bluuebunny/crossref_metadata_2025 huggingface dataset:
Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells
Authors: Rossi Simona W. , Jeker Lukas T. , Ueno Tomoo , Kuse Sachiyo , Keller Marcel P. , Zuklys Saulius , Gudkov Andrei V. , Takahama Yousuke , Krenger Werner , Blazar Bruce R. , Holländer Georg A.
Published: January 2007

The systemic administration of keratinocyte growth factor (KGF) enhances T-cell lymphopoiesis in normal mice and mice that received a bone marrow transplant. KGF exerts protection to thymic stromal cells from cytoablative conditioning and graft-versus-host disease–induced injury. However, little is known regarding KGF's molecular and cellular mechanisms of action on thymic stromal cells. Here, we report that KGF induces in vivo a transient expansion of both mature and immature thymic epithelial cells (TECs) and promotes the differentiation of the latter type of cells. The increased TEC numbers return within 2 weeks to normal values and the microenvironment displays a normal architectural organization. Stromal changes initiate an expansion of immature thymocytes and permit regular T-cell development at an increased rate and for an extended period of time. KGF signaling in TECs activates both the p53 and NF-κB pathways and results in the transcription of several target genes necessary for TEC function and T-cell development, including bone morphogenetic protein 2 (BMP2), BMP4, Wnt5b, and Wnt10b. Signaling via the canonical BMP pathway is critical for the KGF effects. Taken together, these data provide new insights into the mechanism(s) of action of exogenous KGF on TEC function and thymopoiesis.
Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome–positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) LAL0201-B protocol
Authors: Vignetti Marco , Fazi Paola , Cimino Giuseppe , Martinelli Giovanni , Di Raimondo Francesco , Ferrara Felicetto , Meloni Giovanna , Ambrosetti Achille , Quarta Giovanni , Pagano Livio , Rege-Cambrin Giovanna , Elia Loredana , Bertieri Raffaello , Annino Luciana , Foà Robin , Baccarani Michele , Mandelli Franco
Published: January 2007

Thirty elderly (> 60 years) Philadelphia chromosome–positive (Ph+) patients with acute lymphoblastic leukemia (ALL) received imatinib, 800 mg daily, associated to steroids without further chemotherapy as frontline treatment. Median age was 69 years (range, 61-83 years). Twenty-nine patients were evaluable for response and all of them obtained a hematologic complete remission, with a median BCR-ABL reduction of 2.9 and 2.0 logs in p190+ and p210+ cases, respectively. Most of the induction treatment did not require admission of the patients. No major toxicities occurred and the treatment was well tolerated. Median survival from diagnosis was 20 months. This study shows that elderly Ph+ patients with ALL—often considered eligible only for palliative treatment strategies—may benefit from an imatinib-steroids protocol, which does not require chemotherapy nor a long hospitalization, is feasible, highly active, and associated with a good quality of life.
Bioinformatics analysis of the early inflammatory response in a rat thermal injury model
Authors: Yang Eric , Maguire Timothy , Yarmush Martin L , Berthiaume Francois , Androulakis Ioannis P
Published: January 2007

Background

Thermal injury is among the most severe forms of trauma and its effects are both local and systemic. Response to thermal injury includes cellular protection mechanisms, inflammation, hypermetabolism, prolonged catabolism, organ dysfunction and immuno-suppression. It has been hypothesized that gene expression patterns in the liver will change with severe burns, thus reflecting the role the liver plays in the response to burn injury. Characterizing the molecular fingerprint (i.e., expression profile) of the inflammatory response resulting from burns may help elucidate the activated mechanisms and suggest new therapeutic intervention. In this paper we propose a novel integrated framework for analyzing time-series transcriptional data, with emphasis on the burn-induced response within the context of the rat animal model. Our analysis robustly identifies critical expression motifs, indicative of the dynamic evolution of the inflammatory response and we further propose a putative reconstruction of the associated transcription factor activities.

Results

Implementation of our algorithm on data obtained from an animal (rat) burn injury study identified 281 genes corresponding to 4 unique profiles. Enrichment evaluation upon both gene ontologies and transcription factors, verifies the inflammation-specific character of the selections and the rationalization of the burn-induced inflammatory response. Conducting the transcription network reconstruction and analysis, we have identified transcription factors, including AHR, Octamer Binding Proteins, Kruppel-like Factors, and cell cycle regulators as being highly important to an organism's response to burn response. These transcription factors are notable due to their roles in pathways that play a part in the gross physiological response to burn such as changes in the immune response and inflammation.

