bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary conservation analysis increases the colocalization of predicted exonic splicing enhancers in the BRCA1gene with missense sequence changes and in-frame deletions, but not polymorphisms
Authors: Pettigrew Christopher , Wayte Nicola , Lovelock Paul K , Tavtigian Sean V , Chenevix-Trench Georgia , Spurdle Amanda B , Brown Melissa A
Published: September 2005

Introduction

Aberrant pre-mRNA splicing can be more detrimental to the function of a gene than changes in the length or nature of the encoded amino acid sequence. Although predicting the effects of changes in consensus 5' and 3' splice sites near intron:exon boundaries is relatively straightforward, predicting the possible effects of changes in exonic splicing enhancers (ESEs) remains a challenge.

Methods

As an initial step toward determining which ESEs predicted by the web-based tool ESEfinder in the breast cancer susceptibility gene BRCA1 are likely to be functional, we have determined their evolutionary conservation and compared their location with known BRCA1 sequence variants.

Results

Using the default settings of ESEfinder, we initially detected 669 potential ESEs in the coding region of the BRCA1 gene. Increasing the threshold score reduced the total number to 464, while taking into consideration the proximity to splice donor and acceptor sites reduced the number to 211. Approximately 11% of these ESEs (23/211) either are identical at the nucleotide level in human, primates, mouse, cow, dog and opossum Brca1 (conserved) or are detectable by ESEfinder in the same position in the Brca1 sequence (shared). The frequency of conserved and shared predicted ESEs between human and mouse is higher in BRCA1 exons (2.8 per 100 nucleotides) than in introns (0.6 per 100 nucleotides). Of conserved or shared putative ESEs, 61% (14/23) were predicted to be affected by sequence variants reported in the Breast Cancer Information Core database. Applying the filters described above increased the colocalization of predicted ESEs with missense changes, in-frame deletions and unclassified variants predicted to be deleterious to protein function, whereas they decreased the colocalization with known polymorphisms or unclassified variants predicted to be neutral.

Conclusion

In this report we show that evolutionary conservation analysis may be used to improve the specificity of an ESE prediction tool. This is the first report on the prediction of the frequency and distribution of ESEs in the BRCA1 gene, and it is the first reported attempt to predict which ESEs are most likely to be functional and therefore which sequence variants in ESEs are most likely to be pathogenic.
Quantifying bedside-derived imaging of microcirculatory abnormalities in septic patients: a prospective validation study
Authors: Boerma E Christiaan , Mathura Keshen R , van der Voort Peter HJ , Spronk Peter E , Ince Can
Published: September 2005

Introduction

The introduction of orthogonal polarization spectral (OPS) imaging in clinical research has elucidated new perspectives on the role of microcirculatory flow abnormalities in the pathogenesis of sepsis. Essential to the process of understanding and reproducing these abnormalities is the method of quantification of flow scores.

Methods

In a consensus meeting with collaboraters from six research centres in different fields of experience with microcirculatory OPS imaging, premeditated qualifications for a simple, translucent and reproducible way of flow scoring were defined. Consecutively, a single-centre prospective observational validation study was performed in a group of 12 patients with an abdominal sepsis and a new stoma. Flow images of the microcirculation in vascular beds of the sublingual and stoma region were obtained, processed and analysed in a standardised way. We validated intra-observer and inter-observer reproducibility with kappa cross-tables for both types of microvascular beds.

Results

Agreement and kappa coefficients were >85% and >0.75, respectively, for interrater and intrarater variability in quantification of flow abnormalities during sepsis, in different subsets of microvascular architecture.

Conclusion

Semi-quantitative analysis of microcirculatory flow, as described, provides a reproducible and transparent tool in clinical research to monitor and evaluate the microcirculation during sepsis.
Transient conduction analytical solutions for testing of building energy simulation programs
Authors: Xiao Dongyi , Spitler Jeffrey D , Rees Simon J , Dougherty Ronald L
Published: September 2005

As part of a recent effort to develop an analytical verification test suite for building fabric models of whole building energy simulation programs, two new transient conduction analytical tests have been developed. These new tests make it possible to use boundary conditions that are typical of real building conduction heat transfer conditions. This paper describes the corresponding analytical models and the derivation of the solutions. Some details of existing tests are given for the sake of completeness. The zone description and parameter requirements necessary to apply the tests, along with results from two test programs, are also presented.

Practical application: Building energy simulation programs are being increasingly relied upon by practicing engineers for design, performance evaluation and in demonstrating regulation compliance. Accordingly there is a significant demand for simulation model and computer program quality assurance. These tests can be used by developers and users to demonstrate a program’s ability to calculate conduction heat transfer processes.
Inhibitory effect of all-trans retinoic acid on androgen-induced growth of mouse seminal vesicles in vivo and its mechanism
Authors: Sato Hideki , Tanji Nozomu , Tsuji Motomu , Terada Nobuyuki , Yamasaki Kenshi , Wang Jianbo , Sakayama Kenshi , Yokoyama Masayoshi
Published: September 2005

