bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Ways to Segment an Insect
Authors: Purnell Beverly
Published: July 2007

In the
Drosophila
embryo, the bicoid morphogen serves as a maternal anterior determinant during anterior-posterior axis development; however, this transcription factor is not found among all insects. Brent
et al
. compared the molecular mechanisms of development in the fruit fly
Drosophila
and the wasp
Nasonia
.
Drosophila
bicoid serves both an instructive function during anterior patterning and a permissive function for the repression of trunk genes in the anterior region. However, in the wasp, these two functions remain discrete:
Nasonia
orthodenticle
(
otd
) performs bicoid function for anterior development, whereas maternal
giant
represses trunk fate. Thus, in the wasp,
otd
and
giant
jointly accomplish bicoid's role in
Drosophila
.

A. E. Brent, G. Yucel, S. Small, C. Desplan, Permissive and instructive anterior patterning rely on mRNA localization in the wasp embryo.
Science
315
, 1841-1843 (2007).
[Abstract]
[Full Text]
Using Cysteine to Set the Stage for Its Own Degradation
Authors: Adler Elizabeth M.
Published: July 2007

The elimination of misfolded or misassembled proteins through endoplasmic reticulum-associated degradation (ERAD) depends on their polyubiquitination and proteolytic degradation. Thus, it is not surprising that ER stress in yeast leads to an increase in the abundance of the ubiquitin-conjugating enzyme Ubc7 as well as that of Cue1 (coupling of ubiquitin conjugation to ER degradation), which binds Ubc7 and targets it to the ER. Loss of Cue1 leads to Ubc7 mislocalization and, through a mechanism that has been unclear, to its subsequent degradation. Ravid and Hochstrasser found that overexpressed Ubc7 was rapidly degraded under conditions in which endogenous Ubc7 was stable. Degradation was blocked by the overexpression of either wild-type Cue1 or a mutant form that bound Ubc7 but did not associate with the ER. Pharmacological analysis indicated that Ubc7 degradation was mediated by the proteasome. Furthermore, analysis of yeast strains that lacked ubiquitination enzymes indicated that Ubc7 degradation depended on the E3 ligase Ufd4 but not on additional E2 ligases. Mutational analysis indicated that Ubc7 degradation depended on a cysteine residue in its active site (Cys
89
) but not on the presence of any of its lysine residues. The association of ubiquitin chains with Ubc7 was sensitive to the reducing agent dithiothreitol, which indicates that they were associated with cysteine rather than lysine; moreover, ubiquitin chains were absent from Ubc7 in which alanine was substituted for Cys
89
. Although Ufd4 was required for Ubc7 degradation, it was not necessary for its polyubiquitination. Thus, the authors conclude that Ubc7 degradation depends on its autoubiquitination on Cys
89
.

T. Ravid, M. Hochstrasser, Autoregulation of an E2 enzyme by ubiquitin-chain assembly on its catalytic residue.
Nat. Cell Biol.
9
, 422-427 (2007).
[PubMed]
Ubiquitination of Estrogen Receptor α by BRCA1
Authors: Foley John F.
Published: July 2007

The breast cancer suppressor protein BRCA1 is associated with all forms of breast cancer. BRCA1 is an E3 ubiquitin ligase, but none of its known targets explains the association of BRCA1 with breast tumors. BRCA1 must form a heterodimer with BARD1 to have ligase activity. Estrogen receptor α (ERα) is a transcription factor, which, after binding to its ligand, estrogen, forms functional dimers that bind to the promoter regions of target genes to promote transcriptional activation. ERα shares an expression profile with BRCA1-associated tumors, and BRCA1 regulates the transcriptional activation of ERα, so Eakin
et al
. investigated the relationship between BRCA1 and ERα. They used in vitro ubiquitination assays with purified recombinant proteins, followed by Western blotting, to show that the ligand-binding domain (LBD) of ERα was ubiquitinated by BRCA1/BARD1. The authors went on to determine the regions of both BRCA1 and BARD1 that were necessary for this activity. BRCA1/BARD1 was shown to ubiquitinate ERα whether it was bound to an agonist, estrogen, or to an antagonist, tamoxifen. ERα-LBD was not ubiquitinated by BRCA1/BARD complexes containing mutant BRCA1 proteins that had the same mutations as are observed in patients with breast cancer, which suggests that the association of these BRCA1 mutations with breast cancer may be due to disruption in the ubiquitination of ERα. BRCA1/BARD1 activity resulted in monoubiquitination of ERα, a modification associated with regulating activity rather than promoting degradation. This study provides a mechanism whereby BRCA1 mutations may be linked to breast cancer development.

