bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Thermal Circulation of a Grand Plateau: Sensitivity to the Height, Width, and Shape of the Plateau
Authors: Zängl Günther , Chico Silvia Gonzalez 
Published: September 2006

Abstract
Idealized numerical simulations are presented to investigate the sensitivity of the thermal plateau circulation to the plateau height, width, and the presence of a mountain ridge encompassing the plateau. The study concentrates on plateaus surrounded by land with the same surface properties so that the topography is the only source of differential heating. For low plateaus, it is found that the strength of the plateau circulation increases with the plateau height because the excess heating of the plateau increases with its height. The plateau circulation reaches its maximum strength for plateau heights similar to the mixed-layer depth over the surrounding lowlands. For even higher plateaus, the depth of the circulation decreases whereas the peak intensity exhibits little change. The plateau height also controls the temporal evolution of the plateau circulation. For low plateaus, low-level inflow is primarily found during the night because convection cells forming over the lateral slopes prevent an inward mass flux during the day. With increasing plateau height, the phases of the plateau circulation shift toward earlier times. If the plateau height exceeds the mixed-layer depth over the surrounding lowlands, inflow occurs from afternoon until the late evening. After sunset, the inflow layer tends to assume the characteristics of a density current. The convergence of the density currents propagating from each side of the plateau toward the center helps to fill the heat low formed during the day. Moreover gravity waves are triggered that propagate away from the plateau center and terminate the inflow. The propagation speed of the density currents is found to increase with the plateau height, so that their convergence occurs earlier for high plateaus than for low plateaus. For the parameter range considered in this study, the plateau width is found to have only a minor impact on the mass fluxes associated with the plateau circulation. However, the convergence of the density currents over the plateau center occurs later for a wider plateau, implying that the heat low is more persistent. Substantial changes are obtained when the plateau is surrounded by a mountain ridge. In this case, the inflow toward the plateau gets delayed because a slope wind circulation forms over the mountain ridge. Moreover, the mass fluxes toward the plateau are reduced so that the heat low that formed over the plateau during the day is filled only slowly. As a consequence, the inflow lasts throughout the night in the presence of a high mountain ridge surrounding the plateau.
Tissue factor deficiency and PAR-1 deficiency are protective against renal ischemia reperfusion injury
Authors: Sevastos Jacob , Kennedy Sean E. , Davis Darren R. , Sam Melissa , Peake Philip W. , Charlesworth John A. , Mackman Nigel , Erlich Jonathan H. 
Published: September 2006

Abstract
Ischemia/reperfusion (IR) injury is a leading cause of acute renal failure and an important contributor to allograft damage. Tissue factor (TF) is up-regulated during IR, and TF inhibition reduces renal injury. However, the underlying mechanisms by which TF contributes to injury have not been elucidated. We postulated that TF contributes to IR injury by production of coagulation proteases and subsequent signaling by protease activated receptor (PARs). We compared renal injury after 25 minutes of bilateral renal ischemia and varying periods of reperfusion in C57BL/6 mice, those expressing low levels of TF (low-TF), hirudin-treated C57BL/6, and mice lacking either PAR-1 or PAR-2. C57BL/6 mice developed severe renal failure and died within 48 hours of reperfusion. In contrast, low-TF, hirudin-treated C57BL/6, and PAR-1−/− mice were protected from renal failure and had reduced mortality, tubular injury, neutrophil accumulation, and lower levels of the chemokines KC and MIP-2. Importantly, PAR-1−/− mice had lower chemokine levels despite up-regulation of TF and fibrin deposition. In addition, treating PAR-1−/− mice with hirudin conferred no additional benefit. Somewhat surprisingly, PAR-2 deficiency did not protect from renal failure. These experiments indicate that increased TF activity after renal IR leads to increased CXC chemokine expression and subsequent neutrophil-mediated injury predominantly by thrombin-dependent PAR-1 signaling.
Rho GTPase Rac1 is critical for neutrophil migration into the lung
Authors: Filippi Marie-Dominique , Szczur Kathleen , Harris Chad E. , Berclaz Pierre-Yves 
Published: September 2006