We examined the effect of all-trans retinoic acid (ATRA) on the androgen-induced growth of mouse seminal vesicles (SVs) in vivo and its mechanisms. Testosterone propionate (TP) alone or with ATRA was injected daily into adult castrated BALB/c mice. Injections of ATRA significantly inhibited the TP-induced growth of SVs in terms of wet weight and DNA synthesis by a pair of SVs evaluated by [3H]thymidine uptake. The bromodeoxyuridine labelling index showed that ATRA inhibited the proliferation of both epithelial and stromal cells. Immunoreactivity for retinoic acid receptor-a was found in the basal epithelial cells. Injections of ATRA affected neither 5a-reductase activity nor the expression of mRNAs for TGF-b1, 2 and 3 and TGF-b receptor 1 and 2 in the SVs. However, androgen receptor (AR) binding assays and Western blotting revealed a decrease in AR without a change in ligand-binding affinity. The present study showed that retinoid inhibited the androgen-induced growth of mouse SVs in vivo, and suggests that a decrease in AR is one of its mechanisms.
The effect of ethanol and nitric oxide on the N-nitrosodimethylamine formation in HepG2 cells overexpressing CYP2E1
Authors: Jabloński Jakub , Holownia Adam , Jablońska Ewa , Moniuszko-Jakoniuk Janina , Braszko Jan , Iwanowska Jolanta , Marcińczyk Magda
Published: September 2005

The influence of lipopolysaccharide (LPS) and the nitric oxide synthase (iNOS) inhibitor-N-nitro-L-arginine on the formation of N-nitrosodimethylamine (NDMA) by HepG2 cells, engineered to overexpress CYP2E1, was assessed and compared with data from empty vector-transfected cells. HepG2 cells produced significant amounts of NDMA but its levels in the culture media of cells overexpressing CYP2E1 was significantly lower than in empty-vector transfected cells. LPS increased the formation of NDMA, the expression of the iNOS and the production of the nitric oxide (NO). On the other hand, L-NAME significantly decreased NDMA levels. The results above indicate that the synthesis of NDMA by HepG2 cells depends on NO production. Furthermore, ethanol did not affect iNOS expression but decreased NDMA levels in CYP2E1-transfected cells below the detection limit. It is probably caused by the increased N-nitrosodimethylamine metabolism. In conclusion, HepG2 cells' ability to synthesize NO with simultaneous CYP2E1 activation may lead to an increase of carcinogenic products of the NDMA metabolism.
Econazole induces increases in free intracellular Ca2+ concentrations in human osteosarcoma cells
Authors: Chang H-T , Liu C-S , Chou C-T , Hsieh C-H , Chang C-H , Chen W-C , Liu S-I , Hsu S-S , Chen J-S , Jiann B-P , Huang J-K , Jan C-R
Published: September 2005

Econazole is an antifungal drug with different in vitro effects. However, econazole's effect on osteoblast like cells is unknown. In human MG63 osteosarcoma cells, the effect of econazole on intracellular Ca2+ concentrations ([Ca2+]i) was explored by using fura-2. At a concentration of 0.1 μM, econazole started to cause a rise in [Ca2+]i in a concentration-dependent manner. Econazole-induced [Ca2+]i rise was reduced by 74% by removal of extracellular Ca2+. The econazole-induced Ca2+ influx was mediated via a nimodipine-sensitive pathway. In Ca2+ free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ ATPase, caused a [Ca2+]i rise, after which the increasing effect of econazole on [Ca2+]i was abolished. Pretreatment of cells with econazole to deplete Ca2+ stores totally prevented thapsigargin from releasing Ca2+. U73122, an inhibitor of phospholipase C, abolished histamine (an inositol 1,4,5-trisphosphate dependent Ca2+ mobilizer)-induced, but not econazoleinduced, [Ca2+]i rise. Econazole inhibited 76% of thapsigargin-induced store-operated Ca2+ entry. These findings suggest that in MG63 osteosarcoma cells, econazole increases [Ca2+]i by stimulating Ca2+ influx and Ca2+ release from the endoplasmic reticulum via a phospholipase C-independent manner. In contrast, econazole acts as a potent blocker of store-operated Ca2+ entry.
Inflammatory heart disease: a role for cytokines
Authors: Fairweather D , Rose N R
Published: September 2005

Inflammatory heart disease is a rising concern worldwide. Similar mechanisms link autoimmune diseases, including the association of increased disease with proinflammatory cytokines and the importance of regulatory mechanisms in the control of chronic inflammation. Many pathogens including bacteria, protozoa and viruses have been associated with heart disease in patients, and are able to induce similar disease in animal models. Recognition of pathogens by the innate immune system leads to release of proinflammatory cytokines that both reduce infection and increase chronic inflammatory heart disease. Elevated levels of proinflammatory cytokines are able to overcome tolerance to chronic disease, indicating that environmental factors are important in determining progression to chronic heart disease. Understanding the mechanisms leading to chronic heart disease will be critical for developing effective therapies to reduce cardiac dysfunction and heart failure.
Autoimmune myocarditis and dilated cardiomyopathy: focus on cardiac autoantibodies
Authors: Caforio A LP , Daliento L , Angelini A , Bottaro S , Vinci A , Dequal G , Tona F , Iliceto S , Thiene G , McKenna W J
Published: September 2005

