical education from secondary care. Some conclusions are drawn concerning potential solutions including skill mix changes, centralisation of services, a change in attitudes to professional mistakes, increased protected development time, evidence based education, and academic, leadership, and feedback skills for general practitioners. Six recommendations are offered as a prescription for organisational and educational change.
Neuropsychiatric non-motor aspects of Parkinson’s disease
Authors: Thanvi B R , Munshi S K , Vijaykumar N , Lo T C N 
Published: November 2003

Abstract
Parkinson’s disease is often recognised as a motor disease characterised by rest tremor, rigidity, bradykinesia, and postural disturbances. However, there are several non-motor aspects of the disease that are of at least equal importance in the management of patients with Parkinson’s disease. They include depression, cognitive impairment, anxiety, and psychosis among others. It is important to recognise them, as they are common and they contribute significantly to patients’ morbidity, quality of life, and institutionalisation to long term care homes. In addition to the disease duration and severity, other factors including drugs may contribute to their occurrence. Pathogenesis of these aspects is not fully understood, though there has been a significant increase in the knowledge in recent years. Management of these aspects involves a multidisciplinary approach.
The transcriptome of the leukemogenic homeoprotein HOXA9 in human hematopoietic cells
Authors: Dorsam Sheri Tinnell , Ferrell Christina M. , Dorsam Glenn P. , Derynck Mika Kakefuda , Vijapurkar Ulka , Khodabakhsh Daniel , Pau Bonnie , Bernstein Hillary , Haqq Christopher M. , Largman Corey , Lawrence H. Jeffrey 
Published: November 2003

AbstractHematopoietic defects in HOXA9–/– mice demonstrate a key role for this homeoprotein in blood cell development. Conversely, enforced HOXA9 expression is leukemogenic in mice, and HOXA9 is frequently activated in human acute myeloid leukemia (AML). Although HOXA9 is thought to function as a transcription factor, few downstream targets have been identified. We searched for early HOXA9 target genes by using a transient overexpression strategy in 3 hematopoietic cell lines (2 myeloid, 1 lymphoid). cDNA microarray analyses identified 220 genes whose expression was modulated at least 2-fold. Expression signatures in myeloid and lymphoid cells demonstrated that HOXA9 functions as both an activator and repressor of a variety of genes in cell-specific patterns suggesting that the transcriptional effects of HOXA9 are largely dependent on the cell context. Transient transcription assays and target gene expression patterns in HOXA9–/– marrow cells imply that we have identified direct physiologic targets. Many target genes are expressed in CD34+ stem cells or are members of gene families involved in proliferation or myeloid differentiation. Expression of 14 HOXA9 target genes correlated with high-level HOXA9 expression in primary AML. These data suggest that many genes identified in this survey may mediate the biologic effects of HOXA9 in normal and leukemic hematopoiesis.
Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma
Authors: Marshall Neil A. , Christie Linsey E. , Munro Laura R. , Culligan Dominic J. , Johnston Peter W. , Barker Robert N. , Vickers Mark A. 
Published: November 2003

