bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling through CD43 regulates CD4 T-cell trafficking
Authors: Mody Purvi D. , Cannon Judy L. , Bandukwala Hozefa S. , Blaine Kelly M. , Schilling Alexander B. , Swier Kevin , Sperling Anne I. 
Published: July 2007

AbstractThe mucin-like protein CD43 is excluded from the immune synapse, and regulates T-cell proliferation as well as T-cell migration. While the CD43 cytoplasmic domain is necessary for regulation of T-cell activation and proliferation, the mechanism via which CD43 regulates trafficking is not well defined. To investigate whether CD43 phosphorylation regulates its function in T cells, we used tandem mass spectrometry and identified Ser76 in murine CD43 as a previously unidentified site of basal phosphorylation. Interestingly, mutation of this single serine to alanine greatly diminishes T-cell trafficking to the lymph node, while CD43 exclusion and CD43-mediated regulation of T-cell proliferation remain intact. Furthermore, the CD43 extracellular domain was also required for T-cell trafficking, providing a hitherto unknown function for the extracellular domain, and suggesting that the extracellular domain may be required to transduce signals via the cytoplasmic domain. These data reveal a novel mechanism by which CD43 regulates T-cell function, and suggest that CD43 functions as a signaling molecule, sensing extracellular cues and transducing intracellular signals that modulate T-cell function.
Pbx homeodomain proteins pattern both the zebrafish retina and tectum
Authors: French Curtis R , Erickson Timothy , Callander Davon , Berry Karyn M , Koss Ron , Hagey Daniel W , Stout Jennifer , Wuennenberg-Stapleton Katrin , Ngai John , Moens Cecilia B , Waskiewicz Andrew J 
Published: July 2007

Abstract

Background

Pbx genes encode TALE class homeodomain transcription factors that pattern the developing neural tube, pancreas, and blood. Within the hindbrain, Pbx cooperates with Hox proteins to regulate rhombomere segment identity. Pbx cooperates with Eng to regulate midbrain-hindbrain boundary maintenance, and with MyoD to control fast muscle cell differentiation. Although previous results have demonstrated that Pbx is required for proper eye size, functions in regulating retinal cell identity and patterning have not yet been examined.

Results
Analysis of retinal ganglion cell axon pathfinding and outgrowth in pbx2/4 null embryos demonstrated a key role for pbx genes in regulating neural cell behavior. To identify Pbx-dependent genes involved in regulating retino-tectal pathfinding, we conducted a microarray screen for Pbx-dependent transcripts in zebrafish, and detected genes that are specifically expressed in the eye and tectum. A subset of Pbx-dependent retinal transcripts delineate specific domains in the dorso-temporal lobe of the developing retina. Furthermore, we determined that some Pbx-dependent transcripts also require Meis1 and Gdf6a function. Since gdf6a expression is also dependent on Pbx, we propose a model in which Pbx proteins regulate expression of the growth factor gdf6a, which in turn regulates patterning of the dorso-temporal lobe of the retina. This, in concert with aberrant tectal patterning in pbx2/4 null embryos, may lead to the observed defects in RGC outgrowth.

Conclusion
These data define a novel role for Pbx in patterning the vertebrate retina and tectum in a manner required for proper retinal ganglion cell axon outgrowth.
Genotypic variation in genome-wide transcription profiles induced by insect feeding: Brassica oleracea – Pieris rapae interactions
Authors: Broekgaarden Colette , Poelman Erik H , Steenhuis Greet , Voorrips Roeland E , Dicke Marcel , Vosman Ben 
Published: July 2007

Abstract

Background
Transcriptional profiling after herbivore attack reveals, at the molecular level, how plants respond to this type of biotic stress. Comparing herbivore-induced transcriptional responses of plants with different phenotypes provides insight into plant defense mechanisms. Here, we compare the global gene expression patterns induced by Pieris rapae caterpillar attack in two white cabbage (Brassica oleracea var. capitata) cultivars. The two cultivars are shown to differ in their level of direct defense against caterpillar feeding. Because Brassica full genome microarrays are not yet available, 70-mer oligonucleotide microarrays based on the Arabidopsis thaliana genome were used for this non-model plant.