C. M. Eakin, M. J. MacCoss, G. L. Finney, R. E. Klevit, Estrogen receptor α is a putative substrate for the BRCA1 ubiquitin ligase.
Proc. Natl. Acad. Sci. U.S.A.
104
, 5794-5799 (2007).
[Abstract]
[Full Text]
Dual Lipid Pathways for Migration
Authors: Gough Nancy R.
Published: July 2007

Motile cells respond to extracellular gradients of chemoattractants by moving in a directed manner up the gradient in a process called chemotaxis. Studies of chemotaxis in the slime mold
Dictyostelium discoideum
revealed a key role for the polarized production of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P
3
], which is produced by phosphatidylinositol 3-kinase (PI3K) and degraded by the lipid phosphatases PTEN (a PI-3 phosphatase) and SHIP (PI-5 phosphatase). Chen
et al
. now show that, in addition to this PI3K-dependent pathway, there is a parallel pathway dependent on phospholipase A
2
(PLA
2
) and arachidonic acid derivatives. The chemotaxis of wild-type
Dictyostelium
was not diminished by low concentrations of inhibitors of PI3K (such as LY294002) but was blocked by high concentrations of such inhibitors. Chen
et al
. screened for
Dictyostelium
mutants that showed chemotaxis defects in the presence of low concentrations of LY294002 and were resistant to chemotaxis inhibition by high concentrations of LY294002. Characterization of one of the mutants revealed the disrupted gene to be homologous to genes in plants encoding patatin PLA
2
and in animals encoding calcium-independent PLA
2
, so they named the gene
plaA
and the encoded protein PLA
2
A. The purified protein from
Dictyostelium
produced arachidonic acid from phosphatidylcholine in vitro. Targeted disruption of the
plaA
gene phenocopied the chemotaxis defect of the mutant, and these cells were used for further analysis, along with cells in which two of the PI3K genes were disrupted (
pi3k
1
−
/2
−
) and cells in which all three were disrupted (
plaA
−
,
pi3k
1
−
/2
−
). The triple-mutant cells failed to aggregate under starvation conditions and exhibited defective migration toward a cAMP point source. The cells in which PLA
2
A or PI3K signaling was individually disrupted did not show such migration defects unless the parallel pathway was inhibited pharmacologically--the
plaA
−
cells were defective in chemotaxis in the presence of low concentrations of LY294002, and the
pi3k
1
−
/2
−
cells were defective in chemotaxis in the presence of the PLA
2
inhibitor bromoenol lactone. PLA
2
A activity was not required for proper PI(3,4,5)P
3
dynamics based on monitoring PI(3,4,5)P
3
accumulation with a pleckstrin homology domain green fluorescent protein fusion protein. Lipid analysis of wild-type and
plaA
−
cells revealed that the chemoattractant-stimulated
plaA
−
cells had a greatly reduced accumulation of an arachidonic acid derivative that was abundant in the chemoattractant-stimulated wild-type cells. Thus, there appear to be two parallel paths contributing to chemotaxis of
Dictyostelium
, one reliant on PI3K signaling and one reliant on PLA
2
signaling.

