bluuebunny/crossref_metadata_2025 huggingface dataset:
NMDA Receptor Subunit NR2b: Effects on LH Release and GnRH Gene Expression in Young and Middle-Aged Female Rats, with Modulation by Estradiol
Authors: Maffucci Jacqueline A. , Walker Deena M. , Ikegami Aiko , Woller Michael J. , Gore Andrea C.
Published: November 2007

Background/Aims: The loss of reproductive capacity during aging involves changes in the neural regulation of the hypothalamic gonadotropin-releasing hormone (GnRH) neurons controlling reproduction. This neuronal circuitry includes glutamate receptors on GnRH neurons. Previously, we reported an increase in the expression of the NR2b subunit protein of the NMDA receptor on GnRH neurons in middle-aged compared to young female rats. Here, we examined the functional implications of the NR2b subunit on the onset of reproductive aging, using an NR2b-specific antagonist ifenprodil. Methods: Young (3–5 months) and middle-aged (10–13 months) female rats were ovariectomized (OVX), 17β-estradiol (E2) or vehicle (cholesterol) treated, and implanted with a jugular catheter. Serial blood sampling was undertaken every 10 min for 4 h, with ifenprodil (10 mg/kg) or vehicle injected (i.p.) after 1 h of baseline sampling. The pulsatile release of pituitary LH and levels of GnRH mRNA in hypothalamus were quantified as indices of the reproductive axis. Results: Our results showed effects of ifenprodil on both endpoints. In OVX rats given cholesterol, neither age nor ifenprodil had any effects on LH release. In E2-treated rats, aging was associated with significant decreases in pulsatile LH release. Additionally, ifenprodil stimulated parameters of pulsatile LH release in both young and middle-aged animals. Ifenprodil had few effects on GnRH mRNA; the only significant effect of ifenprodil was found in the middle-aged, cholesterol group. Conclusion: Together, these findings support a role for the NR2b subunit of the NMDAR in GnRH/LH regulation. Because most of these effects were exhibited on pituitary LH release in the absence of a concomitant change in GnRH gene expression, it is likely that NMDA receptors containing the NR2b subunit play a role in GnRH-induced LH release, independent of de novo GnRH gene expression.
Debulking Hepatectomy for an Unusual Case of a Grade 1 Stage 1 Granulosa Cell Tumour of the Ovary with Late Metastases
Authors: Lordan Jeffrey T. , Jones Robin L. , Karanjia Nariman D. , Butler-Manuel S.
Published: November 2007

Granulosa cell tumours of the ovary are rare. They are considered low-grade malignant cancers and infrequently metastasise to the liver. We present our experience of a case with a grade 1, stage 1 granulosa cell tumour of the ovary that systemically recurred 15 years following surgical resection. The patient went on to have a debulking hepatic resection 21 years following initial surgery despite a 6-year-long palliative diagnosis.
An Orthotopic Model of Pancreatic Somatostatin Receptor (SSTR)-Positive Tumors Allows Bimodal Imaging Studies Using 3T MRI and Animal PET-Based Molecular Imaging of SSTR Expression
Authors: Stelter Lars , Amthauer Holger , Rexin Annett , Pinkernelle Jens , Schulz Petra , Michel Roger , Denecke Timm , Stiepani Heiner , Hamm Bernd , Wiedenmann Bertram , Scholz Arne
Published: November 2007

Somatostatin receptor (SSTR) scintigraphy is currently used as one standard imaging modality in neuroendocrine tumors (NETs). However, future optimization of NET imaging may be achieved with positron emission tomography based methods utilizing more sensitive and specific tracers in combination with computed tomography or magnetic resonance imaging. Here we established an orthotopic mouse model that reflects relevant aspects of human pancreatic NETs such as SSTR expression, dense vascularization and metastatic disease. This model was then utilized to test the feasibility of combined magnetic resonance imaging and animal positron emission tomography. Orthotopic implantation of amphicrine, SSTR-positive pancreatic AR42J cells resulted in rapidly growing tumors, with concomitant metastatic spread into abdominal lymph nodes and peritoneal cavity. Primary tumors as well as their metastases expressed the neuroendocrine markers chromogranin A and synaptophysin. For imaging experiments, the SSTR ligands 68Ga-DOTATOC or 68Ga-DOTANOC were injected intravenously, and animals were subsequently examined in an animal positron emission tomography scanner and a clinical 3T (tesla) magnetic resonance imager. All animals showed radionuclide accumulation in the primary tumor. Definite anatomical correlation was achieved using digital image fusion of the positron emission tomography and magnetic resonance imaging data. 68Ga-DOTANOC strongly accumulated in the tumor tissue (mean 6.6-fold vs. control tissues) when compared to 68Ga-DOTATOC, which showed a higher renal clearance. In good agreement with the biodistribution data, the kidney-to-tumor ratio was higher for 68Ga-DOTATOC (2.43-fold vs. 1.75-fold). Consequently, 68Ga-DOTANOC achieved better signal enhancement in the primary tumor and allowed for detection of metastatic lesions. In summary, we established a novel orthotopic pancreatic SSTR-positive tumor model and used this model to provide proof of principle for the diagnostic combination of SSTR-based molecular imaging and magnetic resonance imaging. Specifically, the animal model allowed the comparative evaluation of 68Ga-DOTANOC and 68Ga-DOTATOC, with 68Ga-DOTANOC providing better tumor-specific accumulation and renal activity. We conclude that this animal model will be of innovative value for further investigation in the imaging of NETs.
Tumor Necrosis Factor Receptor-2 Signaling Attenuates Vein Graft Neointima Formation by Promoting Endothelial Recovery
Authors: Zhang Lisheng , Sivashanmugam Perumal , Wu Jiao-Hui , Brian Leigh , Exum Sabrina T. , Freedman Neil J. , Peppel Karsten
Published: November 2007