AbstractAlthough immunosuppression has long been recognized in Hodgkin lymphoma (HL), the underlying basis for the lack of an effective immune response against the tumor remains unclear. The aim was to test our hypothesis that regulatory T cells dominate involved lymph nodes. The approach was to assay CD4+ T-cell function in HL-infiltrating lymphocytes (HLILs) and paired peripheral blood mononuclear cells (PBMCs) of 24 patients. Strikingly, unlike PBMCs, HLILs were anergic to stimulation with mitogen, primary, or recall antigens, mounting no proliferative responses and only rare T-helper 1 (Th1) or Th2 cytokine responses. Mixing paired HLILs and PBMCs showed the anergic effect was dominant and suppressed PBMC responses. Furthermore, flow cytometry demonstrated that HLILs contained large populations of both interleukin-10 (IL-10)–secreting T-regulatory 1 (Tr1) and CD4+CD25+ regulatory T cells. We found evidence for 3 mechanisms of action implicated in the suppressive functions of regulatory T cells: the inhibition of PBMCs by HLILs was ameliorated by neutralizing IL-10, by preventing cell-to-cell contact, and by blocking anti–cytotoxic T lymphocyte–associated antigen 4 (anti–CTLA-4). Thus, HLILs are highly enriched for regulatory T cells, which induce a profoundly immunosuppressive environment and so provide an explanation for the ineffective immune clearance of Hodgkin-Reed Sternberg cells.
Antibody-targeted MHC complex–directed expansion of HIV-1– and KSHV-specific CD8+ lymphocytes: a new approach to therapeutic vaccination
Authors: Stebbing Justin , Gazzard Brian , Patterson Steve , Bower Mark , Perumal Dhayaneethie , Nelson Mark , McMichael Andrew , Ogg Graham , Epenetos Agamemnon , Gotch Frances , Savage Philip 
Published: November 2003

AbstractThe ability of therapeutic vaccines to generate large numbers of CD8+ T lymphocytes that have specificity for HIV-1 or other virally infected cells has enormous potential clinical value. However, approaches to produce cytotoxic T lymphocytes (CTLs) in vivo via vaccine technology have thus far been disappointing and the ex vivo production of cells for adoptive transfer is labor intensive and expensive. We describe the results of a 2-step antibody-targeting system for the production of CD8+ T lymphocytes specific for HIV-1 and Kaposi sarcoma–associated herpesvirus (KSHV), suitable for use in vivo. In 8 consecutive human leukocyte antigen–A2 (HLA-A2)–positive HIV-1–infected individuals with Kaposi sarcoma, 2 cycles of this system resulted in more than 1 Log increases of specific anti-HIV and anti-KSHV CD8+ lymphocytes. These expanded cells have an effector phenotype that includes the ability to produce interferon-γ and CD45Ra+/CD69+ staining. We have shown that antibody-targeted B cells can function as effective antigen-presenting molecules and lead to sustained specific T-lymphocyte expansion from peripheral blood mononuclear cells (PBMCs) of immunosuppressed individuals. This approach, which offers an easy and effective protocol for the amplification of specific antiviral and antitumor CTLs, may offer significant advances for in vivo T-cell immunotherapeutic protocols.
Inhibition of Uncoupling Protein Expression during Lactation: Role of Leptin
Authors: Xiao Xiao Qiu , Grove Kevin L. , Grayson Bernadette E. , Smith M. Susan 
Published: November 2003

AbstractUncoupling proteins (UCPs) are mitochondrial proteins that play a role in regulation of energy expenditure by uncoupling respiration from ATP synthesis. Lactation is a physiological condition characterized by negative energy balance due to the loss of energy sources to the production of milk. The objective of the current study was to investigate whether UCP mRNA and protein expressions were altered during lactation compared with those after 48 h of fasting. Lactation significantly reduced serum leptin levels, and removal of pups for 48 h increased serum leptin to higher levels than those observed in control rats. Compared with control rats, mRNA expression of UCP1 and UCP3 in brown adipose tissue (BAT) was dramatically reduced during lactation and fasting. The reduction in mRNAs was reflected by a lowered UCP1 protein level, and to some extent, UCP3 protein. Treatment of lactating rats with exogenous leptin (3 mg/kg) or removal of pups for 48 h completely reversed the down-regulation of UCP1 and UCP3 mRNA expression in BAT, and pup removal led to a recovery of protein expression. In contrast to BAT, UCP3 expression in skeletal muscle was increased in fasted rats and decreased during lactation. Similar changes were observed in serum free fatty acid levels. These changes are consistent with the idea that the utilization of free fatty acids as a fuel source is spared during lactation. As in BAT, leptin treatment and removal of pups were able to restore changes in mRNA expression of UCP3 in skeletal muscle during lactation. The present results suggest that the inhibition of leptin secretion during lactation is involved in the down-regulation of UCP expression in BAT and skeletal muscle, which, in turn, is responsible for the decrease in metabolic fuel oxidation and thermogenesis.
Regulation of outgrowth and apoptosis for the terminal appendage:external genitalia: development by concerted actions of BMP signaling
Authors: Suzuki Kentaro , Bachiller Daniel , Chen YiPing P. , Kamikawa Mami , Ogi Hidenao , Haraguchi Ryama , Ogino Yukiko , Minami Yasuhiro , Mishina Yuji , Ahn Kyung , Crenshaw E. Bryan , Yamada Gen 
Published: November 2003