L. Chen, M. Iijima, M. Tang, M. A. Landree, Y. E. Huang, Y. Xiong, P. A. Iglesias, P. N. Devreotes, PLA
2
and PI3K/PTEN pathways act in parallel to mediate chemotaxis.
Dev. Cell
12
, 603-614 (2007).
[PubMed]
Focus Issue: From Egg to Egg—Cell Signaling in Germ Cells
Authors: Adler Elizabeth M. , Gough Nancy R.
Published: July 2007

In this Focus Issue of
Science
’s STKE, which complements the
Science
Special Issue on germ cells, we take a closer look at cell signaling in germ cells. STKE highlights the migration of germ cells with an article that describes the different mechanisms controlling primordial germ cell movement and survival in mice and flies. Another article describes a mechanism for mediating plant self-incompatibility through control of the pollen tube, to prevent inappropriate delivery of incompatible sperm to the ovule. A common feature found in each of the organisms discussed, be they animal, insect or plant, is that signals from the surrounding tissues control survival and migration of the germ cells or resulting gametes.
The Winners Recall Memories
Authors: Stern Peter
Published: July 2007

Electrophysiological and cellular imaging studies show that only a portion of neurons are involved in a given memory. Why is one neuron, rather than its neighbor, included in a particular memory? Han
et al
. found that neurons in the lateral amygdala that show the greatest activity of the transcription factor CREB at the time of the encoding of an auditory fear memory are those that preferentially express the activity-regulated gene
Arc
after the recall of the memory. Thus, neurons compete during memory formation, and CREB helps to determine the winners.

J.-H. Han, S. A. Kushner, A. P. Yiu, C. J. Cole, A. Matynia, R. A. Brown, R. L. Neve, J. F. Guzowski, A. J. Silva, S. A. Josselyn, Neuronal competition and selection during memory formation.
Science
316
, 457-460 (2007).
[Abstract]
[Full Text]
That’s Far Enough
Authors: Hines Pamela J.
Published: July 2007

In the developing root tip of
Arabidopsis
, the transcription factor SHR moves from cell to cell. However, the cells that are the target of this mobile transcription signal form a layer that is only one cell thick. Cui
et al
. now elucidate the interactions that send the mobile signal just so far, and no further. When SHR moves to the adjacent layer of cells, it meets its mate, the SCR protein, to which it binds. Together, SHR and SCR move to the nucleus and regulate transcription of the SCR gene. An excess of SCR protein scavenges the peripatetic SHR, and with more SCR available on demand, SHR and its developmental signal cannot move out any further than that first cell layer.

H. Cui, M. P. Levesque, T. Vernoux, J. W. Jung, A. J. Paquette, K. L. Gallagher, J. Y. Wang, I. Blilou, B. Scheres, P. N. Benfey, An evolutionarily conserved mechanism delimiting SHR movement defines a single layer of endodermis in plants.
Science
316
, 421-425 (2007).
[Abstract]
[Full Text]

L. Dolan, SCARECROWs at the border.
Science
316
, 377-378 (2007).
[Summary]
[Full Text]
CARD-Bcl10-Malt1 Signalosomes: Missing Link to NF-κB
Authors: Wegener Elmar , Krappmann Daniel
Published: July 2007

CARD11 (CARMA1), Bcl10, and Malt1 are required for nuclear factor NF-κB activation in response to antigen recognition. Initially, gene disruption experiments in mice pointed to a lymphocyte-specific role for CARD11-Bcl10-Malt1 complexes. However, strong evidence suggesting that conserved Bcl10-Malt1 complexes interact with different CARD scaffolds to connect various receptors in different cell types to NF-κB signaling has emerged more recently. The CARD10 (CARMA3)–Bcl10-Malt1 signalosome functions as a link between G protein–coupled receptor (GPCR) signaling and proinflammatory NF-κB activation. Further, Dectin-1–induced antifungal responses to NF-κB in dendritic cells depend on CARD9-Bcl10-Malt1. These results identify CARD-Bcl10-Malt1 signalosomes as pivotal regulators that link not only innate and adaptive immune responses, but also GPCR signaling, to the canonical NF-κB pathway.
Book Review: Plant Gene ExpressionReview and commentary on
Regulation of Gene Expression in Plants: The Role of Transcript Structure and Processing
, edited by Carole L. Bassett. Springer, New York, 2007, 204 pp. $129, ISBN: 978-0-387-35449-1.
Authors: Rose Alan
Published: July 2007