Objective—

Inflammation appears intricately linked to vein graft arterialization. We have previously shown that tumor necrosis factor (TNF) receptor-1 (TNFR1, p55) signaling augments vein graft neointimal hyperplasia (NH) and remodeling through its effects on vascular smooth muscle cells (SMCs). In this study we examined the role of TNFR2 (p75) signaling in vein graft arterialization.

Methods and Results—

Inferior vena cava-to-carotid artery interposition grafting was performed between p75
−/−
and congenic (C57B1/6J) wild-type (WT) mice. Six weeks postoperatively, neointimal and medial dimensions were greater in p75
−/−
grafts placed into p75
−/−
recipients (by 42% or 60%, respectively;
P
<0.05), when compared with WT veins grafted into WT recipients. Relative to WT vein grafts, p75 deficiency augmented early (2-week-old) graft vascular cell adhesion molecule (VCAM)-1 expression (by 2.4-fold,
P
<0.05), increased endothelial cell apoptosis (2-fold), and delayed graft re-endothelialization. Both cellular proliferation in early, and collagen I content of mature (6-week-old) vein grafts were increased (by 70% and 50%, respectively) in p75
−/−
grafts. P75 deficiency augmented TNF-induced apoptosis of cultured endothelial cells, but did not affect TNF-stimulated SMC proliferation or migration induced by co-cultured macrophages.

Conclusions—

TNF signaling via p75 reduces vein graft neointimal hyperplasia through mechanisms involving reduction of adhesion molecule expression and endothelial cell apoptosis.
The Neural Correlate of Speech Rhythm as Evidenced by Metrical Speech Processing
Authors: Geiser Eveline , Zaehle Tino , Jancke Lutz , Meyer Martin
Published: November 2007

The present study investigates the neural correlates of rhythm processing in speech perception. German pseudosentences spoken with an exaggerated (isochronous) or a conversational (nonisochronous) rhythm were compared in an auditory functional magnetic resonance imaging experiment. The subjects had to perform either a rhythm task (explicit rhythm processing) or a prosody task (implicit rhythm processing). The study revealed bilateral activation in the supplementary motor area (SMA), extending into the cingulate gyrus, and in the insulae, extending into the right basal ganglia (neostriatum), as well as activity in the right inferior frontal gyrus (IFG) related to the performance of the rhythm task. A direct contrast between isochronous and nonisochronous sentences revealed differences in lateralization of activation for isochronous processing as a function of the explicit and implicit tasks. Explicit processing revealed activation in the right posterior superior temporal gyrus (pSTG), the right supramarginal gyrus, and the right parietal operculum. Implicit processing showed activation in the left supramarginal gyrus, the left pSTG, and the left parietal operculum. The present results indicate a function of the SMA and the insula beyond motor timing and speak for a role of these brain areas in the perception of acoustically temporal intervals. Secondly, the data speak for a specific task-related function of the right IFG in the processing of accent patterns. Finally, the data sustain the assumption that the right secondary auditory cortex is involved in the explicit perception of auditory suprasegmental cues and, moreover, that activity in the right secondary auditory cortex can be modulated by top-down processing mechanisms.
Radar and Lightning Observations of the 3 June 2000 Electrically Inverted Storm from STEPS
Authors: Tessendorf Sarah A. , Wiens Kyle C. , Rutledge Steven A.
Published: November 2007

This study addresses the kinematic, microphysical, and electrical evolution of an isolated convective storm observed on 3 June 2000 during the Severe Thunderstorm Electrification and Precipitation Study field campaign. Doppler-derived vertical velocities, radar reflectivity, hydrometeor classifications from polarimetric radar, and Lightning Mapping Array (LMA) charge structures are examined over a nearly 3-h period. This storm, characterized as a low-precipitation supercell, produced modest amounts of hail, determined by fuzzy-logic hydrometeor classification as mostly small (<2 cm) hail, with one surface report of large (≥2 cm) hail. Doppler-derived updraft speeds peaked between 20 and 25 m s−1, and reflectivity was never greater than 60 dBZ. The most striking feature of this storm was its total lack of cloud-to-ground (CG) lightning. Though this storm was electrically active, with maximum flash rates near 30 per minute, no CG flashes of either polarity were detected. The charge structure inferred from the LMA observations was consistent with an inverted dipole, defined as having a midlevel positive charge region below upper-level negative charge. Inverted charge structures have typically been considered conducive to producing positive CG lightning; however, the 3 June storm appeared to lack the lower negative charge layer below the inverted dipole that is thought to provide the downward electrical bias necessary for positive CG lightning.
William Paley's Natural Theology: An Anglican Classic?
Authors: Cole Graham
Published: November 2007

