bluuebunny/crossref_metadata_2025 huggingface dataset:
Factor VIIa bound to endothelial cell protein C receptor activates protease activated receptor-1 and mediates cell signaling and barrier protection
Authors: Sen Prosenjit , Gopalakrishnan Ramakrishnan , Kothari Hema , Keshava Shiva , Clark Curtis A. , Esmon Charles T. , Pendurthi Usha R. , Rao L. Vijaya Mohan
Published: January 2011

Recent studies have shown that factor VIIa (FVIIa) binds to the endothelial cell protein C receptor (EPCR), a cellular receptor for protein C and activated protein C, but the physiologic significance of this interaction is unclear. In the present study, we show that FVIIa, upon binding to EPCR on endothelial cells, activates endogenous protease activated receptor-1 (PAR1) and induces PAR1-mediated p44/42 mitogen-activated protein kinase (MAPK) activation. Pretreatment of endothelial cells with FVIIa protected against thrombin-induced barrier disruption. This FVIIa-induced, barrier-protective effect was EPCR dependent and did not involve PAR2. Pretreatment of confluent endothelial monolayers with FVIIa before thrombin reduced the development of thrombin-induced transcellular actin stress fibers, cellular contractions, and paracellular gap formation. FVIIa-induced p44/42 MAPK activation and the barrier-protective effect are mediated via Rac1 activation. Consistent with in vitro findings, in vivo studies using mice showed that administration of FVIIa before lipopolysaccharide (LPS) treatment attenuated LPS-induced vascular leakage in the lung and kidney. Overall, our present data provide evidence that FVIIa bound to EPCR on endothelial cells activates PAR1-mediated cell signaling and provides a barrier-protective effect. These findings are novel and of great clinical significance, because FVIIa is used clinically for the prevention of bleeding in hemophilia and other bleeding disorders.
Shb deficient mice display an augmented TH2 response in peripheral CD4+ T cells
Authors: Gustafsson Karin , Calounova Gabriela , Hjelm Fredrik , Kriz Vitezslav , Heyman Birgitta , Grönvik Kjell-Olov , Mostoslavsky Gustavo , Welsh Michael
Published: January 2011

Background

Shb, a ubiquitously expressed Src homology 2 domain-containing adaptor protein has previously been implicated in the signaling of various tyrosine kinase receptors including the TCR. Shb associates with SLP76, LAT and Vav, all important components in the signaling cascade governing T cell function and development. AShbknockout mouse was recently generated and the aim of the current study was to address the importance ofShbdeficiency on T cell development and function.

Results

Shbknockout mice did not display any major changes in thymocyte development despite an aberrant TCR signaling pattern, including increased basal activation and reduced stimulation-induced phosphorylation. The loss of Shb expression did however affect peripheral CD4+ THcells resulting in an increased proliferative response to TCR stimulation and an elevated IL-4 production of naïve THcells. This suggests a TH2 skewing of theShbknockout immune system, seemingly caused by an altered TCR signaling pattern.

Conclusion

Our results indicate that Shb appears to play an important modulating role on TCR signaling, thus regulating the peripheral CD4+ TH2 cell response.
Autoreactive marginal zone B cells enter the follicles and interact with CD4+ T cells in lupus-prone mice
Authors: Zhou Zhenhai , Niu Haitao , Zheng Ying-Yi , Morel Laurence
Published: January 2011

Backgound

Marginal zone B cells have been implicated in the production of autoantibodies in murine models of lupus. It has been suggested that they contribute to lupus immunopathogenesis through their enhanced effector functions and their repertoire that is biased toward autoreactive specificities. In the B6.NZM2410.Sle.Sle2.Sle3(B6.TC) model of lupus, the majority of marginal zone B cells are located outside the marginal zone and inside the follicles. Genetic alterations of this strain have shown a correlation between autoimmune pathogenesis and the presence of intrafollicular marginal zone B cells. This study was designed first to strengthen our original observations and to determine how the marginal zone B cells from the lupus-prone mice respond to stimulations and interact with T cells.

Results

The intrafollicular location of B6.TC MZB cells starts before disease manifestations and puts MZB cells in direct contact with CD4+T cells. Two different autoreactive B cell receptor (BCR) transgenic models showed that the expression of theSlesusceptibility loci enhances the presence of MZB cells inside the follicles.In vitro, B6.TC MZB cells were better effectors than B6 MZB cells with enhanced proliferation and antibody (Ab) production, including anti-DNA Ab, in response to stimulation with TLR ligands, immune complexes or anti-CD40. Furthermore, B6.TC MZB and CD4+T cells showed a reciprocally enhanced activation, which indicated that their contacts inside B6.TC follicles have functional consequences that suggest an amplification loop between these two cell types.

Conclusions

These results showed that the NZM2410 susceptibility loci induce MZB cells to locate into the follicles, and that this breach of follicular exclusion occurs early in the development of the autoimmune pathogenesis. The enhanced responses to stimulation and increased effector functions of MZB cells from lupus-prone mice as compare to non-autoimmune MZB cells provide a mechanism by which the failure of MZB cell follicular exclusion contributes to the autoimmune process.
Characterization of cp3 reveals a new bri1 allele, bri1-120, and the importance of the LRR domain of BRI1 mediating BR signaling
Authors: Shang Yun , Lee Myeong Min , Li Jianming , Nam Kyoung Hee
Published: January 2011

Background

Since the identification of BRI1 (BRASSINOSTEROID-INSENSITIVE1), a brassinosteroids (BRs) receptor, most of the critical roles of BR in plant development have been assessed using various bri1 mutant alleles. The characterization of individual bri1 mutants has shown that both the extracellular and cytoplasmic domains of BRI1 are important to its proper functioning. Particularly, in the extracellular domain, regions near the 70-amino acid island are known to be critical to BR binding. In comparison, the exact function of the leucine rich-repeats (LRR) region located before the 70-amino acid island domain in the extracellular cellular portion of BRI1 has not yet been described, due to a lack of specific mutant alleles.