Conclusion

Our results indicate that our novel selection/classification algorithm has been successful in selecting out genes with play an important role in thermal injury. Additionally, we have demonstrated the value of an integrative approach in identifying possible points of intervention, namely the activation of certain transcription factors that govern the organism's response.
A multi-treatment experimental system to examine photosynthetic differentiation in the maize leaf
Authors: Sawers Ruairidh JH , Liu Peng , Anufrikova Katya , Hwang JT Gene , Brutnell Thomas P
Published: January 2007

Background

The establishment of C4photosynthesis in maize is associated with differential accumulation of gene transcripts and proteins between bundle sheath and mesophyll photosynthetic cell types. We have physically separated photosynthetic cell types in the leaf blade to characterize differences in gene expression by microarray analysis. Additional control treatments were used to account for transcriptional changes induced by cell preparation treatments. To analyse these data, we have developed a statistical model to compare gene expression values derived from multiple, partially confounded, treatment groups.

Results

Differential gene expression in the leaves of wild-type maize seedlings was characterized using the latest release of a maize long-oligonucleotide microarray produced by the Maize Array Project consortium. The complete data set is available through the project web site. Data is also available at the NCBI GEO website, series record GSE3890. Data was analysed with and without consideration of cell preparation associated stress.

Conclusion

Empirical comparison of the two analyses suggested that consideration of stress helped to reduce the false identification of stress responsive transcripts as cell-type enriched. Using our model including a stress term, we identified 8% of features as differentially expressed between bundle sheath and mesophyll cell types under control of false discovery rate of 5%. An estimate of the overall proportion of differentially accumulating transcripts (1-π0) suggested that as many as 18% of the genes may be differentially expressed between B and M. The analytical model presented here is generally applicable to gene expression data and demonstrates the use of statistical elimination of confounding effects such as stress in the context of microarray analysis. We discuss the implications of the high degree of differential transcript accumulation observed with regard to both the establishment and engineering of the C4syndrome.
Functional analysis of Arabidopsis WRKY25 transcription factor in plant defense against Pseudomonas syringae
Authors: Zheng Zuyu , Mosher Stephen L , Fan Baofang , Klessig Daniel F , Chen Zhixiang
Published: January 2007

Background

A common feature of plant defense responses is the transcriptional regulation of a large number of genes upon pathogen infection or treatment with pathogen elicitors. A large body of evidence suggests that plant WRKY transcription factors are involved in plant defense including transcriptional regulation of plant host genes in response to pathogen infection. However, there is only limited information about the roles of specific WRKY DNA-binding transcription factors in plant defense.

Results

We analyzed the role of the WRKY25 transcription factor from Arabidopsis in plant defense against the bacterial pathogen Pseudomonas syringae. WRKY25 protein recognizes the TTGACC W-box sequences and its translational fusion with green fluorescent protein is localized to the nucleus. WRKY25 expression is responsive to general environmental stress. Analysis of stress-induced WRKY25 in the defense signaling mutants npr1, sid2, ein2 and coi1 further indicated that this gene is positively regulated by the salicylic acid (SA) signaling pathway and negatively regulated by the jasmonic acid signaling pathway. Two independent T-DNA insertion mutants for WRKY25 supported normal growth of a virulent strain of P. syringae but developed reduced disease symptoms after infection. By contrast, Arabidopsis constitutively overexpressing WRKY25 supported enhanced growth of P. syringae and displayed increased disease symptom severity as compared to wild-type plants. These WRKY25-overexpressing plants also displayed reduced expression of the SA-regulated PR1 gene after the pathogen infection, despite normal levels of free SA.

Conclusion

The nuclear localization and sequence-specific DNA-binding activity support that WRKY25 functions as a transcription factor. Based on analysis of both T-DNA insertion mutants and transgenic overexpression lines, stress-induced WRKY25 functions as a negative regulator of SA-mediated defense responses to P. syringae. This proposed role is consistent with the recent finding that WRKY25 is a substrate of Arabidopsis MAP kinase 4, a repressor of SA-dependent defense responses.
Expression of the Na+/l-symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus
Authors: Altorjay Áron , Dohán Orsolya , Szilágyi Anna , Paroder Monika , Wapnir Irene L , Carrasco Nancy
Published: January 2007

Background

The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I-) transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract.

Methods

Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients.

Results

Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps.

Conclusion

That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease.
The impact of vitamin D status on changes in bone mineral density during treatment with bisphosphonates and after discontinuation following long-term use in post-menopausal osteoporosis
Authors: Deane Andrew , Constancio Leonor , Fogelman Ignac , Hampson Geeta
Published: January 2007

Background

It is still unclear whether addition of calcium/vitamin D supplements leads to an incremental benefit in patients taking bisphosphonates and whether achievement of serum level of 25 (OH) vitamin D of at least 70 nmol/L has an impact on the skeletal response to bisphosphonates. Moreover the maintenance of BMD after bisphosphonates withdrawal with the continuation of calcium/vitamin D supplements only, remains uncertain. The aims were to assess the impact of vitamin D status on changes in bone mineral density (BMD) in firstly patients with post-menopausal osteoporosis on bisphosphonates and secondly following discontinuation of bisphosphonates after long-term use.

Methods

Two patient groups were recruited. The first study population comprised of 112 women treated with a bisphosphonate. The second study population consisted of 35 women who had been on bisphosphonates for > 5 years in whom the treatment agent was discontinued. Baseline BMD, changes in BMD following treatment, duration of treatment, serum 25 (OH) vitamin D, parathyroid hormone (PTH), urine C-terminal telopeptides of type 1 collagen (CTX) were obtained on the study participants.