This article pursues the question of whether William Paley's Natural Theology is an Anglican classic. I place Paley's natural theology project in its historical context of skepticism about Christianity's truth claims and in the context of Paley's ‘system’. His teleological argument is briefly explained and four challenges, past and present, to its thesis are considered. The question of what makes a work a classic is explored in terms of its enduring interest, especially in the light of the controversy concerning Intelligent Design Theory, and its enduring value. It is argued that because of its enduring interest and value Paley's Natural Theology may be judged a classic but not of a peculiarly Anglican kind.
what counts as student voice in active citizenship case studies?
Authors: Ross Hamish , Munn Pamela , Brown Jane
Published: November 2007

We analyse a teacher-to-teacher discourse (14 web-published case studies) concerning `participation as citizenship' in schools. Many different mechanisms through which pupils participate are reported (from school councils to paired-reading schemes and community links). The claimed outcomes of these activities are also varied: improving the effectiveness of schools, developing skills, and promoting feelings of involvement and empowerment among the participating pupils. Significantly, the outcomes are not radically or politically transformative and are generally contained within schools' existing structures. The texts reveal their adult authors' range of understandings of children and schooling, which help to explain the relatively conservative pattern of outcomes. However, the pattern is also explained, in part, by the contested interpretations of both participation and citizenship, and by the open and permissive model of education for citizenship favoured in Scotland.
Hematopoietic Development from Human Embryonic Stem Cells
Authors: Bhatia Mickie
Published: November 2007

The most common human cell-based therapy applied today is hematopoietic stem cell (HSC) transplantation. HSCs can be defined by two essential properties: self-renewal and multilineage hematopoietic differentiation. These combined HSC properties allow them to differentiate into all blood cell types (multilineage) in a sustained manner for the lifetime of the animal, which requires their ability to make cellular copies of themselves (self-renewal). These features can be tested by transplantation from donor to recipient and provide a functional basis to define and identify HSCs. Currently, human bone marrow (BM), mobilized peripheral blood, and umbilical cord blood (CB) represent the major sources of transplantable HSCs, but their availability for use is limited by both quantity and compatibility. Although increasing evidence suggests that somatic HSCs can be expanded to meet current needs, their in vivo potential is concomitantly compromised after ex vivo culture. Pluripotent human embryonic stem cells (hESCs) may provide an alternative. hESCs possess indefinite proliferative capacity in vitro, and have been shown to differentiate into the hematopoietic cell fate, giving rise to erythroid, myeloid, and lymphoid lineages using a variety of differentiation procedures. In most cases, hESC-derived hematopoietic cells show similar clonogenic progenitor capacity and primitive phenotype to somatic sources of hematopoietic progenitors, but possess limited in vivo repopulating capacity when transplanted into immunodeficient mice. Although this suggests HSC function can be derived from hESCs, the efficiency and quality of these cells must be characterized using surrogate models for potential clinical applications.
Antibody Therapy in Aggressive Lymphomas
Authors: Habermann Thomas M.
Published: November 2007

The aggressive lymphomas are potentially curable. The natural history of certain aggressive lymphomas has been altered by monoclonal antibody therapy. Targeted monoclonal antibody therapy to the CD20 antigen has altered the outcome of patients with diffuse large B-cell lymphoma in patients of all ages. Anti-CD20–based radioimmunoconjugates are being evaluated as radioimmunotherapy approaches in patients who have relapsed and in stem cell transplant settings. Antibody-directed therapy to the B-cell–specific antigen CD22 are ongoing. New approaches include different CD20 antibodies and an antibody to the CD40 antigen, which is a member of the tumor necrosis factor (TNF) receptor family, which is expressed on B-cells. Antibody therapy has been incorporated into CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) therapy and other regimens such as EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) and HyperCVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone). Single-agent anti-CD20 therapy is active in the post-transplantation lymphoproliferative disorders. T-cell antibodies are under evaluation in a number of T-cell lymphoproliferative disorders. Targeted therapy has changed the natural history of a number of aggressive non-Hodgkin lymphomas. This review will describe the contributions of antibody therapies to the treatment of these diseases.
Stem Cell Transplantation in Multiple Myeloma
Authors: Attal Michel , Moreau Philippe , Avet-Loiseau Herve , Harousseau Jean-Luc
Published: November 2007

Multiple myeloma (MM) is one of the key hematologic malignancies in which the impact of dose intensity has been demonstrated. Consequently, in 2005, MM was the most common disease for which autologous stem cell transplantation (ASCT) was indicated both in Europe and in the U.S. However, ASCT is not curative, and most patients relapse within a median of 3 years. Novel agents such as thalidomide (Thalidomid), bortezomib (Velcade), or lenalidomide (Revlimid) have been introduced to improve high-dose therapy, and promising results have been reported. Conversely, results from myeloablative allogeneic stem cell transplantation remain disappointing due to high transplantation-related mortality, justifying the exploration of strategies such as reduced-intensity conditioning, which have been shown to be feasible but for which proof of efficacy requires continued study.
The Biology of CML Blast Crisis
Authors: Radich Jerald P.
Published: November 2007

The natural history of chronic myeloid leukemia (CML) progresses from a relatively benign chronic phase into a fatal blast crisis, which resembles acute leukemia, but is incurable by chemotherapy. Fortunately, the progression can usually be blocked by tyrosine kinase therapy or allogeneic transplantation. The seemingly stereotypical march of progression involves changes in genetic instability and DNA repair, proliferation, differentiation, and apoptosis, and thus may serve as a unique model of cancer evolution and progression. Given that all treatments work much better in chronic-phase than advanced-phase disease, the clinical dilemma is predicting and detecting patients bound to evolve into advanced disease. This is especially important in the age of tyrosine kinase inhibition (TKI) therapy. The purpose of this review is to address the biology of blast crisis in the age of tyrosine kinase therapy, with an emphasis on what genes or pathways may be future targets of predictive assays or treatments of progression.
Modifying the Epigenome as a Therapeutic Strategy in Myelodysplasia
Authors: Garcia-Manero Guillermo
Published: November 2007