Extra-corporal fertilization depends on the formation of copulatory organs:the external genitalia. Coordinated growth and differentiation of the genital tubercle (GT), an embryonic anlage of external genitalia, generates a proximodistally elongated structure suitable for copulation, erection, uresis and ejaculation. Despite recent progress in molecular embryology, few attempts have been made to elucidate the molecular developmental processes of external genitalia formation.Bone morphogenetic protein genes (Bmp genes) and their antagonists were spatiotemporally expressed during GT development. Exogenously applied BMP increased apoptosis of GT and inhibited its outgrowth. It has been shown that the distal urethral epithelium (DUE), distal epithelia marked by the Fgf8 expression, may control the initial GT outgrowth. Exogenously applied BMP4 downregulated the expression of Fgf8 and Wnt5a,concomitant with increased apoptosis and decreased cell proliferation of the GT mesenchyme. Furthermore, noggin mutants and Bmpr1a conditional mutant mice displayed hypoplasia and hyperplasia of the external genitalia respectively. noggin mutant mice exhibited downregulation of Wnt5aand Fgf8 expression with decreased cell proliferation. Consistent with such findings, Wnt5a mutant mice displayed GT agenesis with decreased cell proliferation. By contrast, Bmpr1a mutant mice displayed decreased apoptosis and augmented Fgf8 expression in the DUE associated with GT hyperplasia. These results suggest that some of the Bmp genes could negatively affect proximodistally oriented outgrowth of GT with regulatory functions on cell proliferation and apoptosis.The DUE region can be marked only until 14.0 dpc (days post coitum) in mouse development, while GT outgrowth continues thereafter. Possible signaling crosstalk among the whole distal GT regions were also investigated.
Synthesis, Characterization, and Nonlinear Optical Study of Metalloporphyrins
Authors: McEwan K. , Lewis K. , Yang G.‐Y. , Chng L.‐L. , Lee Y.‐W. , Lau W.‐P. , Lai K.‐S. 
Published: November 2003

Abstractmeso‐Tetrakis{4‐[2‐(trimethylsilyl)ethynyl]phenyl}porphyrin [TPP(4‐CCTMS)_H2] and its complexes with ZnII, NiII, GaIII, InIII, and SnIV were synthesized and characterized. Their nonlinear optical transmission characteristics were determined using a 532 nm, 5 ns pulsed laser at a repetition rate of 20 Hz. Stronger nonlinear absorption was obtained with the zinc derivative, ZnII‐meso‐tetrakis{4‐[2‐(trimethylsilyl)ethynyl]phenyl}porphyrin (TPP(4‐CCTMS)_Zn), than with the standard analogues, ZnII‐meso‐tetraphenylporphyrin (TPP_Zn), and ZnII‐meso‐tetratolyl‐porphyrin (TTP_Zn), indicating that the excited‐state absorption can be influenced via fine molecular modification on the para‐position of the meso‐phenyl rings, without changing the ground‐state absorption. The nonlinear optical response can be further enhanced via insertion of closed‐shell metal ions. In particular, InIIICl‐meso‐tetrakis{4‐[2‐(trimethylsilyl)ethynyl]phenyl}porphyrin (TPP(4‐CCTMS)_InCl), exhibited a larger change in transmission with increasing energy than C60 and a comparable change to the state‐of‐the‐art phthalocyanine dye, chloro(tetra(tert‐butyl)phthalocyanato)indium(III) (Pc(t‐Bu)_InCl).
Synthesis of Optically Complex Core–Shell Colloidal Suspensions: Pathways to Multiplexed Biological Screening
Authors: Lawrie G.A. , Battersby B.J. , Trau M. 
Published: November 2003