Results

In the first study group, subjects with serum vitamin D concentrations (> 70 nmol/L) had a significantly lower serum PTH level (mean [SEM] 41 [2] ng/L). PTH concentrations of 41 ng/L or less was associated with a significantly higher increase in BMD at the hip following treatment with bisphosphonates compared to patients with PTH > 41 ng/L (2.5% [0.9] v/s -0.2% [0.9], P = 0.04). In the second study group, discontinuation of bisphosphonate for 15 months after long-term treatment did not result in significant bone loss at the lumbar spine and total hip, although a trend towards gradual decline in BMD at the femoral neck was observed.

Conclusion

the data suggest that optimal serum 25 (OH) vitamin D concentration may lead to further reduction in bone loss at the hip in patients on bisphosphonates. A prospective controlled trial is needed to evaluate whether the response to bisphosphonates is influenced by vitamin D status. BMD is preserved at the lumbar spine and total hip following discontinuation of bisphosphonate for a short period following long-term treatment, although a gradual loss occurs at the femoral neck.
A polymorphism in the 3' untranslated region of the gene encoding prostaglandin endoperoxide synthase 2 is not associated with an increase in breast cancer risk: a nested case-control study
Authors: Cox David G , Buring Julie , Hankinson Susan E , Hunter David J
Published: January 2007

Introduction

Prostaglandins are integral components in the cellular response to inflammation, promoting cellular proliferation and angiogenesis. The enzyme responsible for the conversion of arachidonic acid to prostaglandins in response to inflammation is prostaglandin endoperoxide synthase 2/cyclo-oxygenase 2 (PTGS2/COX2). Polymorphisms in the PTGS2 gene have been associated with various diseases, including inflammatory bowel disease and cancer of the lung, colorectum, and breast.

Methods

We genotyped the five most common polymorphisms (rs20417, rs5277, rs20432, rs5275, and rs4648298) in the Nurses' Health Study (1,270 cases, 1,762 controls) to test the hypothesis that polymorphisms in PTGS2 are associated with breast cancer risk, using logistic regression analyses. The Nurses' Health Study 2 (317 cases, 634 controls) and Harvard Women's Health Study (702 cases, 703 controls) were used to further examine putative associations.

Results

The rs5275 polymorphism in the 3' untranslated region of the PTGS2 gene was associated with a decrease in breast cancer risk. We therefore genotyped this single-nucleotide polymorphism in the Nurses' Health Study 2 and Harvard Women's Health Study. Similar results were observed in these subsequent analyses, with no statistically significant heterogeneity in risk estimates between studies. In pooled analyses, women homozygous for the T allele at rs5275 had a 20% lower risk of breast cancer than those homozygous for the C allele (odds ratio 0.80, 95% confidence interval 0.66 to 0.97).

Conclusion

Although this polymorphism may be associated with a decrease in breast cancer risk among Caucasian women, we provide strong evidence that it is not associated with an increased risk of breast cancer.
Adiponectin and Resistin in Human Cerebrospinal Fluid and Expression of Adiponectin Receptors in the Human Hypothalamus
Authors: Kos Katarina , Harte Alison L. , da Silva Nancy F. , Tonchev Anton , Chaldakov Georgi , James Sean , Snead David R. , Hoggart Barbara , O’Hare Joseph P. , McTernan Philip G. , Kumar Sudhesh
Published: January 2007

Context: The adipokine leptin has critical importance in central appetite regulation. In contrast to some suggestion of adiponectin influencing energy homeostasis in rodents, there is no evidence for adiponectin or resistin entering the human blood-brain barrier.

Objective: The objective was to establish the presence of adiponectin or resistin in human cerebrospinal fluid (CSF) and to compare their distribution with leptin. Furthermore, we wished to examine the expression of the adiponectin receptors 1 and 2 (AdipR1, AdipR2) in the human hypothalamus.

Methods: For this purpose, serum and CSF samples were collected from 20 men and 19 women matched for age [men, 69.8 ± 8.6 yr (mean ± sd); women, 69.4 ± 4.3 yr] and BMI (men, 29.4 ± 3.4 kg/m2; women, 27.3 ± 4.8 kg/m2) undergoing elective surgery under spinal anesthesia.

Results: Adiponectin was identified in CSF with levels 1000-fold less than serum, whereas resistin and leptin levels were 100-fold less. Unlike their serum levels, adiponectin CSF levels showed no gender difference or correlation with insulin resistance, which is similar to resistin CSF levels. The adiponectin and leptin CSF/serum ratios in our study exhibit the same pattern of gender-specific BMI association with inverse correlation in women (r = −0.61; P = 0.02) and no correlation in men (r = 0.026; P = not significant). Furthermore, immunostaining established AdipR1 and -2 in the hypothalamus and increased AdipR2 expression in the paraventricular nucleus, which is involved in energy regulation.

