bluuebunny/crossref_metadata_2025 huggingface dataset:
Who Stole the Chemokine?
Authors: Ray L. Bryan
Published: March 2008

Primordial germ cells (PGCs) in the zebrafish embryo face a long migration from the point at which they are specified during development to the location of the future gonad, and it takes some precise signaling to get them there. Major guidance cues are provided by the chemokine SDF-1a (stromal-derived factor-1 alpha), which attracts the PGCs by signaling through its receptor CXCR4b [chemokine (C-X-C motif) receptor 4b]. SDF-1a also binds to another receptor, CXCR7, but the function of this receptor in PGC cell migration has been uncertain. Boldajipour
et al.
’s experiments indicate that CXCR7’s function is not to signal but rather to act as a sink that soaks up stray molecules of SDF-1a, thus adding to the precision of SDF-1a signaling through CXCR4b. Transplantation experiments taking PGCs from animals lacking CXCR7 into wild-type embryos showed that the critical function of CXCR7 was in somatic cells, not the PGCs. Microscopy of fluorescently tagged proteins showed that CXCR7 promoted internalization of SDF-1a, and human cells expressing CXCR7 depleted SDF-1a from the culture medium in which they were grown. In vivo, the inhibited motility of PGCs in embryos lacking CXCR7 was reproduced in embryos overexpressing SDF-1a, and depletion of CXCR4b suppressed the CXCR7 phenotype. Analysis of embryos in which SDF-1a was uniformly expressed but CXCR7 was expressed unevenly showed that PGCs moved to domains lacking CXCR7 (where concentrations of SDF-1a were presumably higher). The authors compare this decoy receptor strategy to a similar mechanism that functions in the resolution of inflammatory responses: In that case, interleukin-10 promotes expression of inflammatory chemokine receptors on mature dendritic cells, where they also appear not to signal but instead act to sequester proinflammatory chemokines.

B. Boldajipour, H. Mahabaleshwar, E. Kardash, M. Reichman-Fried, H. Blaser, S. Minina, D. Wilson, Q. Xu, E. Raz, Control of chemokine-guided cell migration by ligand sequestration.
Cell
132
, 463-473 (2008).
[Online Journal]
Competing for ROCK1
Authors: Gough Nancy R.
Published: March 2008

The ROCK family of kinases is involved in regulation of the cytoskeleton and cell motility. Cells moving in a 3D environment frequently exhibit an amoeboid type of motility, involving membrane blebbing and movement of rounded cells. Pinner and Sahai identified phosphoinositide-dependent kinase 1 (PDK1) in an RNAi screen for proteins involved in maintenance of a rounded-cell morphology of A375 melanoma cells in collagen gels. In 3D cultures, but not in 2D cultures, reduced abundance of PDK1 in several cancer cell lines resulted in elongated cells and inhibited cell movement, which were similar characteristics to those of cells in which ROCK activity was inhibited. When cells in which PDK1 was knocked down were injected into tail veins of nude mice, the cells tended to be elongated and extravasation of the injected cells into the lung was decreased. Reduction of PDK1 abundance disrupted the organization of myosin light chain at the rear of mobile cells and reduced the accumulation of ROCK1, but not ROCK2, at the plasma membrane. The interaction of PDK1 with ROCK1 did not appear to require phosphorylation of ROCK1 by PDK1 as a catalytically inactive mutant of PDK1 rescued cells from the effects of PDK1 knockdown on morphology, motility, and accumulation of ROCK1 at the plasma membrane. In vitro purified PDK1 interacted with a fragment of ROCK1 that contained the putative PDK1 binding site, and this interaction did not require phosphorylation of ROCK1. ROCK1 was not a substrate for PDK1 in vitro. In vitro experiments suggested that PDK1 and RhoE, a negative regulator of ROCK1, competed for binding to ROCK1, and lysates from cells in which PDK1 was knocked down showed enhanced binding of ROCK1 to RhoE in a pull-down assay. Confirming that RhoE and PDK1 serve as opposing regulators of ROCK1 activity, ROCK1 plasma membrane localization, cellular morphology, and cell motility were restored when both RhoE and PDK1 were depleted using RNAi techniques. Thus, PDK1 appears to have a kinase-independent function in regulation of movement in 3D environments through its ability to recruit ROCK1 to the plasma membrane and prevent the interaction of RhoE with ROCK1, thereby enhancing the activity of ROCK1.

S. Pinner, E. Sahai, PDK1 regulates cancer cell motility by antagonizing inhibition of ROCK 1 by RhoE.
Nat. Cell Biol.
10
, 127-137 (2008).
[PubMed]
Mixed-Up Microflora
Authors: Simpson Stephen J.
Published: March 2008

The relationship between an animal host and the complex mixture of microbes it carries in its gut is a delicate one, and the exact role the host immune system plays in maintaining commensal homeostasis remains unclear. Ryu
et al
. (see the Perspective by Silverman and Paquette) examined the expression of antimicrobial proteins in the gut of the fruit fly,
Drosophila melanogaster
. Although the key immune transcriptional regulator nuclear factor κB (NF-κB) was chronically activated in the flies by indigenous gut microflora, only a subset of NF-κB-regulated antimicrobial genes was actually expressed because of transcriptional repression exerted by the intestinal homeobox gene
Caudal
. Disruption of Caudal expression resulted in the expression of a different subset of antimicrobial peptides, as well as a dramatic change in the composition of the intestinal microflora that led to the apoptosis of intestinal epithelial cells and loss of host viability.

