bluuebunny/crossref_metadata_2025 huggingface dataset:
Words and Thoughts
Authors: Stainton Robert
Published: February 2007

It is a near truism of philosophy of language that sentences are prior to words. Sentences, it is said, are what we believe, assert, and argue for; uses of them constitute our evidence in semantics; only they stand in inferential relations, and are true or false. Sentences are, indeed, the only things that fundamentally have meaning. Does this near truism really hold of human languages? This book, drawing on a wide body of evidence, argues forcefully that speakers can and do use mere words, not sentences, to communicate complete thoughts. It considers the implications of this empirical result for language-thought relations, various doctrines of sentence primacy, and the semantics-pragmatics boundary. The book is important both for its philosophical and empirical claims, and for the methodology employed. Stainton illustrates how the methods and detailed results of the various cognitive sciences can bear on central issues in philosophy of language. At the same time, he applies philosophical distinctions to show that arguments which seemingly support the primacy of sentences do not really do so.
A Positive Representational–Pragmatic View
Authors: Stainton Robert J.
Published: February 2007

This chapter discusses what is going on in apparent cases of sub-sentential speech acts. It begins with a relatively broad-strokes account of how agents can communicate using ordinary words and phrases; this provides the ‘general view’. The general view is taken to be the core of the positive position. A preferred way of spelling out the general view is presented — the so-called ‘specific view’ — which introduces internal mental representations of various sorts. The result is a view that is not only pragmatic, but representational.
Sentence Primacy
Authors: Stainton Robert J.
Published: February 2007

This chapter lays out five different ways of reading the context principle: methodological, metasemantic, pragmatic, semantic, and psychological. It notes several rationales for embracing the principle. It then objects to the principle, on several of its readings, from non-sentence use. The suggested result, in the face of this objection, was three parts consistency and two parts inconsistency: (a) the first reading of the principle would be largely untouched; (b) the second would be left unsupported; but (c) the other readings would be outright falsified.
Scepticism About Gods
Authors: Long A. A.
Published: February 2007

The philosophical sceptic attacks, in the doctrines of his rivals, not or not primarily the traditional features of the gods that the doctrinaire schools retain, but the rational innovations — the attempt to justify theological doctrines by appeal to experience, conceptual analysis, and argument. Sextus Empiricus characterizes the sceptic as one who may be in a safer position than other philosophers: he abides by local traditions in saying that gods exist and in worshipping them. Even the official sceptics make no profession of seeking to undermine religious beliefs outside a specific dialectical context. Their object is not to induce atheism, but to show that, for every argument concluding to the existence of gods, an argument of equal strength can be advanced on the opposite side. The sceptic intends to leave himself and his audience in a position whereby they neither affirm nor deny the existence of gods.
Chance and Laws of Nature in Epicureanism
Authors: Long A. A.
Published: February 2007

When Epicurus discharged the gods from running the world, he gave new fuel to a controversy which had been raging off and on for the past hundred years, and which would continue not only through the Hellenistic and early Christian centuries but even up to the present day, as 21st-century evolutionists lock horns with proponents of Intelligent Design. In nominating atoms and void as the basic principles of natural phenomena, Epicurus knew that he was entering an arena where Plato and Aristotle had already done battle against the mechanistic explanations of earlier thinkers. The first question of this study is whether Epicurus did envision a random or chance element in nature. It is argued that if the answer to this question is negative, there is no reason to give the swerve a larger role than that explicitly accorded it by Lucretius.
Stoic Psychology and the Elucidation of Language
Authors: Long A. A.
Published: February 2007

Stoics were enormously influential on the Graeco-Roman grammatical tradition, which extends from the later Hellenistic epoch into the Christian period of the Roman Empire. Recourse to the Stoic influence on that tradition can give the impression that these philosophers were merely pioneers in starting what the grammarians carried forward more fully and systematically. It is argued that such an impression may be seriously misleading in two respects. First, it incorrectly implies that the Stoics approached language as a phenomenon callingprimarilyfor the kind of grammatical and syntactical description later grammarians developed. Secondly, it fails to identify the philosophical considerations that underpin the Stoics' principal interests in language. It is shown that the Stoics had some splendid intuitions about the phonetic, grammatical, and semantic levels of linguistic structure. Although these bear directly on the development of traditional grammar, they also seem to have clear affinities with what modern experts in linguistics call universal grammar.
Stoic Philosophers on Persons, Property‐Ownership, and Community
Authors: Long A. A.
Published: February 2007

This chapter suggests a further tie between Stoicism and later conceptions of the person as a moral, psychological, and legal entity. That tie has to do not only with consciousness or self-consciousness, but also with the concept of property or ownership, a concept that the Stoics connected with self-consciousness and individual identity in a highly original way. It is argued that the Stoics pioneered two key notions of liberal thought: first, that every human individual is the natural and rightful owner of at least one thing — himself or herself; second, that human nature inclines individual human beings to acquire private property and to interact with one another as property-owners. Stoic ideas about human beings as property-owners have striking affinities with 17th-century and Enlightenment thought on property and persons, especially ideas developed by Locke and Hegel.
Reconstructing the Natural Philosopher
Authors: Gaukroger Stephen
Published: February 2007

