bluuebunny/crossref_metadata_2025 huggingface dataset:
RGS4 and RGS5 are
in vivo
substrates of the N-end rule pathway
Authors: Lee Min Jae , Tasaki Takafumi , Moroi Kayoko , An Jee Young , Kimura Sadao , Davydov Ilia V. , Kwon Yong Tae
Published: October 2005

The
ATE1
-encoded Arg-transferase mediates conjugation of Arg to N-terminal Asp, Glu, and Cys of certain eukaryotic proteins, yielding N-terminal Arg that can act as a degradation signal for the ubiquitin-dependent N-end rule pathway. We have previously shown that mouse
ATE1
–/–
embryos die with defects in heart development and angiogenesis. Here, we report that the ATE1 Arg-transferase mediates the
in vivo
degradation of RGS4 and RGS5, which are negative regulators of specific G proteins whose functions include cardiac growth and angiogenesis. The proteolysis of these regulators of G protein signaling (RGS) proteins was perturbed either by hypoxia or in cells lacking ubiquitin ligases UBR1 and/or UBR2. Mutant RGS proteins in which the conserved Cys-2 residue could not become N-terminal were long-lived
in vivo
. We propose a model in which the sequential modifications of RGS4, RGS5, and RGS16 (N-terminal exposure of their Cys-2, its oxidation, and subsequent arginylation) act as a licensing mechanism in response to extracellular and intracellular signals before the targeting for proteolysis by UBR1 and UBR2. We also show that
ATE1
–/–
embryos are impaired in the activation of extracellular signal-regulated kinase mitogen-activated protein kinases and in the expression of G protein-induced downstream effectors such as Jun, cyclin D1, and β-myosin heavy chain. These results establish RGS4 and RGS5 as
in vivo
substrates of the mammalian N-end rule pathway and also suggest that the O
2
-ATE1-UBR1/UBR2 proteolytic circuit plays a role in RGS-regulated G protein signaling in the cardiovascular system.
Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SWI/SNF form a chromatin remodeling complex at the β-globin locus control region
Authors: Mahajan Milind C. , Narlikar Geeta J. , Boyapaty Gokul , Kingston Robert E. , Weissman Sherman M.
Published: October 2005

Locus control regions (LCRs) are regulatory DNA sequences that are situated many kilobases away from their cognate promoters. LCRs protect transgenes from position effect variegation and heterochromatinization and also promote copy-number dependence of the levels of transgene expression. In this work, we describe the biochemical purification of a previously undescribed LCR-associated remodeling complex (LARC) that consists of heterogeneous nuclear ribonucleoprotein C1/C2, nucleosome remodeling SWI/SNF, and nucleosome remodeling and deacetylating (NuRD)/MeCP1 as a single homogeneous complex. LARC binds to the hypersensitive 2 (HS2)-Maf recognition element (MARE) DNA in a sequence-specific manner and remodels nucleosomes. Heterogeneous nuclear ribonucleoprotein C1/C2, previously known as a general RNA binding protein, provides a sequence-specific DNA recognition element for LARC, and the LARC DNA-recognition sequence is essential for the enhancement of transcription by HS2. Independently of the initiation of transcription, LARC becomes associated with β-like globin promoters.
Interface connections of a transmembrane voltage sensor
Authors: Freites J. Alfredo , Tobias Douglas J. , von Heijne Gunnar , White Stephen H.
Published: October 2005

Voltage-sensitive ion channels open and close in response to changes in transmembrane (TM) potential caused by the motion of the S4 voltage sensors. These sensors are α–helices that include four or more positively charged amino acids, most commonly arginine. The so-called paddle model, based on the high-resolution structure of the KvAP K
+
channel [Jiang,
et al.
(2003)
Nature
423, 33–41], posits that the S4 sensors move within the membrane bilayer in response to TM voltage changes. Direct exposure of S4 sensors to lipid is contrary to the classical expectation that the dielectric contrast between the membrane hydrocarbon core and water presents an insurmountable energetic penalty to burial of electric charges. Nevertheless, recent experiments have shown that a helix with the sequence of KvAP S4 can be inserted across the endoplasmic reticulum membrane. To reconcile this result with the classical energetics argument, we have carried out a molecular dynamics simulation of an isolated TM S4 helix in a lipid bilayer. The simulation reveals a stabilizing hydrogen-bonded network of water and lipid phosphates around the arginines that reduces the effective thickness of the bilayer hydrocarbon core to ≈10Åinthe vicinity of the helix. It suggests that bilayer phospholipids can adapt locally to strongly perturbing protein elements, causing the phospholipids to become a structural extension of the protein.
BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1–Chk1 pathway, implicating checkpoint dysfunction in microcephaly
Authors: Lin Shiaw-Yih , Rai Rekha , Li Kaiyi , Xu Zhi-Xiang , Elledge Stephen J.
Published: October 2005