J.-H. Ryu, S.-H. Kim, H.-Y. Lee, J. Y. Bai, Y.-D. Nam, J.-W. Bae, D. G. Lee, S. C. Shin, E.-M. Ha, W.-J. Lee, Innate immune homeostasis by the homeobox gene
Caudal
and commensal-gut mutualism in
Drosophila
.
Science
319
, 777-782 (2008).
[Abstract]
[Full Text]

N. Silverman, N. Paquette, The right resident bugs.
Science
319
, 734-735 (2008).
[Abstract]
[Full Text]
Novel Roles for the NF-κB Signaling Pathway in Regulating Neuronal Function
Authors: Boersma Matt C. , Meffert Mollie K.
Published: March 2008

Two new reports offer exciting evidence of novel roles for components of the nuclear factor κB (NF-κB) pathway in the nervous system. Transcriptional activation by NF-κB and chromatin remodeling by inhibitor of κB (IκB) kinase complex (IKK) have been linked to recall and reconsolidation of conditioned fear memories in the mammalian central nervous system. In the
Drosophila
neuromuscular junction, a member of the NF-κB family has been reported to regulate glutamate receptor clustering. Both reports could have important implications for the function of the NF-κB signaling pathway in neuronal plasticity.
Enter the Intron
Authors: Ray L. Bryan
Published: March 2008

Intron-containing, incompletely spliced mRNAs are normally thought to be retained in the nucleus or degraded if they make it into the cytoplasm, but Bell
et al
. report that an intron-containing mRNA has a role in regulating the distribution of a K
+
channel in neurons and can thus influence the firing properties of the cell. The authors studied large-conductance Ca
2+
-sensitive K
+
(BK
Ca
) channels, which are activated in response to changes in membrane potential and concentrations of intracellular calcium and thus modulate the firing properties of hippocampal neurons. An mRNA encoding the BK
Ca
channel alpha subunit that contained intron 16 (i16) made up about 10% of the cytoplasmic transcripts encoding the channel protein as detected by a matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) base extension method in culture rat hippocampal neurons. The authors also developed a quantum dot-based in situ hybridization protocol that allowed them to detect the i16-containing transcript in the somatodendritic cytoplasm in a gradient, with the concentration decreasing in inverse proportion to the distance from the cell soma. Specific depletion of i16-containing mRNA with siRNA changed the localization of BK
Ca
channels, making them less likely to localize with filamentous actin in dendritic spines. Depletion of the i16-containing mRNA also increased excitability of the treated neurons. The authors propose that these effects likely derive from expression of the alternatively spliced mRNA and suggest that cytoplasmically located intron-containing mRNA may provide a previously unrecognized mechanism by which neuronal membrane excitability can be controlled.

T. J. Bell, K. Y. Miyashiro, J.-Y. Sul, R. McCullough, P. T. Buckley, J. Jochems, D. F. Meaney, P. Haydon, C. Cantor, T. D. Parsons, J. Eberwine, Cytoplasmic BK
Ca
channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons.
Proc. Natl. Acad. Sci. U.S.A.
105
, 1901-1906 (2008).
[Abstract]
[Full Text]
Moving to the Nucleus
Authors: Adler Elizabeth M.
Published: March 2008

Hepatocyte growth factor (HGF) binds to and activates the receptor tyrosine kinase c-Met to stimulate cell proliferation, in part by way of the phospholipase C-γ (PLC-γ)-inositol 1,4,5-trisphosphate (IP
3
)-calcium signaling pathway. Like other receptor tyrosine kinases, c-Met is commonly thought to act at the plasma membrane. However, Gomes
et al
. used a combination of immunoblot analysis, confocal immunofluorescence microscopy, and biotinylation of cell surface proteins to show that, in SkHep1 liver cells, HGF stimulated the translocation of phosphorylated (active) c-Met from the plasma membrane to the nucleus. Constructs containing the ligand-binding domain of the type 1 IP
3
receptor that were targeted to the nucleus blocked c-Met-dependent calcium signaling, whereas constructs targeted to the cytoplasm had little effect on the calcium response to c-Met. In marked contrast, the calcium response to vasopressin [which acts through a plasma membrane heterotrimeric GTP-binding protein (G protein)-coupled receptor] was preferentially blocked by constructs targeted to the cytoplasm. Moreover, HGF elicited a specific decrease in the nuclear content of phosphatidylinositol 4,5-bisphosphate (PIP
2
, which is hydrolyzed by PLC, thereby producing IP
3
). HGF stimulated the nuclear translocation of Gab1 (an adaptor protein that binds c-Met and has a nuclear localization sequence), and siRNA directed against Gab1 decreased nuclear translocation of c-Met and HGF-dependent calcium signaling, as did siRNA directed against importin β1. Thus, the authors conclude that, after stimulation by HGF, initiation of the calcium response to c-Met depends on its translocation to the nucleus.