Conclusion: In summary, our findings show both the presence of adiponectin and resistin in human CSF, with no effect of insulin resistance on CSF levels. The CSF entry of adiponectin and leptin in women appears to be impaired in obesity.
Specification of epibranchial placodes in zebrafish
Authors: Nechiporuk Alexei , Linbo Tor , Poss Kenneth D. , Raible David W.
Published: January 2007

In all vertebrates, the neurogenic placodes are transient ectodermal thickenings that give rise to sensory neurons of the cranial ganglia. Epibranchial (EB) placodes generate neurons of the distal facial,glossopharyngeal and vagal ganglia, which convey sensation from the viscera,including pharyngeal endoderm structures, to the CNS. Recent studies have implicated signals from pharyngeal endoderm in the initiation of neurogenesis from EB placodes; however, the signals underlying the formation of placodes are unknown. Here, we show that zebrafish embryos mutant for fgf3 and fgf8 do not express early EB placode markers, including foxi1 and pax2a. Mosaic analysis demonstrates that placodal cells must directly receive Fgf signals during a specific crucial period of development. Transplantation experiments and mutant analysis reveal that cephalic mesoderm is the source of Fgf signals. Finally, both Fgf3 and Fgf8 are sufficient to induce foxi1-positive placodal precursors in wild-type as well as Fgf3-plus Fgf8-depleted embryos. We propose a model in which mesoderm-derived Fgf3 and Fgf8 signals establish both the EB placodes and the development of the pharyngeal endoderm, the subsequent interaction of which promotes neurogenesis. The coordinated interplay between craniofacial tissues would thus assure proper spatial and temporal interactions in the shaping of the vertebrate head.
Switch from BAX-dependent to BAX-independent germ cell loss during the development of fetal mouse ovaries
Authors: Alton Michelle , Taketo Teruko
Published: January 2007

Female reproductive life is limited by the oocyte/follicle pool, which has been determined by the number of germ cells to enter meiosis and subsequent loss of oocytes. It has been suggested that apoptosis accounts for the elimination of germ cells throughout oogenesis. However, female germ cells are lost continuously while they undergo distinct cell cycles in fetal and neonatal life. No convincing evidence has yet been provided to show apoptotic death of oocytes during meiotic prophase in vivo. In this study, we examined the change in the germ cell population in mice deficient of BAX, a key proapoptotic molecule. The number of germ cells, identified by GCNA1 immunolabeling, approximately doubled in ovaries of Bax-/- mice compared with ovaries of heterozygous Bax+/- mice and wild-type Bax+/+ mice by 14.5 days post coitum (d.p.c.) and remained higher up to 24.5 d.p.c. However, there was a rapid loss of germ cells in Bax-/- ovaries, paralleling that in Bax+/-and Bax+/+ ovaries from 14.5-24.5 d.p.c., a period in which most germ cells entered and progressed in meiotic prophase. These results suggest that, while progressing through meiotic prophase, oocytes are eliminated by a BAX-independent mechanism.
After fertilization of sea urchin eggs, eIF4G is post-translationally modified and associated with the cap-binding protein eIF4E
Authors: Oulhen Nathalie , Salaün Patrick , Cosson Bertrand , Cormier Patrick , Morales Julia
Published: January 2007

Release of eukaryotic initiation factor 4E (eIF4E) from its translational repressor eIF4E-binding protein (4E-BP) is a crucial event for the first mitotic division following fertilization of sea urchin eggs. Finding partners of eIF4E following fertilization is crucial to understand how eIF4E functions during this physiological process. The isolation and characterization of cDNA encoding Sphaerechinus granularis eIF4G (SgIF4G) are reported. mRNA of SgIF4G is present as a single 8.5-kb transcript in unfertilized eggs, suggesting that only one ortholog exists in echinoderms. The longest open reading frame predicts a sequence of 5235 nucleotides encoding a deduced polypeptide of 1745 amino acids with a predicted molecular mass of 192 kDa. Among highly conserved domains, SgIF4G protein possesses motifs that correspond to the poly(A) binding protein and eIF4E protein-binding sites. A specific polyclonal antibody was produced and used to characterize the SgIF4G protein in unfertilized and fertilized eggs by SDS-PAGE and western blotting. Multiple differentially migrating bands representing isoforms of sea urchin eIF4G are present in unfertilized eggs. Fertilization triggers modifications of the SgIF4G isoforms and rapid formation of the SgIF4G-eIF4E complex. Whereas rapamycin inhibits the formation of the SgIF4G-eIF4E complex, modification of these SgIF4G isoforms occurs independently from the rapamycin-sensitive pathway. Microinjection of a peptide corresponding to the eIF4E-binding site derived from the sequence of SgIF4G into unfertilized eggs affects the first mitotic division of sea urchin embryos. Association of SgIF4G with eIF4E is a crucial event for the onset of the first mitotic division following fertilization, suggesting that cap-dependent translation is highly regulated during this process. This hypothesis is strengthened by the evidence that microinjection of the cap analog m7GDP into unfertilized eggs inhibits the first mitotic division.
Parametric Sensitivity Analysis Using Large-Sample Approximate Bayesian Posterior Distributions
Authors: Hazen Gordon B. , Huang Min
Published: January 2007