AbstractThe ability to generate enormous random libraries of DNA probes via split‐and‐mix synthesis on solid supports is an important biotechnological application of colloids that has not been fully utilized to date. To discriminate between colloid‐based DNA probes each colloidal particle must be ‘encoded’ so it is distinguishable from all other particles. To this end, we have used novel particle synthesis strategies to produce large numbers of optically encoded particles suitable for DNA library synthesis. Multi‐fluorescent particles with unique and reproducible optical signatures (i.e., fluorescence and light‐scattering attributes) suitable for high‐throughput flow cytometry have been produced. In the spectroscopic study presented here, we investigated the optical characteristics of multi‐fluorescent particles that were synthesized by coating silica ‘core’ particles with up to six different fluorescent dye shells alternated with non‐fluorescent silica ‘spacer’ shells. It was observed that the diameter of the particles increased by up to 20 % as a result of the addition of twelve concentric shells and that there was a significant reduction in fluorescence emission intensities from inner shells as an increasing number of shells were deposited.
AlxGa1–xN—A New Material System for Biosensors
Authors: Steinhoff G. , Purrucker O. , Tanaka M. , Stutzmann M. , Eickhoff M. 
Published: November 2003

AbstractThe applicability of the group III nitride material system for the fabrication of semiconductor‐based biosensors is demonstrated. The operation of ion‐sensitive field‐effect transistors (ISFETs) based on AlGaN/GaN heterostructures in aqueous electrolytes is shown to be characterized by high sensitivity and low drift. Fibroblasts in contact with oxidized and as‐deposited AlGaN surfaces are demonstrated to survive at least for 24 h, indicating that these surfaces are chemically robust and non‐toxic against living cells. Surface hydrophilization using thermal oxidation allows the deposition of highly mobile lipid membranes by vesicle fusion. The homogeneity and the diffusion properties of phospholipids with different net charges were analyzed by fluorescence microscopy and constant photobleaching, taking advantage of the optical transparency of the AlGaN material system. The obtained results reveal that AlGaN‐based devices are promising candidates for future multifunctional biosensors.
Solar Energy Materials
Authors: Granqvist C.G. 
Published: November 2003

AbstractSolar energy materials have properties tailored to meet requirements set by the spectral distribution, angle of incidence, and intensity of the electromagnetic radiation prevailing in our natural surroundings. Specifically, the optimization can be performed with regard to solar irradiation, thermal emission, atmospheric absorption, visible light, and photosynthetic efficiency. Materials for thermal and electrical conversion of solar energy in man‐made collectors, as well as for energy‐efficient passive design in architecture, are typical examples. This paper reviews solar energy materials with emphasis on the thermal applications of a variety of types. Electrical applications are given a more cursory exposition, the reason being that a systems perspective—rather that a materials perspective—is most fruitful in this case.
Neue Antimalaria‐Wirkstoffe
Authors: Wiesner Jochen , Ortmann Regina , Jomaa Hassan , Schlitzer Martin 
Published: November 2003