D. A. Gomes, M. A. Rodrigues, M. F. Leite, M. V. Gomez, P. Varnai, T. Balla, A. M. Bennett, M. H. Nathanson, c-Met must translocate to the nucleus to initiate calcium signals.
J. Biol. Chem.
283
, 4344-4351 (2008).
[Abstract]
[Full Text]
Bypassing the Golgi
Authors: Adler Elizabeth M.
Published: March 2008

During
Drosophila
development, the follicular epithelium covering the developing oocyte undergoes morphological changes such that columnar epithelial cells that are adherent to each other at Stage 10A separate basally at Stage 10B, exposing regions of basolateral membrane to the underlying extracellular matrix. Schotman
et al
. found that, whereas the Golgi protein dGRASP localized to tER-Golgi units [where transitional endoplasmic reticulum (tER) is in proximity to the Golgi] in follicle cells at Stages 9 to 10A, it localized to the region of cell separation [the open zone of contact (ZOC)] at Stage 10B. dGRASP at the open ZOC did not colocalize with Golgi markers and was associated with the plasma membrane. Fluorescence in situ hybridization (FISH) revealed
dgrasp
mRNA also localized to the open ZOC, where double-labeling indicated that it colocalized with dGRASP protein.
dgrasp
mutation was associated with disruption of the follicular epithelium and failure of the integrin αPS1 subunit to localize to the open ZOC of Stage 10B follicle cells. Wing development (which depends on integrin-mediated epithelial adhesion) was also disrupted. FISH analysis indicated that αPS1 at the open ZOC was newly synthesized from mRNA. A combination of pharmacological and mutational analysis indicated that disruption of protein transport to and through the Golgi failed to block deposition of αPS1 to the open ZOC. Visualization of proteins involved in the exocytic pathway or their encoding mRNAs, or both, suggested that a subset localized with dGRASP. The authors conclude that a developmentally regulated unconventional dGRASP-dependent secretory pathway plays an important role in epithelial remodeling.

H. Schotman, L. Karhinen, C. Rabouille, dGRASP-mediated noncanonical integrin secretion is required for
Drosophila
epithelial remodeling.
Dev. Cell
14
, 171-182 (2008).
[PubMed]
Cadherins on the Road to Multicellularity
Authors: Zahn Laura M.
Published: March 2008

How early organisms made the transition from unicellularity to multicellularity is unknown, although certain genes have been implicated as important players in this process. One such group is the cadherin family of genes that function in cell adhesion and cell-cell signaling. By examining the genome of the unicellular choanoflagellate
Monosiga brevicollis
, Abedin and King show that the genome of
M. brevicollis
contains 23 expressed cadherin genes--as many as several multicellular animals. At least two of the cadherins localized to the actin-filled microvilli of the protozoan feeding collar, where they may participate in the recognition and capture of bacterial prey.

M. Abedin, N. King, The premetazoan ancestry of cadherins.
Science
319
, 946-948 (2008).
[Abstract]
[Full Text]
Full Metal Abscess
Authors: Simpson Stephen J.
Published: March 2008

Tissue abscesses form when bacteria meet cells of the immune system, most notably neutrophils. Corbin
et al
. (see the Perspective by Novick) now find that the abundant neutrophil protein, calprotectin, protects the host against bacterial growth by chelating metal ions used by the bacteria as nutrients. In mice during bacterial infection, calprotectin was localized to tissue abscesses, where it chelated manganese and zinc ions. Infected mice lacking calprotectin had elevated metal levels and increased bacterial growth in tissue abscesses.

B. D. Corbin, E. H. Seeley, A. Raab, J. Feldmann, M. R. Miller, V. J. Torres, K. L. Anderson, B. M. Dattilo, P. M. Dunman, R. Gerads, R. M. Caprioli, W. Nacken, W. J. Chazin, E. P. Skaar, Metal chelation and inhibition of bacterial growth in tissue abscesses.
Science
319
, 962-965 (2008).
[Abstract]
[Full Text]

R. P. Novick, Combating impervious bugs.
Science
319
, 910-911 (2008).
[Summary]
[Full Text]
Cell Stress Gives a Red Light to the Mitochondrial Cell Death Pathway
Authors: Guicciardi M. Eugenia , Gores Gregory J.
Published: March 2008

Although the ultimate outcome of prolonged exposure of cells to stress is often death, the early response appears to be the activation of survival pathways that are likely to give the cell an opportunity to repair low-level damage. How these stress-initiated survival pathways influence B cell lymphoma/leukemia 2 (Bcl-2) proteins, the core cell death machinery, has remained unclear; however, two papers now provide insight into stress-mediated survival mechanisms. The liver is unusually resistant to p53-mediated apoptosis. It appears that p53-mediated induction of the gene that encodes insulin-like growth factor–binding protein-1 (IGFBP1) attenuates the cell death response in hepatocytes by preventing the formation of a complex between p53 and the proapoptotic protein BAK. This is especially interesting as IGFBP1 is not a member of the Bcl-2 family, yet it inhibited BAK. In three unrelated cell lines, another regulatory interaction that influences cell survival occurs at the mitochondria. In this case, protein phosphatase 1γ (PP1γ) regulated the phosphorylation status of the Bcl-2/Bcl-X
L
–associated death promoter (BAD). The prefoldin family member URI is normally phosphorylated by S6 kinase 1, which liberates PP1γ from a URI-PP1γ complex. However, the withdrawal of growth factors or nutrients stabilizes this complex, which renders PP1γ inactive. The net response of this stress stimulus is an increased abundance of phosphorylated BAD, which raises the threshold required to trigger cell death. These two studies have identified new players and mechanisms that integrate stress responses and cell death.
Turning off TLR
Authors: Gough Nancy R.
Published: March 2008