Results
The transcriptional responses of the two cultivars differed in timing as characterized by changes in their expression pattern after 24, 48 and 72 hours of caterpillar feeding. In addition, they also differed qualitatively. Surprisingly, of all genes induced at any time point, only one third was induced in both cultivars. Analyses of transcriptional responses after jasmonate treatment revealed that the difference in timing did not hold for the response to this phytohormone. Additionally, comparisons between Pieris rapae- and jasmonate-induced transcriptional responses showed that Pieris rapae induced more jasmonate-independent than jasmonate-dependent genes.

Conclusion
The present study clearly shows that global transcriptional responses in two cultivars of the same plant species in response to insect feeding can differ dramatically. Several of these differences involve genes that are known to have an impact on Pieris rapae performance and probably underlie different mechanisms of direct defense, present in the cultivars.
Modulation of microglial/macrophage activation by macrophage inhibitory factor (TKP) or tuftsin (TKPR) attenuates the disease course of experimental autoimmune encephalomyelitis
Authors: Bhasin Madhuri , Wu Muzhou , Tsirka Stella E 
Published: July 2007

AbstractBackgroundMyelin Oligodendrocyte Glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is the most commonly used mouse model for multiple sclerosis (MS). During the of progression of EAE, microglia, the immunocompetent cells of the brain, become activated and accumulate around demyelinated lesions. Microglial activation is mediated by the extracellular protease tissue Plasminogen Activator (tPA), and mice lacking tPA display altered EAE progression. In this study, we have used pharmacological inhibitors and stimulators of microglial/macrophage activation to examine the temporal requirement for microglial activation in EAE progression and to determine whether such approaches might potentially be of therapeutic value.ResultsIntervention using the tripeptide macrophage/microglia inhibitory factor MIF (TKP) and the tetrapeptide macrophage/microglial stimulator tuftsin (TKPR) attenuated EAE symptoms and revealed that the timing of macrophage/microglial activation is critical for the clinical outcome of EAE. We show that the disease progression can potentially be manipulated favorably at early stages by altering the timing of microglial activation, which in turn alters the systemic immune response to favor upregulation of T helper cell 2 genes that promote recovery from EAE.ConclusionPreventative and therapeutic modulation of macrophage/microglial activity significantly alters the outcome of EAE at symptomatic stages. Specific molecular targets have been identified that represent potential avenues of exploration for the treatment and prevention of MS.
Short-term and one-year outcome of infective endocarditis in adult patients treated in a Finnish teaching hospital during 1980–2004
Authors: Heiro Maija , Helenius Hans , Hurme Saija , Savunen Timo , Engblom Erik , Nikoskelainen Jukka , Kotilainen Pirkko 
Published: July 2007

Abstract

Background
Previous studies on factors predicting the prognosis of infective endocarditis have given somewhat conflicting results. Our aim was to define the factors predicting the outcome of patients treated in a Finnish teaching hospital.

Methods
A total of 326 episodes of infective endocarditis in 303 patients treated during 1980–2004 were evaluated for short-term and 1-year outcome and complications.

Results
Infection of 2 native valves and the occurrence of neurological complications, peripheral emboli, or heart failure significantly predicted both in-hospital and 1-year mortality, while age ≥65 years or the presence of a major criterion or vegetation on echocardiography predicted death within 1 year. A significant trend was observed between the level of serum C-reactive protein (CRP) on admission and both the short-term and 1-year outcome. In the patients who had CRP values ≥100 mg/l on admission, the hazard ratio for in-hospital death was 2.9-fold and the hazard ratio for 1-year death was 3.9-fold as compared to those with lower CRP values. Male sex and age < 64 years significantly predicted a need for both in-hospital and 1-year surgery, as did the development of heart failure or the presence of a major criterion or vegetation on echocardiography. Peripheral emboli were associated with a need for in-hospital surgery, while Streptococcus pneumoniae as the causative agent or infection of 2 native valves predicted a need for surgery within 1 year from admission.