BRIT1
[BRCT-repeat inhibitor of hTERT expression], a repressor of human telomerase function, is implicated in cellular immortalization. Here, we find that BRIT1 acts as a regulator of both the intra-S and G
2
/M checkpoints. When BRIT1 expression is depleted, cells lose the ionizing radiation (IR)-induced cell cycle arrest and become IR sensitive. BRIT1 is a chromatin-associated protein that forms irradiation-induced nuclear foci that colocalize with γ-H2AX foci. BRIT1 is also required for the expression of both BRCA1 and the checkpoint kinase Chk1 and phosphorylation of Nbs1. Thus, the checkpoint defects in the absence of BRIT1 are likely to result from its regulation of Nbs1, BRCA1, and Chk1. BRIT1 is identical to the recently discovered
MCPH1
gene, found mutant in patients with primary microcephaly. The ataxia telangiectasia mutated-Rad3 related (ATR)–Chk1 pathway is defective in Seckel syndrome, another microcephaly disorder. We propose that the microcephaly observed in patients with MCPH1 deficiencies is due to disruption of the ATR–BRCA1–Chk1 signaling pathway that is also disrupted in Seckel syndrome patients.
Food control or food democracy? Re-engaging nutrition with society and the environment
Authors: Lang Tim
Published: October 2005

Objective

To explore the terms on which nutrition should engage with the global challenges ahead.

Design

Analysis of current orientation of nutrition and policy.

Result

Nutrition faces four conceptual problems. The first is that nutrition has fissured into two broad but divergent directions. One is biologically reductionist, now to the genome; the other sees nutrition as located in social processes, now also requiring an understanding of the physical environment. As a result, nutrition means different things to different people. The second problem is a misunderstanding of the relationship between evidence, policy and practice, assuming that policy is informed by evidence, when there is much evidence to the contrary. The third problem is that nutrition is generally blind to the environment despite the geo-spatial crisis over food supply, which will determine who eats what, when and how. How can we ask people to eat fish when fish stocks are collapsing, or to eat wisely if water shortage dominates or climate change weakens food security? The fourth problem is that, in today's consumerist and supermarketised world, excess choice plus information overload may be nutrition's problem, not solution.

Conclusion

Nutrition science needs to re-engage with society and the environment. The alternative is, at best, to produce an individualised approach to public health or, at worst, to produce brilliant science but be policy-irrelevant.
The social and environmental dimensions of nutrition science
Authors: Pettoello-Mantovani Massimo
Published: October 2005

Objective

To emphasise the importance of defining a new nutrition science and food policy that includes social and environmental dimensions.

Design

Nutrition science and food policy is put in the context of sustainable development. Examples are presented to show that a number of factors including exploitation of resources, disrespect for land and food insecurity contribute to the decline of a culture. The fate of cultures that lack implemented sustainable development strategies is discussed.

Conclusion

Pressure from low-income and economically challenged countries combined with the efforts of not-for-profit private institutions is proposed. The goal is to produce and provide science-based evidence and guidelines to be used as a tool to encourage institutions and organisations to redefine their policies to deal effectively with global issues.
Integrated nutrition science: from theory to practice in South Africa
Authors: Vorster HH , Margetts BM , Venter CS , Wissing MP
Published: October 2005

Objective

To describe an integrated, holistic conceptual framework and research paradigm for a better understanding of the nutrition transition in middle- and low-income countries.

Motivation

Current inability effectively to prevent the increasing burden related to changes in food consumption patterns and other health behaviours of populations in transition motivates a new approach for nutrition research and practice. In this proposed approach, broader and integrated dimensions of science and practice may be applied for a better understanding of this complex phenomenon.

Result

Examples from our own studies are given and quoted to illustrate how results from transdisciplinary studies were used to design an integrated, holistic programme to improve quality of life of people infected with HIV.

Conclusion

Based on these experiences it is argued that the more holistic and integrated approach should and could lead to more effective and sustainable interventions to prevent the adverse health consequences of the nutrition transition. At the same time such an approach will contribute to efforts to conserve the environment and also human, living and natural resources.
Public('s) nutrition
Authors: Beaudry Micheline , Delisle Hélène
Published: October 2005

Objective

To promote the new field of ‘public nutrition’ as a means to address, in a more efficient, sustainable and ethical manner, the world-wide epidemic of malnutrition – undernutrition and specific nutrient deficiencies, and also obesity and other nutrition-related chronic diseases.

Strategy

Grounded in the health promotion model, public nutrition applies the population health strategy to the resolution of nutrition problems. It encompasses ‘public health nutrition’, ‘community nutrition’ and ‘international nutrition’ and extends beyond them. It fits within the conceptual framework of ‘the new nutrition science’ and is an expression of this reformulated science in practice. Its fundamental goal is to fulfil the human right to adequate food and nutrition. It is in the interest of the public, it involves the participation of the public and it calls for partnerships with other relevant sectors beyond health. Public nutrition takes a broader view of nutritional health, addressing the three interrelated determinant categories of food systems and food security; food and health practices; and health systems. It assesses and analyses how these influence the immediate determinants that are dietary intake and health status so as to direct action towards effective progress. To further enhance the relevance and effectiveness of action, public nutrition advocates improved linkages between policies and programmes, research and training. A renewed breed of professionals for dietetics and nutrition, trained along those lines, is suggested.

Conclusion

There is a critical need to develop new knowledge, approaches and skills to meet the pressing nutrition challenges of our times.
The new nutrition science: sustainability and development
Authors: Wahlqvist Mark L
Published: October 2005

Objective

To show that nutrition science is anchored in food systems and is influenced by the social, through the environmental to the cosmological, life's connections and rhythms. To indicate that an integrative approach is now becoming possible with advances in food technology, in the understanding of food choice and of human behaviour, and in a preparedness to recognise nutritional inputs in the full sweep of life-long well-being and health outcomes.