When a decision analyst desires a sensitivity analysis on model parameters that are estimated from data, a natural approach is to vary each parameter within one or two standard errors of its estimate. This approach can be problematic if parameter estimates are correlated or if model structure does not permit obvious standard error estimates. Both of these difficulties can occur when the analysis of time-to-event data—known as survival analysis—plays a significant role in the decision analysis. We suggest that in this situation, a large-sample approximate multivariate normal Bayesian posterior distribution can be fruitfully used to guide either a traditional threshold proximity sensitivity analysis, or a probabilistic sensitivity analysis. The existence of such a large-sample approximation is guaranteed by the so-called Bayesian central limit theorem. We work out the details of this general proposal for a two-parameter cure-rate model, used in survival analysis. We apply our results to conduct both traditional and probabilistic sensitivity analyses for a recently published decision analysis of tamoxifen use for the prevention of breast cancer.
A Bayesian Decision-Theoretic Dose-Finding Trial
Authors: Müller Peter , Berry Don A. , Grieve Andrew P. , Krams Michael
Published: January 2007

We describe the use of a successful combination of Bayesian inference and decision theory in a clinical trial design. The trial involves three important decisions, adaptive dose allocation, optimal stopping of the trial, and the optimal terminal decision upon stopping. For all three decisions we use a formal Bayesian decision-theoretic approach. The application demonstrates how Bayesian posterior inference and decision-theoretic approaches combine to provide a coherent solution in a complex application. The main challenges are the need for a flexible probability model for the unknown dose-response curve, a delayed response, the sequential nature of the stopping decision, and the complex considerations involved in the terminal decision. The main methodological features of the proposed solution are the use of decision theory to achieve optimal learning about the unknown dose-response curve, an innovative grid-based approximation method to implement backward induction for the sequential stopping decision, and a utility function for the terminal decision that is based on a posterior predictive description of a future confirmatory trial.
Some Determinants of Corporate Risk Aversion
Authors: Bickel J. Eric
Published: January 2007

In this paper we roughly quantify the degree of risk aversion induced by three rationales for corporate risk management: the cost of financial distress, costly external finance, and the principal-agent relationship between shareholders and management. In so doing, we provide a foundation for the use of corporate utility functions. However, we are unable to fully support the degree of risk aversion reported in the decision analysis literature. Specifically, financial distress and costly external finance appear to induce relatively little risk aversion, while principal-agent concerns lend only partial support to published corporate risk tolerance guidelines.
From the Editors…
Authors: Clemen Robert T. , Kleinmuntz Don N.
Published: January 2007

This issue begins with two articles on the use of Bayesian methods in decision analysis. Müller, Berry, Grieve, and Krams present a Bayesian approach to the design of clinical trials, and Hazen and Huang develop a parametric sensitivity analysis based on large-sample Bayesian analysis. Also in this issue are articles by Paté-Cornell and Dillon, who discuss relationships between decision and risk analysis, and by Bickel, who investigates the topic of corporate risk aversion. This issue also marks the end of our term as the founding Editors-in-Chief of Decision Analysis with a brief discussion of the state of the journal, our hopes for the future, and our gratitude to all those who have supported the journal’s development.
Etomidate Use for Cushing's Syndrome Caused by an Ectopic Adrenocorticotropic Hormone–Producing Tumor
Authors: Johnson Tami N , Canada Todd W
Published: January 2007

Objective:

To report the preparation and use of etomidate in a patient with Cushing's syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)–producing tumor.

Case Summary:

A 73-year-old man with a 5 year history of prostate cancer was admitted for symptoms consistent with Cushing's syndrome. He was started on oral metyrapone for elevated serum cortisol. ACTH, and 24 hour urinary unbound cortisol levels. Shortly after starting metyrapone, he was transferred to the medical intensive care unit for new-onset atrial fibrillation, neutropenic fever, and respiratory failure. A nasogastric tube could not be inserted to administer metyrapone. Intravenous etomidate 4 mg/h (0.06 mg/kg/h) was initiated to decrease cortisol production and provide sedation for mechanical ventilation. Despite supportive treatment, the patient died from multiple organ dysfunction.

Discussion:

For patients exhibiting signs and symptoms of Cushing's syndrome who have no enteral access, administering etomidate intravenously may be a viable alternative treatment route. Although several articles report the use of etomidate to control cortisol overproduction, the intravenous preparation and stability are discussed only vaguely. In our patient, etomidate was infused via a 30 mL syringe, 2 mg/mL undiluted through a central venous catheter; syringe use was limited to 24 hours. Etomidate should be infused only with continuous monitoring of hemodynamics and periodic assessment of adrenal function.

