bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic association studies of interleukin-13 receptor α1 subunit gene polymorphisms in asthma and atopy
Authors: Konstantinidis A. K. , Barton S. J. , Sayers I. , Yang I. A. , Lordan J. L. , Rorke S. , Clough J. B. , Holgate S. T. , Holloway J. W.
Published: March 2007

Interleukin (IL)-13 plays a central role in asthma pathogenesis by binding to the IL-13 receptor, which is a heterodimer composed of the IL-13 receptor α1 subunit (IL-13Rα1) and IL-4Rα. The genetic diversity at the IL-13Rα1 gene (IL13RA1) locus on chromosome Xq24 was characterised and the association of identified polymorphisms with asthma and atopy phenotypes examined.

The promoter and coding region ofIL13RA1were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (each containing at least two asthmatic siblings) and 182 nonasthmatic control subjects. Genetic association was determined using case–control and transmission disequilibrium test analyses.

Two common polymorphisms were identified, a newly found thymidine (T) to guanine (G) transition of nucleotide -281 (-281T>G) single nucleotide polymorphism in theIL13RA1promoter and the previously described 1365A>G variant in theIL13RA1proximal 3′ untranslated region. No significant association of either -281T>G or 1365A>G with risk of asthma or atopy phenotypes was found, apart from a suggestive association between theIL13RA1-281T/1365A haplotype and raised total serum immunoglobulin E levels in adult female asthmatics.

These findings indicate that the interleukin-13 receptor α1 subunit gene -281T>G and 1365A>G polymorphisms do not contribute to asthma susceptibility or severity, although the interleukin-13 receptor α1 subunit gene locus might be involved in the control of immunoglobulin E production.
A proposed classification system of central airway stenosis
Authors: Freitag L. , Ernst A. , Unger M. , Kovitz K. , Marquette C. H.
Published: March 2007

Tracheobronchial stenosis, a serious problem in adults and children, has multiple causes and has been treated in many ways. While developing an international multicentre study to evaluate efficacy of airway stents, it was realised that no adequate description of central airway stenosis regarding type, location and degree has been published. Thus, comparing results of different treatment modalities in different centres has been difficult due to a lack of uniformity of classification. Reports are typically descriptive and precise classification schemes have not adequately addressed either for the trachea or the main bronchi.

A standardised classification scheme was proposed with descriptive images and diagrams for rapid and uniform classification of central airway stenosis. The present authors’ system divides stenosis into structural and dynamic types and further classifies the disease by degree of stenosis, location and transition zone.

Multiple sites can be described and each is transformed into a simple numerical scoring system prompted by a diagram, which can be easily captured for subsequent uniform analysis across sites.

A pilot validation of the system, with 18 pulmonologists of varying training background, showed strong precision and agreement between observers. Such a system will enhance the ability to study the effectiveness of treatment modalities for central airway stenosis.
The transforming growth factor-β/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension
Authors: Zakrzewicz A. , Kouri F. M. , Nejman B. , Kwapiszewska G. , Hecker M. , Sandu R. , Dony E. , Seeger W. , Schermuly R. T. , Eickelberg O. , Morty R. E.
Published: March 2007

Mutations in genes encoding members of the transforming growth factor (TGF)-β superfamily have been identified in idiopathic forms of pulmonary arterial hypertension (PAH). The current study examined whether perturbations to the TGF-β/Smad2,3 signalling axis occurred in a monocrotaline (MCT) rodent model of experimental PAH.

Expression of the TGF-β signalling machinery was assessed in the lungs and kidneys of MCT-treated rodents with severe PAH by semi-quantitative reverse-transcription (RT)-PCR, real-time RT-PCR and immunoblotting. TGF-β signalling was assessed in the lungs and in pulmonary artery smooth muscle cells (PASMC) from MCT-treated rodents by Smad2 phosphorylation, expression of the connective tissue growth factor gene, activation of theserpinepromoter in a luciferase reporter system and by the induction of apoptosis.

The expression of type1 TGF-β receptor (TGFBR) activin-A receptor-like kinase1, TGFBR-2, TGFBR-3 (endoglin), Smad3 and Smad4; as well as TGF-β signalling and TGF-β-induced apoptosis, were dramatically reduced in the lungs and PASMC, but not the kidneys, of MCT-treated rodents that developed severe PAH.

The current data indicate that the transforming growth factor-β/Smad2,3 signalling axis is functionally impaired in monocrotaline-treated rodents with severe pulmonary arterial hypertension, underscoring the potential importance of transforming growth factor-β/Smad2,3 signalling in the onset or development of pulmonary arterial hypertension.
Twelve-year longitudinal study of respiratory status in dairy farmers
Authors: Gainet M. , Thaon I. , Westeel V. , Chaudemanche H. , Venier A. G. , Dubiez A. , Laplante J. J. , Dalphin J-C.
Published: March 2007

To evaluate respiratory risk in dairy farmers, the present authors conducted a longitudinal study in the Doubs region of France.

From a cohort constituted in 1986 (T1), 157 (62.8%) dairy farmers and 159 (63.6%) controls were re-evaluated in 1998 (T3). The study protocol comprised a medical and occupational questionnaire, spirometric tests at both evaluations, and noninvasive measure of blood oxygen saturation with pulse oximetry (Sp,O2) at T3.