Criteria of organ-specific autoimmunity are fulfilled in a subset of patients with myocarditis/dilated cardiomyopathy (DCM). In particular, circulating heart-reactive autoantibodies are found in patients and symptom-free relatives. These autoantibodies are directed against multiple antigens, some of which are expressed in the heart (organ-specific), others in heart and some skeletal muscle fibres (partially-heart specific) or in heart and skeletal muscle (muscle-specific). Distinct autoantibodies have different frequency in disease and normal controls. Different techniques detect one or more antibodies, thus they cannot be used interchangeably for screening. It is unknown whether the same patients produce more antibodies or different patient groups develop autoimmunity to distinct antigens. IgG antibodies, shown to be cardiac and disease-specific for myocarditis/DCM, can be used as autoimmune markers for identifying patients in whom immunosuppression may be beneficial and relatives at risk. Some autoantibodies may also have a functional role, but further work is needed.
Cardiac involvement in the antiphospholipid syndrome
Authors: Tenedios F , Erkan D , Lockshin M D
Published: September 2005

Antiphospholipid syndrome (APS) is a systemic autoimmune disease, associated with a hypercoagulable state and fetal loss and with other clinical manifestations including cardiac involvement. Cardiac manifestations of APS are valve abnormalities (valve thickening and vegetations), occlusive arterial disease (atherosclerosis and myocardial infarction), intracardiac emboli, ventricular dysfunction, and pulmonary hypertension. Antiphospholipid antibodies (aPLs) may have a role in the accelerated atherosclerotic arterial disease observed in APS, related to their ability to induce endothelial activation. aPLs have been incriminated in the pathogenesis of heart valve lesions in APS patients. Markers of endothelial cell activation are up-regulated with prominent deposition of aPL in heart valves, suggesting aPL deposition initiates an inflammatory process that recruits complement leading to the valve lesion. Autoantibody-mediated endothelial cell activation probably plays a role in sustaining a proadhesive, proinflammatory, and procoagulant phenotype. The heterogeneity of APS clinical manifestations is likely linked to the varied effects that aPL can induce on endothelial cells and to the different functions that endothelial cells display depending on the anatomic localization.
From rheumatic fever to Libman-Sacks endocarditis: is there any possible pathogenetic link?
Authors: Blank M , Aron-Maor A , Shoenfeld Y
Published: September 2005

The heart lesions of rheumatic fever and the heart involvement in antiphospholipid syndrome (APS), have different clinical pictures. Yet, there are several common characteristics linking both diseases: 1) central nervous system (CNS) and heart involvement; 2) molecular mimicry between the a pathogen and the origin of the disease; 3) cross reacting antibodies between the pathogen and self molecules; 4) endothelial cell activation in the ‘crime-area’ i.e., the valves; 5) some of the patients with RF have circulating antiphospholipid antibodies, while APS may be associated with streptococcal infection; and 6) recently, a cross-reactivity between antibodies directed to the streptococcal M-protein and its synthetic derivative in rheumatic fever (RF) and antibodies derived from APS patients targeting the beta-2-glycoprotein-I (β2GPI) and a β2GPI related synthetic peptide. In the current paper, we summarize the possible links between the heart involvement in RF and APS.
Heart involvement and systemic sclerosis
Authors: Ferri C , Giuggioli D , Sebastiani M , Colaci M , Emdin M
Published: September 2005

Scleroderma heart involvement (SHI) is often manifest, and virtually always present when accurately searched and holds a significant prognostic value. Myocardial involvement by patchy fibrosis (secondary to both repeated ischaemia and immunoinflammatory damage) leads to ventricular diastolic dysfunction, whereas right ventricle overload and failure may complicate pulmonary hypertension. Left ventricular systolic dysfunction is present in a minority of patients, namely those presenting atherosclerotic coronary artery disease and/or arterial hypertension, sometimes triggered by sclerodermic renal involvement. Dysrhythmias and conduction disturbances are considered an hallmark of SHI, facilitated by autonomic dysfunction. SHI is frequently linked to parenchimal and/or vascular lung disease; they determine symptom occurrence, particularly dyspnoea, fatigue, palpitations and chest pain when pericardium is affected. Accurate cardiologic baseline screening and subsequent follow-up are mandatory in all patients, initially consisting in some noninvasive diagnostic procedures: visit, electrocardiogram (EKG), chest X-ray, Doppler-echocardiography. When needed, these examinations should be integrated by EKG Holter-monitoring, cardiopulmonary stress tests, cardiac magnetic resonance imaging, nuclear studies of myocardial function and perfusion, cardiac catheterization to better estimate pulmonary hypertension, and cardiac natriuretic hormone evaluation. Several vasodilator approaches (prostacycline or NO/endothelin) may counteract the microvascular dysfunction at peripheral and cardiopulmonary level, and fight the sequelae of pulmonary hypertension.
Behçet’s disease and cardiovascular involvement
Authors: Atzeni F , Sarzi-Puttini P , Doria A , Boiardi L , Pipitone N , Salvarani C
Published: September 2005