Conclusions:

When oral or enteral medications cannot be administered and sedation is required in critically ill patients, etomidate is an appropriate intravenous agent for hypercortisolemia. There were no obvious problems with stability when undiluted etomidate 2 mg/mL was infused through a dedicated central venous catheter lumen.
Glycine-assisted enhancement of 1,4-β-d-xylan xylanohydrolase activity at alkaline pH with a pH optimum shift
Authors: Vathipadiekal Vinod , Verma Anamika , Rao Mala
Published: January 2007

This is the first report describing the enhancement of xylanase activity by the neutral amino acid glycine. Xylanase activity is increased seven-fold at alkaline pH in the presence of glycine and its pH optimum is shifted from pH 7 to 8 without using any protein engineering techniques. Analysis of the steady-state kinetics revealed that glycine in the reaction mixture increases the K
m and k
cat values of the enzyme. Chemoaffinity labeling and studies using glycine esters indicate an involvement of the carboxylate ion of glycine in enhancing xylanase catalytic activity. A novel possible mechanism for the glycine-assisted catalytic action of xylanase is proposed.
Interaction of the cellular prion protein with raft-like lipid membranes
Authors: Elfrink Kerstin , Nagel-Steger Luitgard , Riesner Detlev
Published: January 2007

Conversion of the cellular isoform of the prion protein (PrPC) into the disease-associated isoform (PrPSc) plays a key role in the development of prion diseases. Within its cellular pathway, PrPCundergoes several posttranslational modifications, i.e., the attachment of two N-linked glycans and a glycosyl phosphatidyl inositol (GPI) anchor, by which it is linked to the plasma membrane on the exterior cell surface. To study the interaction of PrPCwith model membranes, we purified posttranslationally modified PrPCfrom transgenic Chinese hamster ovary (CHO) cells. The mono-, di- and oligomeric states of PrPCfree in solution were analyzed by analytical ultracentrifugation. The interaction of PrPCwith model membranes was studied using both lipid vesicles in solution and lipid bilayers bound to a chip surface. The equilibrium and mechanism of PrPCassociation with the model membranes were analyzed by surface plasmon resonance. Depending on the degree of saturation of binding sites, the concentration of PrPCreleased from the membrane into aqueous solution was estimated at between 10-9and 10-7 M. This corresponds to a free energy of the insertion reaction of -48 kJ/mol. Consequences for the conversion of PrPCto PrPScare discussed.
Motion Integration by Neurons in Macaque MT Is Local, Not Global
Authors: Majaj Najib J. , Carandini Matteo , Movshon J. Anthony
Published: January 2007

Direction-selective neurons in primary visual cortex have small receptive fields that encode the motions of local features. These motions often differ from the motion of the object to which they belong and must therefore be integrated elsewhere. A candidate site for this integration is visual cortical area MT (V5), in which cells with large receptive fields compute the motion of patterns. Previous studies of motion integration in MT have used stimuli that fill the receptive field, and thus do not test whether motion information is really integrated across this whole area. For each MT neuron, we identified two regions (“patches”) within the receptive field that were approximately equally effective in driving responses. We then measured responses to plaids whose component gratings overlapped within a patch, and compared them with responses to the same component gratings presented in separate patches. Cells that were selective for the direction of motion of the whole pattern when the gratings overlapped lost this selectivity when the gratings were separated and became selective instead for the direction of motion of the individual components. If MT cells simply pooled all of the inputs that endow them with a receptive field, they would encode all of the motions in the receptive field as belonging to a single object. Our results indicate instead that critical elements of the computations underlying pattern-direction selectivity in MT are done locally, on a scale smaller than the whole receptive field.
Phosphatidylinositol 3-Kinase and Akt Nonautonomously Promote Perineurial Glial Growth inDrosophilaPeripheral Nerves
Authors: Lavery William , Hall Veronica , Yager James C. , Rottgers Alex , Wells Michelle C. , Stern Michael
Published: January 2007

Drosophilaperipheral nerves, structured similarly to their mammalian counterparts, comprise a layer of motor and sensory axons wrapped by an inner peripheral glia (analogous to the mammalian Schwann cell) and an outer perineurial glia (analogous to the mammalian perineurium). Growth and proliferation within mammalian peripheral nerves are increased by Ras pathway activation: loss-of-function mutations inNf1, which encodes the Ras inhibitor neurofibromin, cause the human genetic disorder neurofibromatosis, which is characterized by formation of neurofibromas (tumors of peripheral nerves). However, the signaling pathways that control nerve growth downstream of Ras remain incompletely characterized. Here we show that expression specifically within theDrosophilaperipheral glia of the constitutively activeRasV12increases perineurial glial thickness. Using chromosomal loss-of-function mutations and transgenes encoding dominant-negative and constitutively active proteins, we show that this nonautonomous effect ofRasV12is mediated by the Ras effector phosphatidylinositol 3-kinase (PI3K) and its downstream kinase Akt. We also show that the nonautonomous, growth-promoting effects of activated PI3K are suppressed by coexpression within the peripheral glia ofFOXO+(forkhead box O) a transcription factor inhibited by Akt-dependent phosphorylation. We suggest that Ras–PI3K–Akt activity in the peripheral glia promotes growth of the perineurial glia by inhibiting FOXO. In mammalian peripheral nerves, the Schwann cell releases several growth factors that affect the proliferative properties of neighbors. Some of these factors are oversecreted inNf1mutants. Our results raise the possibility that neurofibroma formation in individuals with neurofibromatosis might result in part from a Ras–PI3K–Akt-dependent inhibition of FOXO within Schwann cells.
Fast Synaptic Vesicle Reuse Slows the Rate of Synaptic Depression in the CA1 Region of Hippocampus
Authors: Ertunc Mert , Sara Yildirim , Chung ChiHye , Atasoy Deniz , Virmani Tuhin , Kavalali Ege T.
Published: January 2007

