bluuebunny/crossref_metadata_2025 huggingface dataset:
Palatability Shifts in Taste and Flavour Preference Conditioning
Authors: Forestell Catherine A. , LoLordo Vincent M.
Published: February 2003

Changes in palatability of tastes and flavours as a result of flavour preference conditioning were examined. In Experiment 1, when tastes were paired with glucose in a reverse-order differential conditioning paradigm, rats acquired conditioned preferences for CS + and displayed more hedonic responses to CS + than to CS − in a postconditioning taste reactivity test. In Experiment 2, rats that received oral infusions of flavours as CSs during a reverse-order conditioning procedure expressed both palatability shifts and conditioned preferences for CS +. Rats that received a forward conditioning procedure acquired a preference for CS +, but the palatability of CS + was unchanged. In Experiment 3, hungry rats drank mixtures of a flavour CS and a calorific or sweet tasting reinforcer in a long-exposure conditioning paradigm. When tested hungry, rats preferred CS + whether they had acquired flavour-calorie or flavour-taste associations. However, CS + became more palatable only for rats that acquired flavour-calorie associations. These results suggest that acquisition of flavour preferences, as measured by 2-bottle tests, may not always be accompanied by enhanced palatability.
West Flemish Negation and the Derivation of SOV-Order in West Germanic
Authors: Haegeman Liliane
Published: February 2003

This paper focuses on the expression of sentential negation in West Flemish (WF), which it examines with respect to competing theories for deriving the West Germanic verb-final sentence pattern. The empirical adequacy of three hypotheses proposed to account for the verb-final order in the West Germanic languages is tested: (i) the ‘traditional’ OV analysis with head-final base structures; (ii) an antisymmetric approach with only head-complement order and without V-to-I movement; (iii) an antisymmetric approach with head-complement order, but with V-to-I movement and remnant movement of the projection containing the trace of V. Specifically, the question is asked to what extent these analyses capture the surface distribution of WF negation markers (niet, enand negative quantifiers). The paper shows that the traditional OV analysis is certainly adequate for the description of the data concerned. As far as antisymmetric approaches are concerned, a double movement analysis fares better than antisymmetric approaches without V-to-I movement. The paper also shows that, contrary to what has often been assumed, the WF morphemeenis not necessarily analysed as the head of NegP, the canonical projection to encode sentential negation, but that it could also plausibly be analysed as the head of PolP, a higher functional projection which encodes polarity.
Adjunction Sites for Negation in Norwegian: Modals and Negation
Authors: Eide Kristin M.
Published: February 2003

This paper investigates a surprising interpretational asymmetry in modal-negation sequences in Norwegian: When the negation wordfollowsthe subject, the sentence is ambiguous with respect to the relative scopes of the negation and the modal. When negationprecedesthe subject, however, the negation unambiguously takes scope over the modal. I argue that this asymmetry can be accounted for by assuming that verb raising has semantic implications; contrary to Chomsky (2001a). Modal-negation sequences in subordinate clauses do not display the same asymmetry, which supports the hypothesis that verb raising causes the observed patterns. Moreover, many speakers reject the sequence negation-subject in subordinate clauses. I propose that, for these speakers, main clauses employ two adjunction sites for negation, whereas subordinate clauses employ only one.
Tumour necrosis factor‐α, interleukin‐2 soluble receptor and different inflammatory parameters in patients with rheumatoid arthritis
Authors: Fröde Tânia Silvia , Tenconi Patrícia , Debiasi Marilei Reynaud , Medeiros Yara Santos
Published: February 2003

Background and aims: Although the participation of cytokines in the pathogenesis of rheumatoid arthritis (RA) seems to be unequivocal, their relationship with current serum markers of this disease is not clear. The present study analyses whether there is any correlation between the levels of tumour necrosis factor‐α (TNF‐α), interlukin‐2 soluble receptor (sIL‐2R) and the concentrations of C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR) and β2‐microglobulin in a group of 21 patients with RA, all rheumatoid factor positive.

Methods: The levels of TNF‐α and sIL‐2R were analysed in association with other parameters of inflammation (ESR, CRP and β2‐microglobulin).

Results: In comparison with the control group, RA patients presented high median levels of both cytokines, TNF‐α (6.4 pg/ml) and sIL‐2R (56 pmol/L), as well as of ESR (34 mm/h), CRP (0.9 mg/dl) and β2‐microglobulin (1.6 mg/dl)
(p < 0.01).
However, only ESR levels in the RA group significantly differ from the control group
(p < 0.01).
No correlation was found between the inflammatory parameters.

Conclusions: These results suggested that TNF‐α and slL‐2R levels are up‐regulated in RA patients but did not significantly differ from the control group. Due to the chronic course of this disease, other inflammatory markers must be identified in order to provide early therapeutic strategies to these patients.
Pro‐inflammatory cytokines in Turkish children with protein‐energy malnutrition
Authors: Dülger Haluk , Arik Mehmet , Şekeroğlu M. Ramazan , Tarakçioğlu Mehmet , Noyan Tevfik , Cesur Yaşar , Balahoroğlu Ragip
Published: February 2003

Background: Protein‐energy malnutrition (PEM) results from food insufficiency as well as from poor social and economic conditions. Development of PEM is due to insufficient nutrition. Children with PEM lose their resistance to infections because of a disordered immune system. It has been reported that the changes occurring in mediators referred to as cytokines in the immune system may be indicators of the disorders associated with PEM.