Whereas many important biological discoveries have been made using plants, subsequent progress in some areas of plant research has fallen behind that in other organisms for which funding and in vitro assays are more readily available. Gene expression is one such field in which importance continues to grow because many potential plant biotechnology–based solutions to global problems depend on regulating the expression of specific genes. Previous limitations to exploring gene expression in plants have been partially mitigated by recent advances in genomics, genetics, and transformation techniques. The book
Regulation of Gene Expression in Plants: The Role of Transcript Structure and Processing
, edited by Carole L. Bassett, summarizes our current understanding of plant gene expression, with an emphasis on transcriptional and posttranscriptional regulation. The topics covered in six chapters include differences in messenger RNA (mRNA) structure caused by variations in transcription start and polyadenylation sites, alternative splicing, regulation by small RNAs, and mRNA transport and degradation. The chapters vary in depth, quality, and the degree to which the emphasis is placed on plants rather than eukaryotes in general. However, this slim volume is a useful review of gene expression in plants. The question of whether or not all differences in mRNA structure have functional importance remains open.
Microfluidic Devices for the Analysis of Single Cells: Leaving No Protein Uncounted
Authors: Navratil Marian , Whiting Christofer E. , Arriaga Edgar A.
Published: July 2007

Microfluidic devices are revolutionizing bioanalysis, and designs capable of detecting single protein molecules are now available. Two recently described microfluidic devices provide information on the number of β
2
-adrenergic receptors in individual cultured insect cells and measure the degradation of phycobilisomes in individual cyanobacteria, respectively. This latter experiment, which included the analysis of three single cells in parallel, heralds a bright future for high-throughput single-cell analyzers. These devices could greatly advance research in signal transduction and studies of the effects of environmental stimuli or xenobiotics on cellular responses.
Setting the Metabolic Beat
Authors: Adler Elizabeth M.
Published: July 2007

Many metabolic processes, like other physiological and behavioral phenomena, ebb and flow in a circadian pattern; the mechanisms linking circadian cycling to energy metabolism, however, have been unclear. Liu
et al
. found that expression of exogenous PGC-1α [for peroxisome proliferator-activated receptor (PPAR) γ coactivator 1 α, an inducible transcriptional coactivator implicated in regulating energy metabolism] in primary hepatocytes and C2C12 myotubes stimulated the expression of the clock genes
Bmal1
and
Clock
. Microarray analysis of transduced hepatocytes revealed that expression of a subset of rhythmically expressed hepatic genes was enhanced by PGC-1α; moreover, expression of mouse liver PGC-1α mRNA and protein themselves oscillated, with peak protein abundance coinciding with transcriptional activation of
Bmal
. PGC-1α enhanced transcriptional activation of a
Bmal
gene reporter by the orphan nuclear receptors ROR (retinoic acid-related orphan receptor) α and γ and increased
Bmal
mRNA abundance synergistically with RORα. Further, chromatin immunoprecipitation (ChIP) analysis in HepG2 cells indicated that PGC-1α associated with the
Bmal
promoter, to which it recruited histone acetyltransferases, near the ROR response element. Diurnal patterns of locomotor activity, body temperature, and oxygen consumption were aberrant in mice lacking PGC-1α, as were the patterns of
Clock
and
Per
expression and those of rhythmically expressed genes encoding various metabolic enzymes. Selective knockdown of liver PGC-1α with RNAi indicated that its peripheral effects were not mediated through the central circadian clock, as did experiments involving cultured fibroblasts lacking PGC-1α. Thus, the authors propose that PGC-1α plays a central role in coordinating the circadian clock with energy metabolism. Grimaldi and Sassone-Corsi provide commentary and discuss implications of this research.