Method

An analysis of the much broader understanding of nutritionally related diseases from an ecological perspective, with attention to economic development, beginning with poverty alleviation. Recognition that the biological dimension of nutrition science is undergoing a profound reappraisal; that technologies will allow us to change the course of nutritionally related diseases for the better; and that nutrition science will find partners in information technology and telecommunications, food technology and energy technology.

Conclusion

A new generation of nutrition scientists can help build a new economy that supports development amongst communities, whether close or distant from each other. The opportunities for this kind of development to be realised between Asia, Latin America and Africa are considerable. At all times, however, nutrition scientists must uphold the paramount importance of good governance, conflict resolution and maternal literacy if their work is to achieve its growing potential.
The new nutrition science project
Authors: Cannon Geoffrey , Leitzmann Claus
Published: October 2005

Objective

To show that nutrition science, with its application to food and nutrition policy, now needs a new conceptual framework. This will incorporate nutrition in its current definition as principally a biological science, now including nutritional aspects of genomics. It will also create new governing and guiding principles; specify a new definition; and add social and environmental dimensions and domains.

Method

A narrative review of nutrition science, its successes and achievements, and its dilemmas, paradoxes, shortcomings, dissonances and challenges. Reference is made to 16 associated papers. Equal use is made of continuous text and of boxed texts that extend the review and give salient examples.

Results

Recent and current interrelated electronic and genomic discoveries and linked sequential demographic, nutritional and epidemiological shifts, in the context of associated and interlinked global social, cultural, environmental, economic, political and other developments, altogether amount to a world in revolution, requiring all disciplines including that of nutrition science to make comparably radical responses.

Conclusion

Nutrition in principle and practice should be a biological and also an environmental and social science. This new broad integrated structure brings much recent and current progressive work into the centre of nutrition science, and in some ways is a renewal of the period when nutrition science had its greatest impact. It amounts to a map charting well-known and also new worlds. The new nutrition science is concerned with personal and population health, and also with planetary health – the welfare and future of the whole physical and living world of which humans are a part. In this way the discipline will make a greater contribution to the preservation, maintenance, development and sustenance of life on Earth, appropriate for the twenty-first century.
The principles, definition and dimensions of the new nutrition science
Authors: Beauman Christopher , Cannon Geoffrey , Elmadfa Ibrahim , Glasauer Peter , Hoffmann Ingrid , Keller Markus , Krawinkel Michael , Lang Tim , Leitzmann Claus , Lötsch Bernd , Margetts Barrie M , McMichael Anthony J , Meyer-Abich Klaus , Oltersdorf Ulrich , Pettoello-Mantovani Massimo , Sabaté Joan , Shetty Prakash , Sória Marco , Spiekermann Uwe , Tudge Colin , Vorster Hester H , Wahlqvist Mark , Zerilli-Marimò Mariuccia
Published: October 2005

Objective

To specify the principles, definition and dimensions of the new nutrition science.

Purpose

To identify nutrition, with its application in food and nutrition policy, as a science with great width and breadth of vision and scope, in order that it can fully contribute to the preservation, maintenance, development and sustenance of life on Earth.

Method

A brief overview shows that current conventional nutrition is defined as a biological science, although its governing and guiding principles are implicit only, and no generally agreed definition is evident. Following are agreements on the principles, definition and dimensions of the new nutrition science, made by the authors as participants at a workshop on this theme held on 5–8 April 2005 at the Schloss Rauischholzhausen, Justus-Liebig University, Giessen, Germany.

Result

Nutrition science as here specified will retain its current [classical] identity as a biological science, within a broader and integrated conceptual framework, and will also be confirmed as a social and environmental science. As such it will be concerned with personal and population health, and with planetary health – the welfare and future of the whole physical and living world of which humans are a part.
Inhibition of cell movement and proliferation by cell–cell contact-induced interaction of Necl-5 with nectin-3
Authors: Fujito Tsutomu , Ikeda Wataru , Kakunaga Shigeki , Minami Yukiko , Kajita Mihoko , Sakamoto Yasuhisa , Monden Morito , Takai Yoshimi
Published: October 2005

Immunoglobulin-like Necl-5/Tage4/poliovirus receptor (PVR)/CD155, originally identified as the PVR, has been shown to be up-regulated in cancer cells and to enhance growth factor–induced cell movement and proliferation. In addition, Necl-5 heterophilically trans-interacts with nectin-3, a cell–cell adhesion molecule known to form adherens junctions in cooperation with cadherin. We show here that Necl-5 was down-regulated from cell surface upon cell–cell contacts in NIH3T3 cells. This down-regulation of Necl-5 was initiated by its interaction with nectin-3 and was mainly mediated by clathrin-dependent endocytosis. Then, the down-regulation of Necl-5 induced in this way reduced movement and proliferation of NIH3T3 cells. These results indicate that the down-regulation of Necl-5 induced by its interaction with nectin-3 upon cell–cell contacts may be at least one mechanism underlying contact inhibition of cell movement and proliferation.
Light-regulated interaction of Dmoesin with TRP and TRPL channels is required for maintenance of photoreceptors
Authors: Chorna-Ornan Irit , Tzarfaty Vered , Ankri-Eliahoo Galit , Joel-Almagor Tamar , Meyer Nina E. , Huber Armin , Payre François , Minke Baruch
Published: October 2005