Results

Among the mutants showing altered growth patterns compared to wild type, we further characterized cp3, which displayed defective growth and reduced BR sensitivity. We sequenced the genomic DNA spanning BRI1 in the cp3 and found that cp3 has a point mutation in the region encoding the 13th LRR of BRI1, resulting in a change from serine to phenylalanine (S399F). We renamed it bri1-120. We also showed that overexpression of the wild type BRI1 protein rescued the phenotype of bri1-120. Using a GFP-tagged bri1-120 construct, we detected the bri1-120 protein in the plasma membrane, and showed that the phenotypic defects in the rosette leaves of bri1-301, a kinase-inactive weak allele of BRI1, can be restored by the overexpression of the bri1-120 proteins in bri1-301. We also produced bri1-301 mutants that were wild type in appearance by performing a genetic cross between bri1-301 and bri1-120 plants.

Conclusions

We identified a new bri1 allele, bri1-120, whose mutation site has not yet been found or characterized. Our results indicated that the extracellular LRR regions before the 70-amino acid island domain of BRI1 are important for the appropriate cellular functioning of BRI1. Also, we confirmed that a successful interallelic complementation occurs between the extracellular domain mutant allele and the cytoplasmic kinase-inactive mutant allele of BRI1 in vivo.
A 3D Freehand Ultrasound System for Multi-view Reconstructions from Sparse 2D Scanning Planes
Authors: Yu Honggang , Pattichis Marios S , Agurto Carla , Beth Goens M
Published: January 2011

Background

A significant limitation of existing 3D ultrasound systems comes from the fact that the majority of them work with fixed acquisition geometries. As a result, the users have very limited control over the geometry of the 2D scanning planes.

Methods

We present a low-cost and flexible ultrasound imaging system that integrates several image processing components to allow for 3D reconstructions from limited numbers of 2D image planes and multiple acoustic views. Our approach is based on a 3D freehand ultrasound system that allows users to control the 2D acquisition imaging using conventional 2D probes.

For reliable performance, we develop new methods for image segmentation and robust multi-view registration. We first present a new hybrid geometric level-set approach that provides reliable segmentation performance with relatively simple initializations and minimum edge leakage. Optimization of the segmentation model parameters and its effect on performance is carefully discussed. Second, using the segmented images, a new coarse to fine automatic multi-view registration method is introduced. The approach uses a 3D Hotelling transform to initialize an optimization search. Then, the fine scale feature-based registration is performed using a robust, non-linear least squares algorithm. The robustness of the multi-view registration system allows for accurate 3D reconstructions from sparse 2D image planes.

Results

Volume measurements from multi-view 3D reconstructions are found to be consistently and significantly more accurate than measurements from single view reconstructions. The volume error of multi-view reconstruction is measured to be less than 5% of the true volume. We show that volume reconstruction accuracy is a function of the total number of 2D image planes and the number of views for calibrated phantom. In clinical in-vivo cardiac experiments, we show that volume estimates of the left ventricle from multi-view reconstructions are found to be in better agreement with clinical measures than measures from single view reconstructions.

Conclusions

Multi-view 3D reconstruction from sparse 2D freehand B-mode images leads to more accurate volume quantification compared to single view systems. The flexibility and low-cost of the proposed system allow for fine control of the image acquisition planes for optimal 3D reconstructions from multiple views.
Synthetic arylquinuclidine derivatives exhibit antifungal activity against Candida albicans, Candida tropicalis and Candida parapsilopsis
Authors: Ishida Kelly , Fernandes Rodrigues Juliany Cola , Cammerer Simon , Urbina Julio A , Gilbert Ian , de Souza Wanderley , Rozental Sonia
Published: January 2011

Background

Sterol biosynthesis is an essential pathway for fungal survival, and is the biochemical target of many antifungal agents. The antifungal drugs most widely used to treated fungal infections are compounds that inhibit cytochrome P450-dependent C14α-demethylase (CYP51), but other enzymes of this pathway, such as squalene synthase (SQS) which catalyses the first committed step in sterol biosynthesis, could be viable targets. The aim of this study was to evaluate the antifungal activity of SQS inhibitors on Candida albicans, Candida tropicalis and Candida parapsilopsis strains.

Methods

Ten arylquinuclidines that act as SQS inhibitors were tested as antiproliferative agents against three ATCC strains and 54 clinical isolates of Candida albicans, Candida tropicalis and Candida parapsilopsis. Also, the morphological alterations induced in the yeasts by the experimental compounds were evaluated by fluorescence and transmission electron microscopy.