Abstract
Neutrophils are critical in the inflammatory process by moving rapidly to tissue sites of inflammation. Members of the small Rho GTPase family, Rac1, Rac2, CDC42, and RhoA, are central regulators of cell migration by cytoskeleton rearrangement. The role of Rac1 in neutrophil migration related to inflammatory processes has remained elusive and has yet to be determined in physiologic in vivo models. We previously demonstrated a role for Rac1 in tail retraction. Here, we present evidence that Rac1-mediated uropod formation may be due to crosstalk with a related Rho GTPase RhoA. To assess the physiologic relevance of these findings, we used adoptive transfer of Rac1flox/flox bone marrow cells which allows postengraftment in vivo deletion of Rac1 only in blood cells. We examined the specific role of Rac1 in neutrophil migration into the lung during the inflammatory process induced by formyl-methionyl-leucyl-phenylalanine exposure. The loss of Rac1 activity in neutrophils is associated with a significant decreased neutrophil recruitment into lung alveolar and attenuation of emphysematous lesions. Overall, this study suggests that Rac1 is a physiologic integrator of signals for neutrophil recruitment into lung tissue during an inflammatory response.
A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study
Authors: Astermark Jan , Donfield Sharyne M. , DiMichele Donna M. , Gringeri Alessandro , Gilbert Steven A. , Waters Jennifer , Berntorp Erik ,   for the FENOC Study Group
Published: September 2006

Abstract
The development of inhibitory antibodies to factor VIII is a serious complication of hemophilia. FEIBA (factor VIII inhibitor-bypassing activity), an activated prothrombin complex concentrate (aPCC), and NovoSeven, recombinant factor VIIa (rFVIIa), are used as hemostatic bypassing agents in treating patients with inhibitors. The FENOC study was designed to test equivalence of the products in the treatment of ankle, knee, and elbow joint bleeding. A prospective, open-label, randomized, crossover, equivalency design was used. The parameters of interest were the percentage of patients who reported efficacy in response to FEIBA and the percentage that reported efficacy in response to NovoSeven. A difference in these percentages of no more than 15% was determined to be a clinically acceptable magnitude for equivalence of the 2 products. The primary outcome was evaluation 6 hours after treatment. Data for 96 bleeding episodes contributed by 48 participants were analyzed. The criterion for declaring the 2 products equivalent at 6 hours was not met; however, the confidence interval of the difference in percentages of efficacy reported for each product only slightly exceeded the 15% boundary (−11.4%-15.7%), P = .059. FEIBA and NovoSeven appear to exhibit a similar effect on joint bleeds, although the efficacy between products is rated differently by a substantial proportion of patients. This trial was registered at www.clinicaltrials.gov as #NCT00166309.
Solenopsin, the alkaloidal component of the fire ant (Solenopsis invicta), is a naturally occurring inhibitor of phosphatidylinositol-3-kinase signaling and angiogenesis
Authors: Arbiser Jack L. , Kau Tweeny , Konar Martha , Narra Krishna , Ramchandran Ramani , Summers Scott A. , Vlahos Chris J. , Ye Keqiang , Perry Betsy N. , Matter William , Fischl Anthony , Cook James , Silver Pamela A. , Bain Jenny , Cohen Philip , Whitmire David , Furness Scott , Govindarajan Baskaran , Bowen J. Phillip 
Published: September 2006