Lower respiratory tract infections are major causes of death by infectious diseases. An initial respiratory tract infection alters the immune response to a second unrelated pathogen, sometimes resulting in a reduced immune response to the second pathogen, which can lead to death. For example, patients with influenza have a higher susceptibility to life-threatening secondary bacterial pneumonia. Didierlaurent
et al
. found that mice infected with influenza and then recovered from infection for 2 to 6 weeks exhibited reduced responsiveness to the administration of Toll-like receptor (TLR) ligands directly into the lungs. The ligands tested were bacterial flagellin (a TLR5 agonist), lipopolysaccharide (LPS, a TLR4 agonist associated with Gram-negative bacteria), or lipoteichoic acid (LTA, a TLR2 agonist associated with Gram-positive bacteria). In each case, neutrophil recruitment was reduced. In addition, the post-influenza mice were much more susceptible to subsequent infection with either the Gram-negative
Pseudomonas aeruginosa
or the Gram-positive
Streptococcus pneumoniae
. The authors ruled out impaired neutrophil recruitment due to impaired neutrophil function, such as from increased neutrophil apoptosis or inability to traverse the epithelial layer. Instead, it appeared that decreased TLR-mediated release of cytokines from alveolar macrophages was responsible for the decreased recruitment of neutrophils to the lung. Alveolar macrophages isolated from control mice and mice exposed to influenza showed that the cells from the influenza-treated animals had normal abundance of TLRs but that the production of inflammatory mediators and the activation of the transcription factor NF-κB in response to flagellin were reduced. If the macrophages and dendritic cells were removed 2 weeks after influenza infection and then the mice were allowed 3 weeks for the cells to replenish, the response to subsequent flagellin exposure was restored. Thus, reduced innate immune responsiveness may be a key factor in lethal secondary bacterial infection after viral lung infection. The authors suggest that a reduced innate immune response may reduce excessive inflammation, the reduction of which is essential for proper maintenance of lung function and which may allow an enhanced adaptive immune response to a second viral infection. However, the cost for this may be increased susceptibility to secondary bacterial infection.

A. Didierlaurent, J. Goulding, S. Patel, R. Snelgrove, L. Low, M. Bebien, T. Lawrence, L. S. van Rijt, B. N. Lambrecht, J.-C. Sirard, T. Hussell, Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection.
J. Exp. Med.
205
, 323-329 (2008).
[Abstract]
[Full Text]
Recruited Resistance
Authors: Foley John F.
Published: March 2008

Type II diabetes is characterized by abnormal glucose homeostasis due to increased insulin resistance. Glucose metabolism leads to the formation of uridine diphosphate-
N
-acetylglucosamine (UDP-GlcNAc), an indicator of metabolic status, and
O
-GlcNAc transferase (OGT) transfers
O
-GlcNAc to target proteins. Because
O
-GlcNAc affects protein function, Yang
et al
. investigated whether
O
-GlcNAc linked metabolism with insulin signaling. Phosphoinositide 3-kinase (PI3K)-mediated phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P
3
] generation in response to insulin recruits insulin receptor substrate (IRS) proteins and Akt to the plasma membrane to mediate IR signaling. The authors found that OGT, which does not contain any known PIP-binding domain, bound to PI(3,4,5)P
3
-coated beads, whereas the OGT mutant KK/AA, in which 2 C-terminal lysine residues were mutated to alanines, did not. Fluorescence imaging of COS-7 cells that expressed either OGT or KK/AA fused to green fluorescent protein (GFP) showed translocation of OGT-GFP, but not KK/AA-GFP, to the plasma membrane after treatment of starved cells with serum, which was blocked by inhibition of PI3K. Endogenous OGT colocalized with Akt at the plasma membrane of serum-treated cells. Adenoviral overexpression of OGT in adipocytes inhibited insulin-stimulated phosphorylation of Akt and increased inhibitory phosphorylation of IRS-1 on serine residues compared with control cells, modifications that are associated with decreased insulin responsiveness. Immunoprecipitation assays confirmed the modification of insulin signaling proteins by OGT. Mice whose livers were treated with adenovirus that expressed OGT had a higher abundance of plasma insulin, decreased basal glucose turnover, and decreased expression of insulin-dependent genes compared to those treated with adenovirus that expressed KK/AA. This study shows that OGT inhibits insulin responsiveness in a PI3K-dependent mechanism, leading the authors to suggest that this may play a role in the development of insulin resistance in type II diabetes.

X. Yang, P. P. Ongusaha, P. D. Miles, J. C. Havstad, F. Zhang, W. V. So, J. E. Kudlow, R. H. Michell, J. M. Olefsky, S. J. Field, R. M. Evans, Phosphoinositide signalling links
O
-GlcNAc transferase to insulin resistance.
Nature
451
, 964-969 (2008).
[PubMed]
Cycling on with Decreased Mitochondrial Function
Authors: Adler Elizabeth M.
Published: March 2008

Erythropoiesis depends on the coordinated proliferation and differentiation of erythroid precursors into mature erythrocytes; thus, erythrocyte maturation is tied to regulation of the cell cycle. Sankaran
et al
. used mice that specifically lacked Rb (retinoblastoma protein) in cells of the erythroid lineage (pRb
Δ/Δ
mice) to investigate the controversial role of this cell cycle regulator in erythropoiesis. The pRb
Δ/Δ
mice exhibited a moderate anemia associated with an increase in circulating erythropoietin; analysis of red blood cell life span and of hematopoiesis in bone marrow and spleen indicated that loss of Rb was associated with the ineffective maturation of early erythroblasts to late erythroblasts. Transplantation experiments suggested that these effects of Rb were not only intrinsic to erythroid lineage cells but also cell autonomous. Gene expression profiling of early erythroblasts revealed up-regulation of various S-phase genes that are typically repressed during exit from the cell cycle; additionally--and unexpectedly--the expression of genes encoding components of the mitochondrial electron transport and oxidative phosphorylation pathways was decreased. Moreover, early erythroblasts from the bone marrow of pRb
Δ/Δ
mice showed a decrease in both functional mitochondria and mitochondrial DNA. Expression of the transcriptional coactivator PGC-1β (which has been implicated in mitochondrial biogenesis) was decreased, and both pharmacological inhibition of mitochondrial biogenesis and siRNA directed against PGC-1β inhibited erythroid differentiation in a cell culture model of late-stage erythropoiesis. The authors present a model for how exit from the cell cycle could be linked to mitochondrial biogenesis to promote erythrocyte differentiation and, noting the similarities between erythropoiesis in pRb
Δ/Δ
mice and that in human myelodysplastic syndrome, propose that these findings may have therapeutic implications.