The development of the persona of the natural philosopher is the key to understanding how natural philosophy becomes inserted into European culture in the 16th and 17th centuries. This chapter shows in detail that notions of truth and justification turn just as much on conceptions of intellectual honesty as they do on notions of method. It looks primarily at the standing of the natural philosopher in Bacon, Galileo, Descartes, Boyle, and Royal Society apologists, focusing on claims that the natural philosopher requires a kind of intellectual honesty lacking in scholastic natural philosophy. This is closely tied in with one of the distinctive features of early-modern natural philosophy: that questions that had earlier been seen in terms of truth are now discussed instead in terms of impartiality and objectivity.
SGN Sim, a Stochastic Genetic Networks Simulator
Authors: Ribeiro Andre S. , Lloyd-Price Jason
Published: February 2007

Summary: We present SGNSim, ‘Stochastic Gene Networks Simulator’, a tool to model gene regulatory networks (GRN) where transcription and translation are modeled as multiple time delayed events and its dynamics is driven by a stochastic simulation algorithm (SSA) able to deal with multiple time delayed events. The delays can be drawn from several distributions and the reaction rates from complex functions or from physical parameters. SGNSim can generate ensembles of GRNs, within a set of user-defined parameters, such as topology. It can also be used to model specific GRNs and systems of chemical reactions. Perturbations, e.g. gene deletion, over-expression, copy and mutation, can be modeled as well. As examples, we present a model of a toggle switch without cooperative binding subject to perturbations, a system of reactions within a compartmentalized environment where membrane crossing is controlled by a negative feedback mechanism and a simulation based on the yeast transcriptional network.

Availability:  SGNSim program, instructions and examples available at http://www.cs.tut.fi/~sanchesr/SGN/SGNSim.html.

Contact:  andre.sanchesribeiro@tut.fi
Gene expression network analysis and applications to immunology
Authors: Nacu Şerban , Critchley-Thorne Rebecca , Lee Peter , Holmes Susan
Published: February 2007

We address the problem of using expression data and prior biological knowledge to identify differentially expressed pathways or groups of genes. Following an idea of Ideker et al. (2002), we construct a gene interaction network and search for high-scoring subnetworks. We make several improvements in terms of scoring functions and algorithms, resulting in higher speed and accuracy and easier biological interpretation. We also assign significance levels to our results, adjusted for multiple testing. Our methods are succesfully applied to three human microarray data sets, related to cancer and the immune system, retrieving several known and potential pathways. The method, denoted by the acronym GXNA (Gene eXpression Network Analysis) is implemented in software that is publicly available and can be used on virtually any microarray data set.

Contact:  serban@stat.stanford.edu

Supplementary information: The source code and executable for the software, as well as certain supplemental materials, can be downloaded from http://stat.stanford.edu/~serban/gxna.
Boolean dynamics of genetic regulatory networks inferred from microarray time series data
Authors: Martin Shawn , Zhang Zhaoduo , Martino Anthony , Faulon Jean-Loup
Published: February 2007

Motivation: Methods available for the inference of genetic regulatory networks strive to produce a single network, usually by optimizing some quantity to fit the experimental observations. In this article we investigate the possibility that multiple networks can be inferred, all resulting in similar dynamics. This idea is motivated by theoretical work which suggests that biological networks are robust and adaptable to change, and that the overall behavior of a genetic regulatory network might be captured in terms of dynamical basins of attraction.

Results: We have developed and implemented a method for inferring genetic regulatory networks for time series microarray data. Our method first clusters and discretizes the gene expression data using k-means and support vector regression. We then enumerate Boolean activation–inhibition networks to match the discretized data. Finally, the dynamics of the Boolean networks are examined. We have tested our method on two immunology microarray datasets: an IL-2-stimulated T cell response dataset and a LPS-stimulated macrophage response dataset. In both cases, we discovered that many networks matched the data, and that most of these networks had similar dynamics.

Contact:  jfaulon@sandia.gov

Supplementary information: Supplementary data are available at Bioinformatics online.
SNPassoc: an R package to perform whole genome association studies
Authors: González Juan R. , Armengol Lluís , Solé Xavier , Guinó Elisabet , Mercader Josep M. , Estivill Xavier , Moreno Víctor
Published: February 2007

Summary: The popularization of large-scale genotyping projects has led to the widespread adoption of genetic association studies as the tool of choice in the search for single nucleotide polymorphisms (SNPs) underlying susceptibility to complex diseases. Although the analysis of individual SNPs is a relatively trivial task, when the number is large and multiple genetic models need to be explored it becomes necessary a tool to automate the analyses. In order to address this issue, we developed SNPassoc, an R package to carry out most common analyses in whole genome association studies. These analyses include descriptive statistics and exploratory analysis of missing values, calculation of Hardy–Weinberg equilibrium, analysis of association based on generalized linear models (either for quantitative or binary traits), and analysis of multiple SNPs (haplotype and epistasis analysis).