In 1998, the prevalence of chronic bronchitis was higher in dairy farmers. In cross-sectional analyses, all respiratory function parameters andSp,O2were significantly lower in dairy farmers. In a multiple linear regression model, farming, age, male sex and smoking were significantly and negatively correlated withSp,O2. However, the mean annual decline in respiratory function parameters did not differ significantly between groups. After adjustment of covariables, accelerated decline in vital capacity and forced expiratory volume in one second was associated with age, smoking and male sex. Decline in vital capacity was accelerated in dairy farmers working in traditional farms and those currently foddering.

The current study demonstrates that dairy farming is associated with an increased risk of lung disorders and a decrease in blood oxygen saturation and suggests that respiratory function impairment is correlated with cumulated exposure to organic dusts.
Aromatic Fluorination Effect on the Mesomorphic Properties of Discotic Liquid Crystal of Alkoxybenzoyloxytriphenylene
Authors: Sasada Yasuyuki , Monobe Hirosato , Ueda Yasukiyo , Shimizu Yo
Published: March 2007

Two homologues, C6F4 and C10F4 having 2,3,5,6-tetrafluorophenylene moieties were synthesized and investigated on the mesomorphic behavior. It was revealed that these exhibit a hexagonal columnar (Colh) phase, and this mesomorphism is quite different from the corresponding nonfluorinated homologues, C6H4 and C10H4 predominantly showing a discotic nematic (ND) phase.
Efficient Synthesis of Fused 1,2,3-Triazolo-δ-lactams Using Huisgen [3 + 2] Dipolar Cycloaddition “Click-chemistry” in Water
Authors: Kumar Indresh , Rode Chandrashekhar V
Published: March 2007

A general approach for the quick synthesis of various 1,2,3-triazolo-δ-lactams has been described, which involves the Huisgen [3 + 2] dipolar cycloaddition of azides derived from different amino acids with dimethyl acetylenedicarboxylate in water followed by cyclization.
Unexpected Ring-opening Reaction of Aziridine with Acetic Anhydride in DMF
Authors: Diao Tianning , Sun Xiaoyu , Fan Renhua , Wu Jie
Published: March 2007

Ring-opening reactions of aziridines with acetic anhydride in DMF afforded the unexpected β-amino formate in moderate to good yields. The possible mechanism is also proposed.
Reproducibility in Protein Profiling by MALDI-TOF Mass Spectrometry
Authors: Albrethsen Jakob
Published: March 2007

Background: Protein profiling with high-throughput sample preparation and MALDI-TOF MS analysis is a new potential tool for diagnosis of human diseases. However, analytical reproducibility is a significant challenge in MALDI protein profiling. This minireview summarizes studies of reproducibility of MALDI protein profiling and current approaches to improve its analytical performance.

Methods: The PubMed database was searched using combinations of the following search terms: MALDI, SELDI, reproducibility, variation, precision, peak intensity, quantification, peptide, biomarkers, and proteomics. Acceptance criteria were detailed reports on the reproducibility with MALDI protein profiling and studies describing efforts to improve the analytical performance with this technology.

Results: The reported intraexperiment CVs of the peak intensity vary highly between individual protein peaks, with the reported mean CV of the peak intensity varying among studies from 4% to 26%. There is additional interexperiment variation in peak intensity. Current approaches to improve the analytical performance of MALDI protein profiling include automated sample processing, extensive prefractionation strategies, immunocapture, prestructured target surfaces, standardized matrix (co)crystallization, improved MALDI-TOF MS instrument components, internal standard peptides, quality-control samples, replicate measurements, and algorithms for normalization and peak detection.

Conclusions: Further evaluation and optimization of MALDI-TOF MS is recommended before use in routine analysis.
Comparative analysis of life-history traits in two species of C alomys (Rodentia: Sigmodontinae) in captivity / Analyse comparative des traits d'histoire de vie de deux espèces de Calomys (Rodentia: Sigmodontinae) en captivité
Authors: Araripe Luciana O. , Aprigliano Paula , Olifiers Natalie , Borodin Pavel , Cerqueira Rui
Published: March 2007

We analyzed life-history traits (fertility, growth and rate of postnatal development) in captive-bred colonies of two closely related sympatric species: Calomys expulsus and C. tener (Rodentia, Sigmodontinae). We found significant differences between the species in growth rate and several reproductive traits. C. tener had a smaller litter size and litter mass, smaller proportion of litter mass to maternal mass, lower growth rate and higher infant mortality. We also found an apparent difference in correlation patterns of life history parameters between the two species of Calomys . The strong correlation between body size and fecundity found in other studies of life history traits and in selection experiments seems to be disrupted in C. tener . We found a significant positive correlation between maternal mass and litter size and mass only for C. expulsus, which means that in C. tener the fertility of females does not depend strongly on body mass. We discuss inbreeding depression and stress reactions as possible reasons for these results.
Sources and Utilization of Amino Acids in Channel Catfish Diets: A Review
Authors: Ambardekar Amogh A , Reigh Robert C
Published: March 2007