Aims: To determine the concentrations of pro‐inflammatory cytokines in children with PEM, and to find out whether there was an association with the clinical presentation of PEM.

Methods: The levels of serum total protein, albumin, tumour necrosis factor‐α, and interleukin‐6 were measured in 25 patients with PEM and in 18 healthy children as a control group. PEM was divided into two groups as kwashiorkor and marasmus. The kwashiorkor group consisted of 15 children and the marasmus group consisted of 10 children.

Results: Levels of serum total protein and albumin of the kwashiorkor group were significantly lower than both the marasmus group and controls
(p < 0.05).
In view of tumour necrosis factor‐α levels, there was no difference between groups
(p > 0.05).
While levels of interleukin‐6 in both the marasmus group and the kwashiorkor group were significantly higher compared with controls
(p < 0.05),
there was no significant difference between the groups of marasmus and kwashiorkor
(p > 0.05).

Conclusions: It was observed that the inflammatory response had increased in children with malnutrition.
The “Protective State” Approach to the “Productive State” in The Wealth of Nations: The Odd Case of Lay Patronage
Authors: Leathers Charles G. , Raines J. Patrick
Published: February 2003

From Jacob Viner (1927) to David A. Reisman (1998), Adam Smith's departures from an advocacy of laissez-faire in The Wealth of Nations have been interpreted by a number of scholars. In this paper, we examine one of the oddest, and perhaps least noticed, of those departures. That was Smith's defense of the civil law of lay patronage in the established Presbyterian Church of Scotland, which appears in his discussion of the social benefits and potential social costs of institutions for religious instruction. A lay patron was a non-cleric individual who held the right under civil law to select the minister of a local parish church. In Smith's time, roughly two-thirds of the lay patrons in Scotland were wealthy landowners and one-third were crown officials. In addition, municipal corporations (cities) and universities held some patronage rights.
An Introduction to “Anarchism, Socialism and Social Reform” by John Bates Clark
Authors: Prasch Robert E.
Published: February 2003

John Bates Clark (1847–1938) holds a secure position in the history of American economic thought. Specifically, he is remembered for developing the marginal product theory of distribution, which was presented in its most complete form inThe Distribution of Wealth(1899). However, Clark's primary intellectual commitment has been largely overlooked. This was his search for the rules and institutions that would create a prosperous economy featuring a just distribution while maintaining the essential structures of competitive capitalism.
Gene expression in plant mitochondria: transcriptional and post–transcriptional control
Authors: Binder Stefan , Brennicke Axel
Published: February 2003

The informational content of the mitochondrial genome in plants is, although small, essential for each cell. Gene expression in these organelles involves a number of distinct transcriptional and post–transcriptional steps. The complex post–transcriptional processes of plant mitochondria such as 5′ and 3′ RNA processing, intron splicing, RNA editing and controlled RNA stability extensively modify individual steady–state RNA levels and influence the mRNA quantities available for translation. In this overview of the processes in mitochondrial gene expression, we focus on confirmed and potential sites of regulatory interference and discuss the evolutionary origins of the transcriptional and post–transcriptional processes.
Biochemical and evolutionary aspects of anaerobically functioning mitochondria
Authors: Hellemond Jaap J. van , Klei Anita van der , Weelden SusanneW. H. van , Tielens Aloysius G. M.
Published: February 2003

Mitochondria are usually considered to be the powerhouses of the cell and to be responsible for the aerobic production of ATP. However, many eukaryotic organisms are known to possess anaerobically functioning mitochondria, which differ significantly from classical aerobically functioning mitochondria. Recently, functional and phylogenetic studies on some enzymes involved clearly indicated an unexpected evolutionary relationship between these anaerobically functioning mitochondria and the classical aerobic type. Mitochondria evolved by an endosymbiotic event between an anaerobically functioning archaebacterial host and an aerobic α–proteobacterium. However, true anaerobically functioning mitochondria, such as found in parasitic helminths and some lower marine organisms, most likely did not originate directly from the pluripotent ancestral mitochondrion, but arose later in evolution from the aerobic type of mitochondria after these were already adapted to an aerobic way of life by losing their anaerobic capacities. This review will focus on some biochemical and evolutionary aspects of these fermentative mitochondria, with special attention to fumarate reductase, the synthesis of the rhodoquinone involved, and the enzymes involved in acetate production (acetate : succinate CoA–transferase and succinyl CoA–synthetase).
How big is the iceberg of which organellar genes in nuclear genomes are but the tip?
Authors: Doolittle W. F. , Boucher Y. , NesbØ C. L. , Douady C. J. , Andersson J. O. , Roger A. J.
Published: February 2003

As more and more complete bacterial and archaeal genome sequences become available, the role of lateral gene transfer (LGT) in shaping them becomes more and more clear. Over the long term, it may be the dominant force, affecting most genes in most prokaryotes. We review the history of LGT, suggesting reasons why its prevalence and impact were so long dismissed. We discuss various methods purporting to measure the extent of LGT, and evidence for and against the notion that there is a core of never–exchanged genes shared by all genomes, from which we can deduce the ‘true’ organismal tree. We also consider evidence for, and implications of, LGT between prokaryotes and phagocytic eukaryotes.
Photosystem II: evolutionary perspectives
Authors: Rutherford A. W. , Faller P.
Published: February 2003