Availability: Package SNPassoc is available at CRAN from http://cran.r-project.org

Contact:  juanramon.gonzalez@crg.es or v.moreno@iconcologia.net

Supplementary information: A tutorial is available on Bioinformatics online and in http://davinci.crg.es/estivill_lab/snpassoc
Matching as Nonparametric Preprocessing for Reducing Model Dependence in Parametric Causal Inference
Authors: Ho Daniel E. , Imai Kosuke , King Gary , Stuart Elizabeth A.
Published: February 2007

Although published works rarely include causal estimates from more than a few model specifications, authors usually choose the presented estimates from numerous trial runs readers never see. Given the often large variation in estimates across choices of control variables, functional forms, and other modeling assumptions, how can researchers ensure that the few estimates presented are accurate or representative? How do readers know that publications are not merely demonstrations that it ispossibleto find a specification that fits the author's favorite hypothesis? And how do we evaluate or even define statistical properties like unbiasedness or mean squared error when no unique model or estimator even exists? Matching methods, which offer the promise of causal inference with fewer assumptions, constitute one possible way forward, but crucial results in this fast-growing methodological literature are often grossly misinterpreted. We explain how to avoid these misinterpretations and propose a unified approach that makes it possible for researchers to preprocess data with matching (such as with the easy-to-use software we offer) and then to apply the best parametric techniques they would have used anyway. This procedure makes parametric models produce more accurate and considerably less model-dependent causal inferences.
Arteriovenous Malformations of the Tongue: A Spectrum of Disease
Authors: Richter Gresham T. , Suen James , North Paula E. , James Charles A. , Waner Milton , Buckmiller Lisa M.
Published: February 2007

Objectives: To examine our vascular anomalies team's experience with tongue arteriovenous malformations (AVM) with specific emphasis on the spectrum on disease and surgical management.

Methods: Retrospective chart review of 11 patients (10 female, 1 male), discovered from 1997 to 2005 with histological, radiographic, and clinical characteristics consistent with tongue AVM.

Results: Four patients displayed advanced disease with malformations involving the tongue, floor of mouth, and neck. Contributions from multiple feeding arteries were identified by angiography as each patient reported a prior history of surgical or embolic procedures. These lesions required preoperative embolization and extensive resection with complex reconstruction (mean operating time, 10.9 hr). One patient had evidence of recurrent disease (mean follow‐up, 24.6 mo). In contrast, seven patients presented with discreet tongue malformations with a single feeding lingual artery. These patients reported no prior intervention, required only one resection (mean operating time, 2.8 hr), and have shown no evidence of recurrence (mean follow‐up, 11 mo). Slight histologic differences between advanced versus focal tongue AVM were identified.

Conclusions: This study suggests that tongue AVM can occur within a spectrum of disease with different clinical presentations, radiographic findings, and histology among patients with focal versus advanced lesions. Inadequate treatment is thought to contribute to collateral flow and disease progression in advanced AVM, making further management difficult. However, focal tongue AVM may represent early lesions that are more amenable to surgical management.
Pediatric Endoscopic Dacryocystorhinostomy Failures: Who and Why?
Authors: Jones Dwight T. , Fajardo Norman F. , Petersen Robert A. , VanderVeen Deborah K.
Published: February 2007

Objective: The objectives of this study are to report outcomes of pediatric patients with nasolacrimal duct obstruction (NLDO) who underwent primary endoscopic dacryocystorhinostomy (DCR) and discuss causes of failure.

Study Design: The authors conducted a retrospective case series.

Methods: Charts of all patients less than 16 years of age who underwent primary endoscopic DCR from 1997 to 2004 were reviewed. Patients were grouped based on the presence or absence of facial anomalies or syndromes and whether the NLDO was congenital or acquired. Success was defined as complete resolution of symptoms, improvement included anatomic patency or partial symptoms, and failure as no improvement or demonstration of patency.

Results: Thirty‐four patients (43 ducts) aged 11 months to 14 years were identified. There were 17 males and 17 females. Follow up ranged from 2 to 54 months (average, 21 months). Twenty‐four patients (29 ducts) had congenital NLDO, seven patients (11 ducts) had congenital syndromes associated with craniofacial abnormalities, and three patients (three ducts) had acquired NLDO. In patients with congenital NLDO without craniofacial abnormalities or syndromes, 22 of 29 eyes (76%) were cured with another three (10%) showing improvement. Only one of 11 (9%) eyes of patients with congenital craniofacial abnormality or syndrome experienced complete resolution and only four of 11 (36%) eyes showed improvement. Of the patients with acquired NLDO, two of three (67%) of the eyes were cured and one (33%) improved.

Conclusions: Endoscopic DCR is safe and effective for most children, although patients with craniofacial abnormalities or syndromes are extremely difficult to cure.
Blepharokymographic Analysis of Eyelid Motion in Bell's Palsy
Authors: Choi Seung‐Ho , Yoon Tae Hyun , Lee Kwang‐Sun , Ahn Joong Ho , Chung Jong Woo
Published: February 2007

Objective: To present characteristics of eyelid motion measured by blepharokymography in Bell's palsy patients and to discuss possible roles and limitations of blepharokymography.

Study Design. Retrospective analysis.

Methods: The study included 72 patients with Bell's palsy who presented to the Department of Otolaryngology at Asan Medical Center, Seoul, Korea, between April 2002 and March 2005, and who underwent both electroneuronography and blepharokymography. Parameters of eyelid motion were measured using revised blepharokymography. Correlations between blepharokymography and electroneuronography or House‐Brackmann grade were examined by Spearman rank correlation and Kendall's τ‐b correlation, respectively.

Results: Compared with the normal side, all parameters of eyelid motion except opening time were decreased on the palsy side, with peak closing velocity showing the greatest difference (40.2%). On average, paralytic eyelids moved down 6.5 mm in 277 ms with a peak velocity of 55.4 mm/s, whereas normal eyelids moved down 9.7 mm in 214 ms, with a peak velocity of 142.6 mm/s. Subtle paralytic eyelid motion or “lid lag” could be objectively documented by blepharokymography to have longer and gentler downward slopes in displacement curves. Most blepharokymographic parameters correlated with ocular electroneuronography and House‐Brackmann grade.