Recent studies in Drosophila melanogaster retina indicate that absorption of light causes the translocation of signaling molecules and actin from the photoreceptor's signaling membrane to the cytosol, but the underlying mechanisms are not fully understood. As ezrin-radixin-moesin (ERM) proteins are known to regulate actin–membrane interactions in a signal-dependent manner, we analyzed the role of Dmoesin, the unique D. melanogaster ERM, in response to light. We report that the illumination of dark-raised flies triggers the dissociation of Dmoesin from the light-sensitive transient receptor potential (TRP) and TRP-like channels, followed by the migration of Dmoesin from the membrane to the cytoplasm. Furthermore, we show that light-activated migration of Dmoesin results from the dephosphorylation of a conserved threonine in Dmoesin. The expression of a Dmoesin mutant form that impairs this phosphorylation inhibits Dmoesin movement and leads to light-induced retinal degeneration. Thus, our data strongly suggest that the light- and phosphorylation-dependent dynamic association of Dmoesin to membrane channels is involved in maintenance of the photoreceptor cells.
Microdomains bounded by endoplasmic reticulum segregate cell cycle calcium transients in syncytial Drosophila embryos
Authors: Parry Huw , McDougall Alex , Whitaker Michael
Published: October 2005

Cell cycle calcium signals are generated by the inositol trisphosphate (InsP3)–mediated release of calcium from internal stores (Ciapa, B., D. Pesando, M. Wilding, and M. Whitaker. 1994. Nature. 368:875–878; Groigno, L., and M. Whitaker. 1998. Cell. 92:193–204). The major internal calcium store is the endoplasmic reticulum (ER); thus, the spatial organization of the ER during mitosis may be important in shaping and defining calcium signals. In early Drosophila melanogaster embryos, ER surrounds the nucleus and mitotic spindle during mitosis, offering an opportunity to determine whether perinuclear localization of ER conditions calcium signaling during mitosis. We establish that the nuclear divisions in syncytial Drosophila embryos are accompanied by both cortical and nuclear localized calcium transients. Constructs that chelate InsP3 also prevent nuclear division. An analysis of nuclear calcium concentrations demonstrates that they are differentially regulated. These observations demonstrate that mitotic calcium signals in Drosophila embryos are confined to mitotic microdomains and offer an explanation for the apparent absence of detectable global calcium signals during mitosis in some cell types.
Structural properties and neuronal toxicity of amyotrophic lateral sclerosis–associated Cu/Zn superoxide dismutase 1 aggregates
Authors: Matsumoto Gen , Stojanovic Aleksandar , Holmberg Carina I. , Kim Soojin , Morimoto Richard I.
Published: October 2005

The appearance of protein aggregates is a characteristic of protein misfolding disorders including familial amyotrophic lateral sclerosis, a neurodegenerative disease caused by inherited mutations in Cu/Zn superoxide dismutase 1 (SOD1). Here, we use live cell imaging of neuronal and nonneuronal cells to show that SOD1 mutants (G85R and G93A) form an aggregate structure consisting of immobile scaffolds, through which noninteracting cellular proteins can diffuse. Hsp70 transiently interacts, in a chaperone activity-dependent manner, with these mutant SOD1 aggregate structures. In contrast, the proteasome is sequestered within the aggregate structure, an event associated with decreased degradation of a proteasomal substrate. Through the use of time-lapse microscopy of individual cells, we show that nearly all (90%) aggregate-containing cells express higher levels of mutant SOD1 and died within 48 h, whereas 70% of cells expressing a soluble mutant SOD1 survived. Our results demonstrate that SOD1 G85R and G93A mutants form a distinct class of aggregate structures in cells destined for neuronal cell death.
Aβ generation in autophagic vacuoles
Authors: Mizushima Noboru
Published: October 2005

Alzheimer's disease (AD) is the most common form of dementia among older people. It is characterized by the extracellular accumulation of β-amyloid (Aβ) deposits called senile or neuritic plaques. Aβ is generated by the proteolytic cleavage of Aβ precursor protein (APP) by β and γ-secretases localized in the secretory and endocytic compartments. In this issue, Yu et al. (on p. 87) report a novel mechanism for the generation of Aβ peptides, which takes place in autophagic vacuoles (AVs) that accumulate in AD brains.
Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve
Authors: Luyer Misha D. , Greve Jan Willem M. , Hadfoune M'hamed , Jacobs Jan A. , Dejong Cornelis H. , Buurman Wim A.
Published: October 2005