Based on the current model of its structure and function, photosystem II (PSII) seems to have evolved from an ancestor that was homodimeric in terms of its protein core and contained a special pair of chlorophylls as the photo–oxidizable cofactor. It is proposed that the key event in the evolution of PSII was a mutation that resulted in the separation of the two pigments that made up the special chlorophyll pair, making them into two chlorophylls that were neither special nor paired. These ordinary chlorophylls, along with the two adjacent monomeric chlorophylls, were very oxidizing: a property proposed to be intrinsic to monomeric chlorophylls in the environment provided by reaction centre (RC) proteins. It seems likely that other (mainly electrostatic) changes in the environments of the pigments probably tuned their redox potentials further but these changes would have been minor compared with the redox jump imposed by splitting of the special pair. This sudden increase in redox potential allowed the development of oxygen evolution. The highly oxidizing homodimeric RC would probably have been not only inefficient in terms of photochemistry and charge storage but also wasteful in terms of protein or pigments undergoing damage due to the oxidative chemistry. These problems would have constituted selective pressures in favour of the lop–sided, heterodimeric system that exists as PSII today, in which the highly oxidized species are limited to only one side of the heterodimer: the sacrificial, rapidly turned–over D1 protein. It is also suggested that one reason for maintaining an oxidizable tyrosine, TyrD, on the D2 side of the RC, is that the proton associated with its tyrosyl radical, has an electrostatic role in confining P
+
to the expendable D1 side.
Mitochondria and hydrogenosomes are two forms of the same fundamental organelle
Authors: Embley Martin , der Giezen Mark van , Horner David S. , Dyal Patricia L. , Foster Peter
Published: February 2003

Published data suggest that hydrogenosomes, organelles found in diverse anaerobic eukaryotes that make energy and hydrogen, were once mitochondria. As hydrogenosomes generally lack a genome, the conversion is probably one way. The sources of the key hydrogenosomal enzymes, pyruvate : ferredoxin oxidoreductase (PFO) and hydrogenase, are not resolved by current phylogenetic analyses, but it is likely that both were present at an early stage of eukaryotic evolution. Once thought to be restricted to a few unusual anaerobic eukaryotes, the proteins are intimately integrated into the fabric of diverse eukaryotic cells, where they are targeted to different cell compartments, and not just hydrogenosomes. There is no evidence supporting the view that PFO and hydrogenase originated from the mitochondrial endosymbiont, as posited by the hydrogen hypothesis for eukaryogenesis. Other organelles derived from mitochondria have now been described in anaerobic and parasitic microbial eukaryotes, including species that were once thought to have diverged before the mitochondrial symbiosis. It thus seems possible that all eukaryotes may eventually be shown to contain an organelle of mitochondrial ancestry, to which different types of biochemistry can be targeted. It remains to be seen if, despite their obvious differences, this family of organelles shares a common function of importance for the eukaryotic cell, other than energy production, that might provide the underlying selection pressure for organelle retention.
On the origin of mitochondria: a genomics perspective
Authors: Andersson G. E. , Karlberg Olof , Canbäck Björn , Kurland Charles G.
Published: February 2003

The availability of complete genome sequence data from both bacteria and eukaryotes provides information about the contribution of bacterial genes to the origin and evolution of mitochondria. Phylogenetic analyses based on genes located in the mitochondrial genome indicate that these genes originated from within the α–proteobacteria. A number of ancestral bacterial genes have also been transferred from the mitochondrial to the nuclear genome, as evidenced by the presence of orthologous genes in the mitochondrial genome in some species and in the nuclear genome of other species. However, a multitude of mitochondrial proteins encoded in the nucleus display no homology to bacterial proteins, indicating that these originated within the eukaryotic cell subsequent to the acquisition of the endosymbiont. An analysis of the expression patterns of yeast nuclear genes coding for mitochondrial proteins has shown that genes predicted to be of eukaryotic origin are mainly translated on polysomes that are free in the cytosol whereas those of putative bacterial origin are translated on polysomes attached to the mitochondrion. The strong relationship with α–proteobacterial genes observed for some mitochondrial genes, combined with the lack of such a relationship for others, indicates that the modern mitochondrial proteome is the product of both reductive and expansive processes.
Exploring self‐organized emergence in an agent‐based synthetic warfare lab
Authors: Ilachinski Andrew
Published: February 2003

Artificial‐life techniques – specifically, agent‐based models and evolutionary learning algorithms – provide a potentially powerful new approach to understanding some of the fundamental processes of war. This paper introduces a simple artificial‐like “toy model” of combat calledEnhancedISAACNeuralSimulationTool (EINSTein). EINSTein is designed to illustrate how certain aspects of land combat can be viewed as self‐organized, emergent phenomena resulting from the dynamical web of interactions among notional combatants. EINSTein's bottom‐up, synthesist approach to the modeling of combat stands in stark contrast to the more traditional top‐down, or reductionist approach taken by conventional military models, and represents a step toward developing a complex systems theoretic toolbox for identifying, exploring, and possibly exploiting self‐organized emergent collective patterns of behavior on the real battlefield. A description of the model is provided, along with examples of emergent agent patterns and behaviors.
Discrete dynamics lab: tools for investigating cellular automata and discrete dynamical networks
Authors: Wuensche Andrew
Published: February 2003