Alternatives to high-cost protein supplements in formulated diets for channel catfish Ictalurus punctatus are desirable to reduce feed costs and increase profits in modern channel catfish farming operations. Channel catfish feed manufacturers are focused on using plant proteins in least-cost diet formulations which typically contain at least 90% plant products. These diets are sometimes supplemented with purified crystalline amino acids to eliminate amino acid deficiencies associated with plant proteins, which often possess amino acid compositions that are less favorable for channel catfish than the animal products they replace. The efficiency with which channel catfish utilize these supplemented amino acids is discussed, and we describe evidence that amino acids provided in purified crystalline form are not used as effectively as the amino acids obtained from intact proteins in the feed ingredients. Because purified amino acids could be absorbed from the intestine faster than amino acids released from intact proteins, the two forms might be metabolized differently. We discuss the differences in the rates at which amino acids are released from the proteins in practical ingredients, as such differences could affect their utilization.
First Report of Yersinia ruckeri Biotype 2 in the USA
Authors: Arias Cova R. , Olivares-Fuster Oscar , Hayden Karl , Shoemaker Craig A. , Grizzle John M. , Klesius Phillip H.
Published: March 2007

A polyphasic characterization of atypical isolates of Yersinia ruckeri (causative agent of enteric redmouth disease in trout) obtained from hatchery-reared brown trout Salmo trutta in South Carolina was performed. The Y. ruckeri isolates were biochemically and genetically distinct from reference cultures, including the type strain, but were unequivocally ascribed to the species Y. ruckeri, based on API 20E, VITEK, fatty acid methyl ester profiles, and 16S rRNA gene sequencing analysis. These isolates were nonmotile and unable to hydrolyze Tween 20/80 and were therefore classified as Y. ruckeri biotype 2. Genetic fingerprint typing of the isolates via enterobacterial repetitive intergenic consensus (amplified by polymerase chain reaction) and fragment length polymorphism showed biotype 2 as a homogeneous group distinguishable from other Y. ruckeri isolates. This is the first report of Y. ruckeri biotype 2 in the USA.
A Science-Based Approach for Identifying Temperature-Sensitive Streams for Rainbow Trout
Authors: Nelitz Marc A. , MacIsaac Erland A. , Peterman Randall M.
Published: March 2007

To regulate human-induced changes to fish habitat, resource managers commonly set standards based on maximum allowable changes. For example, new legislation in British Columbia (BC), Canada, calls for restrictions on harvesting of trees and related activities near temperature-sensitive streams. However, methods for designating such streams are still evolving. Our objective was to help develop such methods by (1) improving understanding of the temperature-dependent responses of fish and (2) devising improved methods for estimating the effects of forestry-related activities on stream temperature as well as the chance of exceeding upper temperature limits. Using previously published models, we found that for rainbow trout Oncorhynchus mykiss particular increases in stream temperature led to different effects on juvenile growth rate, egg survival rate, and resistance to mortality from diseases. In a separate analysis, to evaluate the chance that cumulative forestry activities will increase stream temperature by various amounts, we compiled summer temperature data for 104 streams in central BC that reflected different watershed features, contrasting summer climates, and various levels of land use. A classification and regression tree analysis of a summer maximum weekly average temperature (MWAT) index grouped streams into six categories as a function of watershed size, watershed elevation, and air temperature. We then analyzed the remaining unexplained variation among stream temperature indices using Bayesian regression. We found high probabilities that increases in road density and the density of road crossings of streams within watersheds are associated with increases in residual temperature. For instance, a Bayesian regression indicated a 6-in-10 chance that the MWAT in our study area will increase by 1.25°C for a road density of 2 km/km2 of watershed area and by 3.25°C for a road density of 4 km/km2. These analyses illustrate some possible ways to help designate temperature-sensitive streams.
Changes in Algal Species Composition Affect Juvenile Sockeye Salmon Production at Woss Lake, British Columbia: A Lake Fertilization and Food Web Analysis
Authors: McQueen Donald J. , Hyatt Kim D. , Rankin D. Paul , Ramcharan Charles J.
Published: March 2007

In recent decades, the abundance of sockeye salmon Oncorhynchus nerka in the Nimpkish River watershed (Vancouver Island) has declined by more than 80%. To improve sockeye salmon abundance, one of three Nimpkish nursery lakes (Woss Lake, 13.6 km2) was fertilized; a second (Vernon Lake, 8.4 km2) was maintained as an unmanipulated reference. For 3 years (2000–2002), we assessed changes in phytoplankton, zooplankton, and juvenile sockeye salmon and then used food web analysis to model the fate of fertilizer phosphorus (FP) as it moved up the food web to juvenile sockeye salmon. As the experiment progressed, we found two distinctly different results. During the first 2 years (2000 and 2001), fertilization was associated with higher concentrations of P, chlorophyll, and phytoplankton. However, because most of the algae were inedible diatoms (principally Rhizosolenia eriensis), only 8% of the algal standing stock was available to zooplankton and less than 0.1% of the FP was incorporated into sockeye salmon biomass via limnetic pathways. The result was that juvenile sockeye salmon growth rates in the treated and control lakes were not significantly different. During the third year (2002), a bloom of the diatom Leptocylindrus increased Woss Lake edible algal biomass by a factor of 7; zooplankton production tripled, and juvenile sockeye salmon production increased by 19%. Consequently, Woss Lake juvenile sockeye salmon grew twice as fast as they did in untreated Vernon Lake, and juvenile sockeye salmon fall weights were 50% higher than those recorded before the lake was fertilized. We conclude that for north Pacific coastal lakes, bottom-up effects resulting from changes in phytoplankton species composition can profoundly alter rates of juvenile sockeye salmon production. Regulation of algal species composition through manipulations of fertilizer composition and application timing might be used to reduce blooms of nuisance algae and increase age-0 sockeye salmon yield.
Tag Return Models Allowing for Harvest and Catch and Release: Evidence of Environmental and Management Impacts on Striped Bass Fishing and Natural Mortality Rates
Authors: Jiang Honghua , Pollock Kenneth H. , Brownie Cavell , Hoenig John M. , Latour Robert J. , Wells Brian K. , Hightower Joseph E.
Published: March 2007