Behcet’s disease (BD) is a multisystem disease of unknown etiology characterized by chronic relapsing orogenital ulcers, uveitis and systemic involvement including articular, gastrointestinal, cardiopulmonary, neurological and vascular pathology. The incidence and nature of cardiac involvement are not clearly elucidated. Cardiovascular manifestations have been reported in 7-46% of patients and mortality occurs in up to 20% of those patients with marked vascular involvement. Sporadic cases of endocarditis, myocarditis, pericarditis, acute myocardial infarction, aortic aneurysm, ventricular thrombosis, congestive cardiomyopathy and valvular dysfunction have been reported. This review discusses the general aspects of the pathogenic mechanisms and clinical features cardiovascular involvement in BD, and provides the data of cardiovascular involvement in a cohort of Italian BD patients.
T cells and cytokines in atherogenesis
Authors: Liuzzo G , Giubilato G , Pinnelli M
Published: September 2005

Recent findings suggest that inflammation plays a key role in atherosclerosis from the earliest stage of lesion initiation, to the ultimate complication of thrombosis. In patients who died because of acute coronary syndromes (ACS), coronary atherosclerotic plaques are characterized by the presence of macrophages, and to a lesser extent T-lymphocytes, at the immediate site of either plaque rupture or superficial erosion. The rupture-related inflammatory cells are activated, indicating ongoing inflammation. ACS patients are also characterized by activated circulating lymphocytes, monocytes and neutrophils, and by increased concentrations of proinflammatory cytokines and of the highly sensitive acute phase reactant C-reactive protein. Interestingly, an unusual subset of T cells, CD4+CD28null T cells, involved in vascular complication of rheumatoid arthritis because of their functional profile predisposing for vascular injury, are expanded in the peripheral blood and infiltrate the coronary lesions of ACS patients. The presence of activated T lymphocytes implies antigenic stimulation, but the nature of such antigen(s) remains to be investigated. Several autoantigens expressed in the atherosclerotic plaque, including oxidized LDL and heat shock proteins, and infectious agents are able to elicit an immune response. The inflammatory component is not localized to the ‘culprit’ plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium.
Innate immunity and atherogenesis
Authors: Rattazzi M , Faggin E , Bertipaglia B , Pauletto P
Published: September 2005

Atherosclerosis is recognized as the pathological basis of cardiovascular disease (CVD) and recent advances in basic science have shown that it should be considered as a chronic inflammatory process. Both elements of the innate and the adaptive immunity appear to be actively involved in atherogenesis. In fact, the potential role played by pattern-recognition receptors (Toll-like receptors and scavenger receptors), cytokines (such as IL-1, IL-6, TNFa), chemokines and pentraxines (such as CRP and PTX3) represents an emerging field of investigation in atherogenesis. In the near future we expect a better definition of the real biological and clinical impact on CVD of these mediators. On one side, they could become useful to complement traditional risk factors, in order to identify new categories of subjects prone to CVD development. On the other, they could become an additional potential target for therapeutic strategies.
COX-2 and prostaglandins in atherosclerosis
Authors: Cipollone F
Published: September 2005

Arachidonic acid metabolism is involved in acute ischemic syndromes affecting the coronary or cerebrovascular territory, as demonstrated by biochemical measurements of eicosanoid biosynthesis and the results of inhibitor trials in these settings. In particular, the efficacy of low-dose aspirin in reducing the complications of acute ischemic syndromes has focused attention on the cyclooxygenase (COX) pathway of arachidonic acid metabolism and its products, collectively termed prostanoids.

Two cyclooxygenase (COX)-isozymes have been characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression, tissue distribution, substrate specificity and preferential coupling to upstream and downstream enzymes. While the role of platelet COX-1 in acute ischemic diseases is firmly established, the role of COX-2 in atherothrombosis is still uncertain. Studies from our group suggest that variable expression of upstream and downstream enzymes in the prostanoid biosynthesis may represent important determinants of the functional consequences of COX-2 expression and inhibition in different clinical settings.
Oxidant stress, inflammation and atherogenesis
Authors: Davì G , Falco A
Published: September 2005

Low-grade inflammation, enhanced oxidant stress and lipid peroxidation have been shown in association with increased cardiovascular risk associated with cardiovascular events. It has been hypothesized that the low-grade inflammatory state characterizing metabolic disorders such as obesity, hypercholesterolemia, type 2 diabetes mellitus and homozygous homocystinuria may be the primary trigger of thromboxane-dependent platelet activation mediated, at least in part, through enhanced lipid peroxidation. Interestingly, as the clinical course of systemic lupus erythematosus (SLE), in particular in the presence of antiphospholipid antibodies, may be complicated by vascular disease, several mechanism contributing to vascular complications have been documented also in this setting, including enhanced lipid peroxidation and thromboxane biosynthesis.

Although epidemiological studies show an inverse relationship between antioxidant vitamin intake and cardiovascular disease, several clinical trials have obtained conflicting results on the effects of vitamin E on the risk of cardiovascular events. The availability of analytical tools for measuring F2-isoprostane biosynthesis in man has improved our understanding of the interplay between lipid peroxidation and low-grade inflammation. The use of F2-isoprostane as a biochemical end-point for dose-finding studies may allow reassessing the adequacy of vitamin supplementation in different clinical settings.
Pharmacological modulation of plaque instability
Authors: Mezzetti A
Published: September 2005

Atherosclerotic plaque rupture is promoted by metalloproteinase (MMP)-2 and MMP-9, enzymes that degrade the fibrous cap leading to plaque erosion. MMP biosynthesis is mediated by prostaglandin (PG)E2, the product of cyclooxygenase (COX)-2/inducible PGE synthase (mPGES) activity. We have recently reported the overexpression of COX-2/mPGES-1 in vulnerable plaques as a basis of MMP-mediated plaque instability.