Conclusions: Slow or incomplete closure of paralytic eyelids can be graphically and numerically analyzed by blepharokymography. Blepharokymography may be useful for evaluating status, predicting prognosis, and assessing effects of rehabilitative procedures, including gold weight implants in patients with facial palsy.
Oceanobacillus profundus sp. nov., isolated from a deep-sea sediment core
Authors: Kim Yoon-Gon , Choi Dong Han , Hyun Sangmin , Cho Byung Cheol
Published: February 2007

A halotolerant, facultatively alkaliphilic bacterium, designated CL-MP28T, was isolated from the surface of a sediment core sample collected at a depth of 2247 m in the Ulleung Basin of the East Sea, Korea. Phylogenetic analysis of the 16S rRNA gene sequence of strain CL-MP28T revealed an affiliation with the genus Oceanobacillus. The sequence similarities between the isolate and type strains of members of the genus Oceanobacillus were in the range 95.0–96.0 %, indicating that strain CL-MP28T represented a novel species within the genus. The strain was found to be Gram-positive, rod-shaped and motile by means of peritrichous flagella and was shown to produce ellipsoidal spores. The strain was strictly aerobic and able to grow with NaCl at concentrations in the range 0–14 % (w/v) at pH 7.5. The strain grew at temperatures of 15–42 °C and at pH 6.5–9.5. The major fatty acids were anteiso-C15 : 0 (64.9 %), anteiso-C17 : 0 (11.9 %) and iso-C16 : 0 (7.7 %). The major isoprenoid quinone was MK-7. The DNA G+C content was 40.2 mol%. According to the 16S rRNA gene sequence, DNA–DNA relatedness and physiological data and the fatty acid composition, CL-MP28T could be assigned to the genus Oceanobacillus, but is distinguishable from the recognized species of this genus. Strain CL-MP28T therefore represents a novel species within the genus Oceanobacillus, for which the name Oceanobacillus profundus sp. nov. is proposed. The type strain is CL-MP28T (=KCCM 42318T=DSM 18246T).
Sphingobium aromaticiconvertens sp. nov., a xenobiotic-compound-degrading bacterium from polluted river sediment
Authors: Wittich Rolf-Michael , Busse Hans-Jürgen , Kämpfer Peter , Tiirola Marja , Wieser Monika , Macedo Alexandre J. , Abraham Wolf-Rainer
Published: February 2007

A bacterial strain capable of degrading some monochlorinated dibenzofurans, designated RW16T, was isolated from aerobic River Elbe sediments. The strain was characterized based on 16S rRNA gene sequence analysis, DNA G+C content, physiological characteristics, polyamines, ubiquinone and polar lipid pattern and fatty acid composition. This analysis revealed that strain RW16T represents a novel species of the genus Sphingobium. The DNA G+C content of strain RW16T, 60.7 mol%, is the lowest yet reported for the genus. 16S rRNA gene sequence analysis placed strain RW16T as an outlier in the genus Sphingobium. The name Sphingobium aromaticiconvertens sp. nov. is proposed for this dibenzofuran-mineralizing organism, with type strain RW16T (=DSM 12677T=CIP 109198T).
Sphingomonas molluscorum sp. nov., a novel marine isolate with antimicrobial activity
Authors: Romanenko Lyudmila A. , Uchino Masataka , Frolova Galina M. , Tanaka Naoto , Kalinovskaya Natalia I. , Latyshev Nicolai , Mikhailov Valery V.
Published: February 2007

An aerobic, Gram-negative, yellow-pigmented, non-motile bacterium, designated strain KMM 3882T, was isolated from a marine bivalve (Anadara broughtoni) collected from Peter the Great Bay, Sea of Japan, and was subjected to phenotypic and phylogenetic analyses. Strain KMM 3882Twas found to exert a remarkable inhibitory activity against a number of Gram-positive micro-organisms. Phylogenetic analysis based on 16S rRNA gene sequences placed strain KMM 3882Twithin the genusSphingomonas, as an independent lineage adjacent toSphingomonas dokdonensisDS-4TandSphingomonas panniDSM 15761T. Strain KMM 3882Tshowed the highest 16S rRNA gene sequence similarity toSphingomonas dokdonensisDS-4T(97.3 %); similarities of 96.5–96.7 % were obtained withSphingomonas pituitosaDSM 13101T,Sphingomonas azotifigensNBRC 15497T,Sphingomonas asaccharolyticaNBRC 15499T,Sphingomonas trueperiDSM 7225TandSphingomonas panniDSM 15761T. Chemotaxonomically, strain KMM 3882Tcontained sphingoglycolipid, C16 : 0and C18 : 1as predominant fatty acids and 2-OH C14 : 0as a major 2-hydroxy fatty acid, confirming the affiliation of strain KMM 3882Twith the genusSphingomonas. On the basis of phylogenetic analysis, DNA–DNA hybridization and physiological and biochemical characterization, strain KMM 3882Tshould be classified as representing a novel species of the genusSphingomonas, for which the nameSphingomonas molluscorumsp. nov. is proposed. The type strain is KMM 3882T(=An 18T=NRIC 0685T=JCM 14122T=CIP 109223T).
Leifsonia ginsengi sp. nov., isolated from ginseng root
Authors: Qiu Fubin , Huang Ying , Sun Lei , Zhang Xiaoxia , Liu Zhiheng , Song Wei
Published: February 2007