Results

The most potent arylquinuclidine derivative (3-[1'-{4'-(benzyloxy)-phenyl}]-quinuclidine-2-ene) (WSP1267) had a MIC50 of 2 μg/ml for all species tested and MIC90 varying from 4 μg/ml to 8 μg/ml. Ultrathin sections of C. albicans treated with 1 μg/ml of WSP1267 showed several ultrastructural alterations, including (a) loss of cell wall integrity, (b) detachment of the plasma membrane from the fungal cell wall, (c) accumulation of small vesicles in the periplasmic region, (d) presence of large electron-dense vacuoles and (e) significantly increased cell size and cell wall thickness. In addition, fluorescence microscopy of cells labelled with Nile Red showed an accumulation of lipid droplets in the cytoplasm of treated yeasts. Nuclear staining with DAPI revealed the appearance of uncommon yeast buds without a nucleus or with two nuclei.

Conclusion

Taken together, our data demonstrate that arylquinuclidine derivatives could be useful as lead compounds for the rational synthesis of new antifungal drugs.
The impact of plasma triglyceride and apolipoproteins concentrations on high-density lipoprotein subclasses distribution
Authors: Tian Li , Xu Yanhua , Fu Mingde , Peng Tao , Liu Yinghui , Long Shiyin
Published: January 2011

Objective

To investigate the effect of triglyceride (TG) integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos) interaction in the processes of high density lipoprotein (HDL) mature metabolic and atherosclerosis related diseases.

Methods

Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects.

Results

Contents of preβ1-HDL, HDL3a, and apoB-100 level along with apoB-100/A-I ratio were significantly increased, whereas there was a significant reduction in the contents of HDL2, apoA-I level as well as apoC-III/C-II ratio with increased TG concentration. Moreover, preβ1-HDL contents is elevated about 9 mg/L and HDL2b contents can be reduced 21 mg/L for 0.5 mmol/L increment in TG concentration. Moreover, with increase of apoA-I levels, HDL2b contents were marginally elevated in any TG concentration group. Furthermore, despite of in the apoB-100/A-I < 0.9 group, the contents of preβ1-HDL increased, and those of HDL2b decreased significantly for subjects in both high and very high TG levels compared to that in normal TG levels. Similarly, in the apoB-100/A-I ≥ 0.9 group, the distribution of HDL subclasses also showed abnormality for subjects with normal TG levels.

Conclusions

The particle size of HDL subclasses tend to small with TG levels increased which indicated that HDL maturation might be impeded and efficiency of reverse cholesterol transport(RCT) might be weakened. These data suggest that TG levels were not only significantly associated with but liner with the contents of preβ1-HDL and HDL2b. They also raise the possibility that the TG levels effect on HDL maturation metabolism are subjected to plasma apolipoproteins and apolipoproteins ratios.
Modification of fatty acids composition in erythrocytes lipids in arterial hypertension associated with dyslipidemia
Authors: Novgorodtseva Tatyana P , Kantur Tatyana A , Karaman Yulia K , Antonyuk Marina V , Zhukova Natalia V
Published: January 2011

Background

Modification of fatty acids (FA) composition in erythrocytes lipids as an early indicator of the development of arterial hypertension (AH) and lipid disorders.

Methods

We included 34 patients with arterial hypertension and 11 healthy individuals. Each patient was examined the lipid composition of serum. From erythrocytes by gas chromatography were identified fatty acids. The quantitative composition of the erythrocyte lipids FA in patients with AH presented with saturated and polyunsaturated monoenic acids with carbon chain lengths from C12 to C22.

Results

In all hypertensive patients is disturbed lipid FA composition of erythrocytes. The patients with a normal level of serum lipids revealed deficiency of polyunsaturated acids n6-linoleic (18:2 n6), arachidonic (20:4 n6), dokozatetraenic 14,4% (22:4 n6). The patients with dislipidemia installed more profound restructuring of the lipid matrix of the membrane of erythrocytes. A decrease in polyunsaturated fatty acids family n3: dokozapentaenovoy (22:5 n3), docosahexaenoic PUFA (22:6 n3), the total value of n3 PUFA in 1,3 times was revealed.

Conclusion

Thus, modification of erythrocyte FA are fairly subtle indicator of pathology of lipid metabolism, which manifest themselves much earlier than changes in the lipoprotein of blood plasma.
Hepatitis G Virus associated aplastic anemia: A recent case from Pakistan
Authors: Riaz Shah Shahida Amjad , Idrees Muhammad , Hussain Abrar
Published: January 2011

Background

Aplastic anemia (AA) is a serious and rare disorder characterized by a hypocellular bone marrow. Hepatitis associated aplastic anemia (HAAA) is a variant of aplastic anemia in which aplastic anemia follows an acute attack of hepatitis. Several reports have noted an association between HGV and hepatitis-associated aplastic anemia besides other hepatitis causing viruses.

Case presentation

A female girl of age 11 year with a history of loose motion for one month, vomiting for last 15 days and poor oral intake for last few days is reported here. The physical examination presents fever, pallor whereas bleeding, hepatomegaly, Splenomegaly and bruising were absent, abdominal ultrasonography confirmed the absence of hepatomegaly, Splenomegaly and lymphodenopathy. The laboratory investigation parameters were: haemoglobin 6.2 g/L, total leucocytes count 1.51, neutrophils 0.47%, absolute reticulocyte count 0.5%, Monocytes 0.16%, red cell count 3.2 mil/uL, Picked cell volume (PCV) 30.13%, Mean Corpuscular Volume (MCV) 78 fL, Mean Corpuscular Hemoglobin (MCH) 26.3 pg. The liver enzymes were alanine aminotransferease (ALT) 98 IU/L, aspartate aminotransferase (AST) 114 IU/L. Serologic and molecular tests for hepatitis A, B, C, D, E, TTV, B19 were negative, whereas HGV RNA PCR test was found positive for hepatitis G virus. The bone marrow aspirate and trephine biopsy examination revealed hypo- cellularity, erythropoiesis, myelopoiesis and megakaryopoiesis.