Catch-and-release fisheries have become very important in the management of overexploited recreational fish stocks. Tag return studies, where the tag is removed regardless of fish disposition, have been used to assess the effectiveness of restoration efforts for these fisheries. We extend the instantaneous rate formulation of tag return models to allow for catch and release as well as harvest. The key point of our methods is that, given an estimate of the tag reporting rate, the fishing mortality rate (F) is separated into two components: the mortality on harvested fish and the “mortality” on tags (because the tags are removed) of fish released alive. The total fishing mortality rate for untagged fish is the sum of the Fs due to harvest and hooking mortality suffered by fish released alive. Natural mortality rates can also be estimated. Both age-independent models and age-dependent models are constructed, and the age-dependent models are illustrated by application to data from a study of striped bass Morone saxatilis in Chesapeake Bay from 1991 to 2003 by the Maryland Department of Natural Resources. By fitting models of the natural mortality rate with limited age and year dependence, we demonstrate an overall decrease in natural mortality rates as fish age and provide evidence of an increase in natural mortality beginning in the late 1990s, when an outbreak of the disease mycobacteriosis is thought to have begun. Our results indicate that fishing mortality is age dependent; selectivity increases up to age 6, when fish appear to be fully recruited to the fishery. There is also evidence of an increase in fishing mortality since 1995, when regulations were relaxed.
Nine Things Every Teacher Should Know About Words and Vocabulary Instruction
Authors: Bromley Karen
Published: March 2007

Vocabulary knowledge contributes to comprehension, fluency, and student achievement. The goal of vocabulary instruction should be to build students' independent word‐learning strategies.

This article provides research and theory in support of nine key ideas about words and vocabulary instruction. These ideas are important for middle and secondary teachers to know and understand in order to provide sound vocabulary teaching across the content areas. Topics discussed include

The English language and the consistency of its rules

How language competence grows from oral to written

How words are learned

Multiple meanings

Multisyllabic words

The importance of teachers' modeling word consciousness and their own excitement about learning new words

For each key idea, the author provides several practical suggestions for classroom instruction, including strategies for individuals, small groups, and the whole class. Several websites for developing vocabulary as well as professional resources for teachers are suggested.

This article is also the source for a Class Acts podcast. Download “Teaching vocabulary in middle and high school” from

www.reading.orgresourcespodcastsindex.html
Reflections on Native American Reading: A Seed, a Tool, and a Weapon
Authors: White‐Kaulaity Marlinda
Published: March 2007

Oral tradition has a long and valued history in Native American cultures and communities. In the past and still today, reading has had lesser value among many Native Americans. But oral tradition can be a vehicle toward improved literacy.

This article uses literacy stories from Native American people, as well as quotes from prominent Native American writers, as a rationale for increased personal reading among Native Americans. Each literacy story describes or explains the positive impact reading has had on that particular person's life. Also, a theory that discusses how people attain literary appreciation, as they move from the earliest stages in preschool into adulthood, is used as a framework. From the stories and voices of the people quoted comes the message that oral literacy and print literacy can and should work together to affect positive reading practices and attitudes. Implications and examples of literacy activities are given at the end of the article for teachers and other adults to promote reading as a valuable and necessary activity.
Vocabulary assessment: What we know and what we need to learn
Authors: PEARSON P. DAVID , HIEBERT ELFRIEDA H. , KAMIL MICHAEL L.
Published: March 2007

The authors assert that, in order to teach vocabulary more effectively and better understand its relation to comprehension, we need first to address how vocabulary knowledge and growth are assessed. They argue that “vocabularly assessment is grossly undernourished, both in its theoretical and practical aspects—that it has been driven by tradition, convenience, psychometric standards, and a quest for economy of effort rather than a clear conceptualization of its nature and relation to other aspects of reading expertise, most notably comprehension.”
Drawing and redrawing the map of writing studies
Authors: GLASSWELL KATHRYN , KAMBERELIS GEORGE
Published: March 2007

Book reviewed in this article:

Handbook of Writing Research. Charles A. MacArthur, Steve Graham, and Jill Fitzgerald (Eds.). 2006.
Story Discussion in the Primary Grades: Balancing Authenticity and Explicit Teaching
Authors: McIntyre Ellen
Published: March 2007

Literature discussion groups have become a popular instructional alternative to traditional reading groups. Yet, literature discussion does not happen naturally in the classroom, and some teachers find it particularly difficult to implement with primary‐grade students.