DDLab is interactive graphics software for creating and visualizing discrete dynamical networks, and studying their behavior in terms of both space‐time patterns and basins of attraction. The networks can range from cellular automata to random Boolean networks. This article provides some general background, and gives the flavor of DDLab with a range of examples. Further details can be found atwww.ddlab.comwww.ddlab.com
Evolving sonic ecosystems
Authors: McCormack Jon
Published: February 2003

A novel type of artistic Artificial Life environment is introduced and where evolving agents, who have the ability to make and listen to sound, populate a synthetic world are described. An evolvable, rule‐based system which drives agent behaviour and where agents compete for limited resources in a virtual environment that is influenced by the presence and movement of the artwork's audience is discussed. It is shown that through a link between the real and virtual spaces, virtual agents evolve implicitly and try to maintain the interest of the human audience.
Simulated breeding – a framework of breeding artifacts on the computer
Authors: Unemi Tatsuo
Published: February 2003

A basic framework of Simulated Breeding, a type of interactive evolutionary computing to breed artifacts of which origin is Blind Watchmaker by R. Dawkins is considered. These methods, make it easy for humans; to design a complex object adapted to his/her subjective criteria, just similar to agricultural products that we have been developing over thousands of years. Starting from randomly initialised genome, the solution candidates are improved through several generations with artificial selection. Graphical user interface helps the process of breeding with techniques of multi‐field user interface and partial breeding. The former improves the diversity of individuals that prevents being trapped at local optimum. The latter makes it possible for the user to fix features that he/she already satisfied. These methods were examined through artistic applications by the author, SBART for graphics art and SBEAT for music. Combining with direct genome editor and exportation to another graphical or musical tool on the computer, they can be powerful tools for artistic creation. These systems may contribute to create a type of new culture.
Quality assurance of the knowledge exchange process: a factor in the success of child health programs in developing countries
Authors: Yassin Khaled M. , Antia Bassey E.
Published: February 2003

This article views the many national and international programs concerned with child survival in developing countries as sharing one important objective, i.e. the exchange of specialized knowledge to mothers who are the primary caretakers of children under age five. If mothers do not possess the knowledge required to develop proper care‐seeking practices, then return on investments in infrastructure, drugs, and human resources development, as these relate to child‐killer diseases such as diarrhea and acute respiratory infection, may not be optimal. Cognizant of reports of the limited impact of health promotion programs, in spite of the investments made, the article models the knowledge exchange process to pinpoint possible sources of problems. Pertinent issues of quality assurance are raised and the consequences of neglecting them pointed out. Some empirical evidence is offered in support of these predicted consequences. Proposes a value analysis framework, to make the point that paying attention to quality assurance concerns is more about optimizing the fit between available resources and ideal outcomes, rather than always being about additional resources.
A conceptual framework for hospital quality management
Authors: Eggli Yves , Halfon Patricia
Published: February 2003

Most current conceptual frameworks used for hospital quality management exhibit shortcomings, terminology barriers or too much complexity. We propose a rigorous and simple model specific to hospitals, based on four entities (patients, activities, resources and effects) and six levels in order to measure the development of quality management systems. The proposed model is compatible with other substantiated models, robust in coping with falsifiability and provides flexibility to avoid a too unilateral approach.
Issues in quality of high‐tech home care: sources of information and staff training in Quebec primary care organizations and relationships with hospitals
Authors: Lehoux P. , Pineault R. , Richard L. , St‐Arnaud J. , Law S. , Rosendal H.
Published: February 2003

This study examined the provision of high‐tech home care by Quebec primary care organizations (CLSCs). Four technologies were selected: IV antibiotic therapy, oxygen therapy, parenteral nutrition, and peritoneal dialysis. A postal survey was sent to all CLSCs and a response rate of 69 percent was obtained; 57 percent of CLSCs have been involved in the provision of services related to three of the high‐tech interventions. The most frequently used sources of information are written material provided by manufacturers or by hospitals. CLSCs relied heavily on peer‐to‐peer training and training provided by manufacturers and hospitals. Formal agreements with hospitals regarding patient flow management were established; aspects related to the “content” of care were much less formalized. CLSCs have integrated high‐tech home care to a substantial extent. Our findings raise quality‐of‐care issues. The interface with hospitals needs to be reinforced and emphasis given to the appropriate use of technology.
Late Pliocene
Homo
and Hominid Land Use from Western Olduvai Gorge, Tanzania
Authors: Blumenschine Robert J. , Peters Charles R. , Masao Fidelis T. , Clarke Ronald J. , Deino Alan L. , Hay Richard L. , Swisher Carl C. , Stanistreet Ian G. , Ashley Gail M. , McHenry Lindsay J. , Sikes Nancy E. , van der Merwe Nikolaas J. , Tactikos Joanne C. , Cushing Amy E. , Deocampo Daniel M. , Njau Jackson K. , Ebert James I.
Published: February 2003