Hypercholesterolemia and hypertension are two important risk factors for atherosclerosis. Recent trial showed that statins and AT1 receptor blockers significantly reduce the incidence of cardiovascular events in humans. Since anti-inflammatory effects have been reported in association to therapy with statins or AT1 receptor blockers, in two different studies we hypothesized that these drugs can stabilize atherosclerotic plaques through modulation of COX-2/mPGES-1-dependent MMP biosynthesis. Our data demonstrated the stabilizing effect of atherosclerotic plaques by simvastatin or irbesartan, that is due, at least in part, to the reduction of inflammatory burden and suppression of PGE2-dependent metalloproteinases release.
Bisphosphonates and atherosclerosis: why?
Authors: Bevilacqua M , Dominguez L J , Rosini S , Barbagallo M
Published: September 2005

The increasing knowledge on bone calcification processes has revealed some similarities with vascular tissue, where calcifications of arteries and cardiac valves contribute to several cardiovascular problems, such as heart failure, systolic hypertension, and myocardial and peripheral ischemic disease. Bisphosphonates have been used extensively for over two decades for the treatment of diseases associated with excessive bone resorption, i.e., osteoporosis, osteolytic bone metastasis, hypercalcemia and Paget’s disease, by blocking osteoclastic function. Etidronate, pamidronate and clodronate has been shown to inhibit the development of experimental atherosclerosis, and proposed mechanisms for this action include inhibition of arterial calcification and lipid accumulation, degradation of atherogenic LDL-cholesterol and reduced foam cell formation. Bisphosphonates inhibit various enzymes involved in cholesterol biosynthesis and suppress macrophages in atheromatous lesions. The possibility of pharmacological agents that effectively treat both osteoporosis and atherosclerosis is attractive, however, current evidence is not conclusive and further research is necessary to confirm these actions in the clinical setting.
Tumor necrosis factor-a, biologic agents and cardiovascular risk
Authors: Sarzi-Puttini P , Atzeni F , Doria A , Iaccarino L , Turiel M
Published: September 2005

The increased risk of premature cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients may depend on traditional risk factors but may also be attributable to RA-specific risk factors such as disease-related dyslipidemia, or cytokines such as tumor necrosis factor-a (TNF-a). TNF-a is a proinflammatory cytokine that can produce widespread deleterious effects when expressed in large amounts. It is produced in the heart by both cardiac myocytes and resident macrophages under conditions of cardiac stress, and is thought to be responsible for many of the untoward manifestations of cardiac disease. TNF-a may play a role in the triggering and perpetuation of atherosclerosis. Treatment with biologic agents directed against TNF-a has significant clinical benefits in inflammatory diseases such as RA and may be able to reduce cardiovascular risk. The disappointing results of the recent studies to antagonize TNF-a in CVD may have various explanations. However, the effects of TNF-a blockers on incident cases of congestive heart failure (CHF) in RA remains controversial. Due to the lack of evidence of a beneficial effect of anti-TNF-a agents in treatment of CHF, they should not be used to treat patients with New York Heart Association (NYHA) class III or IV heart failure.
Buyers Versus Sellers: How They Differ in Their Responses to Framed Outcomes
Authors: Monga Ashwani , Zhu Rui (Juliet)
Published: September 2005

Consumers’ reactions to a difference in price can depend on how it is framed. If buyers interpret paying $60 rather than $65 as getting a $5 discount, then they are likely to consider paying $60 to be a gain and paying $65 to be a nongain. Alternatively, if they interpret having to pay $65 rather than $60 as incurring a $5 penalty, then they may consider paying $60 to be a nonloss and paying $65 to be a loss. Similarly, sellers can also experience gains, nongains, nonlosses, and losses. This article suggests that buyers are prevention focused and consequently place a greater emphasis on loss‐related frames, whereas sellers are promotion focused and place a greater emphasis on gain‐related frames. Therefore, for equivalent positive outcomes, buyers feel better about nonlosses, but sellers feel better about gains. For equivalent negative outcomes, buyers feel worse about losses, but sellers feel worse about nongains. These effects, however, disappear when there is little motivation to process information about the monetary transaction.
Cultural Chameleons: Biculturals, Conformity Motives, and Decision Making
Authors: Briley Donnel A. , Morris Michael W. , Simonson Itamar
Published: September 2005

Prior research suggests that bicultural individuals (i.e., individuals with 2 distinct sets of cultural values) shift the values they espouse depending on cues such as language. The authors examined whether the effects of language extend to a potentially less malleable domain, behavioral decisions, exploring the extent to which bilingual individuals shift the underlying strategies used to resolve choice problems. Although past research has explained language‐induced shifts in terms of knowledge accessibility principles, the motivation to conform to observers’ norms can also drive these shifts. This article focuses on shifts in the general strategy of avoiding losses rather than pursuing gains, which is more often exhibited by Chinese than by Westerners. Five studies of Hong Kong bicultural individuals found that language manipulation (Cantonese vs. English) increases tendencies to choose compromise options in a product decision task, endorse associated decision guidelines that advocate moderation as opposed to extreme paths, defer decision making in problems where it can be postponed, and endorse decision guidelines that advocate caution rather than decisive action. A motivational explanation of these effects was confirmed.
Viewing a Map Versus Reading a Description of a Map: Modality‐Specific Encoding of Spatial Information
Authors: Tlauka Michael , Keage Hannah , Clark C. Richard
Published: September 2005