During short-term synaptic depression, neurotransmission rapidly decreases in response to repetitive action potential firing. Here, by blocking the vacuolar ATPase, alkalinizing the extracellular pH, or exposing hippocampal slices to pH buffers, we impaired neurotransmitter refilling, and electrophysiologically tested the role of vesicle reuse in synaptic depression. Under all conditions, synapses onto hippocampal CA1 pyramidal cells showed faster depression with increasing stimulation frequencies. At 20 Hz, compromising neurotransmitter refilling increased depression within 300 ms reaching completion within 2 s, suggesting a minimal contribution of reserve vesicles to neurotransmission. In contrast, at 1 Hz, depression emerged gradually and became significant within 100 s. Moreover, the depression induced by pH buffers was reversible with a similar frequency dependence, suggesting that the frequency-dependent increase in depression was caused by impairment of rapid synaptic vesicle reuse. These results indicate that synaptic vesicle trafficking impacts the kinetics of short-term synaptic plasticity at an extremely rapid time scale.
Bidirectional Modulation of Transmitter Release by Calcium Channel/Syntaxin InteractionsIn Vivo
Authors: Keith Ryan K. , Poage Robert E. , Yokoyama Charles T. , Catterall William A. , Meriney Stephen D.
Published: January 2007

Protein interactions within the active zone of the nerve terminal are critical for regulation of transmitter release. The SNARE protein syntaxin 1A, primarily known for important interactions that control vesicle fusion, also interacts with presynaptic voltage-gated calcium channels. Based on recordings of calcium channel functionin vitro, it has been hypothesized that syntaxin 1A–calcium channel interactions could alter calcium channel function at synapses. However, results at synapsesin vitrosuggest two potentially opposing roles: enhancement of neurotransmitter release by positioning docked vesicles near calcium channels and inhibition of calcium channel function by interaction with SNARE proteins. We have examined the possibility that these two effects of syntaxin can occur at synapses by studying the effects on transmitter release of manipulating syntaxin 1A–calcium channel interactions atXenopustadpole tail neuromuscular synapsesin vivo. Introduction of synprint peptides, which competitively perturb syntaxin 1A–calcium channel interactions, decreased quantal content at these synapses and increased paired-pulse and tetanic facilitation. In contrast, injecting mRNA for mutant (A240V, V244A) syntaxin 1A, which reduces calcium channel modulation but not bindingin vitro, increased quantal content and decreased paired-pulse and tetanic facilitation. Injection of wild-type syntaxin 1A mRNA had no effect. The opposing effects of synprint peptides and mutant syntaxin 1A providein vivosupport for the hypothesis that these interactions serve both to colocalize calcium channels with the release machinery and to modulate the functional state of the calcium channel. As such, these two effects of syntaxin on calcium channels modulate transmitter release in a bidirectional manner.
Vascular Endothelial Growth Factor Overexpression Delays Neurodegeneration and Prolongs Survival in Amyotrophic Lateral Sclerosis Mice
Authors: Wang Yaoming , Ou Mao Xiao , Xie Lin , Banwait Surita , Marti Hugo H. , Greenberg David A. , Jin Kunlin
Published: January 2007

We sought genetic evidence for the involvement of neuronal vascular endothelial growth factor (VEGF) in amyotrophic lateral sclerosis (ALS). Mice expressing human ALS mutant superoxide dismutase-1 (SOD1) were crossed with mice that overexpress VEGF in neurons (VEGF+/+). We report that SOD1G93A/VEGF+/+double-transgenic mice show delayed motor neuron loss, delayed motor impairment, and prolonged survival compared with SOD1G93Asingle transgenics. These findings indicate that neuronal VEGF protects against motor neuron degeneration, and may have therapeutic implications for ALS.
An Exploration of the Salience of Christianity for National Identity in Europe
Authors: Kunovich Robert M.
Published: January 2007