The immune system in vertebrates senses exogenous and endogenous danger signals by way of complex cellular and humoral processes, and responds with an inflammatory reaction to combat putative attacks. A strong protective immunity is imperative to prevent invasion of pathogens; however, equivalent responses to commensal flora and dietary components in the intestine have to be avoided. The autonomic nervous system plays an important role in sensing luminal contents in the gut by way of hard-wired connections and chemical messengers, such as cholecystokinin (CCK). Here, we report that ingestion of dietary fat stimulates CCK receptors, and leads to attenuation of the inflammatory response by way of the efferent vagus nerve and nicotinic receptors. Vagotomy and administration of antagonists for CCK and nicotinic receptors significantly blunted the inhibitory effect of high-fat enteral nutrition on hemorrhagic shock-induced tumor necrosis factor-α and interleukin-6 release (P < 0.05). Furthermore, the protective effect of high-fat enteral nutrition on inflammation-induced intestinal permeability was abrogated by vagotomy and administration of antagonists for CCK and nicotinic receptors. These data reveal a novel neuroimmunologic pathway, controlled by nutrition, that may help to explain the intestinal hyporesponsiveness to dietary antigens, and shed new light on the functionality of nutrition.
SOCS-1 regulates IL-15–driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential
Authors: Davey Gayle M. , Starr Robyn , Cornish Ann L. , Burghardt J. Theodore , Alexander Warren S. , Carbone Francis R. , Surh Charles D. , Heath William R.
Published: October 2005

Mice that are deficient in suppressor of cytokine signaling–1 (SOCS-1) succumb to neonatal mortality that is associated with extensive cellular infiltration of many tissues. T cells seem to be necessary for disease, which can be alleviated largely by neutralizing interferon-γ. Examining T cell receptor (TCR) specificity shows that even monospecific T cells can mediate disease in SOCS-1–deficient mice, although disease onset is substantially faster with a polyclonal T cell repertoire. A major phenotype of SOCS-1−/− mice is the accumulation of CD44highCD8+ peripheral T cells. We show that SOCS-1–deficient CD8, but not CD4, T cells proliferate when transferred into normal (T cell–sufficient) mice, and that this is dependent on two signals: interleukin (IL)-15 and self-ligands that are usually only capable of stimulating homeostatic expansion in T cell–deficient mice. Our findings reveal that SOCS-1 normally down-regulates the capacity of IL-15 to drive activation and proliferation of naive CD8 T cells receiving TCR survival signals from self-ligands. We show that such dysregulated proliferation impairs the deletion of a highly autoreactive subset of CD8 T cells, and increases their potential for autoimmunity. Therefore, impaired deletion of highly autoreactive CD8 T cells, together with uncontrolled activation of naive CD8 T cells by homeostatic survival ligands, may provide a basis for the T cell–mediated disease of SOCS-1−/− mice.
Endogenous human cytomegalovirus gB is presented efficiently by MHC class II molecules to CD4+ CTL
Authors: Hegde Nagendra R. , Dunn Claire , Lewinsohn David M. , Jarvis Michael A. , Nelson Jay A. , Johnson David C.
Published: October 2005

Human cytomegalovirus (HCMV) infects endothelial, epithelial, and glial cells in vivo. These cells can express MHC class II proteins, but are unlikely to play important roles in priming host immunity. Instead, it seems that class II presentation of endogenous HCMV antigens in these cells allows recognition of virus infection. We characterized class II presentation of HCMV glycoprotein B (gB), a membrane protein that accumulates extensively in endosomes during virus assembly. Human CD4+ T cells specific for gB were both highly abundant in blood and cytolytic in vivo. gB-specific CD4+ T cell clones recognized gB that was expressed in glial, endothelial, and epithelial cells, but not exogenous gB that was fed to these cells. Glial cells efficiently presented extremely low levels of endogenous gB—expressed by adenovirus vectors or after HCMV infection—and stimulated CD4+ T cells better than DCs that were incubated with exogenous gB. Presentation of endogenous gB required sorting of gB to endosomal compartments and processing by acidic proteases. Although presentation of cellular proteins that traffic into endosomes is well known, our observations demonstrate for the first time that a viral protein sorted to endosomes is presented exceptionally well, and can promote CD4+ T cell recognition and killing of biologically important host cells.
Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing
Authors: Johansson-Lindbom Bengt , Svensson Marcus , Pabst Oliver , Palmqvist Caroline , Marquez Gabriel , Förster Reinhold , Agace William W.
Published: October 2005

Gut-associated lymphoid tissue (GALT) dendritic cells (DCs) display a unique ability to generate CCR9+α4β7+ gut-tropic CD8+ effector T cells. We demonstrate efficient induction of CCR9 and α4β7 on CD8+ T cells in mesenteric lymph nodes (MLNs) after oral but not intraperitoneal (i.p.) antigen administration indicating differential targeting of DCs via the oral route. In vitro, lamina propria (LP)–derived DCs were more potent than MLN or Peyer's patch DCs in their ability to generate CCR9+α4β7+ CD8+ T cells. The integrin α chain CD103 (αE) was expressed on almost all LP DCs, a subset of MLN DCs, but on few splenic DCs. CD103+ MLN DCs were reduced in number in CCR7−/− mice and, although CD8+ T cells proliferated in the MLNs of CCR7−/− mice after i.p. but not oral antigen administration, they failed to express CCR9 and had reduced levels of α4β7. Strikingly, although CD103+ and CD103− MLN DCs were equally potent at inducing CD8+ T cell proliferation and IFN-γ production, only CD103+ DCs were capable of generating gut-tropic CD8+ effector T cells in vitro. Collectively, these results demonstrate a unique function for LP-derived CD103+ MLN DCs in the generation of gut-tropic effector T cells.
Approaching the microjoule frontier with femtosecond laser oscillators: theory and comparison with experiment
Authors: Kalashnikov V L , Podivilov E , Chernykh A , Naumov S , Fernandez A , Graf R , Apolonski A
Published: October 2005