Abstract
Phosphatidylinositol-3-kinase (PI3K), and its downstream effector Akt, or protein kinase Bα (PKBα), play a major regulatory role in control of apoptosis, proliferation, and angiogenesis. PI3K and Akt are amplified or overexpressed in a number of malignancies, including sarcomas, ovarian cancer, multiple myeloma, and melanoma. This pathway regulates production of the potent angiogenic factor vascular endothelial growth factor (VEGF), and protects tumor cells against both chemotherapy and reactive oxygen–induced apoptosis through phosphorylation of substrates such as apoptotic peptidase–activating factor-1 (APAF-1), forkhead proteins, and caspase 9. Given its diverse actions, compounds that suppress the PI3K/Akt pathway have potential pharmacologic utility as angiogenesis inhibitors and antineoplastic agents. Using the SVR angiogenesis assay, a screen of natural products, we isolated the alkaloid solenopsin, and found that it is a potent angiogenesis inhibitor. We also found that solenopsin inhibits the PI3K signaling pathway in cells upstream of PI3K, which may underlie its affects on angiogenesis. Consistent with inhibition of the activation of PI3K, solenopsin prevented the phosphorylation of Akt and the phosphorylation of its substrate forkhead box 01a (FOXO1a), a member of the forkhead family of transcription factors. Interestingly, solenopsin also inhibited Akt-1 activity in an ATP-competitive manner in vitro without affecting 27 of 28 other protein kinases tested.
Functional characterization of natural telomerase mutations found in patients with hematologic disorders
Authors: Xin Zhong-Tao , Beauchamp Adam D. , Calado Rodrigo T. , Bradford Jennifer W. , Regal Joshua A. , Shenoy Aarthi , Liang Yuying , Lansdorp Peter M. , Young Neal S. , Ly Hinh 
Published: September 2006

Abstract
Human telomerase hTERC RNA serves as a template for the catalytic hTERT protein to synthesize telomere repeats at chromosome ends. We have recently shown that some patients with bone marrow failure syndromes are heterozygous carriers for hTERC or hTERT mutations. These sequence variations usually lead to a compromised telomerase function by haploinsufficiency. Here, we provide functional characterization of an additional 8 distinct hTERT sequence variants and 5 hTERC variants that have recently been identified in patients with dyskeratosis congenita (DC) or aplastic anemia (AA). Among the mutations, 2 are novel telomerase variants that were identified in our cohort of patients. Whereas most of the sequence variants modulate telomerase function by haploinsufficiency, 2 hTERC variants with sequence changes located within the template region appear to act in a dominant-negative fashion. Inherited telomerase gene mutations, therefore, operate by various mechanisms to shorten telomere lengths, leading to limited marrow stem cell reserve and renewal capacity in patients with hematologic disorders.
Somatic revertant mosaicism in a patient with leukocyte adhesion deficiency type 1
Authors: Tone Yumi , Wada Taizo , Shibata Fumie , Toma Tomoko , Hashida Yoko , Kasahara Yoshihito , Koizumi Shoichi , Yachie Akihiro 
Published: September 2006

Abstract
Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive disorder caused by mutations in the ITGB2 (CD18) gene and characterized by recurrent severe infections, impaired pus formation, and defective wound healing. We describe an unusual case of severe phenotypic LAD-1 presenting with somatic mosaicism. The patient is a compound heterozygote bearing 2 different frameshift mutations that abrogate protein expression. However, CD18 expression was detected in a small proportion of T cells but was undetectable in granulocytes, monocytes, B cells, and natural killer (NK) cells. The T cells were not of maternal origin, lacked the paternal mutation, and showed a selective advantage in vivo. Molecular analysis using sorted CD18+ cells revealed them to be derived from a single CD8+ T cell carrying T-cell receptor VB22. These findings suggest that spontaneous in vivo reversion was responsible for the somatic mosaicism in our patient.
The complete mitochondrial genome of a basal teleost, the Asian arowana (Scleropages formosus, Osteoglossidae)
Authors: Yue Gen Hua , Liew Woei Chang , Orban Laszlo 
Published: September 2006

Abstract

Background
Mitochondrial DNA-derived sequences have become popular markers for evolutionary studies, as their comparison may yield significant insights into the evolution of both the organisms and their genomes. From the more than 24,000 teleost species, only 254 complete mtDNA sequences are available (GenBank status on 06 Sep 2006). In this paper, we report the complete mitochondrial genome sequence of Asian arowana, a basal bonytongue fish species, which belongs to the order of Osteoglossiformes.