C. Liu, S. Li, T. Liu, J. Borjigin, J. D. Lin, Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism.
Nature
447
, 477-481 (2007).
[PubMed]

B. Grimaldi, P. Sassone-Corsi, Metabolic clockwork.
Nature
447
, 386-387 (2007).
[PubMed]
Watching Your Weight with Retinaldehyde?
Authors: Adler Elizabeth M.
Published: July 2007

Retinol, the major form of the fat-soluble vitamin A, is converted into various metabolites. Retinoic acid (RA), the chief metabolite, acts through the retinoic acid and retinoid X receptors (RAR and RXR) to regulate the transcription of target genes; no direct role outside the retina has been identified for the intermediate metabolite retinaldehyde (see Desvergne). Using reduction to retinaldehyde oximes to measure the unstable retinaldehyde, Ziouzenkova
et al.
identified retinaldehyde in rodent fat and determined that it was present at a lower concentration in fat from obese mice than it was in fat from lean mice. Retinaldehyde inhibited the expression of mRNA encoding adipogenic genes in 3T3-L1 mouse preadipocytes. Its effects were distinct from those of retinoic acid: Whereas retinaldehyde and 9-
cis
and all-
trans
isomers of retinoic acid all inhibited expression of the gene encoding adiponectin (
Adipoq
) when added early in adipogenesis, only retinaldehyde inhibited
Adipoq
later in this process. Retinaldehyde inhibited adipogenesis in response to stimulation of peroxisome proliferator-activated receptor-γ (PPAR-γ, which heterodimerizes RXR) and agonist-dependent activation of a gene reporter containing the PPAR response element. Experiments using siRNA directed against RXR-α and RXR-β, however, suggested that inhibition of adipogenesis by retinaldehyde involved both RXR-dependent and RXR-independent effects. Adipocytes from mice lacking retinaldehyde dehydrogenase-1 (Raldh1), which catabolizes retinaldehyde to RA, were smaller than those from wild-type mice, and in vitro adipogenesis of fibroblasts from

Raldh1
–/–

mice was reduced. Intriguingly,

Raldh1
–/–

mice gained less weight in response to a high-fat diet than did wild-type mice, showed decreased body fat, increased metabolism, and were less susceptible to developing insulin resistance. Moreover, retinaldehyde (or an Raldh1 inhibitor) decreased body fat and increased glucose tolerance in transgenic mice that become obese on a normal diet. Thus, the authors conclude that retinaldehyde plays a distinct role in inhibiting adipogenesis and in mediating the metabolic response to diet.

O. Ziouzenkova, G. Orasanu, M. Sharlach, T. E. Akiyama, J. P. Berger, J. Viereck, J. A. Hamilton, G. Tang, G. G. Dolnikowski, S. Vogel, G. Duester, J. Plutzky, Retinaldehyde represses adipogenesis and diet-induced obesity.
Nat. Med.
13
, 695-702 (2007).
[PubMed]

B. Desvergne, Retinaldehyde: More than meets the eye.
Nat. Med.
13
, 671-673 (2007).
[PubMed]
Release from the ER
Authors: Gough Nancy R.
Published: July 2007

In the absence of external signals, yeast enter the cell cycle once they have achieved a critical size, and this is controlled by the G1 cyclin Cln3 and its partner, the cyclin-dependent kinase Cdc28. Vergés
et al
. found that a population of Cln3 and Cdc28 was associated with the cytosolic side of the endoplasmic reticulum (ER) and that the abundance of these proteins in this fraction was highest in "newly born" cells and less in cells in late G1. Cln3 contains a domain, the J domain, like that found in regulators of heat shock protein 70 (HSP70) chaperones such as Ydj1; however, the Cln3 J domain lacked key residues required for adenosine triphosphatase (ATPase) activation of HSP70 chaperones. Cells in which the Cln3 J domain was deleted or mutated were larger, and these mutant versions of Cln3 did not associate with the ER and accumulated in the nucleus. Although Cdc28 was associated with the ER in early G1 cells, a Cln3 mutant that could not interact with Cdc28 accumulated in the nucleus, suggesting that the interaction with Cdc28 was necessary for ER retention. The J chaperone Ydj1, which activates the ATPase activity of the HSP70 chaperones Ssa1 and Ssa2, interacts with Cln3 and promotes Cln3 phosphorylation and degradation. However, deficiencies in Ydj1 or its HSP70 partners Ssa1 and Ssa2 lead to cells with a larger than normal size, and Cln3 does not accumulate in the nucleus of these cells. Chimeric proteins in which the J domains had been swapped between Cln3 and Ydj1 showed that each of these J domains interacted with Ssa1, but only the Ydj1 J domain stimulated ATPase activity. Overexpression of Ydj1 and Ssa1 caused Cln3 to accumulate in the nucleus, and the cells budded at smaller cell sizes than did wild-type cells; premature cell division did not occur in cells deficient for Cln3. In a cell-free assay, excess Ydj1 and Ssa1 released Cln3. The authors suggest that as cells grow and Ydj1 becomes more abundant, it competes with Cln3 for interaction with Ssa1 at the ER, thereby promoting release of Cln3 and Cdc28 to translocate to the nucleus and stimulate entry into the cell cycle.