A detailed numerical analysis of heavily chirped pulses in the positive-dispersion regime (PDR) is presented on the basis of the distributed cubic–quintic generalized complex nonlinear Ginzburg–Landau equation. It is demonstrated that there are three main types of pulse spectra: truncated parabolic-top, Π- and M-shaped profiles. The strong chirp broadens the pulse spectrum up to 100 nm for a Ti:Sa oscillator, which provides compressibility of the picosecond pulse down to sub-30 fs. Since the picosecond pulse has a peak power lower than the self-focusing power inside a Ti:Sa crystal, the microjoule energies become directly available from a femtosecond oscillator. The influence of the third- and fourth-order dispersions on the pulse spectrum and stability is analysed. It is demonstrated that the dynamic gain saturation plays an important role in pulse stabilization. The common action of dynamic gain saturation, self-amplified modulation (SAM) and saturation of the SAM provides pulse stabilization inside the limited range of the positive group-delay dispersions (GDDs). Since the stabilizing action of the SAM cannot be essentially enhanced for a pure Kerr-lens mode-locking regime, a semiconductor saturable absorber is required for pulse energies of >0.7 μJ inside an oscillator. The basic results of the numerical analysis are in an excellent agreement with experimental data obtained from oscillators with repetition rates ranging from 50 to 2 MHz.
Syntons, metabolons and interactons: an exact graph-theoretical approach for exploring neighbourhood between genomic and functional data
Authors: Boyer Frédéric , Morgat Anne , Labarre Laurent , Pothier Joël , Viari Alain
Published: October 2005

Motivation: Modern comparative genomics does not restrict to sequence but involves the comparison of metabolic pathways or protein–protein interactions as well. Central in this approach is the concept of neighbourhood between entities (genes, proteins, chemical compounds). Therefore there is a growing need for new methods aiming at merging the connectivity information from different biological sources in order to infer functional coupling.

Results: We present a generic approach to merge the information from two or more graphs representing biological data. The method is based on two concepts. The first one, the correspondence multigraph, precisely defines how correspondence is performed between the primary data-graphs. The second one, the common connected components, defines which property of the multigraph is searched for. Although this problem has already been informally stated in the past few years, we give here a formal and general statement together with an exact algorithm to solve it.

Availability: The algorithm presented in this paper has been implemented in C. Source code is freely available for download at:

Contact: Alain.Viari@inrialpes.fr
QUASAR—scoring and ranking of sequence–structure alignments
Authors: Birzele Fabian , Gewehr Jan E. , Zimmer Ralf
Published: October 2005

Summary: Sequence–structure alignments are a common means for protein structure prediction in the fields of fold recognition and homology modeling, and there is a broad variety of programs that provide such alignments based on sequence similarity, secondary structure or contact potentials. Nevertheless, finding the best sequence–structure alignment in a pool of alignments remains a difficult problem. QUASAR (quality of sequence–structure alignments ranking) provides a unifying framework for scoring sequence–structure alignments that aids finding well-performing combinations of well-known and custom-made scoring schemes. Those scoring functions can be benchmarked against widely accepted quality scores like MaxSub, TMScore, Touch and APDB, thus enabling users to test their own alignment scores against ‘standard-of-truth’ structure-based scores. Furthermore, individual score combinations can be optimized with respect to benchmark sets based on known structural relationships using QUASAR's in-built optimization routines.

Availability: The software, examples, the Java documentation and a tutorial are available at

Contact:  fabian.birzele@ifi.lmu.de
Spirit, Mind and Body in Chumash Healing
Authors: Adams James D. , Garcia Cecilia
Published: October 2005

This article discusses the importance of the spirit and mind in health and well‐being among Chumash people. Prayer was the first step in healing since prayer invites the participation of God. Initiation practices are discussed that encouraged young people to develop the maturity and spiritual strength to become productive members of society. Pictographs were used in healing usually not only as a relaxation therapy, but also as a mode of education. A supportive environment was an important factor in Chumash health care, since the support of friends helps, comforts and relieves anxiety that is detrimental to healing.
Treatment Expectations for CAM Interventions in Pediatric Chronic Pain Patients and their Parents
Authors: Tsao Jennie C. I. , Meldrum Marcia , Bursch Brenda , Jacob Margaret C. , Kim Su C. , Zeltzer Lonnie K.
Published: October 2005

Patient expectations regarding complementary and alternative medicine (CAM) interventions have important implications for treatment adherence, attrition and clinical outcome. Little is known, however, about parent and child treatment expectations regarding CAM approaches for pediatric chronic pain problems. The present study examined ratings of the expected benefits of CAM (i.e. hypnosis, massage, acupuncture, yoga and relaxation) and conventional medicine (i.e. medications, surgery) interventions in 45 children (32 girls; mean age = 13.8 years ± 2.5) and parents (39 mothers) presenting for treatment at a specialty clinic for chronic pediatric pain. Among children, medications and relaxation were expected to be significantly more helpful than the remaining approaches (P < 0.01). However, children expected the three lowest rated interventions, acupuncture, surgery and hypnosis, to be of equal benefit. Results among parents were similar to those found in children but there were fewer significant differences between ratings of the various interventions. Only surgery was expected by parents to be significantly less helpful than the other approaches (P < 0.01). When parent and child perceptions were compared, parents expected hypnosis, acupuncture and yoga, to be more beneficial than did children, whereas children expected surgery to be more helpful than did parents (P < 0.01). Overall, children expected the benefits of CAM to be fairly low with parents′ expectations only somewhat more positive. The current findings suggest that educational efforts directed at enhancing treatment expectations regarding CAM, particularly among children with chronic pain, are warranted.
Micromechanics investigation of expansive reactions in chemoelastic concrete
Authors: Lemarchand Eric , Dormieux Luc , Ulm Franz-Josef
Published: October 2005