Results
The complete mitochondrial genomic sequence (mtDNA) of Asian arowana (Scleropages formosus) was determined by using shotgun sequencing method. The length of Asian arowana mtDNA is ca. 16,650 bp (its variation is due to polymorphic repeats in the control region), containing 13 protein-coding genes, 22 tRNA and 2 rRNA genes. Twelve of the thirteen protein coding genes were found to be encoded by the heavy strand in the order typically observed for vertebrate mitochondrial genomes, whereas only nad6 was located on the light strand. An interesting feature of Asian arowana mitogenome is that two different repeat arrays were identified in the control region: a 37 bp tandem repeat at the 5' end and an AT-type dinucleotide microsatellite at the 3' end. Both repeats show polymorphism among the six individuals tested; moreover the former one is present in the mitochondrial genomes of several other teleost groups. The TACAT motif described earlier only from mammals and lungfish was found in the tandem repeat of several osteoglossid and eel species. Phylogenetic analysis of fish species representing Actinopterygii and Sarcopterygii taxa has shown that the Asian arowana is located near the baseline of the teleost tree, confirming its status among the ancestral teleost lineages.

Conclusion
The mitogenome of Asian arowana is very similar to the typical vertebrate mitochondrial genome in terms of gene arrangements, codon usage and base composition. However its control region contains two different types of repeat units at both ends, an interesting feature that to our knowledge has never been reported before for other vertebrate mitochondrial control regions. Phylogenetic analysis using the complete mtDNA sequence of Asian arowana confirmed that it belongs to an ancestral teleost lineage.
Brain-derived proteins in the CSF, do they correlate with brain pathology in CJD?
Authors: Boesenberg-Grosse Constanze , Schulz-Schaeffer Walter J , Bodemer Monika , Ciesielczyk Barbara , Meissner Bettina , Krasnianski Anna , Bartl Mario , Heinemann Uta , Varges Daniela , Eigenbrod Sabina , Kretzschmar Hans A , Green Alison , Zerr Inga 
Published: September 2006

Abstract

Background
Brain derived proteins such as 14-3-3, neuron-specific enolase (NSE), S 100b, tau, phosphorylated tau and Aβ1–42 were found to be altered in the cerebrospinal fluid (CSF) in Creutzfeldt-Jakob disease (CJD) patients. The pathogenic mechanisms leading to these abnormalities are not known, but a relation to rapid neuronal damage is assumed. No systematic analysis on brain-derived proteins in the CSF and neuropathological lesion profiles has been performed.

Methods
CSF protein levels of brain-derived proteins and the degree of spongiform changes, neuronal loss and gliosis in various brain areas were analyzed in 57 CJD patients.

Results
We observed three different patterns of CSF alteration associated with the degree of cortical and subcortical changes. NSE levels increased with lesion severity of subcortical areas. Tau and 14-3-3 levels increased with minor pathological changes, a negative correlation was observed with severity of cortical lesions. Levels of the physiological form of the prion protein (PrPc) and Aβ1–42 levels correlated negatively with cortical pathology, most clearly with temporal and occipital lesions.

Conclusion
Our results indicate that the alteration of levels of brain-derived proteins in the CSF does not only reflect the degree of neuronal damage, but it is also modified by the localization on the brain pathology. Brain specific lesion patterns have to be considered when analyzing CSF neuronal proteins.
Adenoid cystic carcinoma of the lacrimal gland metastasising to the liver: report of a case
Authors: Zeidan Bashar A , Hilal Mohammed Abu , Al-Gholmy Mohammed , El-Mahallawi Hanan , Pearce Neil W , Primrose John N 
Published: September 2006

Abstract

Background
Adenoid Cystic Carcinoma of the lacrimal gland is a rare tumour. Their aggressive behaviour, with a high-risk of local recurrence, and late distant spread of the tumour even after aggressive management has been reported. Metastasis to the liver is rare and when it occurs, it is usually part of widespread metastasis, and therefore surgical treatment is seldom considered.

Case presentation
We report a rare case of an isolated liver metastasis from a lacrimal gland adenoid cystic carcinoma 20 years after resection of the primary tumour. The patient presented with right upper quadrant pain radiating to the back and shortness of breath of 3 months duration. No local recurrence was detected during a 15 year follow-up with computerized tomography (CT) of the head. Abdominal CT scan demonstrated a solitary liver tumour with no other primary source, and the bone scan was normal. The patient was treated with an extended right hemihepatectomy. The histology revealed a predominantly cribriform tumour with focal areas of basaloid type metastatic lacrimal gland adenoid cystic carcinoma.