Excavation in the previously little-explored western portion of Olduvai Gorge indicates that hominid land use of the eastern paleobasin extended at least episodically to the west. Finds included a dentally complete
Homo
maxilla (OH 65) with lower face, Oldowan stone artifacts, and butchery-marked bones dated to be between 1.84 and 1.79 million years old. The hominid shows strong affinities to the KNM ER 1470 cranium from Kenya (
Homo rudolfensis
), a morphotype previously unrecognized at Olduvai. ER 1470 and OH 65 can be accommodated in the
H. habilis
holotype, casting doubt on
H. rudolfensis
as a biologically valid taxon.
COMT

val
158
met

Genotype Affects µ-Opioid Neurotransmitter Responses to a Pain Stressor
Authors: Zubieta Jon-Kar , Heitzeg Mary M. , Smith Yolanda R. , Bueller Joshua A. , Xu Ke , Xu Yanjun , Koeppe Robert A. , Stohler Christian S. , Goldman David
Published: February 2003

Responses to pain and other stressors are regulated by interactions between multiple brain areas and neurochemical systems. We examined the influence of a common functional genetic polymorphism affecting the metabolism of catecholamines on the modulation of responses to sustained pain in humans. Individuals homozygous for the

met
158

allele of the catechol-
O
-methyltransferase (COMT) polymorphism (

val
158
met

) showed diminished regional μ-opioid system responses to pain compared with heterozygotes. These effects were accompanied by higher sensory and affective ratings of pain and a more negative internal affective state. Opposite effects were observed in

val
158

homozygotes. The COMT

val
158
met

polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli.
Giant Supramolecular Liquid Crystal Lattice
Authors: Ungar Goran , Liu Yongsong , Zeng Xiangbing , Percec Virgil , Cho Wook-Dong
Published: February 2003

Self-organized supramolecular organic nanostructures have potential applications that include molecular electronics, photonics, and precursors for nanoporous catalysts. Accordingly, understanding how self-assembly is controlled by molecular architecture will enable the design of increasingly complex structures. We report a liquid crystal (LC) phase with a tetragonal three-dimensional unit cell containing 30 globular supramolecular dendrimers, each of which is self-assembled from 12 dendron (tree-like) molecules, for the compounds described here. The present structure is one of the most complex LC phases yet discovered. A model explaining how spatial arrangement of self-assembled dendritic aggregates depends on molecular architecture and temperature is proposed.
Proteomic Screen Finds pSer/pThr-Binding Domain Localizing Plk1 to Mitotic Substrates
Authors: Elia Andrew E. H. , Cantley Lewis C. , Yaffe Michael B.
Published: February 2003

We have developed a proteomic approach for identifying phosphopeptide binding domains that modulate kinase-dependent signaling pathways. An immobilized library of partially degenerate phosphopeptides biased toward a particular protein kinase phosphorylation motif is used to isolate phospho-binding domains that bind to proteins phosphorylated by that kinase. Applying this approach to cyclin-dependent kinases (Cdks), we identified the polo-box domain (PBD) of the mitotic kinase polo-like kinase 1 (Plk1) as a specific phosphoserine (pSer) or phosphothreonine (pThr) binding domain and determined its optimal binding motif. This motif is present in known Plk1 substrates such as Cdc25, and an optimal phosphopeptide containing the motif disrupted PBD-substrate binding and localization of the PBD to centrosomes. This finding reveals how Plk1 can localize to specific sites within cells in response to Cdk phosphorylation at those sites and provides a structural mechanism for targeting the Plk1 kinase domain to its substrates.
Separate Evolutionary Origins of Teeth from Evidence in Fossil Jawed Vertebrates
Authors: Smith Moya Meredith , Johanson Zerina
Published: February 2003

Placoderms are extinct jawed fishes of the class Placodermi and are basal among jawed vertebrates. It is generally thought that teeth are absent in placoderms and that the phylogenetic origin of teeth occurred after the evolution of jaws. However, we now report the presence of tooth rows in more derived placoderms, the arthrodires. New teeth are composed of gnathostome-type dentine and develop at specific locations. Hence, it appears that these placoderm teeth develop and are regulated as in other jawed vertebrates. Because tooth development occurs only in derived forms of placoderms, we suggest that teeth evolved at least twice, through a mechanism of convergent evolution.
Coaxing Sounds from Circuits
Authors: Machover Tod
Published: February 2003

Analog Days
The Invention and Impact of the Moog Synthesizer. Trevor Pinch and Frank Trocco. Harvard University Press, Cambridge, MA, 2002. 384 pp. $29.95. ISBN 0-674-00889-8.