Conclusion

HAAA is an uncommon but severe condition, which may occur following idiopathic cases of acute hepatitis. Our finding suggests the involvement of HGV in the development of aplastic anemia. In patients presenting with pancytopenia after an episode of acute hepatitis, the definitive diagnosis should be considered and confirmed by RT-PCR and if possible by bone marrow biopsy.
Coating carbon nanotubes with a polystyrene-based polymer protects against pulmonary toxicity
Authors: Tabet Lyes , Bussy Cyrill , Setyan Ari , Simon-Deckers Angélique , Rossi Michel J , Boczkowski Jorge , Lanone Sophie
Published: January 2011

Background

carbon nanotubes (CNT) can have adverse effects on health. Therefore, minimizing the risk associated with CNT exposure is of crucial importance. The aim of this work was to evaluate if coating multi-walled CNT (MWCNT) with polymers could modify their toxicity, thus representing a useful strategy to decrease adverse health effects of CNT. We used industrially-produced MWCNT uncoated (NT1) or coated (50/50 wt%) with acid-based (NT2) or polystyrene-based (NT3) polymer, and exposed murine macrophages (RAW 264.7 cell line) or Balb/c mice by intratracheal administration. Biological experiments were performed both in vitro and in vivo, examining time- and dose-dependent effects of CNT, in terms of cytotoxicity, expression of genes and proteins related to oxidative stress, inflammation and tissue remodeling, cell and lung tissue morphology (optical and transmission electron microscopy), and bronchoalveolar lavage fluid content analysis.

Results

extensive physico-chemical characterization of MWCNT was performed, and showed, although similar dimensions for the 3 MWCNT, a much smaller specific surface area for NT2 and NT3 as compared to NT1 (54.1, 34 and 227.54 m2/g respectively), along with different surface characteristics. MWCNT-induced cytotoxicity, oxidative stress, and inflammation were increased by acid-based and decreased by polystyrene-based polymer coating both in vitro in murine macrophages and in vivo in lung of mice monitored for 6 months.

Conclusions

these results demonstrate that coating CNT with polymers, without affecting their intrinsic structure, may constitute a useful strategy for decreasing CNT toxicity, and may hold promise for improving occupational safety and that of general the user.
Potassium Channels as a Potential Therapeutic Target for Trigeminal Neuropathic and Inflammatory Pain
Authors: Takeda Mamoru , Tsuboi Yoshiyuki , Kitagawa Junichi , Nakagawa Kazuharu , Iwata Koichi , Matsumoto Shigeji
Published: January 2011

Previous studies in several different trigeminal nerve injury/inflammation models indicated that the hyperexcitability of primary afferent neurons contributes to the pain pathway underlying mechanical allodynia. Although multiple types of voltage-gated ion channels are associated with neuronal hyperexcitability, voltage-gated K+ channels (Kv) are one of the important physiological regulators of membrane potentials in excitable tissues, including nociceptive sensory neurons. Since the opening of K+ channels leads to hyperpolarization of cell membrane and a consequent decrease in cell excitability, several Kv channels have been proposed as potential target candidates for pain therapy. In this review, we focus on common changes measured in the Kv channels of several different trigeminal neuropathic/inflammatory pain animal models, particularly the relationship between changes in Kv channels and the excitability of trigeminal ganglion (TRG) neurons. We also discuss the potential of Kv channel openers as therapeutic agents for trigeminal neuropathic/inflammatory pain, such as mechanical allodynia.
The value of shoe size for prediction of the timing of the pubertal growth spurt
Authors: Busscher Iris , Kingma Idsart , Wapstra Frits Hein , Bulstra Sjoerd K , Verkerke Gijsbertus J , Veldhuizen Albert G
Published: January 2011

Background

Knowing the timing of the pubertal growth spurt of the spine, represented by sitting height, is essential for the prognosis and therapy of adolescent idiopathic scoliosis. There are several indicators that reflect growth or remaining growth of the patient. For example, distal body parts have their growth spurt earlier in adolescence, and therefore the growth of the foot can be an early indicator for the growth spurt of sitting height. Shoe size is a good alternative for foot length, since patients can remember when they bought new shoes and what size these shoes were. Therefore the clinician already has access to some longitudinal data at the first visit of the patient to the outpatient clinic.

The aim of this study was to describe the increase in shoe size during adolescence and to determine whether the timing of the peak increase could be an early indicator for the timing of the peak growth velocity of sitting height.

Methods

Data concerning shoe sizes of girls and boys were acquired from two large shoe shops from 1991 to 2008. The longitudinal series of 242 girls and 104 boys were analysed for the age of the "peak increase" in shoe size, as well as the age of cessation of foot growth based on shoe size.

Results

The average peak increase in shoe size occurred at 10.4 years (SD 1.1) in girls and 11.5 years (SD 1.5) in boys. This was on average 1.3 years earlier than the average peak growth velocity of sitting height in girls, and 2.5 years earlier in boys. The increase in shoe size diminishes when the average peak growth velocity of sitting height takes place at respectively 12.0 (SD 0.8) years in girls, and 13.7 (SD 1.0) years in boys.