Expansive reactions damage porous materials through the formation of reaction products of a volume in excess of the available space left by the reactants and the natural porosity of the material. This leads to pressurizing the pore space accessible to the reaction products, which differs when the chemical reaction is through-solution or topochemical or both in nature. This paper investigates expansive reactions from a micromechanical point of view, which allows bridging the scale from the local chemo-mechanical mechanisms to the macroscopically observable stress-free expansion. In particular, the study of the effect of morphology of the pore space, in which the chemical expansion occurs locally, on the macroscopically observable expansion is the main focus of this paper. The first part revisits the through-solution and the topochemical reaction mechanism within the framework of micro–macro-homogenization theories, and the effect of the microscopic geometry of pores and microcracks in the solid matrix on the macroscopic chemical expansion is examined. The second part deals with the transition from a topochemical to a through-solution-like mechanism that occurs in a solid matrix with inclusions (cracks, pores) of different morphology.
Comparative Plant Genomics Resources at PlantGDB
Authors: Dong Qunfeng , Lawrence Carolyn J. , Schlueter Shannon D. , Wilkerson Matthew D. , Kurtz Stefan , Lushbough Carol , Brendel Volker
Published: October 2005

PlantGDB (http://www.plantgdb.org/) is a database of plant molecular sequences. Expressed sequence tag (EST) sequences are assembled into contigs that represent tentative unique genes. EST contigs are functionally annotated with information derived from known protein sequences that are highly similar to the putative translation products. Tentative Gene Ontology terms are assigned to match those of the similar sequences identified. Genome survey sequences are assembled similarly. The resulting genome survey sequence contigs are matched to ESTs and conserved protein homologs to identify putative full-length open reading frame-containing genes, which are subsequently provisionally classified according to established gene family designations. For Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), the exon-intron boundaries for gene structures are annotated by spliced alignment of ESTs and full-length cDNAs to their respective complete genome sequences. Unique genome browsers have been developed to present all available EST and cDNA evidence for current transcript models (for Arabidopsis, see the AtGDB site at http://www.plantgdb.org/AtGDB/; for rice, see the OsGDB site at http://www.plantgdb.org/OsGDB/). In addition, a number of bioinformatic tools have been integrated at PlantGDB that enable researchers to carry out sequence analyses on-site using both their own data and data residing within the database.
Plant-Based Microarray Data at the European Bioinformatics Institute. Introducing AtMIAMExpress, a Submission Tool for Arabidopsis Gene Expression Data to ArrayExpress
Authors: Mukherjee Gaurab , Abeygunawardena Niran , Parkinson Helen , Contrino Sergio , Durinck Steffen , Farne Anna , Holloway Ele , Lilja Per , Moreau Yves , Oezcimen Ahmet , Rayner Tim , Sharma Anjan , Brazma Alvis , Sarkans Ugis , Shojatalab Mohammadreza
Published: October 2005

ArrayExpress is a public microarray repository founded on the Minimum Information About a Microarray Experiment (MIAME) principles that stores MIAME-compliant gene expression data. Plant-based data sets represent approximately one-quarter of the experiments in ArrayExpress. The majority are based on Arabidopsis (Arabidopsis thaliana); however, there are other data sets based on Triticum aestivum, Hordeum vulgare, and Populus subsp. AtMIAMExpress is an open-source Web-based software application for the submission of Arabidopsis-based microarray data to ArrayExpress. AtMIAMExpress exports data in MAGE-ML format for upload to any MAGE-ML-compliant application, such as J-Express and ArrayExpress. It was designed as a tool for users with minimal bioinformatics expertise, has comprehensive help and user support, and represents a simple solution to meeting the MIAME guidelines for the Arabidopsis community. Plant data are queryable both in ArrayExpress and in the Data Warehouse databases, which support queries based on gene-centric and sample-centric annotation. The AtMIAMExpress submission tool is available at http://www.ebi.ac.uk/at-miamexpress/. The software is open source and is available from http://sourceforge.net/projects/miamexpress/. For information, contact miamexpress@ebi.ac.uk.
Induction Period for Oxygen Permeation through Calcia‐Stabilized Zirconia Ceramic
Authors: Dou Shixue , Masson Charles R. , Pacey Philip D.
Published: October 2005

Chemical diffusion of oxygen in calcia‐stabilized zirconia, with impurities of A12O3, SiO2, MgO, Fe2O3, and TiO2, was studied by the non‐steady‐state permeation technique at 960° to 1450°C. The apparent chemical diffusion coefficient, D, was found to decrease with increasing content of Fe2O3, and with decreasing oxygen pressure. The results were consistent with a trapping mechanism involving free and trapped electron holes or with partial control by surface processes.
Oxidation of Chemically‐Vapor‐Deposited Silicon Nitride and Slnglem‐Crystal Silicon
Authors: Choi Doo J. , Fischbach David B. , Scott William D.
Published: October 2005