V. G. Sankaran, S. H. Orkin, C. R. Walkley,
Rb
intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis.
Genes & Dev.
22
, 463-475 (2008).
[Abstract]
[Full Text]
Tagging + Recruitment = Learning
Authors: Stern Peter R.
Published: March 2008

Stabilizing long-term memories requires the expression of new gene products in the nucleus to generate physical changes or "tags" at a small subset of synapses on the dendrites of a neuron. Synthesis of AMPA receptors is increased during learning, which is suggestive of a possible role in this process. Matsuo
et al
. developed transgenic mice to monitor the trafficking and turnover of newly synthesized AMPA receptors in a fear-conditioning paradigm. By coupling expression of fluorescent receptors to neuronal activity, they specifically examined the pool of newly synthesized receptors. New receptors were delivered to spines several hours after behavioral training, which suggests that at the time of learning, changes occur in some spines that allow the capture of newly synthesized AMPA receptors at later time points.

N. Matsuo, L. Reijmers, M. Mayford, Spine-type-specific recruitment of newly synthesized AMPA receptors with learning.
Science
319
, 1104-1107 (2008).
[Abstract]
[Full Text]
Tau and Microtubule Motors
Authors: Hurtley Stella M.
Published: March 2008

The microtubule-associated protein tau is implicated in neurodegenerative diseases, including Alzheimer’s disease, but neither its normal nor its pathological role are well understood. Microtubules in cells are densely coated with microtubule-associated proteins, including tau, and Dixit
et al
. wanted to learn how motor proteins navigate on coated microtubules. The authors incorporated several isoforms and truncations of tau in a cell-free assay to build a complex system mimicking the cell environment. Encounters between individual motor proteins and tau on microtubules were observed directly, which revealed dramatic differences between the effects of tau on the motility of two microtubule-based motors, dynein versus kinesin. It appears likely that tau can spatially regulate the balance of microtubule-dependent axonal transport in neurons.

R. Dixit, J. L. Ross, Y. E. Goldman, E. L. F. Holzbaur, Differential regulation of dynein and kinesin motor proteins by tau.
Science
319
, 1086-1089 (2008).
[Abstract]
[Full Text]
A Cytoskeletal Platform for Local Translation in Axons
Authors: Van Horck Francisca P. G. , Holt Christine E.
Published: March 2008

Recent data indicate that local translation in growth cones is critical for axon guidance. Evidence from the
Drosophila
midline axon guidance system suggests that the F-actin-microtubule cross-linker Short stop (Shot) might link the translation machinery to the cytoskeleton in the growth cone. The identification of a complex of translation factors attached to the actin and microtubule networks points to a mechanism by which cytoskeletal dynamics regulate translation in axons and vice versa.
Fruit Flies, Mosquitoes, and CO
2
Sensations
Authors: Stern Peter R.
Published: March 2008

Many insects have neurons dedicated to CO
2
sensation. The fruit fly
Drosophila
is repelled by CO
2
and has its sensing neurons on its antennae. Mosquitoes, however, are attracted to CO
2
and have their sensing neurons on their maxillary palps. Cayirlioglu
et al
. found that mutating a microRNA in the
Drosophila
genome produces a new class of CO
2
-sensing neurons on the maxillary palps. These olfactory receptor neurons also express two odorant receptors that are normally expressed in the fruit fly palps, and they project both to normal palp target glomeruli and to the glomerulus, which receives projections from the CO
2
neurons in the antennae. Thus, the anatomy of the fruit fly CO
2
-sensing system is switched to an arrangement that resembles a hybrid between the fruit fly and the mosquito.

P. Cayirlioglu, I. G. Kadow, X. Zhan, K. Okamura, G. S. B. Suh, D. Gunning, E. C. Lai, S. L. Zipursky, Hybrid neurons in a microRNA mutant are putative evolutionary intermediates in insect CO
2
sensory systems.
Science
319
, 1256-1260 (2008).
[Abstract]
[Full Text]
Explaining Polarized Growth Patterns
Authors: Hurtley Stella M.
Published: March 2008

The ability of certain cells to grow in a polarized fashion has been studied for many years, but the mechanisms involved in the process, particularly in plant cell systems, remain unclear. Takeda
et al.
report the discovery of a positive feedback mechanism that regulates the development of a polarized cell shape in the commonly studied model plant
Arabidopsis thaliana
. The positive feedback system is generated by the local interaction of Ca
2+
and reactive oxygen species in root hair cells and is central to the maintenance of active growth at spatially restricted sites during polarized cell elongation.