Conclusions

Present data suggest that the course of the shoe size of children visiting the outpatient clinic can be a useful first tool for predicting the timing of the pubertal growth spurt of sitting height, as a representative for spinal length.

This claim needs verification by direct comparison of individual shoe size and sitting height data and than a step forward can be made in clinical decision making regarding adolescent idiopathic scoliosis.
Exogenous glucagon-like peptide-1 attenuates the glycaemic response to postpyloric nutrient infusion in critically ill patients with type-2 diabetes
Authors: Deane Adam M , Summers Matthew J , Zaknic Antony V , Chapman Marianne J , Fraser Robert JL , Di Bartolomeo Anna E , Wishart Judith M , Horowitz Michael
Published: January 2011

Introduction

Glucagon-like peptide-1 (GLP-1) attenuates the glycaemic response to small intestinal nutrient infusion in stress-induced hyperglycaemia and reduces fasting glucose concentrations in critically ill patients with type-2 diabetes. The objective of this study was to evaluate the effects of acute administration of GLP-1 on the glycaemic response to small intestinal nutrient infusion in critically ill patients with pre-existing type-2 diabetes.

Methods

Eleven critically ill mechanically-ventilated patients with known type-2 diabetes received intravenous infusions of GLP-1 (1.2 pmol/kg/minute) and placebo from t = 0 to 270 minutes on separate days in randomised double-blind fashion. Between t = 30 to 270 minutes a liquid nutrient was infused intraduodenally at a rate of 1 kcal/min via a naso-enteric catheter. Blood glucose, serum insulin and C-peptide, and plasma glucagon were measured. Data are mean ± SEM.

Results

GLP-1 attenuated the overall glycaemic response to nutrient (blood glucose AUC30-270 min: GLP-1 2,244 ± 184 vs. placebo 2,679 ± 233 mmol/l/minute; P = 0.02). Blood glucose was maintained at < 10 mmol/l in 6/11 patients when receiving GLP-1 and 4/11 with placebo. GLP-1 increased serum insulin at 270 minutes (GLP-1: 23.4 ± 6.7 vs. placebo: 16.4 ± 5.5 mU/l; P < 0.05), but had no effect on the change in plasma glucagon.

Conclusions

Exogenous GLP-1 in a dose of 1.2 pmol/kg/minute attenuates the glycaemic response to small intestinal nutrient in critically ill patients with type-2 diabetes. Given the modest magnitude of the reduction in glycaemia the effects of GLP-1 at higher doses and/or when administered in combination with insulin, warrant evaluation in this group.

Trial registration

ANZCTR:ACTRN12610000185066
Integrated Genomic Analysis of Nodular Tissue in Macronodular Adrenocortical Hyperplasia: Progression of Tumorigenesis in a Disorder Associated with Multiple Benign Lesions
Authors: Almeida Madson Q. , Harran Michelle , Bimpaki Eirini I. , Hsiao Hui-Pin , Horvath Anelia , Cheadle Chris , Watkins Tonya , Nesterova Maria , Stratakis Constantine A.
Published: January 2011

Context:

Massive macronodular adrenocortical disease or ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a clinically and genetically heterogeneous disorder.

Objective and Design:

Whole-genome expression profiling and oligonucleotide array comparative genomic hybridization changes were analyzed in samples of different nodules from the same patients with AIMAH. Quantitative RT-PCR and staining were employed to validate the mRNA array data.

Results:

Chromosomal gains were more frequent in larger nodules when compared with smaller nodules from the same patients. Among the 50 most overexpressed genes, 50% had a chromosomal locus that was amplified in the comparative genomic hybridization data. Although the list of most over- and underexpressed genes was similar between the nodules of different size, the gene set enrichment analysis identified different pathways associated with AIMAH that corresponded to the size; the smaller nodules were mainly enriched for metabolic pathways, whereas p53 signaling and cancer genes were enriched in larger nodules. Confirmatory studies demonstrated that BCL2, E2F1, EGF, c-KIT, MYB, PRKCA, and CTNNB1 were overexpressed in the larger nodules at messenger and/or protein levels. Chromosomal enrichment analysis showed that chromosomes 20q13 and 14q23 might be involved in progression of AIMAH from smaller to larger tumors.

Conclusion:

Integrated transcriptomic and genomic data for AIMAH provides supporting evidence to the hypothesis that larger adrenal lesions, in the context of this chronic, polyclonal hyperplasia, accumulate an increased number of genomic and, subsequently, transcript abnormalities. The latter shows that the disease appears to start with mainly tissue metabolic derangements, as suggested by the study of the smaller nodules, but larger lesions showed aberrant expression of oncogenic pathways.
The Water Permeability Channels Aquaporins 1–4 Are Differentially Expressed in Granulosa and Theca Cells of the Preovulatory Follicle during Precise Stages of Human Ovulation
Authors: Thoroddsen Asgeir , Dahm-Kähler Pernilla , Lind Anna Karin , Weijdegård Birgitta , Lindenthal Bernhard , Müller Jörg , Brännström Mats
Published: January 2011

Context:

Changes in vascular permeability and expansion of the fluid-filled antrum are major events in the LH-induced ovulatory process.

Objectives:

Our objective was to investigate the presence and expression levels of aquaporins (AQPs) in the granulosa and theca cell compartments of the follicle during defined phases of human ovulation.

Design and Setting:

We conducted a prospective experimental study at the Department of Obstetrics and Gynaecology at a university hospital.