Conclusion
This case illustrates the unpredictable behaviour of adenoid cystic carcinoma and the need for a life long follow up for these patients after treatment. The possibility of surgical resection for liver metastasis from adenoid cystic carcinoma should always be considered.
Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts
Authors: Komano Yukiko , Nanki Toshihiro , Hayashida Kenji , Taniguchi Ken , Miyasaka Nobuyuki 
Published: September 2006

AbstractIncreased bone resorption mediated by osteoclasts causes various diseases such as osteoporosis and bone erosion in rheumatoid arthritis (RA). Osteoclasts are derived from the monocyte/macrophage lineage, but the precise origin remains unclear. In the present study, we show that the purified CD16- human peripheral blood monocyte subset, but not the CD16+ monocyte subset, differentiates into osteoclast by stimulation with receptor activator of NF-κB ligand (RANKL) in combination with macrophage colony-stimulating factor (M-CSF). Integrin-β3 mRNA and the integrin-αvβ3 heterodimer were only expressed on CD16- monocytes, when they were stimulated with RANKL + M-CSF. Downregulation of β3-subunit expression by small interfering RNA targeting β3 abrogated osteoclastogenesis from the CD16- monocyte subset. In contrast, the CD16+ monocyte subset expressed larger amounts of tumor necrosis factor alpha and IL-6 than the CD16- subset, which was further enhanced by RANKL stimulation. Examination of RA synovial tissue showed accumulation of both CD16+ and CD16- macrophages. Our results suggest that peripheral blood monocytes consist of two functionally heterogeneous subsets with distinct responses to RANKL. Osteoclasts seem to originate from CD16- monocytes, and integrin β3 is necessary for osteoclastogenesis. Blockade of accumulation and activation of CD16- monocytes could therefore be a beneficial approach as an anti-bone resorptive therapy, especially for RA.
Activin A Decreases glucagon and arx Gene Expression in α-Cell Lines
Authors: Mamin Aline , Philippe Jacques 
Published: September 2006

AbstractActivin A is a potent growth and differentiation factor involved in development, differentiation, and physiological functions of the endocrine pancreas; it increases insulin and pax4 gene expression in β-cells and can induce transdifferentiation of the exocrine acinar cell line AR42J into insulin-producing cells. We show here that Activin A decreases glucagon gene expression in the α-cell lines InR1G9 and αTC1 in a dose- and time-dependent manner and that the effect is blocked by Follistatin. This effect is also observed in adult human islets. Glucagon gene expression is inhibited at the transcriptional level by the Smad signaling pathway through the G3 DNA control element. Furthermore, Activin A decreases cell proliferation of InR1G9 and αTC1 cells as well as cyclin D2 and arx gene expression, whose protein product Arx has been shown to be critical for α-cell differentiation. Overexpression of Arx in Activin A-treated InR1G9 cells does not prevent the decrease in glucagon gene expression but corrects the inhibition of cell proliferation, indicating that Arx mediates the Activin A effects on the cell cycle. We conclude that Activin A has opposite effects on α-cells compared with β-cells, a finding that may have relevance during pancreatic endocrine lineage specification and physiological function of the adult islets.
Parathyroid-Specific Double Knockout of Gq and G11 α-Subunits Leads to a Phenotype Resembling Germline Knockout of the Extracellular Ca2+-Sensing Receptor
Authors: Wettschureck Nina , Lee EunAh , Libutti Steven K. , Offermanns Stefan , Robey Pamela G. , Spiegel Allen M. 
Published: September 2006

Abstract
Germline knockout of the extracellular Ca2+-sensing receptor (CaR) leads to a phenotype that includes severe hypercalcemia, hyperparathyroidism, relative hypocalciuria, skeletal abnormalities, retarded growth, and early postnatal death. To investigate the role of heterotrimeric G proteins in CaR signaling, we used cre/lox technology to delete the respective α-subunits of Gq and G11 selectively in parathyroid cells. Mice that were PTH-Cre+/−; Gnaqflox/flox; Gna11−/− (PTH-Gαq/Gα11-double knockouts) were viable, but showed all the features of germline knockout of the CaR except hypocalcuria. Our results demonstrate the critical role of both Gq and G11 in mediating inhibition of PTH secretion by extracellular Ca2+.