A Gram-positive, rod-shaped, non-motile bacterium, designated strain wged11T, was isolated from the root of ginseng, and its taxonomic position was established using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that this organism formed a robust clade with recognized species of the genus Leifsonia. Strain wged11T was characterized by a high content of ω-cyclohexylundecanoic and anteiso- and iso-branched saturated fatty acids, MK-11 as the major menaquinone and dl-2,4-diaminobutyric acid in its cell-wall peptidoglycan. The DNA G+C content of strain wged11T was 66.4 mol%. Levels of similarity between the 16S rRNA gene sequence of strain wged11T and those of the type strains of other members of the genus Leifsonia ranged from 94.7 to 97.6 %. The mean level of DNA–DNA relatedness between strain wged11T and Leifsonia poae DSM 15202T, its nearest phylogenetic neighbour, was 35.3 %. Based on these findings, strain wged11T (=CGMCC 4.3491T=JCM 13908T) is proposed as the type strain of a novel species of the genus Leifsonia, Leifsonia ginsengi sp. nov.
Kazachstania siamensis sp. nov., an ascomycetous yeast species from forest soil in Thailand
Authors: Limtong Savitree , Yongmanitchai Wichien , Tun Moe Moe , Kawasaki Hiroko , Seki Tatsuji
Published: February 2007

Two strains (S-34T and S-35) of a novel ascomycetous yeast species belonging to the genus Kazachstania were isolated from soil from a mixed deciduous forest in Amphoe Wang Nam Khiao, Nakhon Ratchasima Province, Thailand. The D1/D2 domains of the large-subunit rDNA sequences of the two strains were identical and also indicated a close relationship with respect to Kazachstania aquatica, Kazachstania unispora, Kazachstania aerobia, Kazachstania servazzii and Kazachstania solicola. The most closely related species, K. aquatica, has 14 nucleotide substitutions and three gaps in 566 nt. The phenotypic characteristics of the two strains were typical of those of members of the genus Kazachstania. These characteristics include the formation of a single globose ascospore in an unconjugated and persistent ascus, multilateral budding, the absence of arthrospores and ballistospores, the fermentation of glucose, the inability to assimilate nitrate, negative diazonium blue B and urease reactions, and the presence of ubiquinone Q-6. The novel strains can be distinguished from K. aquatica on the basis of a number of phenotypic characteristics and represent a novel species in the genus Kazachstania, for which the name Kazachstania siamensis sp. nov. is proposed. The type strain is S-34T (=CBS 10361T=NBRC 101968T=BCC 21230T).
Nitrogen-fixing and cellulose-producing Gluconacetobacter kombuchae sp. nov., isolated from Kombucha tea
Authors: Dutta Debasree , Gachhui Ratan
Published: February 2007

A few members of the familyAcetobacteraceaeare cellulose-producers, while only six members fix nitrogen. Bacterial strain RG3T, isolated from Kombucha tea, displays both of these characteristics. A high bootstrap value in the 16S rRNA gene sequence-based phylogenetic analysis supported the position of this strain within the genusGluconacetobacter, withGluconacetobacter hanseniiLMG 1527Tas its nearest neighbour (99.1 % sequence similarity). It could utilize ethanol, fructose, arabinose, glycerol, sorbitol and mannitol, but not galactose or xylose, as sole sources of carbon. Single amino acids such asl-alanine,l-cysteine andl-threonine served as carbon and nitrogen sources for growth of strain RG3T. Strain RG3Tproduced cellulose in both nitrogen-free broth and enriched medium. The ubiquinone present was Q-10 and the DNA base composition was 55.8 mol% G+C. It exhibited low values of 5.2–27.77 % DNA–DNA relatedness to the type strains of related gluconacetobacters, which placed it within a separate taxon, for which the nameGluconacetobacter kombuchaesp. nov. is proposed, with the type strain RG3T(=LMG 23726T=MTCC 6913T).
Molecular cloning of a translocation breakpoint hotspot in 22q11
Authors: Kurahashi Hiroki , Inagaki Hidehito , Hosoba Eriko , Kato Takema , Ohye Tamae , Kogo Hiroshi , Emanuel Beverly S.
Published: February 2007

It has been well documented that 22q11 contains one of the most rearrangement-prone sites in the human genome, where the breakpoints of a number of constitutional translocations cluster. This breakage-sensitive region is located within one of the remaining unclonable gaps from the human genome project, suggestive of a specific sequence recalcitrant to cloning. In this study, we cloned a part of this gap and identified a novel 595-bp palindromic AT-rich repeat (PATRR). To date we have identified three translocation-associated PATRRs. They have common characteristics: (1) they are AT-rich nearly perfect palindromes, which are several hundred base pairs in length; (2) they possess non-AT-rich regions at both ends of the PATRR; (3) they display another nearby AT-rich region on one side of the PATRR. All of these features imply a potential for DNA secondary structure. Sequence analysis of unrelated individuals indicates no major size polymorphism, but shows minor nucleotide polymorphisms among individuals and cis-morphisms between the proximal and distal arms. Breakpoint analysis of various translocations indicates that double-strand-breakage (DSB) occurs at the center of the palindrome, often accompanied by a small symmetric deletion at the center. The breakpoints share only a small number of identical nucleotides between partner chromosomes. Taken together, these features imply that the DSBs are repaired through nonhomologous end joining or single-strand annealing rather than a homologous recombination pathway. All of these results support a previously proposed paradigm that unusual DNA secondary structure plays a role in the mechanism by which palindrome-mediated translocations occur.
Comparative sequence analyses reveal rapid and divergent evolutionary changes of theWFDClocus in the primate lineage
Authors: Hurle Belen , Swanson Willie ,   NISC Comparative Sequencing Program, Green Eric D.
Published: February 2007