Participants:

Twenty-eight women underwent laparoscopic sterilization and at the same time follicle retrieval at four periovulatory phases.

Main Outcome Measures:

mRNA levels of AQP1-4 were measured in separated granulosa and theca cells from preovulatory phase, early ovulatory (EO) phase, late ovulatory phase, and postovulatory phase. Immunohistochemistry was done for AQP1-4 in intact human follicles.

Results:

All four AQPs were expressed in both the theca and granulosa cells during ovulation. In granulosa cells, AQP1 levels increased in the late ovulatory and postovulatory phases. Expression of AQP2-3 followed a similar pattern with a marked increase in the EO phase, whereas AQP4 levels decreased from preovulatory to the EO phase. The presence of AQP1-4 in the human follicle was verified by immunohistochemistry.

Conclusions:

The results show for the first time the presence of AQP1-4 in human follicles during ovulation. The marked early rise in expression of AQP2 and AQP3 suggests a role during the process leading to follicular rupture, and the late rise of AQP1 suggests a role in corpus luteum formation.
Testable Implications of Gross Substitutes in Demand for Two Goods
Authors: Chambers Christopher P , Echenique Federico , Shmaya Eran
Published: January 2011

We present a nonparametric “revealed-preference test” for gross substitutes in demand for two goods. (JEL D01, D11)
A Welfare Analysis of Arbitration
Authors: Olszewski Wojciech
Published: January 2011

The paper compares conventional and final-offer arbitration. One party is supposed to make a payment to another party, whose amount depends on a state. Under one scenario, parties obtain signals about the state, which cannot be recognized by the opponents. If the arbitrator's ability of recognizing signals is high, the frequency of requesting arbitration is lower under conventional than under final-offer arbitration. If this ability is low, final-offer arbitration dominates conventional arbitration in quite a similar sense. Under the second scenario, parties believe that their opponents have wrong signals. Then, conventional arbitration approximates the original outcome better than final-offer arbitration. (JEL C78, D82, D86, J52)
Ensuring Sales: A Theory of Inter-Firm Credit
Authors: Daripa Arup , Nilsen Jeffrey
Published: January 2011

We propose a simple theory to account for the prevalence of inter-firm credit at an interest rate of zero. A downstream firm trades off inventory holding costs against lost sales. Lost final sales impose a negative externality on the upstream firm. The solution requires a subsidy limited by the value of inputs. Allowing the downstream firm to pay with a delay is precisely such a solution. A reverse externality accounts for the use of prepayment. We clarify how input prices vary with such policies, and when trade credit/prepayment is more efficient than pure input price adjustments. (JEL D21, D62, D92, G31, L25)
“Personal Influence”: Social Context and Political Competition
Authors: Galeotti Andrea , Mattozzi Andrea
Published: January 2011

This paper studies the effect of social learning on political outcomes in a model of informative campaign advertising. Voters' communication network affects parties' incentives to disclose political information, voters' learning about candidates running for office, and polarization of the electoral outcome. In richer communication networks, parties disclose less political information and voters are more likely to possess erroneous beliefs about the characteristics of the candidates. In turn, a richer communication network among voters may lead to political polarization. These results are reinforced when interpersonal communication occurs more frequently among ideologically homogeneous individuals and parties can target political advertising. (JEL D72, D85, M37, Z13)
Experimentation, Patents, and Innovation
Authors: Acemoglu Daron , Bimpikis Kostas , Ozdaglar Asuman
Published: January 2011

This paper studies a simple model of experimentation and innovation. Our analysis suggests that patents improve the allocation of resources by encouraging rapid experimentation and efficient ex post transfer of knowledge. Each firm receives a signal on the success probability of a project and decides when to experiment. Successes can be copied. First, we assume that signal qualities are the same. Symmetric equilibria involve delayed and staggered experimentation, whereas the optimal allocation never involves delays and may involve simultaneous experimentation. Appropriately designed patents implement the optimal allocation. Finally, we discuss the case when signals differ and are private information. (JEL D82, D83, O31, O33, O34)
Portfolio Dynamics for Customers of a Multiservice Provider
Authors: Schweidel David A. , Bradlow Eric T. , Fader Peter S.
Published: January 2011

Multiservice providers, such as telecommunication and financial service companies, can benefit from understanding how customers' service portfolios evolve over the course of their relationships. This can provide guidance for managerial issues such as customer valuation and predicting customers' future behavior, whether it is acquiring additional services, selectively dropping current services, or ending the relationship entirely. In this research, we develop a dynamic hidden Markov model to identify latent states that govern customers' affinity for the available services through which customers evolve. In addition, we incorporate and demonstrate the importance of separating two other sources of dynamics: portfolio inertia and service stickiness. We then examine the relationship between state membership and managerially relevant metrics, including customers' propensities for acquiring additional services or terminating the relationship, and customer lifetime value. Through a series of illustrative vignettes, we show that customers who have discarded a particular service may have an increased risk of canceling all services in the near future (as intuition would suggest) but also may be more prone to acquire more services, a provocative finding of interest to service providers. Our findings also emphasize the need to look beyond the previous period, as in much current research, and consider how customers have evolved over their entire relationship in order to predict their future actions.