E. Vergés, N. Colomina, E. Garí, C. Gallego, M. Aldea, Cycline Cln3 is retained at the ER and released by the J chaperone Ydj1 in late G1 to trigger cell cycle entry.
Mol. Cell
26
, 649-662 (2007).
[Online Journal]
BRCA1 Control of Steroid Receptor Ubiquitination
Authors: Heine George F. , Parvin Jeffrey D.
Published: July 2007

The ubiquitin ligase activity of the breast and ovarian cancer–associated tumor suppressor protein BRCA1, as part of a heterodimer with BARD1 (BRCA1-associated RING domain 1), is critical for its role as a tumor suppressor, but its targets, and the consequences of ubiquitin modification, by the BRCA1 protein complex are only now being discovered. BRCA1 is now known to control the ubiquitination of the estrogen and progesterone receptors, and although the consequences of the ubiquitination of these steroid receptors are unknown, the identification of these specific substrates suggests a link between the ubiquitin ligase activity of BRCA1 and its specificity as a tumor suppressor in breast and ovarian tissues.
Actin to Safeguard Transcription
Authors: Purnell Beverly A.
Published: July 2007

Besides its well-characterized function as a cytoskeletal component, actin has emerged as a regulator of nuclear processes, including transcription. MAL, a coactivator of the transcription factor serum response factor (SRF), directly binds to and senses cellular levels of monomeric actin (G-actin). MAL responds to serum-induced depletion of cellular G-actin with nuclear accumulation and SRF activation. Vartiainen
et al
. (see the Perspective by Wu and Crabtree) report that MAL rapidly shuttles between the nucleus and the cytoplasm in resting cells. Actin binding in the nucleus targets MAL for efficient nuclear export and, furthermore, prevents activation of SRF during the short time that MAL spends in the nucleus. When growth factor stimulation interferes with actin binding, this lock on MAL activity is released.

M. K. Vartiainen, S. Guettler, B. Larijani, R. Treisman, Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL.
Science
316
, 1749-1752 (2007).
[Abstract]
[Full Text]

J. I. Wu, G. R. Crabtree, Nuclear actin as choreographer of cell morphology and transcription.
Science
316
, 1710-1711 (2007).
[Summary]
[Full Text]
Cathepsin S's Cuts Cause Pain
Authors: Ray L. Bryan
Published: July 2007