This article explores how two teachers used a balance of explicit teaching and techniques of authentic dialogue to help students participate in meaningful discussions of literature. The teachers began by emphasizing telling, defining, and modeling at the beginnings of their lessons—moves that appeared to be critical to students' eventual participation. Gradually, the teachers lessened their scaffolding, allowing students to lead more of the discussion. Within an atmosphere of respect for students, shown by much student choice and decision making, literature discussion became more successful.
Student‐Focused Coaching: A Model for Reading Coaches
Authors: Hasbrouck Jan , Denton Carolyn A.
Published: March 2007

There has been rapid growth in the number of reading coaches working in schools to support teachers as they develop students' literacy skills. However, few approaches to coaching seem to link to relevant and informative research. The authors' research‐based model, Student‐Focused Coaching, incorporates aspects of several coaching strategies and is sufficiently multifaceted to cover the wide variety of tasks that coaches are typically called upon to perform.
Children's Books and Technology in the Classroom: A Dynamic Combo for Supporting the Writing Workshop
Authors: Kara‐Soteriou Julia , Zawilinski Lisa , Henry Laurie A.
Published: March 2007

Weaving literature and technology into writing workshop provides students of all ages with powerful resources, engaging activities, a genuine purpose for writing, and authentic audiences with whom to share their work. The authors describe instructional approaches for effective technology use and make specific recommendations for outstanding children's books to use in the writing classroom.
The Forgotten Genre of Children's Poetry
Authors: Gill Sharon Ruth
Published: March 2007

The author argues that 20th‐century children's poetry is often ignored and that the emphasis on teaching the adult poetry canon can give children mistaken ideas about what poetry is. Poetry is not a collection of “classics” whose meanings must be explained but something written to capture thoughts, feelings, and experiences. Ideas for teaching poetry are included.
“Reading” the Painting: Exploring Visual Literacy in the Primary Grades
Authors: Williams T. Lee
Published: March 2007

Traditional literacy practices and educational policymakers define reading as a process of vocabulary recognition and print‐based decoding. This perspective is especially prevalent in the primary‐grade literacy classroom. Yet, a growing movement sees literacy encompassing not only printed text, but a wide range of cultural, technological, and visual experiences.

In this article, a teacher discusses her efforts to incorporate this broadened definition of reading in a second‐grade classroom. In an innovative activity, students created personal, written interpretations of a wide range of artwork from the National Gallery in London, England. Without historical and contextual clues about the artists or paintings, students used critical thinking skills to craft interesting and unique stories about the artwork. This project illustrates the potential of incorporating visual literacy into a primary‐grade classroom and how responsive even young children can be to an expanded view of literacy. The author details the project's background, implementation steps, and outcomes.
Web‐Based Inquiry Learning: Facilitating Thoughtful Literacy With WebQuests
Authors: Ikpeze Chinwe H. , Boyd Fenice B.
Published: March 2007

An action research study investigated how the multiple tasks found in WebQuests facilitate fifth‐grade students' literacy skills and higher order thinking.

Findings indicate that WebQuests are most successful when activities are carefully selected and systematically delivered. Implications for teaching include the necessity for adequate planning, organization, supervision, and scaffolding of learning in a Web environment. For students, benefits of WebQuests include enhancement of thoughtful literacy through multiple knowledge representations and making learning meaningful through connections to real‐life contexts. The study also highlighted interdisciplinary teaching and learning of social studies, science, and language arts.
“The Discovery Channel Said So” and Other Barriers to Comprehension
Authors: Massey Dixie D.
Published: March 2007

With increasing attention focused on comprehension, there is a need for research regarding how to implement comprehension instruction for struggling readers and assess its effectiveness. This article describes reading instruction as it occurred over two years with one struggling reader in third and fourth grade. A comprehension checklist provided a framework for instruction that was both systematic and responsive to the reader's needs. The result was improved comprehension and metacognition for the student, though the progress was slow and often cyclical instead of sequential.
Making Magazine Covers That Visually Count: Learning to Summarize With Technology
Authors: Assaf Lori , Garza Rubén
Published: March 2007

A step‐by‐step guide helps teachers direct 9‐ to 11‐year‐olds as they summarize what they are reading by creating magazine covers. In this activity, young readers use visual images and multiple graphics to connect important ideas, synthesize those ideas, and capture the big picture of a text.

The article outlines the theory and research in support of learning to summarize. It highlights how the magazine‐cover activity motivates learners, integrates technology into instruction, and expands readers' ability to summarize and make meaning.
Incidence and familial risks in pituitary adenoma and associated tumors
Authors: Hemminki Kari , Försti Asta , Ji Jianguang
Published: March 2007

Reliable data on familial risks are important for clinical counseling and cancer genetics. We wanted to study incidence trends and familial risks for pituitary adenomas and associated tumors through parental and sibling probands, using the nation-wide Swedish Family-Cancer Database on 10.5 million individuals, containing families with parents and offspring. Cancer data were retrieved from the Swedish Cancer Registry from years 1958 to 2002, including 3239 pituitary tumor patients. Familial risk for offspring was defined through standardized incidence ratio (SIR), adjusted for many variables. The incidence of pituitary adenoma has increased moderately from 1958 to the 1990s and declined thereafter. There were only three offspring–parent pairs with a concordant pituitary tumor, the SIR was not significant. Parental skin cancer (SIR 1.60) and leukemia (1.90, chronic lymphatic leukemia 2.59) were associated with offspring pituitary adenoma diagnosed at any age up to 70 years. There was a strong association of pituitary adenomas with nervous system hemangiopericytomas, SIR 182. The only significant association among siblings was between pituitary tumors and breast cancer (1.46). The risk of pituitary adenoma was marginally increased in individuals whose siblings were diagnosed with colorectal cancer. The results suggest an association of pituitary adenomas with nervous system hemangiopericytomas and breast and colorectal cancers, in addition to some other tumor types. Whether these associations can be explained by the recently identified pituitary adenoma predisposing gene, AIP, remains to be established.
Role of ERβ palmitoylation in the inhibition of human colon cancer cell proliferation
Authors: Galluzzo Paola , Caiazza Francesco , Moreno Sandra , Marino Maria
Published: March 2007