This paper was accepted by Pradeep Chintagunta, marketing.
Testosterone deficiency in the aging male and its relationship with sexual dysfunction and cardiovascular diseases
Authors: Corona Giovanni , Rastrelli Giulia , Ricca Valdo , Maggi Mario
Published: January 2011

Background: The relationship between age-associated dec-line of testosterone (T), cardiovascular (CV) risk and sexual dysfunction in males is not completely clear. The aim of the present study was to report our experience in a large series of patients seeking medical care for sexual dysfunction and comparing our results with current evidence.

Materials and methods: Here, we review published data from our laboratory and reported data from a cross-sectional analysis on a consecutive series of 3149 patients seeking medical care at our Unit for sexual dysfunction (between 2000 and 2010). Among them, 1687 (studied between 2000 and 2007) patients were also longitudinally evaluated (mean follow-up 4.3±2.6 years) for forthcoming major cardiovascular events (MACEs). All major findings were discussed in comparison with data reported in the literature.

Results: T levels were associated with a wide array of biological and psychological factors, which substantially differ as a function of age. Some of these associations were more evident in the youngest patients (psychological symptoms), whereas sexual symptoms, including erectile function, sexual desire and the frequency of sexual intercourse, were associated with T levels only in the oldest patients. We did not find any association between T and MACEs, whereas we reported a close link between CV mortality and low T. Both these observations are in line with data obtained in community-dwelling men.

Conclusions: T plays a crucial role in regulating different aspects of male sexual function. The effect of T on CV risk needs to be confirmed in larger epidemiological and interventional studies.
Aldosterone and the cardiovascular system: a dangerous association
Authors: Cachofeiro Victoria , López-Andrés Natalia , Miana Maria , Martín-Fernández Beatriz , de las Heras Natalia , Martínez Ernesto , Lahera Vicente , Fortuño María Antonia
Published: January 2011

Initial studies have focussed on the actions of aldosterone in renal electrolyte handling and, as a consequence, blood pressure control. More recently, attention has primarily been focussed on its actions on the heart and vascular system, where it is locally produced. Aldosterone by binding mineralocorticoid receptors causes oxidative stress, fibrosis and triggers an inflammatory response in the cardiovascular system. All these effects could be underlying the role of aldo-sterone on cardiac and vascular remodelling associated with different pathological situations. At the vascular level, aldo-sterone affects endothelial function because administration of aldosterone to rats impaired endothelium-dependent relaxations. In addition, the administration of mineralocorticoid receptor antagonists ameliorates endothelium-dependent relaxation in models of both hypertension and atherosclerosis, and in patients with heart failure. Several mechanisms can participate in this effect, including production of vasoconstrictor factors and a reduction in nitric oxide levels. This reduction can involve both a decrease in its production as well as an increase in its degradation by reactive oxygen species. Aldosterone can produce oxidative stress by the activation of transcription factors such as the NF-κB system, which can also trigger an inflammatory process through the production of different cytokines. At cardiac level, high levels of aldosterone can also adversely impact heart function by producing cardiac hypertrophy, diastolic dysfunction and electrical remodelling through changes in ionic channels. All these effects can explain the beneficial effect of mineralocorticoid blockade in the cardiovascular system.
The distribution of placental oxidoreductase isoforms provides different milieus of steroids influencing pregnancy in the maternal and fetal compartment
Authors: Hill Martin , Pařízek Antonín , Velíková Marta , Kubátová Jana , Kancheva Radmila , Dušková Michaela , Šimůnková Kateřina , Klímková Michaela , Pašková Andrea , Žižka Zdeněk , Jirásek Jan Evangelista , Jirkovská Marie , Stárka Luboslav
Published: January 2011

Using information based on the steroid metabolome in maternal and fetal body fluids, we attempted to ascertain whether there is a common mechanism, which is based on the placental distribution of various isoforms of 17β-hydroxysteroid dehydrogenases and aldo-keto reductases. This system simultaneously provides a higher proportion of active progestogens in fetal circulation and a higher proportion of active estrogens and GABAergic steroids in the maternal compartment. The data obtained using gas chromatography-mass spectrometry completely support the aforementioned hypothesis. We confirmed a common trend to higher ratios of steroids with hydroxy-groups in the 3α-, 17β-, and 20α-positions to the corresponding 3-oxo-, 17-oxo-, and 20-oxo-metabolites, respectively, in the maternal blood when compared with the fetal circulation, and the same tendency was obvious in the 3α-hydroxy/3β-hydroxy steroid ratios. A decreasing trend was observed in the ratios of active estrogens and neuro-inhibitory steroids to their inactive counterparts in fetal and maternal body fluids. This was probably associated with a limited capacity of placental oxidoreductases in the converting of estrone to estradiol during the transplacental passage. Although we observed a decreasing trend in pregnancy-sustaining steroids with increasing gestational age, we recorded rising levels of estradiol and particularly of estriol, regardless of the limited capacity of placental oxidoreductases. Besides the estradiol, which is generally known as an active estrogen, estriol may be of importance for the termination of pregnancy with respect to its excessive concentrations near term which allows its binding to estrogen receptors.
Mechanisms of estrogen protection in diabetes and metabolic disease
Authors: Cignarella Andrea , Bolego Chiara
Published: January 2011