Chronic pain caused by damage to the nervous system (neuropathic pain) results in part from the immune response in the damaged tissue. Clark
et al
. provide new insight into how microglial cells (cells of the immune system that function in the central nervous system) contribute to such effects. After partial neuronal ligation of the sciatic nerve in rats, the authors noted (by immunofluorescence microscopy) increased abundance of the protease cathepsin S in microglial cells in the area of the spinal cord where the injured nerve fibers terminated. If they continuously exposed the spinal cord cells to an irreversible inhibitor of cathepsin S in vivo, the hyperalgesia (increased sensitivity to pain) and allodynia (sensation of pain from a stimulus that is not normally painful) experienced by the animals 7 to 14 days after injury was reduced. Administration of recombinant rat cathepsin S, on the other hand, increased hyperalgesia and allodynia in uninjured rats. The authors therefore searched for potential target molecules expected from their protein sequence to be susceptible to cleavage by cathepsin S. One such protein was the membrane-bound chemokine fractalkine, which is expressed on the surface of neuronal cells and activates receptors on microglial cells; the hypothetical cleavage event was expected to release the biologically active extracellular domain of the molecule. Indeed, exposure of cultured neurons to cathepsin S increased release of fractalkine into the culture medium. Furthermore, inhibiting the action of fractalkine with a neutralizing antibody in vivo reduced hyperalgesia and allodynia caused by administration of cathepsin S or fractalkine at the spinal cord. The allodynia produced by administration of cathepsin S was not observed in mice lacking the CX3CR1 receptor for fractalkine. Fractalkine presumably enhances release of other cytokines that enhance perception of pain. Thus the authors propose that blocking these events through inhibition of cathepsin S could provide a mechanism to therapeutically limit chronic pain.

A. K. Clark, P. K. Yip, J. Grist, C. Gentry, A. A. Staniland, F. Marchand, M. Dehvari, G. Wotherspoon, J. Winter, J. Ullah, S. Bevan, M. Malcangio, Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain.
Proc. Natl. Acad. Sci. U.S.A.
104
, 10655-10660 (2007).
[Abstract]
[Full Text]
Scar Formation
Authors: Gough Nancy R.
Published: July 2007

Injured tissue produces fibrin, which makes a provisional extracellular matrix (ECM). Degradation of this fibrin ECM by plasmin is required for minimizing scar formation. Plasmin is produced by proteolytic cleavage of plasminogen by plasminogen activators (tPA and uPA), which are inhibited by plasminogen activator inhibitor-1 (PAI-1). Sachs
et al
. find that mice deficient in p75 neurotrophin receptor (p75
NTR
) exhibit reduced fibrin deposition after sciatic nerve crush injury or lipopolysaccharide-induced pulmonary fibrosis. The decrease in fibrin associated with sciatic nerve injury was due to increased expression and activity of tPA, whereas the decrease in fibrin associated with pulmonary fibrosis was due to decreased PAI-1 abundance. In wild-type mice after sciatic nerve injury, Schwann cells in which p75
NTR
was abundant lacked tPA, which suggests that cells expressing p75
NTR
did not express tPA. The increased proteolytic activity toward fibrin (measured by in situ zymography) associated with the nerve injury in

p75
NTR

−/−
mice was prevented by application of a specific inhibitor of tPA or by crossing the mice with
tPA
−/−
mice to produce mice deficient in both tPA and p75
NTR
. When cultured on a fibrin gel, Schwann cells from the

p75
NTR

−/−
mice degrade the fibrin, whereas wild-type Schwann cells form a monolayer. Studies with a transfected fibroblast cell line overexpressing p75
NTR
showed increased abundance of transcripts for PAI-1 and decreased transcripts and activity of tPA. Transcriptional regulation of tPA required a cAMP (adenosine 3′,5′-monophosphate) pathway. Inhibition of tPA activity in the p75
NTR
-overexpressing cells was prevented if cAMP concentrations were increased pharmacologically and cAMP concentrations were decreased in the p75
NTR
-overexpressing cells. The injured sciatic nerves also showed increased cAMP in the

p75
NTR

−/−
mice compared with injured nerves from wild-type mice. Coimmunoprecipitation studies and in vitro interaction studies indicated that p75
NTR
and phosphodiesterase 4A5 (PDE4A5) interacted. The authors propose that recruitment of PDE4A5 to the membrane inhibited cAMP signaling, a hypothesis supported by decreased activation of a plasma membrane protein kinase A reporter in the p75
NTR
-overexpressing cells. Tissue remodeling and scar formation appear to be additional ways that p75
NTR
signaling is involved in response to injury.