The term epigenetics refers to a number of biochemical modifications of chromatin that, without altering the primary sequence of DNA, have a role in genomic regulation and in particular gene expression control. These modifications can occur at the DNA level (i.e., DNA methylation), and affect the chromatin protein scaffold (i.e., histone code modifications), among several others. The study of these modifications is a very active area of research both at the basic and clinical levels. Clinical interest in these epigenetic alterations stems mainly from two observations. First, detection of specific epigenetic alterations could be used to develop cancer biomarkers (e.g., for the early detection or prognostication of cancer). Second, most epigenetic alterations are reversible both in vitro and in vivo, leading the way to the development of new anticancer therapies. This review focuses on the current clinical information regarding different forms of epigenetic therapy in patients with myelodysplastic syndromes (MDS). Basic aspects of DNA methylation or histone code alterations are not covered in detail in this review.
Targeting Treatment in AML
Authors: Burnett Alan K. , Knapper Steve
Published: November 2007

Currently available chemotherapy has probably reached the limits of its potential in treating acute myeloid leukemia (AML). In considering the next steps it is appropriate to exploit on the one hand knowledge of the molecular, immunophenotypic and biological characteristics of the disease and on the other the biology of the patient. The aim is to move towards a more targeted approach.

Immunophenotyping has defined an adequate target (CD33) for antibody-directed treatment, although this is not leukemia specific. Monotherapy has produced important response rates in relapsed disease but it is unlikely to displace conventional chemotherapy. Several randomized trials of antibody directed chemotherapy in combination with chemotherapy nearing completion will establish the usefulness of this approach. In most patients a leukemia-specific immunophenotype can be characterized that can be used to monitor treatment. Minimal residual disease (MRD) detection in morphological remission can detect patients at high risk of relapse, as can a limited number of molecular markers. The clinical value of intervening at the time of MRD detection is not clear. Among the increasing molecular abnormalities described in AML, FLT-3 mutations appear the most attractive for therapeutic intervention. Several phase 2 studies have shown limited efficacy, and randomized trials in combination are underway. Other mechanisms that can be specifically targeted include farnesylation, methylation status, and histone deacelylation. Newer knowledge about the immunophenotypic and biological characteristics of the leukemic stem cell population has opened opportunities to develop treatments that exploit characteristics of the leukemic stem cells that differ from the normal stem cell. Some of these initiatives are now discussed.
The Yin and Yang of Stem Cell Gene Therapy: Insights into Hematopoiesis, Leukemogenesis, and Gene Therapy Safety
Authors: Dunbar Cynthia E.
Published: November 2007

Over the past decade, success in the treatment of serious genetic disorders via gene therapy was finally achieved. However, this progress was tempered by the occurrence of serious adverse events related to vector integration into the genome and activation of adjacent proto-oncogenes. Investigators are now focused on retaining the clinical potential of integrating vectors while decreasing the risk of insertional mutagenesis.
Trials and Tribulations of Systematic Reviews and Meta-Analyses
Authors: Crowther Mark A. , Cook Deborah J.
Published: November 2007

Systematic reviews can help practitioners keep abreast of the medical literature by summarizing large bodies of evidence and helping to explain differences among studies on the same question. A systematic review involves the application of scientific strategies, in ways that limit bias, to the assembly, critical appraisal, and synthesis of all relevant studies that address a specific clinical question. A meta-analysis is a type of systematic review that uses statistical methods to combine and summarize the results of several primary studies. Because the review process itself (like any other type of research) is subject to bias, a useful review requires rigorous methods that are clearly reported. Used increasingly to inform medical decision making, plan future research agendas, and establish clinical policy, systematic reviews may strengthen the link between best research evidence and optimal health care. In this article, we discuss key steps in how to critically appraise and how to conduct a systematic review or meta-analysis.
Coagulation in the Pathophysiology of Hemolytic Anemias
Authors: Cappellini Maria Domenica
Published: November 2007

Coagulation abnormalities are frequently reported in hemolytic anemias (HA). Several pathophysiologic mechanisms are common to different HA. In this review three different hemolytic disorders will be discussed.

In sickle cell disease and in β-thalassemia, a thrombophilic status has been well documented as multifactorial involving hemostatic changes and activation of the coagulation cascade. Moreover, in such disorders, elevated levels of endothelial adhesion protein (ICAM-1, ELAM-1, VCAM-1, von Willebrand factor, and thrombomodulin) are often increased, suggesting that endothelial activation may be involved in vascular occlusion. As an additional mechanism of hypercoagulability in thalassemia, a procoagulant status of thalassemic red cells was recognized.

The main clinical manifestation of paroxysmal nocturnal hemoglobinuria (PNH) is HA, and the most common complications are thrombosis, pancytopenia, and myelodysplastic syndrome or acute leukemia. The intravascular hemolysis is explained by a deficiency of glycosil phosphatidylinositol (GPI)-anchored complement regulatory proteins such as CD59 and CD55 on the membrane of red blood cells (RBCs), but the mechanism responsible for the increased incidence of thrombotic events in PNH remains unclear.