S. Takeda, C. Gapper, H. Kaya, E. Bell, K. Kuchitsu, L. Dolan, Local positive feedback regulation determines cell shape in root hair cells.
Science
319
, 1241-1244 (2008).
[Abstract]
[Full Text]
Using Web-Based Discussion Forums as a Model of the Peer-Review Process and a Tool for Assessment
Authors: Jenkins Sherry L. , Iyengar Ravi , Diverse-Pierluissi Maria A. , Chan Andrew M. , Devi Lakshmi A. , Sobie Eric A. , Ting Adrian T. , Weinstein Daniel C.
Published: March 2008

This Teaching Resource describes how to use an online asynchronous discussion as a mechanism to introduce students to the peer-review process, as well as to assess student performance and understanding. This method was applied to a graduate course on signal transduction and the Teaching Resource includes a syllabus, detailed plan for incorporating the online discussion, sample journal club questions, and sample student responses to the discussion forum, faculty responses, and student revisions.
DETECTING SECONDARY BOTTLENECKS IN PARALLEL QUANTUM CHEMISTRY APPLICATIONS USING MPI
Authors: MAHAJAN REEMA , KRANZLMÜLLER DIETER , VOLKERT JENS , HANSMANN ULRICH H. E. , HÖFINGER SIEGFRIED
Published: March 2008

Profiling tools such as gprof and ssrun are used to analyze the run-time performance of a scientific application. The profiling is done in serial and in parallel mode using MPI as the communication interface. The application is a quantum chemistry program using Hartree Fock theory and Pulays DIIS method. An extensive set of test cases is taken into account in order to reach uniform conclusions. A known problem with decreased parallel scalability can thus be narrowed down to a single subroutine responsible for the reduction in Speed Up. The critical module is analyzed and a typical pitfall with triple matrix multiplications is identified. After overhauling the critical subroutine re-examination of the run-time behavior shows significantly improved performance and markedly improved parallel scalability. The lessons learned here might be of interest to other people working in similar fields with similar problems.
SYNCHRONIZATION IN THE FAMILY OF CHAOTIC SMALL-WORLD NETWORKS
Authors: HE LIANGMING , SHI DUANWEN
Published: March 2008

In this paper we investigate by computer simulation the synchronizability of the family of small-world networks, which consists of identical chaotic units, such as the Lorenz chaotic system, the Chen chaotic system, Lü chaotic system, and the unified chaotic system (unit). It is shown that for weak coupling, synchronization clusters emerge in the networks whose disorder probabilities p are large but do not emerge in the networks whose disorder probabilities p are small; while for strong coupling under which the regular networks do not exhibit synchronization, all dynamical nodes, behaving as in the random networks, mutually synchronize in the networks which own very small disorder probability p and have both high degree of clustering and small average distance. Based on the concepts of clustering coefficient C(p), characteristic path length L(p) and global efficiency E(G), these phenomena are discussed briefly.
AN IMPROVED THERMAL LATTICE BOLTZMANN MODEL FOR FLOWS WITHOUT VISCOUS HEAT DISSIPATION AND COMPRESSION WORK
Authors: LI Q. , HE Y. L. , WANG Y. , TANG G. H.
Published: March 2008

An improved lattice Boltzmann model is proposed for thermal flows in which the viscous heat dissipation and compression work by the pressure can be neglected. In the improved model, the whole complicated gradient term in the internal energy density distribution function model is correctly discarded by modifying the velocity moments' condition. The corresponding macroscopic energy equation is exactly derived through Chapman–Enskog expansion. In particular, based on the improved thermal model, a double-distribution-function lattice BGK model is developed for two-dimensional Boussinesq flow, which is a typical flow with negligible viscous heat dissipation and compression work. A two-dimensional plane flow and the natural convection of air in a square cavity with various Rayleigh numbers are simulated by using the double-distribution-function lattice BGK model. It is found that there is excellent agreement between the present results with the analytical or benchmark solutions.
PERSISTENCE IN A RANDOM BOND ISING MODEL OF SOCIO-ECONO DYNAMICS
Authors: JAIN S. , YAMANO T.
Published: March 2008

We study the persistence phenomenon in a socio-econo dynamics model using computer simulations at a finite temperature on hypercubic lattices in dimensions up to five. The model includes a "social" local field which contains the magnetization at time t. The nearest neighbour quenched interactions are drawn from a binary distribution which is a function of the bond concentration, p. The decay of the persistence probability in the model depends on both the spatial dimension and p. We find no evidence of "blocking" in this model. We also discuss the implications of our results for possible applications in the social and economic fields. It is suggested that the absence, or otherwise, of blocking could be used as a criterion to decide on the validity of a given model in different scenarios.
DECISION COMBINATION OF MULTIPLE CLASSIFIERS
Authors: SHIH FRANK Y. , FU GANG
Published: March 2008

In order to improve the performance in pattern classification, we utilize multiple classifiers and combine their individual decisions to make a final decision. In this paper, we present the combination using Bayesian method and compare minimum errors. This method requires the posteriori probabilities from all classifiers, which may be difficult to calculate in real world because tremendous amounts of training samples are needed. Alternatively, a confusion matrix is developed for approximation. We also use different combining rules for comparisons and apply them to handwritten digit recognition.
APPROXIMATE IMAGE QUALITY MEASURE IN LOW-DIMENSIONAL DOMAIN BASED ON RANDOM PROJECTION
Authors: SHIH FRANK Y. , FU YAN-YU
Published: March 2008

Image Quality Measure (IQM) is used to automatically measure the degree of image artifacts such as blocking, ringing and blurring effects. It is calculated traditionally in the image spatial domain. In this paper, we present a new method of transforming an image into a low-dimensional domain based on random projection, so we can efficiently obtain the compatible IQM. From the transformed domain, we can calculate the Peak Signal-to-Noise Ratio (PSNR) and apply fuzzy logic to generate a Low-Dimensional Quality Index (LDQI). Experimental results show that the LDQI can approximate the IQM in the image spatial domain. We observe that the LDQI is suited for measuring the compression blur due to its relatively low distortion. The relative error is about 0.15 as the compression blur increases.
POLYNOMIAL NETWORKS VERSUS OTHER TECHNIQUES IN TEXT CATEGORIZATION
Authors: AL-TAHRAWI MAYY M. , ABU ZITAR RAED
Published: March 2008