The cellular functions regulated by 17β-estradiol (E2) start after the hormone binds to its receptors (i.e., ERα and ERβ ). These act as ligand-dependent transcription factor transactivating target genes. In addition, E2 induces non-genomic actions, whose activation is triggered by a fraction of the ERs localized at the plasma membrane. Palmitoylation allows ERα to localize at the plasma membrane, to associate with caveolin-1, and, upon E2 stimulation, to activate rapid signals relevant for cell proliferation. The existence of a mechanism, which allows ERβ localization at the plasma membrane and its putative role in anti-proliferative E2 effects is completely unknown. Here, the susceptibility of ERβ to undergo palmitoylation and the role played by this process has been analyzed in DLD-1 containing endogenous ERβ or in HeLa cells transiently transfected with ERβ or ERα expression vectors. As for ERα , palmitoylation is necessary for ERβ localization at the plasma membrane and its association with caveolin-1 but, in contrast to ERα , the E2 binding increases ERβ association with caveolin-1 and the p38 member of MAPK family. Moreover, the palmitoyl acyl transferase (PAT) inhibitor blocks the ability of ERβ –E2 complex to activate p38 impairing the receptor-dependent activation of downstream proapoptotic cascade (i.e., caspase-3 activation and poly(ADP-ribose)polymerase (PARP) cleavage). Consequently, palmitoylation must be considered to be a molecular device for ERβ , which allows these receptors to interact with the plasma membrane and to regulate E2-induced non-genomic functions relevant to the anti-proliferative effect of this hormone.
p53 family proteins in thyroid cancer
Authors: Malaguarnera R , Vella V , Vigneri R , Frasca F
Published: March 2007

At variance with other human malignancies, p53 mutations are not frequent in thyroid cancer and are believed to be responsible mainly for cancer progression to poorly differentiated and aggressive phenotype. p63 and p73, two proteins with a high degree of homology with p53, are overexpressed in thyroid cancer, but their role in cancer initiation or progression is controversial. Regulation of p53 family protein function depends on: (1) the balance between the expression of transcriptionally active (p53, TAp63, and TAp73) and inactive isoforms (ΔNp63 and ΔNp73); (2) their interaction and competition at DNA-responsive elements; (3) their interaction with regulatory proteins, either inhibitory or activating. In thyroid cancer, therefore, although mutations of the p53 oncosuppressor protein family are rare, other mechanisms are present, including aberrant expression of p53 family dominant negative isoforms, up-regulation of inhibitory proteins, and functional inhibition of activating proteins. The overall result is a defective oncosuppressor activity. These inactivating mechanisms may be present in the early stages of thyroid cancer and in different cancer histotypes. A better understanding of this complex network may not only ameliorate our comprehension of cancer biology, but also open the possibility of innovative diagnostic procedures and the development of targeted therapies.
Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC)
Authors: Peeters Petra H M , Lukanova Annekatrin , Allen Naomi , Berrino Franco , Key Tim , Dossus Laure , Rinaldi Sabina , van Gils Carla H , Bueno-de-Mesquita H Bas , Boeing Heiner , Schulz Mandy , Chang-Claude Jenny , Linseisen Jakob , Panico Salvatore , Sacerdote Carlotta , Palli Domenico , Tumino Rosario , Trichopoulou Antonia , Trichopolos Dimitrios , Bamia Christina , Larranaga Nerea , Ardanaz Eva , Pera Guillem , Quirós J Ramón , Martínez-García Carmen , Navarro Carmen , Bingham Sheila A , Khaw Kay-Tee , Clavel Françoise , Tjonneland Anne , Olsen Anja , Overvad Kim , Tetsche Mette S , Lund Eiliv , Lundin Eva , Berglund Göran , Riboli Elio , Kaaks R
Published: March 2007

We set out to study the relationship between circulating levels of IGF-I and its major binding protein (IGFBP-3) in relation to ovarian cancer risk. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of IGF-I and IGFBP-3 were measured in prediagnostic serum samples of 214 women who subsequently developed ovarian cancer, and 388 matched control subjects. Conditional logistic regression models were used to estimate relative risks of ovarian cancer by tertiles of IGF-I and IGFBP-3 levels. For all women, there was no association between the circulating IGF-I or IGFBP-3 levels and the risk of ovarian cancer. However, among women diagnosed with ovarian cancer aged 55 or younger, the relative risk was higher in the middle or top tertiles of serum IGF-I, when compared with women in the lowest tertile (odds ratios (OR) = 1.8 (95%CI 0.7–4.3) and OR = 2.4 (95%CI 0.9–6.4); Ptrend = 0.08) respectively. These results were adjusted for body mass index, previous hormone use, fertility problems, and parity. Restricting the analysis to women who were premenopausal at blood donation, relative risks for ovarian cancer diagnosed before age 55 were higher (OR = 5.1 (95%CI 1.5–18.2) and OR = 5.6 (95%CI 1.5–20.8) respectively, for second and third tertiles; Ptrend = 0.02). Adjustment for serum IGFBP-3 levels only slightly attenuated relative risk estimates. Relations between IGFBP-3 and ovarian cancer before age 55 were in the same direction as for IGF-I, but less strong and statistically not significant. In women aged over 55, there was no association between serum IGF-I or IGFBP-3 and ovarian cancer risk. Our results suggest that the circulating levels of IGF-I may play a potentially important role in the development of ovarian cancer in women of a pre- or perimenopausal age.
Strength assessment of flat slabs on non-rectangular column grid
Authors: Baskaran K. , Morley C. T.
Published: March 2007