Recent advances have been made in understanding the coagulation involvement in a heterogeneous group of diseases, thrombotic microangiopathies (TMA) characterized by microangiopathic hemolytic anemia and thrombocytopenia due to platelet clumping in the microcirculation, leading to ischemic organ dysfunction with neurologic symptoms and renal impairment.
Current Issues in Sickle Cell Pain and Its Management
Authors: Ballas Samir K.
Published: November 2007

Pain is the insignia of sickle cell disease and the acute painful crisis is the number-one cause of hospital admissions. Tissue damage due to vaso-occlusion releases numerous inflammatory mediators that initiate the transmission of painful stimuli and the perception of pain. The acute sickle cell painful crisis evolves along four distinct phases coupled with changes in certain markers of the disease. Hospital readmission within 1 week occurs in about 16% of discharged patients. Failure to treat acute pain aggressively may lead to chronic pain syndrome. Management of sickle pain is primarily pharmacologic in nature, and opioids are the analgesics used most often. Cellular and molecular mechanisms of opioids explain individual differences among patients and justify the use of individualized treatment plans.
Identification of single nucleotide polymorphisms in bovine CARD15 and their associations with health and production traits in Canadian Holsteins
Authors: Pant Sameer D , Schenkel Flavio S , Leyva-Baca Ivan , Sharma Bhawani S , Karrow Niel A
Published: November 2007

Background

Toll-like receptor-2 (TLR2) and Caspase Recruitment Domain 15 (CARD15) are important pattern recognition receptors that play a role in the initiation of the inflammatory and subsequent immune response. They have been previously identified as susceptibility loci for inflammatory bowel diseases in humans and are, therefore, suitable candidate genes for inflammatory disease resistance in cattle. The objective of this study was to identify single nucleotide polymorphisms (SNPs) in the bovine TLR2 and CARD15 and evaluate the association of these SNPs with health and production traits in a population of Canadian Holstein bulls.

Results

A selective DNA pool was constructed based on the estimated breeding values (EBVs) for SCS. Gene segments were amplified from this pool in PCR reactions and the amplicons sequenced to reveal polymorphisms. A total of four SNPs, including one in intron 10 (c.2886-14A>G) and three in the exon 12 (c.3020A>T, c.4500A>C and c.4950C>T) were identified in CARD15; none were identified in TLR2. Canadian Holstein bulls (n = 338) were genotyped and haplotypes were reconstructed. Two SNPs, c.3020A>T and c.4500A>C, were associated with EBVs for health and production traits. The SNP, c.3020A>T, for example, was associated with SCS EBVs (p = 0.0097) with an allele substitution effect of 0.07 score. When compared to the most frequent haplotype Hap12(AC), Hap22(TC) was associated with increased milk (p < 0.0001) and protein (p = 0.0007) yield EBVs, and hap21(TA) was significantly associated with increased SCS EBV(p = 0.0120). All significant comparison-wise associations retained significance at 8% experimental-wise level by permutation test.

Conclusion

This study indicates that SNP c.3020A>T might play a role in the host response against mastitis and further detailed studies are needed to understand its functional mechanisms.
Bursts and horizontal evolution of DNA transposons in the speciation of pseudotetraploid salmonids
Authors: de Boer Johan G , Yazawa Ryosuke , Davidson William S , Koop Ben F
Published: November 2007

Background

Several genome duplications have occurred in the evolutionary history of teleost fish. In returning to a stable diploid state, the polyploid genome reorganized, and large portions are lost, while the fish lines evolved to numerous species. Large scale transposon movement has been postulated to play an important role in the genome reorganization process. We analyzed the DNA sequence of several large loci in Salmo salar and other species for the presence of DNA transposon families.

Results

We have identified bursts of activity of 14 families of DNA transposons (12 Tc1-like and 2 piggyBac-like families, including 11 novel ones) in genome sequences of Salmo salar. Several of these families have similar sequences in a number of closely and distantly related fish, lamprey, and frog species as well as in the parasite Schistosoma japonicum. Analysis of sequence similarities between copies within the families of these bursts demonstrates several waves of transposition activities coinciding with salmonid species divergence. Tc1-like families show a master gene-like copying process, illustrated by extensive but short burst of copying activity, while the piggyBac-like families show a more random copying pattern. Recent families may include copies with an open reading frame for an active transposase enzyme.

Conclusion

We have identified defined bursts of transposon activity that make use of master-slave and random mechanisms. The bursts occur well after hypothesized polyploidy events and coincide with speciation events. Parasite-mediated lateral transfer of transposons are implicated.
Selective Oxytocin Receptor Activation in the Ventrolateral Portion of the Ventromedial Hypothalamus Is Required for Mating-Induced Pseudopregnancy in the Female Rat
Authors: Northrop Lesley E. , Erskine Mary S.
Published: November 2007