The initial comparison of the human and chimpanzee genome sequences revealed 16 genomic regions with an unusually high density of rapidly evolving genes. One such region is the whey acidic protein (WAP) four-disulfide core domain locus (orWFDClocus), which contains 14WFDCgenes organized in two subloci on human chromosome 20q13. WAP protease inhibitors have roles in innate immunity and/or the regulation of a group of endogenous proteolytic enzymes called kallikreins. In human, the centromericWFDCsublocus also contains the rapidly evolving seminal genes, semenogelin 1 and 2 (SEMG1andSEMG2). The rate ofSEMG2evolution in primates has been proposed to correlate with female promiscuity and semen coagulation, perhaps related to post-copulatory sperm competition. We mapped and sequenced the centromericWFDCsublocus in 12 primate species that collectively represent four different mating systems. Our analyses reveal a 130-kb region with a notably complex evolutionary history that has included nested duplications, deletions, and significant interspecies divergence of both coding and noncoding sequences; together, this has led to striking differences of this region among primates and between primates and rodents. Further, this region contains six closely linked genes (WFDC12,PI3,SEMG1,SEMG2,SLPI, andMATN4) that show strong patterns of adaptive selection, although an unambiguous correlation between gene mutation rates and mating systems could not be established.
Memory is not extinguished along with CS presentation but within a few seconds after CS-offset
Authors: Pérez-Cuesta Luis María , Hepp Yanil , Pedreira María Eugenia , Maldonado Héctor
Published: February 2007

Prior work with the crab’s contextual memory model showed that CS-US conditioned animals undergoing an unreinforced CS presentation would either reconsolidate or extinguish the CS-US memory, depending on the length of the reexposure to the CS. Either memory process is only triggered once the CS is terminated. Based on these results, the following questions are raised. First, when is extinction memory acquired, if not along extinction training, and how long does it take? Second, can acquisition and consolidation of extinction memory be pharmacologically dissected? Here we address these questions performing three series of experiments: a first one aimed to study systematically the relationship between extinction and increasing periods of unreinforced CS presentations, a second one to determine the time boundaries of the extinction memory acquisition, and the third one to assay the requirement for protein synthesis and NMDA-like receptors of acquisition and consolidation of extinction memory. Our results confirm that it is CS-offset and not the mere retrieval (CS-onset) that triggers acquisition of extinction memory and that it is completed in less than 45 sec after CS-offset. In addition, protein synthesis is required for consolidation but not for acquisition of this memory and, conversely, NMDA-like receptor activity is required for its acquisition but not for its consolidation. Finally, we offer an interpretative scheme of our results and we discuss to what extent it could apply to multitrial extinction.
The Impact of Exercise Training on Blood Lipids in Older Adults
Authors: Boardley Debra , Fahlman Mariane , Topp Robert , Morgan Amy L. , McNevin Nancy
Published: February 2007

Increasing physical activity is often prescribed to improve blood lipids; however, the efficacy of exercise in improving blood lipids in older adults is not clear. The objective of this study was to examine the effects of different exercise modes on blood lipid levels in previously sedentary older adults engaging in a 16‐week exercise intervention. One hundred thirty‐one subjects (mean age 74.6±6 years) were randomly assigned to a resistance training group, aerobic walking group, combined exercise group, or nonexercising control group. Blood lipids were measured at baseline, 8 weeks, and postintervention. Exercise mode did not impact blood lipids. All groups had lower lipid levels over time. Total cholesterol, low‐ and high‐density lipoprotein, and triglycerides were significantly lower. The decrease in all groups, including the controls, may be due to a seasonal effect in older adults that has been documented in younger individuals.
Estimation of digestion rates for herring Clupea harengus L. feeding on fish larvae
Authors: Hallfredsson E. H. , Pedersen T. , Præbel K.
Published: February 2007

Two methods for estimating digestion rate were evaluated and the digestion rate to disappearance was estimated to be 0·30 h−1 for herring Clupea harengus feeding on capelin Mallotus villosus larvae. Due to high individual variability in feeding rates in schooling fish species, groups should be fed in separate tanks and stomach contents collected from each group at a predetermined time.
Autoradiographic confirmation of mucus‐mediated absorption in the halfbeak Hyporhamphus regularis ardelio (Whitley, 1931)
Authors: Carseldine L. , Tibbetts I. R.
Published: February 2007

In an investigation of the relationship between acidic glycoproteins released in the pharynx and oesophagus of Hyporhamphus regularis ardelio and ‘juice’ released from Zostera capricorni by pharyngeal milling, autoradiographs of thin sections of guts of fish fed C14 labelled seagrass leaves revealed high emission densities in the acidic glycoprotein sheath surrounding the ingesta. This indicates that ‘juice’ liberated from seagrass is taken up by the mucus.
Size at hatching and incubation period of Sympterygia bonapartii (Müller & Henle, 1841) (Chondrichthyes, Rajidae) bred in captivity at the Temaiken Aquarium
Authors: Jañez J. A. , Sueiro M. C.
Published: February 2007