Many techniques and algorithms for automatic text categorization had been devised and proposed in the literature. However, there is still much space for researchers in this area to improve existing algorithms or come up with new techniques for text categorization (TC). Polynomial Networks (PNs) were never used before in TC. This can be attributed to the huge datasets used in TC, as well as the technique itself which has high computational demands. In this paper, we investigate and propose using PNs in TC. The proposed PN classifier has achieved a competitive classification performance in our experiments. More importantly, this high performance is achieved in one shot training (noniteratively) and using just 0.25%–0.5% of the corpora features. Experiments are conducted on the two benchmark datasets in TC: Reuters-21578 and the 20 Newsgroups. Five well-known classifiers are experimented on the same data and feature subsets: the state-of-the-art Support Vector Machines (SVM), Logistic Regression (LR), the k-nearest-neighbor (kNN), Naive Bayes (NB), and the Radial Basis Function (RBF) networks.
FROM DYNAMICAL EMERGING PATTERNS TO PATTERNS IN VISUAL ART
Authors: BUCOLO M. , BUSCARINO A. , FORTUNA L. , FRASCA M. , XIBILIA M. G.
Published: March 2008

In this communication the relationship between emerging patterns generated by using CNN Universal Machine and patterns appearing in visual art masterpieces is discussed. The template based programming tools are outlined and a gallery of impressive examples is presented. The paper remarks the impressive role of Cellular Nonlinear Networks in covering the gap among art, science and information technology.
EXAMPLES OF FORCED SYMMETRY-BREAKING TO HOMOCLINIC CYCLES IN THREE-DIMENSIONAL EUCLIDEAN-INVARIANT SYSTEMS
Authors: PARKER M. J. , STEWART IAN , GOMES M. G. M.
Published: March 2008

We study perturbations of cubic planforms, proving there exists perturbations with homoclinic cycles between persistent steady states. Our results do not depend on the representation of the symmetry group of the lattice, and are thus quite general.

The problem is studied using group theory rather than direct methods. We use the abstract action of the symmetry group of the perturbation on the group orbit to determine the existence of zero- and one-dimensional flow-invariant subspaces. The residual symmetry of the perturbation constrains the flows on these subspaces and, in certain cases, homoclinic cycles are guaranteed to exist.

Cubic planforms are physically interesting due to their relevance to certain physical systems. Applications to reaction–diffusion systems, nonlinear optical systems and the polyacrylamide methylene blue oxygen reaction are discussed.
COMPLEX INTERMITTENCY IN SWITCHING CONVERTERS
Authors: ZHOU YUFEI , CHEN JUN-NING , IU HERBERT H. C. , TSE CHI K.
Published: March 2008

Intermittent instability is commonly observed in switching power supplies during the design and development phase. It manifests as symmetrical period-doubling bifurcation in the time domain with long intermittent periods. Such intermittent operation is considered undesirable in practice and is usually avoided by appropriate adjustments of circuit parameters. This paper explores the mechanism and conditions for the emergence of intermittency in a common voltage-mode controlled buck converter. It is found that interference at frequencies near the switching frequency or its rational multiples will induce intermittent operation. The strengths and frequencies of the interfering signals determine the type and period of intermittency. The problem is analyzed by transforming the conventional parameter-bifurcation analysis to a time-bifurcation analysis. Analytical results are verified by simulations and experimental measurements.
EXISTENCE AND STABILITY OF PERIODIC ORBITS OF PERIODIC DIFFERENCE EQUATIONS WITH DELAYS
Authors: ALSHARAWI ZIYAD , ANGELOS JAMES , ELAYDI SABER
Published: March 2008

In this paper, we investigate the existence and stability of periodic orbits of the p-periodic difference equation with delays xn = f(n - 1, xn-k). We show that the periodic orbits of this equation depend on the periodic orbits of p autonomous equations when p divides k. When p is not a divisor of k, the periodic orbits depend on the periodic orbits of gcd(p, k) nonautonomous p/gcd(p, k)-periodic difference equations. We give formulas for calculating the number of different periodic orbits under certain conditions. In addition, when p and k are relatively prime integers, we introduce what we call the pk-Sharkovsky's ordering of the positive integers, and extend Sharkovsky's theorem to periodic difference equations with delays. Finally, we characterize global stability and show that the period of a globally asymptotically stable orbit must be divisible by p.
NONLINEAR VIBRATION OF A CANTILEVER WITH A DERJAGUIN–MÜLLER–TOPOROV CONTACT END
Authors: HU Q.-Q. , LIM C. W. , CHEN L.-Q.
Published: March 2008

In this paper, the principal resonance is investigated for a cantilever with a contact end. The cantilever is modeled as an Euler–Bernoulli beam, and the contact is modeled by the Derjaguin–Müller–Toporov theory. The problem is formulated as a linear nonautonomous partial-differential equation with a nonlinear autonomous boundary condition. The method of multiple scales is applied to determine the steady-state response. The equation of response curves is derived from the solvability condition of eliminating secular terms. The stability of steady-state responses is analyzed by using the Lyapunov-linearized stability theory. Numerical examples are presented to highlight the effects of the excitation amplitude, the damping coefficient, and the coefficients related to the contact.
A SIMPLE MODELING AND EXPERIMENT ON DYNAMIC STABILITY OF A DISK ROTATING IN AIR
Authors: WANG XINGZHE , HUANG X. Y.
Published: March 2008