This study investigated whether brain neural activity that accompanied the processing of previously learned map information was influenced by the modality in which the spatial parameters of the maps were originally learned. Participants learned a map by either viewing it directly or by reading an equivalent verbal description. Following learning, the participants' ability to use their spatial knowledge was tested in a spatial orientation task. Electrophysiological recordings identified significant effects of prior learning modality on event‐related brain activity within 300 ms following the presentation of map orientation instructions. The results indicate that modality‐specificity in spatial memory is present at a very early stage of processing.
Convergence results for compound Poisson distributions and applications to the standard Luria–Delbrück distribution
Authors: Möhle M.
Published: September 2005

We provide a scaling for compound Poisson distributions that leads (under certain conditions on the Fourier transform) to a weak convergence result as the parameter of the distribution tends to infinity. We show that the limiting probability measure belongs to the class of stable Cauchy laws with Fourier transformt↦ exp(−c|t|− iatlog|t|). We apply this convergence result to the standard discrete Luria–Delbrück distribution and derive an integral representation for the corresponding limiting density, as an alternative to that found in a closely related paper of Kepler and Oprea. Moreover, we verify local convergence and we derive an integral representation for the distribution function of the limiting continuous Luria–Delbrück distribution.
Sensitivity of hidden Markov models
Authors: Mitrophanov Alexander Yu. , Lomsadze Alexandre , Borodovsky Mark
Published: September 2005

We derive a tight perturbation bound for hidden Markov models. Using this bound, we show that, in many cases, the distribution of a hidden Markov model is considerably more sensitive to perturbations in the emission probabilities than to perturbations in the transition probability matrix and the initial distribution of the underlying Markov chain. Our approach can also be used to assess the sensitivity of other stochastic models, such as mixture processes and semi-Markov processes.
Minimum dynamic discrimination information models
Authors: Asadi Majid , Ebrahimi Nader , Hamedani G. G. , Soofi Ehsan S.
Published: September 2005

In this paper, we introduce the minimum dynamic discrimination information (MDDI) approach to probability modeling. The MDDI model relative to a given distribution G is that which has least Kullback-Leibler information discrepancy relative to G, among all distributions satisfying some information constraints given in terms of residual moment inequalities, residual moment growth inequalities, or hazard rate growth inequalities. Our results lead to MDDI characterizations of many well-known lifetime models and to the development of some new models. Dynamic information constraints that characterize these models are tabulated. A result for characterizing distributions based on dynamic Rényi information divergence is also given.
A stochastic competing-species model and ergodicity
Authors: Chen Zengjing , Kulperger Reg
Published: September 2005

We consider a classic competing-species model with the rates changed to include Gaussian white noise. We show that if the noise is not too large, then the stochastic version is ergodic. An explicit relation between the noise and the original competing-species parameters gives a sufficient condition for ergodicity.
Transient solution to the time-dependent multiserver Poisson queue
Authors: Margolius B. H.
Published: September 2005

We derive an integral equation for the transient probabilities and expected number in the queue for the multiserver queue with Poisson arrivals, exponential service for time-varying arrival and departure rates, and a time-varying number of servers. The method is a straightforward application of generating functions. We can express pĉ−1(t), the probability that ĉ − 1 customers are in the queue or being served, in terms of a Volterra equation of the second kind, where ĉ is the maximum number of servers working during the day. Each of the other transient probabilities is expressed in terms of integral equations in pĉ−1(t) and the transition probabilities of a certain time-dependent random walk. In this random walk, the rate of steps to the right equals the arrival rate of the queue and the rate of steps to the left equals the departure rate of the queue when all servers are busy.
On increasing-failure-rate random variables
Authors: Ross Sheldon M. , Shanthikumar J. George , Zhu Zegang
Published: September 2005

We provide sufficient conditions for the following types of random variable to have the increasing-failure-rate (IFR) property: sums of a random number of random variables; the time at which a Markov chain crosses a random threshold; the time until a random number of events have occurred in an inhomogeneous Poisson process; and the number of events of a renewal process, and of a general counting process, that have occurred by a randomly distributed time.
Conditional tail expectations for multivariate phase-type distributions
Authors: Cai Jun , Li Haijun
Published: September 2005

The conditional tail expectation in risk analysis describes the expected amount of risk that can be experienced given that a potential risk exceeds a threshold value, and provides an important measure of right-tail risk. In this paper, we study the convolution and extreme values of dependent risks that follow a multivariate phase-type distribution, and derive explicit formulae for several conditional tail expectations of the convolution and extreme values for such dependent risks. Utilizing the underlying Markovian property of these distributions, our method not only provides structural insight, but also yields some new distributional properties of multivariate phase-type distributions.
Stopping at the maximum of geometric Brownian motion when signals are received
Authors: Guo X. , Liu J.
Published: September 2005