Flat slab construction has proved efficient and large numbers have been built. Often the layout of columns is limited to rectangular grid owing to the scarcity of structural analysis tools validated by experimental evidence. Recently, to break through this barrier, two irregular flat slabs were tested at Nanyang Technological University, Singapore. However, they failed at almost twice the design ultimate load, showing the need for more work. Also, there are efforts to apply yield line analysis to flat slabs on irregular column grid. However, such efforts need validation through comparison with experimental results. To fill this vacuum, nine flat slab panels supported on non-rectangular column grid were designed and tested at Cambridge University Engineering Department (CUED). The current paper presents experimental details and analytical results of five flat slab specimens tested at CUED: three interior panel specimens and one corner panel specimen of parallelogram column layout and an irregular seven-column specimen. Failure loads are predicted using yield line analyses based on energy approach and nonlinear finite element analyses using a commercially available finite element package (DIANA). Further confirmation of predictions is made by comparisons with experimental observations.
Defective Insulin and Acetylcholine Induction of Endothelial Cell–Nitric Oxide Synthase Through Insulin Receptor Substrate/Akt Signaling Pathway in Aorta of Obese Rats
Authors: Zecchin Henrique G. , Priviero Fernanda B.M. , Souza Claudio T. , Zecchin Karina G. , Prada Patrícia O. , Carvalheira José B.C. , Velloso Licio A. , Antunes Edson , Saad Mario J.A.
Published: March 2007

The actions of acetylcholine (ACh) on endothelium mainly are mediated through muscarinic receptors, which are members of the G protein–coupled receptor family. In the present study, we show that ACh induces rapid tyrosine phosphorylation and activation of Janus kinase 2 (JAK2) in rat aorta. Upon JAK2 activation, tyrosine phosphorylation of insulin receptor substrate (IRS)-1 is detected. In addition, ACh induces JAK2/IRS-1 and IRS-1/phosphatidylinositol (PI) 3-kinase associations, downstream activation of Akt/protein kinase B, endothelial cell–nitric oxide synthase (eNOS), and extracellular signal–regulated kinase (ERK)-1/2. The pharmacological blockade of JAK2 or PI 3-kinase reduced ACh-stimulated eNOS phosphorylation, NOS activity, and aorta relaxation. These data indicate a new signal transduction pathway for IRS-1/PI 3-kinase/Akt/eNOS activation and ERK1/2 by means of JAK2 tyrosine phosphorylation stimulated by ACh in vessels. Moreover, we demonstrate that in aorta of obese rats (high-fat diet), there is an impairment in the insulin- and ACh-stimulated IRS-1/PI 3-kinase pathway, leading to reduced activation with lower protein levels of eNOS associated with a hyperactivated ERK/mitogen-activated protein kinase pathway. These results suggest that in aorta of obese rats, there not only is insulin resistance but also ACh resistance, probably mediated by a common signaling pathway that controls the activity and the protein levels of eNOS.
Rosiglitazone Inhibits Acyl-CoA Synthetase Activity and Fatty Acid Partitioning to Diacylglycerol and Triacylglycerol via a Peroxisome Proliferator–Activated Receptor-γ–Independent Mechanism in Human Arterial Smooth Muscle Cells and Macrophages
Authors: Askari Bardia , Kanter Jenny E. , Sherrid Ashley M. , Golej Deidre L. , Bender Andrew T. , Liu Joey , Hsueh Willa A. , Beavo Joseph A. , Coleman Rosalind A. , Bornfeldt Karin E.
Published: March 2007

Rosiglitazone is an insulin-sensitizing agent that has recently been shown to exert beneficial effects on atherosclerosis. In addition to peroxisome proliferator–activated receptor (PPAR)-γ, rosiglitazone can affect other targets, such as directly inhibiting recombinant long-chain acyl-CoA synthetase (ACSL)-4 activity. Because it is unknown if ACSL4 is expressed in vascular cells involved in atherosclerosis, we investigated the ability of rosiglitazone to inhibit ACSL activity and fatty acid partitioning in human and murine arterial smooth muscle cells (SMCs) and macrophages. Human and murine SMCs and human macrophages expressed Acsl4, and rosiglitazone inhibited Acsl activity in these cells. Furthermore, rosiglitazone acutely inhibited partitioning of fatty acids into phospholipids in human SMCs and inhibited fatty acid partitioning into diacylglycerol and triacylglycerol in human SMCs and macrophages through a PPAR-γ–independent mechanism. Conversely, murine macrophages did not express ACSL4, and rosiglitazone did not inhibit ACSL activity in these cells, nor did it affect acute fatty acid partitioning into cellular lipids. Thus, rosiglitazone inhibits ACSL activity and fatty acid partitioning in human and murine SMCs and in human macrophages through a PPAR-γ–independent mechanism likely to be mediated by ACSL4 inhibition. Therefore, rosiglitazone might alter the biological effects of fatty acids in these cells and in atherosclerosis.
Effects of Palmitate on Ca2+ Handling in Adult Control and ob/ob Cardiomyocytes
Authors: Fauconnier Jérémy , Andersson Daniel C. , Zhang Shi-Jin , Lanner Johanna T. , Wibom Rolf , Katz Abram , Bruton Joseph D. , Westerblad Håkan
Published: March 2007