Two mature Sympterygia bonapartii held in captivity laid a total of 136 egg cases, 33 of them were incubated at constant temperature (16·5° C), salinity (36) and photoperiod (12L:12D). The hatching rate was 100%. Juvenile fish hatched after 135 ± 10 days (mean ±s.d.) and the mean total length, disc width and mass at hatching were 140 mm, 86 mm and 15·1 g respectively.
Activation of downstream epidermal growth factor receptor (EGFR) signaling provides gefitinib‐resistance in cells carrying EGFR mutation
Authors: Uchida Akiko , Hirano Seiki , Kitao Hiroyuki , Ogino Atsuko , Rai Kanmei , Toyooka Shinichi , Takigawa Nagio , Tabata Masahiro , Takata Minoru , Kiura Katsuyuki , Tanimoto Mitsune
Published: February 2007

Patients with pulmonary adenocarcinoma carrying the epidermal growth factor receptor (EGFR) mutation tend to display dramatic clinical response to treatment with the EGFR tyrosine kinase inhibitor gefitinib. Unfortunately, in many cases the cancer cells eventually acquire resistance, and this limits the duration of efficacy. To gain insight into these acquired resistance mechanisms, we first prepared HEK293T cell line stably transfected with either wild‐type (WT) or mutant (L858R) EGFR, and then expressed oncogenic K‐Ras12V mutant in the latter transfectant. Although 293T cells expressing wild‐type EGFR did not show any growth inhibition by gefitinib treatment similarly to the non‐transfected cells, the cells expressing the EGFR‐L858R were exquisitely sensitive. Consistently, phospho‐Akt levels were decreased in response to gefitinib in cells expressing EGFR‐L858R but not in cells with EGFR‐WT. In contrast, 293T cells expressing both EGFR‐L858R and oncogenic K‐Ras were able to proliferate even in the presence of high concentration of gefitinib probably by inducing Erk1/2 activation. We also expressed K‐Ras12V in the gefitinib‐sensitive pulmonary adenocarcinoma cell line PC‐9, which harbors an in‐frame deletion in the EGFR gene. The activated K‐Ras inhibited the effects of gefitinib treatment on cell growth, cell death induction and levels of phospho‐Akt, as well as phospho‐Erk. These data indicate that activated Ras could substitute most of the upstream EGFR signal, and are consistent with the hypothesis that mutational activation of targets immediately downstream from the EGFR could induce the secondary resistance to gefitinib in patients with lung cancer carrying EGFR mutation. (Cancer Sci 2007; 98: 357–363)
Gene expression profiling in a mouse model of Helicobacter‐induced gastric cancer
Authors: Takaishi Shigeo , Wang Timothy C.
Published: February 2007

We have previously reported that a synergistic interaction between hypergastrinemia and Helicobacter felis (H. felis) infection accelerates gastric carcinogenesis in mice, but the precise mechanism for this interaction has not been clarified. Consequently, we undertook an oligonucleotide cDNA microarray study to investigate changes in gene expression in this model system. Male hypergastrinemic transgenic (INS‐GAS) mice with 6‐months H. felis infection were compared with three different age, strain and gender‐matched control groups: (i) INS‐GAS mice without H. felis infection; (ii) non‐transgenic FVB/N mice with H. felis infection; and (iii) non‐transgenic FVB/N mice without H. felis infection. Complementary RNA derived from whole stomach were hybridized to the Affymetrix GeneChip murine U74Av2 array. Among 12 000 cDNA spotted on each chip, 35 cDNA were upregulated and 41 cDNA were downregulated more than twofold in H. felis‐infected INS‐GAS mice compared with all three control groups. Expression changes were validated in 12 selected genes by northern hybridization and/or quantitative real‐time reverse transcription polymerase chain reaction (RT‐PCR). Confirmed upregulated genes included Reg I, amphiregulin, MMP‐10, MMP‐13, claudin‐7 and chitinase 3‐like 1, while confirmed downregulated genes included H/K‐ATPase alpha and beta subunits, intrinsic factor, somatostatin, galectin‐2 and apolipoprotein A‐I. Immunohistochemical analysis of MMP‐10, amphiregulin, H/K‐ATPase beta subunit and galectin‐2 confirmed these expression changes at the protein level, and MMP‐10 was mainly detected in stromal cells of submucosal region, while the other three genes were expressed in gastric epithelial cells. Taken together, gene expression profiling of this mouse model may provide novel insights into Helicobacter‐induced gastric carcinogenesis. (Cancer Sci 2007; 98: 284–293)
The expression of ezrin in NPC and its interaction with NGX6, a novel candidate suppressor
Authors: Peng Shuping , Fan Songqing , Li Xiaoling , Wang Li , Liu Huaying , Zhou Ming , Wang Lili , Shen Shourong , Li Guiyuan
Published: February 2007