Conclusion
Some of the factors (e.g. heart failure, neurological complications, peripheral emboli) predicting a poor prognosis and/or need for surgery were the same observed in previous studies. A new finding was that high CRP values (≥100 mg/l) on admission significantly predicted both short-term and 1-year mortality.
Lentiviral vectors encoding tetracycline-dependent repressors and transactivators for reversible knockdown of gene expression: a comparative study
Authors: Pluta Krzysztof , Diehl William , Zhang Xian-Yang , Kutner Robert , Bialkowska Agnieszka , Reiser Jakob 
Published: July 2007

Abstract

Background
RNA interference (RNAi)-mediated by the expression of short hairpin RNAs (shRNAs) has emerged as a powerful experimental tool for reverse genetic studies in mammalian cells. A number of recent reports have described approaches allowing regulated production of shRNAs based on modified RNA polymerase II (Pol II) or RNA polymerase III (Pol III) promoters, controlled by drug-responsive transactivators or repressors such as tetracycline (Tet)-dependent transactivators and repressors. However, the usefulness of these approaches is often times limited, caused by inefficient delivery and/or expression of shRNA-encoding sequences in target cells and/or poor design of shRNAs sequences. With a view toward optimizing Tet-regulated shRNA expression in mammalian cells, we compared the capacity of a variety of hybrid Pol III promoters to express short shRNAs in target cells following lentivirus-mediated delivery of shRNA-encoding cassettes.

Results
RNAi-mediated knockdown of gene expression in target cells, controlled by a modified Tet-repressor (TetR) in the presence of doxycycline (Dox) was robust. Expression of shRNAs from engineered human U6 (hU6) promoters containing a single tetracycline operator (TO) sequence between the proximal sequence element (PSE) and the TATA box, or an improved second-generation Tet-responsive promoter element (TRE) placed upstream of the promoter was tight and reversible as judged using quantitative protein measurements. We also established and tested a novel hU6 promoter system in which the distal sequence element (DSE) of the hU6 promoter was replaced with a second-generation TRE. In this system, positive regulation of shRNA production is mediated by novel Tet-dependent transactivators bearing transactivation domains derived from the human Sp1 transcription factor.

Conclusion
Our modified lentiviral vector system resulted in tight and reversible knockdown of target gene expression in unsorted cell populations. Tightly regulated target gene knockdown was observed with vectors containing either a single TO sequence or a second-generation TRE using carefully controlled transduction conditions. We expect these vectors to ultimately find applications for tight and reversible RNAi in mammalian cells in vivo.
Selective sigma-2 ligands preferentially bind to pancreatic adenocarcinomas: applications in diagnostic imaging and therapy
Authors: Kashiwagi Hiroyuki , McDunn Jonathan E , Simon Peter O , Goedegebuure Peter S , Xu Jinbin , Jones Lynne , Chang Katherine , Johnston Fabian , Trinkaus Kathryn , Hotchkiss Richard S , Mach Robert H , Hawkins William G 
Published: July 2007

AbstractBackgroundResistance to modern adjuvant treatment is in part due to the failure of programmed cell death. Therefore the molecules that execute the apoptotic program are potential targets for the development of anti-cancer therapeutics. The sigma-2 receptor has been found to be over-expressed in some types of malignant tumors, and, recently, small molecule ligands to the sigma-2 receptor were found to induce cancer cell apoptosis.ResultsThe sigma-2 receptor was expressed at high levels in both human and murine pancreas cancer cell lines, with minimal or limited expression in normal tissues, including: brain, kidney, liver, lung, pancreas and spleen. Micro-PET imaging was used to demonstrate that the sigma-2 receptor was preferentially expressed in tumor as opposed to normal tissues in pancreas tumor allograft-bearing mice. Two structurally distinct sigma-2 receptor ligands, SV119 and WC26, were found to induce apoptosis to mice and human pancreatic cancer cellsin vitroandin vivo. Sigma-2 receptor ligands induced apoptosis in a dose dependent fashion in all pancreatic cell lines tested. At the highest dose tested (10 μM), all sigma-2 receptor ligands induced 10–20% apoptosis in all pancreatic cancer cell lines tested (p < 0.05). In pancreas tumor allograft-bearing mice, a single bolus dose of WC26 caused approximately 50% apoptosis in the tumor compared to no appreciable apoptosis in tumor-bearing, vehicle-injected control animals (p < 0.0001). WC26 significantly slowed tumor growth after a 5 day treatment compared to vehicle-injected control animals (p < 0.0001) and blood chemistry panels suggested that there is minimal peripheral toxicity.ConclusionWe demonstrate a novel therapeutic strategy that induces a significant increase in pancreas cancer cell death. This strategy highlights a new potential target for the treatment of pancreas cancer, which has little in the way of effective treatments.
RASSF1A promoter methylation and expression analysis in normal and neoplastic kidney indicates a role in early tumorigenesis
Authors: Peters Inga , Rehmet Kristina , Wilke Nadine , Kuczyk Markus A , Hennenlotter Jörg , Eilers Tyark , Machtens Stefan , Jonas Udo , Serth Jürgen 
Published: July 2007