Obesity and insulin resistance are associated with enhanced fatty acid utilization, which may play a central role in diabetic cardiomyopathy. We now assess the effect of the saturated fatty acid palmitate (1.2 mmol/l) on Ca2+ handling, cell shortening, and mitochondrial production of reactive oxygen species (ROS) in freshly isolated ventricular cardiomyocytes from normal (wild-type) and obese, insulin-resistant ob/ob mice. Cardiomyocytes were electrically stimulated at 1 Hz, and the signal of fluorescent indicators was measured with confocal microscopy. Palmitate decreased the amplitude of cytosolic Ca2+ transients (measured with fluo-3), the sarcoplasmic reticulum Ca2+ load, and cell shortening by ∼20% in wild-type cardiomyocytes; these decreases were prevented by the general antioxidant N-acetylcysteine. In contrast, palmitate accelerated Ca2+ transients and increased cell shortening in ob/ob cardiomyocytes. Application of palmitate rapidly dissipated the mitochondrial membrane potential (measured with tetra-methyl rhodamine-ethyl ester) and increased the mitochondrial ROS production (measured with MitoSOX Red) in wild-type but not in ob/ob cardiomyocytes. In conclusion, increased saturated fatty acid levels impair cellular Ca2+ handling and contraction in a ROS-dependent manner in normal cardiomyocytes. Conversely, high fatty acid levels may be vital to sustain cardiac Ca2+ handling and contraction in obesity and insulin-resistant conditions.
Novel Function of the Ciliogenic Transcription Factor RFX3 in Development of the Endocrine Pancreas
Authors: Ait-Lounis Aouatef , Baas Dominique , Barras Emmanuèle , Benadiba Carine , Charollais Anne , Nlend Nlend Rachel , Liègeois Delphine , Meda Paolo , Durand Bénédicte , Reith Walter
Published: March 2007

The transcription factor regulatory factor X (RFX)-3 regulates the expression of genes required for the growth and function of cilia. We show here that mouse RFX3 is expressed in developing and mature pancreatic endocrine cells during embryogenesis and in adults. RFX3 expression already is evident in early Ngn3-positive progenitors and is maintained in all major pancreatic endocrine cell lineages throughout their development. Primary cilia of hitherto unknown function present on these cells consequently are reduced in number and severely stunted in Rfx3−/− mice. This ciliary abnormality is associated with a developmental defect leading to a uniquely altered cellular composition of the islets of Langerhans. Just before birth, Rfx3−/− islets contain considerably less insulin-, glucagon-, and ghrelin-producing cells, whereas pancreatic polypeptide–positive cells are markedly increased in number. In adult mice, the defect leads to small and disorganized islets, reduced insulin production, and impaired glucose tolerance. These findings suggest that RFX3 participates in the mechanisms that govern pancreatic endocrine cell differentiation and that the presence of primary cilia on islet cells may play a key role in this process.
Transcriptional Regulation of the Endoplasmic Reticulum Stress Gene Chop in Pancreatic Insulin-Producing Cells
Authors: Pirot Pierre , Ortis Fernanda , Cnop Miriam , Ma Yanjun , Hendershot Linda M. , Eizirik Décio L. , Cardozo Alessandra K.
Published: March 2007

Endoplasmic reticulum stress–mediated apoptosis may play an important role in the destruction of pancreatic β-cells, thus contributing to the development of type 1 and type 2 diabetes. One of the regulators of endoplasmic reticulum stress–mediated cell death is the CCAAT/enhancer binding protein (C/EBP) homologous protein (Chop). We presently studied the molecular regulation of Chop expression in insulin-producing cells (INS-1E) in response to three pro-apoptotic and endoplasmic reticulum stress–inducing agents, namely the cytokines interleukin-1β + interferon-γ, the free fatty acid palmitate, and the sarcoendoplasmic reticulum pump Ca2+ ATPase blocker cyclopiazonic acid (CPA). Detailed mutagenesis studies of the Chop promoter showed differential regulation of Chop transcription by CPA, cytokines, and palmitate. Whereas palmitate- and cytokine-induced Chop expression was mediated via a C/EBP–activating transcription factor (ATF) composite and AP-1 binding sites, CPA induction required the C/EBP-ATF site and the endoplasmic reticulum stress response element. Cytokines, palmitate, and CPA induced eIF2α phosphorylation in INS-1E cells leading to activation of the transcription factor ATF4. Chop transcription in response to cytokines and palmitate depends on the binding of ATF4 and AP-1 to the Chop promoter, but distinct AP-1 dimers were formed by cytokines and palmitate. These results suggest a differential response of β-cells to diverse endoplasmic reticulum stress inducers, leading to a differential regulation of Chop transcription.