The ventrolateral region of the ventromedial hypothalamus (VMHvl) plays an essential role in female sexual behavior. Oxytocin (OT) is released from the paraventricular nucleus to downstream sites such as the VMHvl to facilitate female sexual behavior and shows characteristics of a prolactin (PRL)-releasing factor. During mating, vaginal cervical stimulation (VCS) received from a vasectomized male triggers twice-daily PRL surges that persist up to 12+ d, a period known as pseudopregnancy (PSP). To determine whether OT is involved in PSP by acting within the VMHvl, female rats were infused bilaterally with an oxytocin receptor antagonist (OTR-A), a vasopressin receptor-1a antagonist (V1a-A), or artificial cerebral spinal fluid 30 min before mating. All females received a sufficient amount of VCS, 15 intromissions, to induce PSP. Females infused with OTR-A (20 ng/0.4 μl) with implants targeting the VMHvl showed only a 22% induction of PSP, as measured using vaginal diestrus and serum PRL concentrations. In contrast, controls and V1a-A (80 ng/0.4 μl) infused females exhibited 100% induction of PSP. Females infused with OTR-A returned to estrus after 5 d, whereas females infused with either artificial cerebral spinal fluid or V1a-A remained in diestrus for 12–13 d in both the correct and missed placement groups. Although OT can act as a PRL releasing factor, the PRL surge does not begin until 18–24 h after mating. Together, our results suggest that OT release in the VMHvl mediates the effects of VCS on the induction of the PRL secretion needed to establish PSP.
Human Prolactin Gene Promoter Regulation by Estrogen: Convergence with Tumor Necrosis Factor-α Signaling
Authors: Adamson A. D. , Friedrichsen S. , Semprini S. , Harper C. V. , Mullins J. J. , White M. R. H. , Davis J. R. E.
Published: November 2007

Estrogens have been implicated in the regulation of prolactin gene expression in man, although previous studies have not defined the molecular mechanism whereby estradiol activates the human prolactin gene promoter (hPrl). We found that estradiol induced a reproducible 1.8-fold activation of the hPrl gene promoter, using pituitary GH3 cells stably transfected with a 5000-bp hPrl promoter fragment linked to luciferase reporter gene. This activation was blocked by treatment with estrogen receptor (ER) antagonists 4-hydroxytamoxifen and ICI-182,780. Promoter deletion and mutagenesis experiments identified a functional estrogen response element (ERE) sequence 1189 bp upstream of the transcription start site that was responsible for estrogen-mediated promoter activation. This site differed from the consensus ERE sequence by two base pairs, one in each half-site. This ERE was identified to be functional through binding ERα in EMSAs. Chromatin immunoprecipitation assays confirmed ERα binding to this sequence in vivo in the absence of ligand, with increased recruitment when cells were cultured in the presence of estradiol. When cells were treated with both estradiol and TNFα, we observed synergistic activation of the hPrl promoter, which was mediated by the −1189-bp ERE. Mutagenesis of this ERE abolished the promoter-activating effect not only of estradiol but also of TNFα. These data suggest a novel, promoter-specific signaling interaction between estrogen and TNFα signaling, which is likely to be important for prolactin regulation in vivo.
Rescue of Pituitary Function in a Mouse Model of Isolated Growth Hormone Deficiency Type II by RNA Interference
Authors: Shariat Nikki , Ryther Robin C. C. , Phillips John A. , Robinson Iain C. A. F. , Patton James G.
Published: November 2007

Splicing mutations in the human GH (hGH) gene (GH-1) that cause skipping of exon 3 result in a form of GH deficiency termed isolated GH deficiency type II (IGHD II). The GH-1 gene contains five exons; constitutive splicing produces the wild-type 22-kDa hormone, whereas skipping of exon 3 results in transcripts encoding a 17.5-kDa isoform that acts as a dominant-negative to block secretion of the wild-type hormone. Common characteristics of IGHD II include short stature due to impaired bone elongation, growth, and, in severe cases, anterior pituitary hypoplasia. Typically, IGHD II is treated by sc delivery of hGH, which can rescue stature but, unfortunately, does not inhibit pituitary hypoplasia. Direct destruction of transcripts encoding the dominant-negative 17.5-kDa isoform should both rescue stature and prevent hypoplasia. Here, we have used delivery of short hairpin RNAs to rescue a murine model of IGHD II by specifically targeting transcripts encoding the 17.5-kDa isoform using RNA interference. To our knowledge, this is the first example where a short hairpin RNA has been expressed to specifically degrade an incorrectly spliced transcript and rescue a dominant-negative disease phenotype in vivo.
Direct singular positions of the parallel manipulator Tricept
Authors: Liu C H , Hsu F-K
Published: November 2007

In this article, the direct singular positions of the parallel manipulator Tricept are determined. An alternative 3 × 3 Jacobian matrix, simpler than the existing one, is obtained in this study. For a given moving platform's orientation, the determinant of this Jacobian matrix may be expressed as a cubic polynomial in moving platform's equation length. Direct singular positions may thus be obtained by solving cubic polynomial equations. For an arbitrarily chosen moving platform's orientation, there exists at least one moving platform's extension length that causes direct kinematic singularity. It is found that if moving platform's size is larger than a specific value, then within the moving platform's domain there exist two regions, in which direct kinematic singularities can only occur at positions impossible to reach.
Linear systems with a polynomial uncertainty structure: Stability margins and control
Authors: Bozorg M
Published: November 2007

In this paper, the stability and control of linear systems with parameter uncertainty are considered. The characteristic equations of such systems are derived as functions of uncertain parameters. The cases in which the coefficients are polynomial functions of the uncertain parameters are studied and an algorithm is presented for the calculation of stability margins in the parameter space in general lp-norms. The stability is defined with respect to arbitrary regions in the complex plane (so-called D-stability). The algorithm requires a search on the contour of the region (frequency search) and to solve a system of equations at each step. Using the above algorithm, a method is also presented for the design of robust controllers for systems with uncertain parameters and robust pole placement inside the regions of interest is addressed.
Recent Developments in Hydraulic Couplings
Authors: Sinclair Harold
Published: November 2007