Oxidation of {111} single‐crystal silicon and dense, chemically‐vapor‐deposited silicon nitride was done in clean silica tubes at temperatures of 1000° to woo°C. The oxidation rates of silicon nitride under various atmospheres (dry O2, wet O2, wet inert gas, and steam) were several orders of magnitude slower than those of silicon under the identical conditions. The activation energy for the oxidation of silicon nitride decreased from 330 to 259 kJ/mol in going from dry O2 to steam while that for Si decreased from 120 to 94 kJ/mol. The parabolic rate constant for Si increased linearly as the water vapor pressure increased. However, the parabolic rate constant for silicon nitride showed nonlinear dependency on the water vapor pressure in the presence of oxygen. The oxidation kinetics of silicon nitride is explained by the formation of nitrogen compounds (NO and NH3) at the reaction interface and the counterpermeation of these reaction products.
Production of Fine Ceramic Powders from Chloromethylsilanes Using Pulsed Excimer Radiation
Authors: O'Neill J.A. , Horsburgh M. , Tann J. , Grant K. J. , Paul G.L. , Sinclair W.
Published: October 2005

Ceramic powders have been produced by the photodecomposition of chloromethylsilanes using a pulsed excimer laser operating at 193 nm. These feedstocks are cheaper and easier to handle than SiH4, the main feedstock used in earlier work using continuous–wave CO2 lasers as the irradiation source. Powders were produced from photolysis of silanes containing methyl groups without the addition of any coreagents, while the two silanes tested containing only chlorine and hydrogen ligands, SiCI3H and SiCI4, required the addition of H2 as a coreagent for significant yields of powder to be produced. The powders produced were found to be low in chlorine, with amorphous Si powders or β‐SiC being produced depending on feedstock. Particle sizes measured from electron micrographs varied from less than 10 nm to 1.5 μm.
Elimination of large Pores During Gas‐Pressure Sintering of β′‐Sialon
Authors: Kang Suk‐Joong L. , Greil Peter , Mitomo Mamoru , Moon Jong‐Ha
Published: October 2005

The effect of N2‐gas pressure on the liquid filling of large pores (20 to 120 μm in diameter) is studied in sintered β′‐sialon (z= 1). The initially sintered sialon with large pores is sintered again and infitrated by a liquid (41A12O3‐41Y2O3‐14Si3Y4‐4AIN (wt%)) at 17800°C for various times under 0.1‐, 0.3‐, and 0.5‐MPa (1‐, 3‐, and 5‐atm) N2. The liquid fills large interconnected pores; the size of the pores filled with liquid increases with N2‐gas pressure and time. In some liquid pockets, gas bubbles are formed and subsequently disappear during prolonged sintering treatment. The liquid‐filling be havior with sintering pressure and time is explained by gas pressure in the pore and thermal decomposition of the material. The benefit of gas‐pressure sintering for the elimination of large pores is assessed.
Density Determination of Thin Coatings by X‐ray Methods
Authors: Kalman Zwi H. , Johnson Lois A. , Wachtman John B.
Published: October 2005

A method is proposed and demonstrated for measuring the area density of coatings of known chemical composition on poly crystalline‐substrates by means of an X‐ray technique. The method is based on measuring the absorption in the coating by comparing intensities of substrate Bragg reflections from uncoated and coated substrates at varying angles of incidence. From these measurements, in conjunction with beam‐path geometry and the mass absorption coefficient, the coating area density is determined. Densities are determined for coatings of alumina, boehmite, gold, and other materials.
Effect of Crack‐Interface Bridging on Subcritical Crack Growth in Ferrites
Authors: Beauchamp Edwin K. , Monroe S. L.
Published: October 2005

A transition between transgranular fracture and intergranular fracture in polycrystalline manganese zinc ferrites has been investigated by measuring subcritical crack growth in double‐cantilever‐beam specimens. Log velocity vs K1 plots are like those for other ceramic materials with three well‐defined regions of growth. Unlike other ceramics, however, the K1 values at which crack growth became critical showed large variations with relative humidity. Crack velocities depended on prior history and, at K1 > 1.1 MPa · m1/2 in dry N2, crack growth was intermittent. All of these features were related to an increase in intergranular fracture with K1. A model is presented to explain the data in terms of the generation ad removal of crack‐interface bridges which were produced by intergranular fracture.
Binder Distribution in Ceramic Greenware During Thermolysis
Authors: Cima Michael J , Lewis Jennifer Alan , Devoe Alan D.
Published: October 2005

Capillary forces were shown to influence the distribution of polymer‐plasicizer mixtures within ceramic green bodies during binder thermolysis. Isothermal thermogravimetric analysis was performed on tape‐cast sheets of an aluminapoly(vinyl butyrall‐dibutyl phthalate composite and direct observations were made of the binder distribution and pore growth after partial pyrolysis. This led to the investigation of a model system, an alumina‐eicosane composite, by similar experimental techniques. The early stage of binder removal was found to be similar to the drying of particle beds in which capillary forces draw liquid into the smaller pores at the surface. The morphology of the binder distribution produced by these processes dictates which mass‐transfer resistances may be controlling in binder burnout. A model is described that determines the length scale over which capillarity acts based on measurable physical parameters of the binder system and the packing of the ceramic particles.