Most scholars of identity focus on processes of boundary maintenance rather than on the cultural content of identity categories (e.g., language, religion). In this article, the author explores the cultural content of national identity categories in Europe. He focuses on individual and collective factors that are associated with the salience of Christianity for national identity in seventeen European countries. At the individual level, the author focuses on the relationships between the salience of Christianity for national identity and religious majority and minority status, the frequency of attendance of religious services, and their interaction. At the country level, using a group-threat perspective, he examines the relationships between the salience of Christianity for national identity and the size of various non-Christian populations, diversity in the non-Christian population, and their statistical interaction. Individual-level survey data are from the International Social Survey Programme 1995: National Identity (Zentralarchive 1998), and country-level data are from the World Christian Encyclopedia (Barrett, Kurian, and Johnson 2001). The author uses multilevel modeling techniques to analyze these data. Results support group-threat and constructionist perspectives of national identity and suggest key factors at multiple units of analysis that promote a link between Christianity and national identity in Europe.
How Does “Culture” Become “Capital”? Cultural and Institutional Struggles over “Character and Personality” at Harvard
Authors: Stampnitzky Lisa
Published: January 2007

Although the concept of cultural capital has been widely adopted in sociological studies of culture, education, and stratification, few studies have addressed the processes through which specific instantiations of cultural capital become important in particular institutional locations. This article, based on an analysis of primary documents relating to changes in admissions policies at Harvard College between 1945 and 1965, addresses the question of how nonacademic factors came to have such a significant role in undergraduate admissions at elite American universities. It argues that in relatively autonomous fields such as higher education in the mid–twentieth century United States, cultural capital is shaped not only by the relations of cultural qualities and economic classes but also through specific intra- and extra-institutional struggles within the field in question.
From Traditional to Liberal Racism: Living Racism in the Everyday
Authors: Zamudio Margaret M. , Rios Francisco
Published: January 2007

This article examines hundreds of entries in student journals collected at a university in the Mountain West and captures a striking contradiction between an articulated understanding of racism as “a thing of the past” and the reality of a persistent and pervasive racism. This qualitative study documents everyday racist events taking place in the life of students. These events are coded into either a traditional or modern “liberal” category to demonstrate the link between past and present race projects. The authors conclude that the contemporary “colorblind” discourse of the liberal era suggests an ongoing race project centered on the maintenance of white privilege. The mediating role institutions play between individual and structural relations of inequality implicates the university in the maintenance of white privilege.
Using Power: An Exploration of Control Work in the Sport Marriage
Authors: Ortiz Steven M.
Published: January 2007

Drawing from long-term ethnographic research, this article provides valuable insight into the power and control processes that emerge from the work/family issues of professional athletes and their wives. It examines from the wives' perspective how these husbands engage in the interrelated processes of gender work and “control work” in their marital relationships and how wives respond. The “spoiled athlete syndrome” is introduced and discussed within the context of a typology of control work. As processes of learning, cultivating, and exerting control, this syndrome begins with early male, sport, and power-control socialization and continues through occupational socialization. This article seeks to explore the possible consequences and implications of such “control management” by husbands who have learned to define the male self and sport involvement as aspects of a hegemonic masculinity and how such definitions affect their wives and marriages.
The Trouble with the Multiethnic Placement Act: An Empirical Look at Transracial Adoption
Authors: Jennings Patricia K.
Published: January 2007

In this study, the author brings an empirical lens to bear on the transracial adoption debate. She observes infertility support group meetings and conducts face-to-face interviews with a group of White, economically privileged, infertile women. She explores how race relations shape women's responses to infertility. She asks if women view transracial adoption as a viable way to meet their parenting needs, and she explores how women negotiate and renegotiate their understanding of race as treatment options fail and as they encounter a shortage of healthy White infants. The author's findings complicate several of the assumptions that underscored the dominant discourse surrounding the 1994 passage of the Multi Ethnic Placement Act (MEPA) and its 1996 amendment the Inter-ethnic Adoption Provision (IEP). Advocates of transracial adoption argue that the race-matching policies established by the National Association of Black Social Workers create placement delays. Grounded in a “best interest of the child” standard, the passage of the MEPA-IEP overturned race-matching policies and made it illegal to consider race, ethnicity, or national origins when placing children for adoption. In situating the transracial adoption debate in a discourse of reverse discrimination, advocates advance a simplistic picture of race and adoption–an understanding that, the author argues, is based on faulty assumptions. Her findings generate a more complex picture of race and adoption.
“He Didn't Go in Doing a Skydive”: Sustaining the Illusion of Control in an Edgework Activity
Authors: Laurendeau Jason
Published: January 2007

Exploring Lyng's notion of “edgework,” this article draws on ethnographic data to explore the ways skydivers create and sustain the belief that they can maintain control while working the “edge” in this sport. The article focuses on the ways skydivers construct and maintain the “illusion” that they can exercise control as they negotiate their particular edge. It elaborates the ways this sense of control is constructed and the extent to which it informs the ways risk recreators approach the edge. In the choices jumpers make about how they participate in the sport and the ways they interpret the experiences of themselves and other jumpers, they defend the position that their hazardous environments are within their control. When this position becomes untenable, they often draw on the notion of fate to construct certain hazards as outside of the sport, thereby sustaining their sense of control.