Consider a geometric Brownian motion Xt(ω) with drift. Suppose that there is an independent source that sends signals at random times τ1 < τ2 < ⋯. Upon receiving each signal, a decision has to be made as to whether to stop or to continue. Stopping at time τ will bring a reward Sτ, where St = max(max0≤u≤tXu, s) for some constant s ≥ X0. The objective is to choose an optimal stopping time to maximize the discounted expected reward E[e−rτiSτi | X0 = x, S0 = s], where r is a discount factor. This problem can be viewed as a randomized version of the Bermudan look-back option pricing problem. In this paper, we derive explicit solutions to this optimal stopping problem, assuming that signal arrival is a Poisson process with parameter λ. Optimal stopping rules are differentiated by the frequency of the signal process. Specifically, there exists a threshold λ* such that if λ>λ*, the optimal stopping problem is solved via the standard formulation of a ‘free boundary’ problem and the optimal stopping time τ* is governed by a threshold a* such that τ* = inf{τn: Xτn≤a*Sτn}. If λ≤λ* then it is optimal to stop immediately a signal is received, i.e. at τ* = τ1. Mathematically, it is intriguing that a smooth fit is critical in the former case while irrelevant in the latter.
Width of a scale-free tree
Authors: Katona Zsolt
Published: September 2005

Consider the random graph model of Barabási and Albert, where we add a new vertex in every step and connect it to some old vertices with probabilities proportional to their degrees. If we connect it to only one of the old vertices then this will be a tree. These graphs have been shown to have a power-law degree distribution, the same as that observed in some large real-world networks. We are interested in the width of the tree and we show that it is at the nth step; this also holds for a slight generalization of the model with another constant. We then see how this theoretical result can be applied to directory trees.
The moment problem for some Wiener functionals: corrections to previous proofs (with an appendix by H. L. Pedersen)
Authors: Hörfelt Per
Published: September 2005

In this paper, we describe a class of Wiener functionals that are ‘indeterminate by their moments’, that is, whose distributions are not uniquely determined by their moments. In particular, it is proved that the integral of a geometric Brownian motion is indeterminate by its moments and, moreover, shown that previous proofs of this result are incorrect. The main result of this paper is based on geometric inequalities in Gauss space and on a generalization of the Krein criterion due to H. L. Pedersen.
Resolving embryonic blood cell fate choice inDrosophila:interplay of GCM and RUNX factors
Authors: Bataillé Laetitia , Augé Benoit , Ferjoux Géraldine , Haenlin Marc , Waltzer Lucas
Published: September 2005

The differentiation of Drosophila embryonic blood cell progenitors(prohemocytes) into plasmatocytes or crystal cells is controlled by lineage-specific transcription factors. The related proteins Glial cells missing (GCM) and GCM2 control plasmatocyte development, whereas the RUNX factor Lozenge (LZ) is required for crystal cell differentiation. We have investigated the segregation process that leads to the formation of these two cell types, and the interplay between LZ and GCM/GCM2. We show that,surprisingly, gcm is initially expressed in all prohemocytes but is rapidly downregulated in the anterior-most row of prohemocytes, which then initiates lz expression. However, the lz+ progenitors constitute a mixed-lineage population whose fate depends on the relative levels of LZ and GCM/GCM2. Notably, we demonstrate that GCM/GCM2 play a key role in controlling the size of the crystal cell population by inhibiting lz activation and maintenance. Furthermore, we show that prohemocytes are bipotent progenitors, and that downregulation of gcm/gcm2 is required for lz-induced crystal cell formation. These results provide new insight into the mechanisms controlling Drosophila hematopoiesis and establish the basis for an original model for the resolution of the choice of blood cell fate.
A microtubule-binding Rho-GEF controls cell morphology during convergent extension ofXenopus laevis
Authors: Kwan Kristen M. , Kirschner Marc W.
Published: September 2005

During Xenopus development, convergent extension movements mediated by cell intercalation drive axial elongation. While many genes required for convergent extension have been identified, little is known of regulation of the cytoskeleton during these cell movements. Although microtubules are required for convergent extension, this applies only to initial stages of gastrulation, between stages 10 and 10.5. To examine the cytoskeleton more directly during convergent extension, we visualized actin and microtubules simultaneously in live explants using spinning disk confocal fluorescence microscopy. Microtubule depolymerization by nocodazole inhibits lamellipodial protrusions and cell-cell contact, thereby inhibiting convergent extension. However, neither taxol nor vinblastine, both of which block microtubule dynamics while stabilizing a polymer form of tubulin, inhibits lamellipodia or convergent extension. This suggests an unusual explanation:the mass of polymerized tubulin, not dynamics of the microtubule cytoskeleton,is crucial for convergent extension. Because microtubule depolymerization elicits striking effects on actin-based protrusions, the role of Rho-family GTPases was tested. The effects of nocodazole are partially rescued using dominant negative Rho, Rho-kinase inhibitor, or constitutively active Rac,suggesting that microtubules regulate small GTPases, possibly via a guanine-nucleotide exchange factor. We cloned full-length XLfc, a microtubule-binding Rho-GEF. Nucleotide exchange activity of XLfc is required for nocodazole-mediated inhibition of convergent extension; constitutively active XLfc recapitulates the effects of microtubule depolymerization. Morpholino knockdown of XLfc abrogates the ability of nocodazole to inhibit convergent extension. Therefore, we believe that XLfc is a crucial regulator of cell morphology during convergent extension, and microtubules limit its activity through binding to the lattice.
Activation of protein kinase CβI constitutes a new neurotrophic pathway for deafferented spiral ganglion neurons
Authors: Lallemend François , Hadjab Saïda , Hans Grégory , Moonen Gustave , Lefebvre Philippe P. , Malgrange Brigitte
Published: September 2005