Ezrin, the linker between membrane protein and cytoskeleton, plays an important role in the cellular morphology, cytoskeleton reorganization, adhesion, invasion and metastasis. In this study, ezrin was found to express in high levels either in nasopharyngeal carcinoma tissues or in nasopharyngeal carcinoma 5‐8F cells and the knockdown of ezrin expression in the 5‐8F cells by RNA interferance could reduce invasive ability, suggesting that ezrin is involved in the progression and invasion of nasopharyngeal carcinoma. Nasopharyngeal carcinoma‐associated gene 6 is a novel candidate suppressor gene of tumor metastasis, which was originally cloned in nasopharyngeal carcinoma high‐frequency heterozygosity loss region 9p21‐22 and is down‐regulated in nasopharyngeal carcinoma. In the present study, we hypothesize that nasopharyngeal carcinoma‐associated gene 6 plays an inhibitory role in the migration and invasion of nasopharyngeal carcinoma cells via modulating the function of ezrin. Firstly, different mutants of NGX6 were constructed and transfected into nasopharyngeal carcinoma 5‐8F cells. The invasion and migration of 5‐8F cells overexpressing nasopharyngeal carcinoma‐associated gene 6 or mutants were measured. The results showed that enhanced expression of nasopharyngeal carcinoma‐associated gene 6 could reduce invasive and migratory abilities of 5‐8F cells, and the cytoplasmic domain was essential for nasopharyngeal carcinoma‐associated gene 6 to modulate cell migration and invasion. Further experiment results showed that nasopharyngeal carcinoma‐associated gene 6 protein was associated with ezrin by its cytoplasm region, and it could down‐regulate the expression level of ezrin. These results demonstrated that nasopharyngeal carcinoma‐associated gene 6 was probably involved in the modulation of invasive and adhesive ability of nasopharyngeal carcinoma cells by down‐regulating the expression level of ezrin. (Cancer Sci 2007; 98: 341–349)
Courtship displays in anurans and lizards: theoretical and empirical contributions to our understanding of costs and selection on males due to female choice
Authors: SULLIVAN BRIAN K. , KWIATKOWSKI MATTHEW A.
Published: February 2007

Male frogs and toads expend considerable energy and experience potential predation risk while calling in breeding aggregations; similarly, male lizards display behaviourally and exhibit striking colour patterns during courtship interactions. These apparently costly displays of male anuran amphibians and squamate reptiles have been argued to play an important role in mate selection by females. Although female preferences for male display traits under controlled conditions have been documented for both taxonomic groups, directional selection on male displays has rarely been adequately assessed under natural conditions.

We discuss theoretical and empirical considerations of display costs in the context of sexual selection due to female preferences in anurans and lizards. We review experimental evidence of female preferences for apparently costly displays by males and estimation of selection on male traits due to female choice in the field in these taxonomic groups.

Evidence of female preferences for apparently costly display traits is not uncommon for thoroughly studied populations, and there is some field evidence of significant selection on these traits in at least one well studied group: prolonged breeding toads. Studies have been hampered by confusion over the definitions of costs, difficulty in adequately describing variation in male displays, and overly simplistic approaches to documentation of female preferences.

Future work should include recognition of variation in definitions of cost in relation to male display behaviour, acknowledgement that female choice may be based on multiple male characteristics, and that considerable effort, including documentation of consistency in male behaviour, is required before inferences regarding the importance of female choice in sexual selection can be drawn.
Mouse homolog of SALL1, a causative gene for Townes–Brocks syndrome, binds to A/T‐rich sequences in pericentric heterochromatin via its C‐terminal zinc finger domains
Authors: Yamashita Kazunari , Sato Akira , Asashima Makoto , Wang Pi‐Chao , Nishinakamura Ryuichi
Published: February 2007

The Spalt (sal) gene family is conserved from Drosophila to humans. Mutations of human SALL1 cause Townes–Brocks syndrome, with features of ear, limb, anal, renal and heart anomalies. Sall1, a murine homolog of SALL1, is essential for kidney formation, and both Sall1 and SALL1 localize to heterochromatin in the nucleus. Here, we present a molecular mechanism for the heterochromatin localization of Sall1. Mutation analyses revealed that the 7th−10th C‐terminal double zinc finger motifs were required for the localization. A recombinant protein of the most C‐terminal double zinc finger (9th−10th) bound to specific A/T‐rich sequences. Furthermore, Sall1 associated with A/T‐rich sequences of the major satellite DNA in heterochromatin. Thus Sall1 may bind to A/T‐rich sequences of the major satellite DNA via its C‐terminal double zinc fingers, thereby mediating its localization to heterochromatin.
The dual function of hepatic SOCS3 in insulin resistance in vivo
Authors: Torisu Takehiro , Sato Naoichi , Yoshiga Daigo , Kobayashi Takashi , Yoshioka Tomoko , Mori Hiroyuki , Iida Mitsuo , Yoshimura Akihiko
Published: February 2007

Inflammation associates with insulin resistance, which dysregulates nutrient homeostasis and leads to diabetes. The suppressor of cytokine signaling 3 (SOCS3), which is induced by pro‐inflammatory cytokines, such as TNFα and IL‐6, has been implicated in inflammation‐mediated insulin resistance in the liver and adipocytes. However, no genetic evidence has been provided for the involvement of SOCS3 on insulin resistance. Here, we generated hepatocyte‐specific SOCS3‐deficient (L‐SOCS3 cKO) mice and examined insulin sensitivity. Being consistent with a previous idea, the loss of SOCS3 in the liver apparently improved insulin sensitivity. However, unexpectedly, L‐SOCS3 cKO mice exhibited obesity and systemic insulin resistance with age. Insulin signaling was rather suppressed in muscles, suggesting that deletion of the SOCS3 gene in the liver modulates insulin sensitivity in other organs. Anti‐inflammatory reagent, sodium salicylate, partial improved insulin resistance of aged L‐SOCS3 cKO mice, suggesting that enhanced inflammatory status is associated with the phenotype of these mice. STAT3 was hyperactivated and acute‐phase proteins were elevated in L‐SOCS3 cKO mice liver, which were reduced by sodium salicylate treatment. We conclude that hepatic SOCS3 is a mediator of insulin resistance in the liver; however, lack of SOCS3 in the liver promotes systemic insulin resistance by mimicking chronic inflammation.