In this paper, the dynamic stability of a disk rotating in air has been modeled and analyzed numerically as well as observed from experiments. A simple expression on the aerodynamic loading acting on the rotating disk is applied in the modeling, and the dynamic stability results of the disks are evaluated based on the eigenvalues for the vibration modes. The disk critical speeds and the flutter speeds are calculated and compared with the results from experiments, which are conducted on two steel disks with different diameters and thicknesses. The modeling predicts that the rotating disk flutter starts with the mode (0, 3)B, which agrees with the results reported in the literature and the observation in the present experimental study.
PARAMETRIC RESONANCE CHARACTERISTICS OF ANGLE-PLY TWISTED CURVED PANELS
Authors: SAHU S. K. , ASHA A. V.
Published: March 2008

The present study deals with the dynamic stability of laminated composite pre-twisted cantilever panels. The effects of various parameters on the principal instability regions are studied using Bolotin's approach and finite element method. The first-order shear deformation theory is used to model the twisted curved panels, considering the effects of transverse shear deformation and rotary inertia. The results on the dynamic stability studies of the laminated composite pre-twisted panels suggest that the onset of instability occurs earlier and the width of dynamic instability regions increase with introduction of twist in the panel. The instability occurs later for square than rectangular twisted panels. The onset of instability occurs later for pre-twisted cylindrical panels than the flat panels due to addition of curvature. However, the spherical pre-twisted panels show small increase of nondimensional excitation frequency.
THREE-DIMENSIONAL ANALYSIS OF THICK PLATES BY MLS-RITZ METHOD
Authors: ZHOU L. , ZHENG W. X.
Published: March 2008

This paper presents a three-dimensional (3D) moving least-square Ritz (MLS-Ritz) formulation for the free vibration analysis of homogeneous elastic thick plates with mixed boundary constraints. The analysis is based on the linear elasticity theory. The Ritz trial functions are established through the moving least-square technique for the displacement fields of the plates. Vibration frequencies for thick square plates and right-angled isosceles triangular plates are obtained by the MLS-Ritz method. The reliability and accuracy of the presented method are examined by extensive convergence and comparison studies and it is established herein that the MLS-Ritz method is a powerful and effective numerical method for the 3D analysis of thick plates.
EFFECT OF RANDOM SYSTEM PROPERTIES ON INITIAL BUCKLING OF COMPOSITE PLATES RESTING ON ELASTIC FOUNDATION
Authors: LAL ACHCHHE , SINGH B. N. , KUMAR RAKESH
Published: March 2008

In this paper, the effects of randomness in the material properties and foundation stiffness parameters on the elastic buckling of laminated composite plate resting on elastic foundation subjected to uniform in-plane edge compression are studied. Higher order shear deformation theory has been used for the plates. The interaction between the plate and foundation is included in the formulation of a two-parameter Pasternak model. A C0finite element method is used for treating the random eigenvalue problem. The uncertain lamina material properties and the foundation stiffness parameters are modeled as independent basic random variables. A mean-centered first order perturbation technique is adopted to examine the stochastic characteristics of the buckling load. From the results presented for laminated composite plates resting on elastic foundations with different boundary conditions, the influence of variation of material constant, foundation stiffness parameters, edge in-plane forces, side-to-thickness ratio, plate aspect ratio, and variation in standard deviation of material properties on the buckling response has been investigated. The results have been compared with those available in the literature and from an independent Monte Carlo simulation.
ON THE APPLICABILITY OF FIXED POINT THEORY TO THE BEHAVIOR OF COUPLED CORE WALLS
Authors: HULL DANIEL H. , HARRIES KENT A.
Published: March 2008

The performance-based design of coupled core wall systems offers a number of advantages over conventional strength-based methods in terms of constructability and structural performance. Under large seismic loads, the expected degradation of the coupling beams in coupled wall structures results in an evolution of the lateral force resisting system from a coupled wall system to a system of linked cantilever wall piers. The present study focuses on the performance of the eventually obtained linked wall pier systems and defines their performance in a novel way: as the minimization of transmissibility of horizontal ground motion. In this paper, fixed point theory (FPT) is used to establish initial design values for the coupling beams required to optimize the dynamic response of the linked wall pier system. An initial parametric study of the application of FPT to optimizing the behavior of linked wall piers is presented. The resulting optimized wall systems are compared with practically obtainable, rigid and uncoupled systems subject to a linear time history analysis to assess the extent and practicality of optimization obtained.
PARAMETRIC STUDY ON MULTIPLE TUNED MASS DAMPERS USING INTERCONNECTED MASSES
Authors: CARNEIRO RÚBIA BORGES , AVILA SUZANA MOREIRA , DE BRITO JOSÉ LUÍS VITAL
Published: March 2008

In this paper, the dynamic performance of a controlled high building is numerically investigated considering the effects of different numbers of mass dampers and their interconnection. The numerical analysis is conducted on a 20-story building considered as a shear frame and reduced to an SDOF system by means of the mode-superposition method. The system is subjected to harmonic load. Numerical searches are conducted based on the Min. Max. procedure in order to obtain efficient interconnected (I) multiple tuned mass dampers (MTMD). Comparisons are made among the uncontrolled system, the system controlled by non-interconnected (NI) MTMD, and the system controlled by (I) MTMD in frequency and time domain. Both (NI) and (I) MTMD reduce significantly frequency response peak amplitude. It is observed that the (I) MTMD produces great reductions on maximum displacement, rms displacement, steady-state peak response, and story displacements close to the reductions obtained by (NI) MTMD using review parameters. Mass maximum displacements analysis shows that the space required for (I) MTMD installation is smaller than (NI) MTMD.