Until menopause, women are largely protected against several metabolic disorders, implicating a role for sex hormones. Adiposity and insulin resistance are fundamental features in the pathogenesis of type 2 diabetes mellitus. Emerging data suggest that sex-steroid hormones and adipocyte-derived hormones and cytokines could be associated with type 2 diabetes risk and that some of these novel markers can exhibit a sexual dimorphism with regard to this risk. Evidence suggests that the female hormone, 17β-estradiol protects insulin production and prevents diabetes. Although 17β-estradiol acts primarily via two distinct estrogen receptors (ERs), ERα and ERβ, it appears that ERα protects β-cell survival, whereas ERβ reduces ERα function and provokes β-cell apoptosis. Accordingly, use of menopausal hormone therapy has been shown to reduce diabetes incidence and weight gain. Recent findings that benefits of menopausal hormone therapy might not outweigh the risks in some women do not negate the importance of identifying mechanisms by which 17β-estradiol attenuates the development and progression of metabolic disease. This could lay the ground to the design of pharmacological treatments for the prevention of menopause-associated metabolic disorders that are safer and more efficacious than current hormone-based regimens.
Larval Morphology of Meruidae (Coleoptera: Adephaga) and Its Phylogenetic Implications
Authors: Alarie Yves , Short Andrew E Z , Garcia Mauricio , Joly Luis
Published: January 2011

Meruidae, or comb-clawed cascade beetles, are a recently discovered monotypic family of Adephaga endemic to Venezuela. The larvae of Meruidae are described for the first time, based on material of Meru phyllisaeSpangler & Steiner, 2005, collected together with adults in southern Venezuela. External morphological features, including chaetotaxy, are reported for the mature larva and an assessment made of the polarity of larval characters of phylogenetic utility in Adephaga. Larvae of Meruidae possess a mixture of primitive and derived character states, and they are unique within the Adephaga in that here the mandibles are asymmetrical, the respiratory system is comprised of only two pairs of spiracles (= oligopneustic), the claws are pectinate, and the abdominal sternite VIII is prolonged overlapping the abdominal sternite IX. A parsimony analysis based on 18 informative larval characteristics was conducted with the program PAUP*. The most parsimonious trees confirm Meruidae as a relatively basal lineage within the Dytiscoidea. Both Meru Spangler & Steiner and Noteridae are hypothesized to have diverged anterior to Amphizoidae, Aspidytidae, Hygrobiidae, and Dytiscidae.
Ecologically and Morphologically Remarkable New Cosmet Moth Species of the Genus Hyposmocoma (Lepidoptera: Cosmopterigidae) Endemic to the Hawaiian Islands, with Reference to the Spectacular Diversity of Larval Cases
Authors: Schmitz Patrick , Rubinoff Daniel
Published: January 2011

Hyposmocoma is an endemic Hawaiian moth genus with >330 recognized species occupying a remarkable range of ecological habits and exhibiting a high degree of variation typical of adaptive radiations. Within this diverse genus, some species have evolved intriguing and globally rare lifestyles, such as predatory or aquatic caterpillars. There are still many undescribed species in the genus, and no current work succinctly covers the range of their diversity. We describe nine new species in an attempt to demonstrate some of the remarkable ecological and phenotypic diversity displayed by species in the genus in a concise format: Hyposmocoma carnivora sp. nov. from the island of Hawaii; Hyposmocoma eliai sp. nov. Hyposmocoma nohomaalewa sp. nov., and Hyposmocoma waikamoi sp. nov. from the island of Kauai; and Hyposmocoma papaiili sp. nov., Hyposmocoma pukoa sp. nov., Hyposmocoma pupumoehewa sp. nov., Hyposmocoma opuulaau sp. nov., and Hyposmocoma waikamoi sp. nov. from the island of Maui. Although the taxa presented here do not represent a monophyletic group with respect to the rest of Hyposmocoma, they represent some of the most striking aspects of Hyposmocoma diversity as a whole.
A New North American Species of Pseudacteon (Diptera: Phoridae), Parasitic on Nylanderia arenivaga (Hymenoptera: Formicidae)
Authors: Brown Brian V , Schneider Scott A , LaPolla John S
Published: January 2011

A new species of ant-parasitizing Pseudacteon Coquillett phorid is described. Pseudacteon gracilisetus n. sp. was discovered parasitizing the ant species Nylanderia arenivaga (Wheeler). This species is the second known Pseudacteon parasite of Nylanderia ants.
Effects of Indol-3-Acetic Acid on Biological Parameters of the Larval Endoparasitoid Apanteles galleriae (Hymenoptera: Braconidae)
Authors: Uçkan Fevzi , Haftaci İpek , Ergin Ekrem
Published: January 2011

The nontarget effects of the plant growth regulator indol-3-acetic acid (IAA) on parasitoid development and reproduction were examined using the endoparasitoid Apanteles galleriae Wilkinson (Hymenoptera: Braconidae). The effects of IAA were assessed by rearing A. galleriae on hosts fed different doses of the growth regulator and then measuring a range of life history traits such as immature developmental time, adult longevity, body size, fecundity, and sex ratios in F1 and F2 generations. Wasp development from egg to adult took 27–47 d. However, adult emergence of parasitoids reared on hosts exposed to IAA doses required 14–24 d longer than controls to complete development at doses >200 ppm. Longevity of IAA-treated adult wasps was lower than that of controls at any dose. For example, at IAA doses >200 ppm, the life span of both male and female adult wasps decreased >50% compared with parasitoids that developed inside IAA-free hosts. Adult length also decreased at 500 and 1,000 ppm with respect to the control and lesser dosages. The total number of progeny decreased >50% and female sex ratio increased at doses >200 ppm compared with controls. Our results showed that the developmental biology of parasitoids exposed indirectly to IAA might be affected by high doses.