Constructing their account from interviews with the inventors, engineers, and musicians who worked with the Moog, the authors discuss the invention, development, and impact of electronic synthesizers in the 1960s through mid-1970s.
Spontaneous Cell Polarization Through Actomyosin-Based Delivery of the Cdc42 GTPase
Authors: Wedlich-Soldner Roland , Altschuler Steve , Wu Lani , Li Rong
Published: February 2003

Cell polarization can occur in the absence of any spatial cues. To investigate the mechanism of spontaneous cell polarization, we used an assay in yeast where expression of an activated form of Cdc42, a Rho-type guanosine triphosphatase (GTPase) required for cell polarization, could generate cell polarity without any recourse to a preestablished physical cue. The polar distribution of Cdc42 in this assay required targeted secretion directed by the actin cytoskeleton. A mathematical simulation showed that a stable polarity axis could be generated through a positive feedback loop in which a stochastic increase in the local concentration of activated Cdc42 on the plasma membrane enhanced the probability of actin polymerization and increased the probability of further Cdc42 accumulation to that site.
Impact of Genetic Manipulation on the Fitness of
Anopheles stephensi
Mosquitoes
Authors: Catteruccia Flaminia , Godfray H. Charles J. , Crisanti Andrea
Published: February 2003

Genetic modification of mosquitoes offers exciting possibilities for controlling malaria, but success will depend on how transformation affects the fitness of modified insects. The expression of an exogenous gene, the mutations caused by its insertion, and inbreeding while transformed lines are established can all lead to reductions in fitness. Factors influencing fitness were investigated in cage experiments with four lines of transgenic
Anopheles stephensi
, a vector species of human malaria. The results indicate direct costs of the introduced transgene in at least three out of the four lines, as well as an apparent cost of the inbreeding involved in making transgenic homozygotes.
Regions of PspA/EF3296 Best Able To Elicit Protection against
Streptococcus pneumoniae
in a Murine Infection Model
Authors: Roche Hazeline , Håkansson Anders , Hollingshead Susan K. , Briles David E.
Published: February 2003

Pneumococcal surface protein A (PspA) can elicit protection against
Streptococcus pneumoniae
in mouse infection models. PspA is classified by serology and amino acid sequence into two major families that are divided by sequence into five clades. The most variable portion of the molecule is the α-helical domain, which comprises the N-terminal half of PspA. Prior studies of a family 1 PspA protein observed that protective antibodies are reactive with epitopes in the α-helical domain and that most cross-protective epitopes mapped to the 108 most C-terminal amino acids of the α-helical region. In these studies, we have used six overlapping recombinant fragments of family 2, clade 3 PspA/EF3296 to map the protection-eliciting regions of its α-helical domain. The three fragments, which included the 104 most C-terminal amino acids of the α-helical domain (314 to 418), could each elicit protection against EF3296. A fragment comprising amino acids 75 to 305 failed to elicit significant protection. A fragment containing amino acids 1 to 115 elicited protection against EF3296 in BALB/c mice but not in CBA/N mice. All three fragments containing amino acids 314 to 418 were able to elicit cross-protection against pneumococci expressing PspA proteins of clades 2, 3, 4, and 5. Cross-protection elicited by these three fragments was easier to demonstrate in CBA/N mice than in BALB/c mice. The 1-to-115 fragment, however, elicited some cross-protection against clades 2 and 4 in BALB/c mice but not in CBA/N mice. These studies provide support for the importance of the C-terminal 104 and N-terminal 115 amino acids of the α-helical region of PspA in the elicitation of cross-protection.
Antibodies Raised against Bcvir15, an Extrachromosomal Double-Stranded RNA-Encoded Protein fromBabesia canis, Inhibit the In Vitro Growth of the Parasite
Authors: Drakulovski P. , Carcy B. , Moubri K. , Carret C. , Depoix D. , Schetters T. P. M. , Gorenflot A.
Published: February 2003

As part of a search for homologous members of thePlasmodium falciparumPf60 multigene family in the intraerythrocytic protozoan parasiteBabesia canis, we report here the characterization of a cDNA of 1,115 bp, which was designatedBcvirfor its potential viral origin. TheBcvircDNA contained two overlapping open reading frames (ORFs) (ORF1 from nucleotide [nt] 61 to 486 and ORF2 from nt 417 to 919), where Bcvir15, the deduced ORF1 peptide (M1to I141), is the main expressed product. TheBcvircDNA was derived from an extrachromosomal dsRNA element of 1.2 kbp that was always found associated with a double-stranded RNA (dsRNA) of 2.8 kbp by hybridization, and no copy of this cDNA sequence was found inB. canisgenomic DNA. Biochemical characterization of Bcvir15, by using polyclonal rabbit sera directed against recombinant proteins, indicated that it is a soluble protein which remained associated with the cytoplasm of theB. canismerozoite. Interestingly, purified immunoglobulins from the anti-glutathioneS-transferase-Bcvir15 (at a concentration of 160 μg/ml) induced 50% inhibition of the in vitro growth ofB. canis, and the inhibitory effect was associated with morphological damage of the parasite. Our data suggest that the extrachromosomal dsRNA-encoded Bcvir15 protein might interfere with the intracellular growth of the parasite rather than with the process of invasion of the host cell by the merozoite. Epitope mapping of Bcvir15 identified three epitopes that might be essential for the function of the protein.
Enteral Immunization with Attenuated RecombinantListeria monocytogenesas a Live Vaccine Vector: Organ-Dependent Dynamics of CD4 T Lymphocytes Reactive to aLeishmania majorTracer Epitope
Authors: Saklani-Jusforgues Hélène , Fontan Elisabeth , Soussi Neirouz , Milon Geneviève , Goossens Pierre L.
Published: February 2003