AbstractEtwa 40 % der Weltbevölkerung leben in Malariagebieten. Jährlich erkranken 300 bis 500 Millionen Menschen an Malaria, bis zu 2.5 Millionen sterben an den Krankheitsfolgen. Obwohl Malaria in vielen Teilen der Welt bereits als ausgerottet galt, nimmt die Zahl der Fälle auch in diesen Gebieten wieder zu. Der wichtigste Grund für diese bedrohliche Entwicklung ist die zunehmende Verbreitung von Resistenzen gegen Antimalaria‐Wirkstoffe, insbesondere gegen das am häufigsten verwendete Chloroquin. Seit Mitte der siebziger Jahre wurde die Entwicklung neuer Wirkstoffe vernachlässigt. Dafür ist neben dem Wegfall kolonialer und militärischer Interessen auch das beschränkte Marktpotenzial verantwortlich. Unterstützt durch öffentliche Förderprogramme werden erst seit kurzem wieder intensivere Forschungsaktivitäten unternommen. Fortschritte verspricht man sich vor allem von der Sequenzierung des Genoms von Plasmodium falciparum, dem Malaria‐Erreger, sowie von modernem Wirkstoff‐Design.
New Antimalarial Drugs
Authors: Wiesner Jochen , Ortmann Regina , Jomaa Hassan , Schlitzer Martin 
Published: November 2003

AbstractApproximately 40 % of the world population live in areas with the risk of malaria. Each year, 300–500 million people suffer from acute malaria, and 0.5–2.5 million die from the disease. Although malaria has been widely eradicated in many parts of the world, the global number of cases continues to rise. The most important reason for this alarming situation is the rapid spread of malaria parasites that are resistant to antimalarial drugs, especially chloroquine, which is by far the most frequently used. The development of new antimalarial drugs has been neglected since the 1970s owing to the end colonialism, changes in the areas of military engagement, and the restricted market potential. Only in recent years, in part supported by public funding programs, has interest in the development of antimalarial drugs been renewed. New data available from the recently sequenced genome of the malaria parasite Plasmodium falciparum and the application of methods of modern drug design promise to bring significant development in the fight against this disease.
Coronary artery angiography in systemic lupus erythematosus patients with abnormal myocardial perfusion scintigraphy
Authors: Sella E. M. C. , Sato E. I. , Barbieri A. 
Published: November 2003

AbstractObjectiveAccording to published studies, 16–82% of systemic lupus erythematosus (SLE) patients have abnormal findings on myocardial perfusion tests, but it has not been established whether these patients also have abnormal findings on coronary angiography. The aim of this study was to evaluate the frequency of abnormal findings on coronary angiography in SLE patients in whom myocardial perfusion scintigraphy revealed abnormalities.MethodsNinety female SLE patients (ages 20–55 years, disease duration >5 years, and current or previous steroid treatment for ≥1 year) underwent myocardial perfusion scintigraphy with single‐photon–emission computed tomography using 99mTc‐sestamibi. Images were taken while the patient was at rest and after dipyridamole‐induced stress. Myocardial perfusion defects were identified in 30 patients (33%). Twenty‐one of these patients (mean ± SD age 42 ± 9; mean ± SD disease duration 132 ± 66 months) agreed to undergo coronary angiography.ResultsAtherosclerotic plaques were identified by angiography in 8 of the 21 patients (38%). The majority of coronary abnormalities were localized in the anterior descending artery. The mean ± SD number of risk factors for coronary artery disease (CAD) was significantly higher in the subgroup with (4.5 ± 0.8) compared with the subgroup without (2.5 ± 1.9) abnormal angiographic findings (P = 0.006). Arterial hypertension and postmenopause status were significantly associated with abnormal angiographic findings. Of the patients with at least 4 risk factors for CAD, coronary stenosis was present in 67% (P = 0.005). The number of American College of Rheumatology (ACR) criteria for SLE and scores on the SLE Disease Activity Index and the Systemic Lupus International Collaborating Clinics/ACR damage index were also higher in the subgroup with coronary stenosis (P < 0.05).ConclusionThis is the first study to examine coronary angiography results in SLE patients with abnormal findings on myocardial scintigraphy. Our data suggest that myocardial scintigraphy can be used to screen SLE patients and that all patients with abnormal findings plus at least 4 risk factors for CAD should undergo coronary angiography.