The use of hydraulic couplings in practically all fields of engineering has increased rapidly during the last few years. The paper traces the history of the Vulcan-Sinclair hydraulic coupling, which is of the turbo or hydro-kinetic type, from the days of its inception up to the present time, and gives details of other designs of the displacement or hydro-static type that have been developed, and the principles upon which they operate. The main advantages of the turbo design are enumerated and considerable test data are given, with particular reference to the Vulcan coupling, which, in theory, is the forerunner of the Vulcan-Sinclair designs. Advantage is taken to explain the difference between fluid couplings and torque converters, concerning which a good deal of confusion exists.

The differences between the various types of Vulcan-Sinclair hydraulic couplings and the improvements that have been effected in design during recent years are described in detail. The paper deals comprehensively with numerous applications of the different types of couplings covering both the industrial and automotive fields. The difficulties, and their cures, which have arisen in connexion with a number of applications are given prominence. A section deals with change-speed gearboxes arranged in conjunction with hydraulic couplings for use in Diesel traction.
A Study of Light/Darkness in Sacred Settings: Digital Simulations
Authors: Geva Anat , Mukherji Anuradha
Published: November 2007

Studying light/darkness and sacred architecture reveals that the “holy” light dramatizes the spiritual state and affects the mood of the user in the sacred space. Furthermore, it shows that faith dictates the treatment of light/darkness in the sacred setting as means to enhance the spiritual experience. These two premises were investigated by conducting digital daylight simulations on the Brihadeshvara Hindu Temple (1010 AD) of Tanjore, Tamilnadu, India. This sacred monument, listed as one of UNESCO's World Heritage Sites, is an intriguing case study since the treatment of the ‘holy light’ in the temple is actually the treatment of the ‘holy darkness’. The simulated values were compared to the Illuminating Engineering Society (IES) standards. The results demonstrate that digitized simulations can illustrate the significance of light/darkness in sacred settings as a spiritual experience. Moreover, this quantitative investigation can augment the qualitative studies in the field of historic sacred architecture. The work presented here unites and extends some previously published work [20],[29].
P-Selectin–Coated Microtube for Enrichment of CD34+ Hematopoietic Stem and Progenitor Cells from Human Bone Marrow
Authors: Narasipura Srinivas D , Wojciechowski Joel C , Charles Nichola , Liesveld Jane L , King Michael R
Published: November 2007

Background: Enrichment and purification of hematopoietic stem and progenitor cells (HSPCs) is important in transplantation therapies for hematologic disorders and in basic stem cell research. Primitive CD34+ HSPCs have demonstrated stronger rolling adhesion on selectins than mature CD34− mononuclear cells (MNCs). We have exploited this differential rolling behavior to capture and purify HSPCs from bone marrow by perfusing MNCs through selectin-coated microtubes.

Methods: Bone marrow MNCs were perfused through the cell-capture microtubes coated with adhesion molecules. We washed the device lumen and visualized and estimated captured cells by video microscopy. Adherent cells were eluted by high shear, calcium-free buffer, and air embolism. We used immunofluorescence staining followed by flow cytometry to analyze CD34+ HSPCs.

Results: CD34+ HSPC purity of cells captured in adhesion molecule–coated devices was significantly higher than the fraction of CD34+ cells found in bone marrow MNCs [mean (SE) 2.5% (0.8%)]. P-selectin–coated surfaces yielded 16% to 20% CD34+ cell purity, whereas antibody-coated surfaces yielded 12% to 18%. Although CD34+ cell purity was comparable between selectin and antibody surfaces, the total number of CD34+ HSPCs captured was significantly higher in P-selectin devices (approximately 5.7 × 104 to 7.1 × 104) than antibody devices (approximately 1.74 × 104 to 2.61 × 104).

Conclusions: P-selectin can be used in a compact flow device to capture HSPCs. Selectin-mediated capture of CD34+ HSPCs resulted in enrichment approximately 8-fold higher than the CD34+ cell population from bone marrow MNCs. This study supports the hypothesis that flow-based, adhesion molecule–mediated capture may be a viable alternative approach to the capture and purification of HSPCs.
Ultraviolet B radiation induces cell shrinkage and increases osmolyte transporter mRNA expression and osmolyte uptake in HaCaT keratinocytes
Authors: Warskulat Ulrich , Brookmann Stefanie , Reinen Andrea , Häussinger Dieter
Published: November 2007