Listeria monocytogenesis considered as a potential live bacterial vector, particularly for the induction of CD8 T cells. The CD4 T-cell immune response triggered after enteral immunization of mice has not yet been thoroughly characterized. The dynamics of gamma interferon (IFN-γ)- and interleukin-4 (IL-4)-secreting CD4 T cells were analyzed after priming through intragastric delivery of an attenuated ΔactArecombinantL. monocytogenesstrain expressing theLeishmania majorLACK protein; a peptide of this protein, LACK158-173peptide (pLACK), is a well-characterized CD4 T-cell target in BALB/c mice. Five compartments were monitored: Peyer's patches, mesenteric lymph nodes (MLN), spleen, liver, and blood. A single intragastric inoculation ofΔactA-LACK-LM in BALB/c mice led to colonization of the MLN and spleen at a significant level for at least 3 days. Efficient priming of IFN-γ-secreting pLACK-reactive CD4 T cells was observed in all tested compartments. Interestingly, IL-4-secreting pLACK-reactive CD4 T cells were detectable at day 6 or 7 only in blood and liver. The absence of translocation of viable bacteria through the intestinal epithelium after furtherΔactA-LACK-LM inoculations was concomitant with the absence of an increase in the level of IFN-γ secreted by the MLN, blood, and splenic pLACK-reactive Th1 T cells, although the levels remained significantly above the basal level. No change in this population size was detected in the spleen. However, an increase in the number of intragastric inoculations had a clinical beneficial effect inL. major-infected BALB/c mice.L. monocytogenesthus presents the potential of an efficient vector for induction of CD4 T cells when administered by the enteral route.
Identification of Genetic Loci Required for Capsular Expression in
Vibrio vulnificus
Authors: Smith Amy B. , Siebeling Ronald J.
Published: February 2003

Transposon mutagenesis of an encapsulated, virulent strain of
Vibrio vulnificus
1003(O) led to the identification of four genetic regions that are essential to capsular polysaccharide (CPS) expression and virulence. Of the four regions, three are believed to be part of a capsule gene locus comprised of biosynthesis, polymerization, and transport genes clustered on a single chromosomal fragment. Genes indicating a Wzy-dependent system of polymerization and transmembrane export are present, suggesting that the CPS of
V. vulnificus
is lipid linked. The fourth region, while it contains a gene essential for CPS expression, is characteristic of an integron-gene cassette region, similar to the super integron of
V. cholerae.
It is not believed to be part of a CPS gene locus and is located in a region of the chromosome separate from the putative CPS loci. It is comprised of open reading frames (ORFs) carrying genes of unknown function surrounded by direct repeats. This region also contains IS
492
, an insertion sequence located numerous times throughout a region of the genome, demonstrating a restriction fragment length polymorphism among an encapsulated and nonencapsulated morphotype of
V. vulnificus.
Collectively, 22 ORFs were recognized: 13 capsule synthesis genes, 4 insertion sequences, 1 truncated biosynthesis gene, and 4 genes of unknown function. This study has led to the identification of previously unrecognized genetic loci that may help to increase the understanding of capsular genetics and antigenic diversity among
V. vulnificus
strains.
Position-Based Scanning for Comparative Genomics and Identification of Genetic Islands in
Haemophilus influenzae
Type b
Authors: Bergman Nicholas H. , Akerley Brian J.
Published: February 2003

Bacteria exhibit extensive genetic heterogeneity within species. In many cases, these differences account for virulence properties unique to specific strains. Several such loci have been discovered in the genome of the type b serotype of
Haemophilus influenzae
, a human pathogen able to cause meningitis, pneumonia, and septicemia. Here we report application of a PCR-based scanning procedure to compare the genome of a virulent type b (Hib) strain with that of the laboratory-passaged Rd KW20 strain for which a complete genome sequence is available. We have identified seven DNA segments or
H. influenzae
genetic islands (HiGIs) present in the type b genome and absent from the Rd genome. These segments vary in size and content and show signs of horizontal gene transfer in that their percent G+C content differs from that of the rest of the
H. influenzae
genome, they contain genes similar to those found on phages or other mobile elements, or they are flanked by DNA repeats. Several of these loci represent potential pathogenicity islands, because they contain genes likely to mediate interactions with the host. These newly identified genetic islands provide areas of investigation into both the evolution and pathogenesis of
H. influenzae
. In addition, the genome scanning approach developed to identify these islands provides a rapid means to compare the genomes of phenotypically diverse bacterial strains once the genome sequence of one representative strain has been determined.
Enteric Salmonella Infection Inhibits Paneth Cell Antimicrobial Peptide Expression
Authors: Salzman Nita H. , Chou Margaret M. , de Jong Hendrik , Liu Lide , Porter Edith M. , Paterson Yvonne
Published: February 2003

Paneth cells, highly secretory epithelial cells found at the bases of small intestinal crypts, release a variety of microbicidal molecules, including α-defensins and lysozyme. The secretion of antimicrobials by Paneth cells is thought to be important in mucosal host defense against invasion by enteric pathogens. We explored whether enteric pathogens can interfere with this arm of defense. We found that oral inoculation of mice with wild-typeSalmonella entericaserovar Typhimurium decreases the expression of α-defensins (called cryptdins in mice) and lysozyme. Oral inoculation withSalmonellaserovar Typhimurium strains that are heat killed, lack the PhoP regulon, and lack the SPI1 type III secretion system or withListeria monocytogenesdoes not have this effect.Salmonellamay gain a specific survival advantage in the intestinal lumen by decreasing the expression of microbicidal peptides in Paneth cells through direct interactions betweenSalmonellaand the small intestinal epithelium.
Allelic Variation inTLR4Is Linked to Susceptibility toSalmonella entericaSerovar Typhimurium Infection in Chickens
Authors: Leveque Gary , Forgetta Vincenzo , Morroll Shaun , Smith Adrian L. , Bumstead Nat , Barrow Paul , Loredo-Osti J. C. , Morgan Kenneth , Malo Danielle
Published: February 2003