AbstractBackgroundEpigenetic silencing of the RAS association domain family 1A (RASSF1A) tumor suppressor gene promoter has been demonstrated in renal cell carcinoma (RCC) as a result of promoter hypermethylation. Contradictory results have been reported forRASSF1Amethylation in normal kidney, thus it is not clear whether a significant difference betweenRASSF1Amethylation in normal and tumor cells of the kidney exists. Moreover, RASSF1A expression has not been characterized in tumors or normal tissue as yet.ResultsUsing combined bisulfite restriction analysis (COBRA) we compared RASSF1A methylation in 90 paired tissue samples obtained from primary kidney tumors and corresponding normal tissue. Bisulfite sequence analysis was carried out using both pooled amplicons from the tumor and normal tissue groups and subclones obtained from a single tissue pair. Expression of RASSF1A was analyzed by the use of tissue arrays and immunohistochemistry. We found significantly increased methylation in tumor samples (mean methylation, 20%) compared to corresponding normal tissues (mean methylation, 11%;P< 0.001). Densely methylated sequences were found both in pooled and individual sequences of normal tissue. Immunohistochemical analysis revealed a significant reduced expression of RASSF1A in most of the tumor samples. Heterogeneous expression patterns of RASSF1A were detected in a subgroup of histologically normal tubular epithelia.ConclusionOur methylation and expression data support the hypothesis thatRASSF1Ais involved in early tumorigenesis of renal cell carcinoma.
The economic burden of treating neonates in Intensive Care Units (ICUs) in Greece
Authors: Geitona Mary , Hatzikou Magdalini , Hatzistamatiou Zoi , Anastasiadou Aggeliki , Theodoratou T D 
Published: July 2007

AbstractBackgroundIn a period when a public-private mix in Greece is under consideration and hospital budgets become restrained, economic assessment is important for rational decision making. The study aimed to estimate the hospitalization cost of neonates admitted to the ICUs and demonstrate discrepancies with reimbursement.MethodsChosen methodology was based on the selection of medical records of all NICUs and intermediate care admissions within February to April 2004. Neonates (n = 99) were classified according to birthweight and gestational age.ResultsMean cost per infant was estimated at €5.485 while reimbursement from social funds arises to €3.952. Costs per birthweight or gestational age show an inverse relationship. Personnel costs accounted for 59.9%, followed by enteral/parenteral feeding (16.14%) and pharmaceuticals expenses (11.10%) of all resources consumed. Sensitivity analysis increases the robustness of the resultsConclusionNeonatal intensive care in Greece is associated with significant costs that exceed reimbursement from social funds. Reimbursement should be adjusted to make neonatal intensive care economically viable to private hospitals and thus, increase capacity of the services provided.
15d-PGJ2 induces apoptosis of mouse oligodendrocyte precursor cells
Authors: Xiang Zhongmin , Lin Tong , Reeves Steven A 
Published: July 2007

Abstract

Background
Prostaglandin (PG) production is associated with inflammation, a major feature in multiple sclerosis (MS) that is characterized by the loss of myelinating oligodendrocytes in the CNS. While PGs have been shown to have relevance in MS, it has not been determined whether PGs have a direct effect on cells within the oligodendrocyte lineage.

Methods
Undifferentiated or differentiated mouse oligodendrocyte precursor (mOP) cells were treated with PGE2, PGF2α, PGD2 or 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2). Cell growth and survival following treatment were examined using cytotoxicity assays and apoptosis criteria. The membrane receptors for PGD2 and the nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ, as well as reactive oxygen species (ROS) in the death mechanism were examined.