We have previously shown that compatible organic osmolytes, such as betaine, myo-inositol and taurine, are part of the stress response of normal human keratinocytes (NHKs) to ultraviolet B (UVB) radiation. In this regard, we tested human HaCaT keratinocytes as a surrogate cell line for NHK. HaCaT cells osmo-dependently express mRNA specific for transport proteins for betaine (BGT-1), myo-inositol (SMIT) and taurine (TAUT). Compared to normoosmotic (305 mosmol/l) controls, which strongly constitutively expressed BGT-1 mRNA, strong induction of SMIT and TAUT mRNA as well as low induction of BGT-1 mRNA expression was observed between 3 and 9 h after hyperosmotic exposure (405 mosmol/l). This expression correlated with an increased osmolyte uptake. Conversely, hypoosmotic (205 mosmol/l) stimulation led to a significant efflux of osmolytes. Exposure to UVB (290–315 nm) radiation induced cell shrinkage which was followed by an upregulation of osmolyte transporter mRNA levels and osmolyte uptake. These results demonstrate that human HaCaT keratinocytes possess an osmolyte strategy including UVB-induced cell shrinkage and following increased osmolyte uptake. However, several differences in osmolyte transporter expression and uptake were noted between NHK and HaCaT cells, indicating that the use of HaCaT cells as a surrogate cell line for NHK has limitations.
FOXM1, a typical proliferation-associated transcription factor
Authors: Wierstra Inken , Alves Jürgen
Published: November 2007

FOXM1 is a typical proliferation-associated transcription factor: it stimulates proliferation by promoting S-phase entry as well as M-phase entry and is involved in proper execution of mitosis. Accordingly, FOXM1 regulates genes that control G1/S-transition, S-phase progression, G2/M-transition and M-phase progression. Consistently, its expression and its activity are antagonistically regulated by many important proliferation and anti-proliferation signals. Furthermore, FOXM1 is implicated in tumorigenesis and contributes to both tumor initiation and progression. In addition to its function as a conventional transcription factor, FOXM1 transactivates the human c-myc P1 and P2 promoters directly via their TATA-boxes by a new transactivation mechanism, which it also employs for transactivation of the human c-fos, hsp70 and histone H2B/a promoters. This review summarizes the current knowledge on FOXM1, in particular its two different transactivation mechanisms, the regulation of its transcriptional activity by proliferation versus anti-proliferation signals and its function in normal cell cycle progression and tumorigenesis.
Ultrasonic Testing of Concrete Structures Using Indirect Transmission
Authors: Stergiopoulou Christina , McCuen Richard H. , Aggour M. Sherif
Published: November 2007

Laboratory studies and computer simulation were used to develop a procedure for the interpretation of the results of nondestructive testing of concrete structures using the indirect transmission method. The results of the laboratory studies indicate a 10-cm spacing is best for making ultrasonic pulse measurements. A new method of calculating the velocity of the pulse is presented. The method enables concrete quality to be evaluated over short distances rather than the existing method which gives a mean velocity over an extended distance. The method can thus determine the extent of delamination of concrete at a specific location. The laboratory analyses verified using computer simulations show the effect of concrete heterogeneity on the detection of variation in concrete quality. Ultrasonic pulse velocities have a coefficient of variation of about 2 %.
The formation and characterization of three-dimensional gold nanocrystal superlattices
Authors: Constantinides Michael G. , Jaeger Heinrich M. , Li Xuefa , Wang Jin , Lin Xiao-Min
Published: November 2007

Highly-ordered, three-dimensional superlattices were self-assembled from dodecanethiol-ligated gold nanocrystals using a simple drop-drying technique. The superlattices had the shape of truncated pyramids (frustums) and reached lateral dimensions of several micrometers. The formation and thermal stability were studied by grazing-incidence small-angle x-ray scattering. We found that the superlattice frustums adopt a hcp packing structure. When annealed above 50 °C in vacuum, the lattices started to disorder and the average lattice spacing was observed to decrease. This could be associated with the onset of ligand melting transition as well as the continuous desorption of ligand in vacuum.
Crystal growth from cluster to bulk materials via nanomaterials
Authors: Goubet Nicolas , Pileni Marie-Paule
Published: November 2007

In this short paper we propose the hypothesis that, in highly pure media, the cluster shape can be retained at various scales. Impurities and/or the additives can control the shape of the developing crystals by adsorption on selective sites.
Local Processing Advantage in Musicians: Evidence from Disembedding and Constructional Tasks
Authors: Stoesz Brenda M. , Jakobson Lorna S. , Kilgour Andrea R. , Lewycky Samantha T.
Published: November 2007

WHEN PROCESSING MUSIC STIMULI, MOST PEOPLE show a global bias (e.g., Evers et al., 1999). Extensive music training, however, develops both global (Halpern & Bower, 1982) and local (Burton et al., 1989) music processing abilities. Our goal was to determine whether enhancement of musicians' local processing abilities is domain-specific or extends to processing nonmusical, visual stimuli. Musicians outperformed nonmusicians on the Group Embedded Figures Test (Experiment 1) and on Block Design (Experiment 2). Additionally, musicians' ability to copy drawings of physically impossible objects accurately was also superior to that of nonmusicians (Experiment 2). These effects could not be accounted for by group differences in several demographic indicators (age, education, gender, or SES), or (in Experiment 2) in verbal intelligence. The results provide converging evidence that extensive music training is specifically associated with superior visual processing of local details, beyond any benefits it may have on verbal intelligence.
Music as Socio-Affective Confluential Communication? Response to Graham
Authors: Bispham John
Published: November 2007

IN THIS RESPONSE I LARGELY CONCUR WITH THE commentary offered by Graham and argue that a label such as that proposed by Graham could additionally be useful in drawing primary attention to crucial social and affective features of music-making that have at times been undervalued in interdisciplinary investigations into music. I suggest two changes to the label proposed by Graham arguing that "affective"—rather than emotional—and "communication"—rather than signal—more broadly and precisely describe the boundaries of relevance that should be applied to music.