In mammals, degeneration of peripheral auditory neurons constitutes one of the main causes of sensorineural hearing loss. Unfortunately, to date, pharmacological interventions aimed at counteracting this condition have not presented complete effectiveness in protecting the integrity of cochlear neural elements. In this context, the protein kinase C (PKC) family of enzymes are important signalling molecules that play a role in preventing neurodegeneration after nervous system injury. The present study demonstrates, for the first time, that the PKC signalling pathway is directly neurotrophic to axotomised spiral ganglion neurons (SGNs). We found that PKCβI was strictly expressed by postnatal and adult SGNs both in situ and in vitro. In cultures of SGNs, we observed that activators of PKC, such as phorbol esters and bryostatin 1, induced neuronal survival and neurite regrowth in a manner dependent on the activation of PKCβI. The neuroprotective effects of PKC activators were suppressed by pre-treatment with LY294002 (a PI3K inhibitor) and with U0126 (a MEK inhibitor), indicating that PKC activators promote the survival and neurite outgrowth of SGNs by both PI3K/Akt and MEK/ERK-dependent mechanisms. In addition, whereas combining the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) was shown to provide only an additive effect on SGN survival, the interaction between PKC and neurotrophin signalling gave rise to a synergistic increase in SGN survival. Taken together, the data indicate that PKCβI activation represents a key factor for the protection of the integrity of neural elements in the cochlea.
Netrin-1 regulates invasion and migration of mouse mammary epithelial cells overexpressing Cripto-1 in vitro and in vivo
Authors: Strizzi Luigi , Bianco Caterina , Raafat Ahmed , Abdallah Wissam , Chang Cindy , Raafat Dina , Hirota Morihisa , Hamada Shin , Sun Youping , Normanno Nicola , Callahan Robert , Hinck Lindsay , Salomon David
Published: September 2005

The neuronal guidance molecule, Netrin-1, has been suggested to play a role in the adhesion and migration of the mammary gland epithelium. Human and mouse Cripto-1 induce proliferation, migration, invasion and colony formation by epithelial cells in 3D matrices. Here we investigate whether Netrin-1 affects these Cripto-1-dependent activities in mouse mammary epithelial cells. Overexpression of Cripto-1 in EpH4 and HC-11 cells (EpH4/Cripto-1 or HC-11/Cripto-1) was associated with low expression of Netrin-1 and increased expression of its receptor Neogenin compared to that of wild-type cells. No change was observed in the expression of the other Netrin-1 receptor, UNC5H1. Treating EpH4/Cripto-1 or HC-11/Cripto-1 mammary cells with exogenous soluble Netrin-1 resulted in increased expression of E-cadherin and UNC5H1, decreased expression of vimentin and decreased activation of Akt as determined by western blotting. Colony formation by Eph4/Cripto-1 cells in 3D gels was significantly reduced in proximity to a Netrin-1 source, and mammary glands of transgenic mice overexpressing human Cripto-1 showed altered ductal growth in proximity to implanted Netrin-1-releasing pellets. Terminal end buds in the treated transgenic mice mammary glands also showed increased expression of E-cadherin and UNC5H1 and decreased expression of active Akt determined by immunohistochemistry. Together, these results suggest that regulation of Netrin-1 expression is important in regulating Cripto-1-dependent invasion and migration of mammary epithelial cells.
Negative regulation of retinal-neurite extension by β-catenin signaling pathway
Authors: Ouchi Yasuo , Tabata Yoko , Arai Ken-ichi , Watanabe Sumiko
Published: September 2005

Although there have been many studies on the regulation of neurite extension in mouse brain, such a mechanism in neural retina has remained to be clarified. To delineate the role of Wnt signaling in retinal development, we used a retrovirus-vector-mediated expression system to express various mutants forms of Wnt signaling members in E17.5 mouse retinal explant cultures, which are an excellent system to examine retinal development in vitro. Expression of constitutively active β-catenin or Lef-1 in the retinal cells resulted in failure of neurite extension, suggesting that β-catenin negatively regulates neurite extension in the retina through Lef-1 transcriptional activity. However, proliferation and differentiation of retinal cells into mature retinal cells such as rod-photoreceptor cells and Muller glia cells were not affected by perturbation of the Wnt-Lef-1 pathway. As in retinal cells, activation of β-catenin-Lef-1 signaling inhibited NGF-induced neurite extension in PC12 cells without affecting their proliferation. Interestingly, the Wnt-Lef-1 signaling pathway suppressed neurite extension without affecting Mek-1 signal activity, which is known to promote neurite extension. We found that MAPK was activated in retinal explant cultures, but that perturbation of MAPK signals did not affect neurite extension. Taken together, our data suggest that the Wnt pathway functions in proper neurite extension by opposing positive signals for promotion of neurite extension that are distinct from those of the MAPK pathway.