Results
PGE2 and PGF2α had minimal effects on the growth and survival of mOP cells. In contrast, PGD2 and 15d-PGJ2 induced apoptosis of undifferentiated mOP cells at relatively low micromolar concentrations. 15d-PGJ2 was less toxic to differentiated mOP cells. Apoptosis was independent of membrane receptors for PGD2 and the nuclear receptor PPARγ. The cytotoxicity of 15d-PGJ2 was associated with the production of ROS and was inversely related to intracellular glutathione (GSH) levels. However, the cytotoxicity of 15d-PGJ2 was not decreased by the free radical scavengers ascorbic acid or α-tocopherol.

Conclusion
Taken together, these results demonstrated that 15d-PGJ2 is toxic to early stage OP cells, suggesting that 15d-PGJ2 may represent a deleterious factor in the natural remyelination process in MS.
Clear cell sarcoma of the soft parts arising in the rectus abdominis in a child – aspiration cytology of a rare case
Authors: Murugan Paari , Basu Debdatta , Kumar Surendra , Jagadish Sadasivan 
Published: July 2007

Background
Clear cell sarcoma of soft parts is most commonly found associated with the tendons and aponeuroses of distal extremities in young adults with a peak incidence in the third decade. Location in the abdominal wall and in a child is very rare.

Case presentation
A nine-year-old female child presented with a swelling in the anterior abdominal wall in the suprapubic region. Fine needle aspiration revealed predominantly discrete cells with loose clustering at places. The cytoplasm was abundant, finely granular, and eosinophilic with some cells exhibiting clear vacuolated zones. No pigment was seen. The nuclei were rounded and eccentrically placed with a striking single eosinophilic macro nucleolus present in all the cells. Taking into consideration, the history, age of the patient, location of the tumor and absence of melanin pigment, a diagnosis of soft tissue sarcoma was made, the differential including Clear cell sarcoma. This was subsequently confirmed on histopathological examination and immunohistochemistry

Conclusion
The atypical presentation of the case made the cytological diagnosis rather challenging. Clear cell sarcoma should be considered when cytology of a soft-tissue tumor shows uncharacteristically high cellularity and relatively uniform cells with macronucleoli.
Micro-morphologic changes around biophysically-stimulated titanium implants in ovariectomized rats
Authors: Akca Kivanc , Sarac Ebru , Baysal Ugur , Fanuscu Mete , Chang Ting-Ling , Cehreli Murat 
Published: July 2007

Abstract

Background
Osteoporosis may present a risk factor in achievement of osseointegration because of its impact on bone remodeling properties of skeletal phsiology. The purpose of this study was to evaluate micro-morphological changes in bone around titanium implants exposed to mechanical and electrical-energy in osteoporotic rats.

Methods
Fifteen 12-week old sprague-dowley rats were ovariectomized to develop osteoporosis. After 8 weeks of healing period, two titanium implants were bilaterally placed in the proximal metaphyses of tibia. The animals were randomly divided into a control group and biophysically-stimulated two test groups with five animals in each group. In the first test group, a pulsed electromagnetic field (PEMF) stimulation was administrated at a 0.2 mT 4 h/day, whereas the second group received low-magnitude high-frequency mechanical vibration (MECHVIB) at 50 Hz 14 min/day. Following completion of two week treatment period, all animals were sacrificed. Bone sites including implants were sectioned, removed en bloc and analyzed using a microCT unit. Relative bone volume and bone micro-structural parameters were evaluated for 144 μm wide peri-implant volume of interest (VOI).

Results
Mean relative bone volume in the peri-implant VOI around implants PEMF and MECHVIB was significantly higher than of those in control (P < .05). Differences in trabecular-thickness and -separation around implants in all groups were similar (P > .05) while the difference in trabecular-number among test and control groups was significant in all VOIs (P < .05).

Conclusion
Biophysical stimulation remarkably enhances bone volume around titanium implants placed in osteoporotic rats. Low-magnitude high-frequency MECHVIB is more effective than PEMF on bone healing in terms of relative bone volume.