Toll-like receptor 4 (TLR4) is part of a group of evolutionarily conserved pattern recognition receptors involved in the activation of the immune system in response to various pathogens and in the innate defense against infection. We describe here the cloning and characterization of the avian orthologue of mammalianTLR4. ChickenTLR4encodes a 843-amino-acid protein that contains a leucine-rich repeat extracellular domain, a short transmembrane domain typical of type I transmembrane proteins, and a Toll-interleukin-1R signaling domain characteristic of all TLR proteins. The chicken TLR4 protein shows 46% identity (64% similarity) to human TLR4 and 41% similarity to other TLR family members. Northern blot analysis reveals thatTLR4is expressed at approximately the same level in all tissues tested, including brain, thymus, kidney, intestine, muscle, liver, lung, bursa of Fabricius, heart, and spleen. The probe detected only one transcript of ca. 4.4 kb in length for all tissues except muscle where the size ofTLR4mRNA was ca. 9.6 kb. We have mappedTLR4to microchromosome E41W17 in a region harboring the gene for tenascin C and known to be well conserved between the chicken and mammalian genomes. This region of the chicken genome was shown previously to harbor aSalmonellasusceptibility locus. By using linkage analysis,TLR4was shown to be linked to resistance to infection withSalmonella entericaserovar Typhimurium in chickens (likelihood ratio test of 10.2,P= 0.00138), suggesting a role of TLR4 in the host response of chickens toSalmonellainfection.
Microarray Analysis of mRNA Levels from RAW264.7 Macrophages Infected withBrucella abortus
Authors: Eskra Linda , Mathison Angela , Splitter Gary
Published: February 2003

Identification of host responses at the gene transcription level provides a molecular profile of the events that occur following infection.Brucella abortusis a facultative intracellular pathogen of macrophages that induces chronic infection in humans and domestic animals. Using microarray technology, the response of macrophages 4 h followingB. abortusinfection was analyzed to identify early intracellular infection events that occur in macrophages. Of the >6,000 genes, we identified over 140 genes that were reproducibly differentially transcribed. First, an increase in the transcription of a number of proinflammatory cytokines and chemokines, such as tumor necrosis factor alpha, interleukin-1β (IL-1β), IL-1α, and members of the SCY family of proteins, that may constitute a general host recruitment of antibacterial defenses was evident. Alternatively,Brucellamay subvert newly arriving macrophages for additional intracellular infection. Second, transcription of receptors and cytokines associated with antigen presentation, e.g., major histocompatibility complex class II and IL-12p40, were not evident at this 4-h period of infection. Third,Brucellainhibited transcription of various host genes involved in apoptosis, cell cycling, and intracellular vesicular trafficking. Identification of macrophage genes whose transcription was inhibited suggests thatBrucellautilizes specific mechanisms to target certain cell pathways. In conclusion, these data suggest thatB. abortuscan alter macrophage pathways to recruit additional macrophages for future infection while simultaneously inhibiting apoptosis and innate immune mechanisms within the macrophage, permitting intracellular survival of the bacterium. These results provide insights into the pathogenic strategies used byBrucellafor long-term survival within a hostile environment.
Evidence that Development of Severe Cardiomyopathy in Human Chagas' Disease Is Due to a Th1-Specific Immune Response
Authors: Gomes J. A. S. , Bahia-Oliveira L. M. G. , Rocha M. O. C. , Martins-Filho O. A. , Gazzinelli G. , Correa-Oliveira R.
Published: February 2003

The role of interleukin 10 (IL-10) and gamma interferon (IFN-γ) on the development of pathology in human Chagas' disease was investigated. Two categories of patients, low and high producers of IFN-γ, were identified based on the levels of secretion of this cytokine in the supernatant of peripheral blood mononuclear cell (PBMC) cultures. Eighty-three percent of the patients presenting with cardiac disease (CARD) of different degrees and 59% of the patients with the indeterminate form of disease (IND) were identified as high IFN-γ producers. PBMC from IND patients classified as low IFN-γ producers secreted significantly higher amounts of IL-10 than did those from other groups. Flow cytometry analysis demonstrated that in PBMC from the IND group, the majority of the IL-10-producing cells were monocytes (CD14High+cells), whereas in the CARD group, the major sources of IFN-γ were T lymphocytes (CD3+CD4+cells). These results suggest an association between the production of IFN-γ by CD3+CD4+cells and morbidity in Chagas' disease, whereas the production of IL-10 by macrophages/monocytes leads to regulation of the immune response in IND patients. We hypothesize that an exacerbated production of IFN-γ againstTrypanosoma cruziantigens favors the development of a strong Th1 response in CARD patients, which leads to progression of heart disease.