B. D. Sachs, G. S. Baillie, J. R. McCall, M. A. Passino, C. Schachtrup, D. A. Wallace, A. J. Dunlop, K. F. MacKenzie, E. Klussmann, M. J. Lynch, S. L. Sikorski, T. Nuriel, I. Tsigelny, J. Zhang, M. D. Houslay, M. V. Chao, K. Akassoglou, p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway.
J. Cell Biol.
177
, 1119-1132 (2007).
[Abstract]
[Full Text]
Sequence and transcriptional study ofHNRPKpseudogenes, and expression and molecular modeling analysis of hnRNP K isoforms
Authors: Leopoldino Andréia M. , Carregaro Fernanda , Silva Carlos H.T.P. , Feitosa Olavo , Mancini Ulises M. , Freitas Jorge M. , Tajara Eloiza H.
Published: July 2007

The heterogeneous nuclear ribonucleoproteins (hnRNPs) comprise a large family of proteins that play important roles in telomere biogenesis, DNA repair, cellular signaling, and the regulation of expression at both the transcriptional and translational levels. One of the most extensively studied hnRNP family members, hnRNP K, has been implicated in a variety of processes, including chromatin remodeling, transcription, splicing, and translation events. In this study, we analyzed processed HNRPK pseudogenes (HNRPK ψ1–ψ4) and coding sequences. HNRPK pseudogenes are apparently nonfunctional, and ψ1 might correspond to transcripts from an ancestral gene. Phylogenetic and sequence analyses suggest that HNRP genes arose by duplication, and that new structural and sequence features expanded the functions of hnRNPs. The expression analysis of hnRNP K isoforms showed that isoform a is expressed in normal testis and in non-small cell lung cancer (NCI-H1155 NSCLC cell line), although the shorter isoform (isoform b) is expressed in different tumor cell lines (IM9 B-lymphoblastoid, Hs578T human breast cancer epithelial, T98G human glioma cell lines). Using molecular modeling, we obtained KH1 and KH3 models, which pointed to important residues for DNA–protein binding and no structural differences between isoforms a and b. To our knowledge, this is the first phylogenetic study including vertebrate HNRP genes and HNRPK pseudogenes, and the first report comparing the KH1 and KH3 domains of isoforms a and b of the hnRNP K protein. New investigations in tumor samples must be done to validate the differential expression observed here. The results shown are important because the hnRNP K protein might represent a new target for pharmacologic intervention in virus replication and cancer.
The α-tubulin gene family in wheat (Triticum aestivum L.) and differential gene expression during cold acclimation
Authors: Ridha Farajalla Mohammed , Gulick Patrick J.
Published: July 2007

The α-tubulins and β-tubulins are the major constituents of microtubules, which have been recognized as important structural elements in cell growth and morphogenesis, and, recently, for their role in regulation and signal transduction. We have identified 15 full-length cDNAs for the members of the α-tubulin gene family in hexaploid bread wheat (Triticum aestivum L.). The genes were clustered into 5 homeologous groups of 3 genes. Representatives of the 5 homeologous groups were mapped to different chromosome arms, and the genome of origin was determined for each gene. Changes in mRNA levels were observed for the paralogous members of the gene family during cold acclimation. Three members of the family had initial decreases in mRNA levels in response to cold treatment, which were followed by increases, each with a different pattern of reinduction. One gene-family member showed increased mRNA for up to 14 d during cold acclimation and had decreased levels after 36 d of cold treatment; a fifth paralogous member of the gene family had slowly declining mRNA levels up to 36 d. Subtle differences in the level of gene expression among homeologs and large differences among paralogs were detected by comparing the relative abundance of wheat α-tubulin expressed sequence tags (ESTs) in public databases.
Elimination of altered karyotypes by sexual reproduction preserves species identity
Authors: Heng Henry H.Q.
Published: July 2007

Resolving the persistence of sexual reproduction despite its overwhelming costs (known as the paradox of sex) is one of the most persistent challenges of evolutionary biology. In thinking about this paradox, the focus has traditionally been on the evolutionary benefits of genetic recombination in generating offspring diversity and purging deleterious mutations. The similarity of pattern between evolution of organisms and evolution among cancer cells suggests that the asexual process generates more diverse genomes owing to less controlled reproduction systems, while sexual reproduction generates more stable genomes because the sexual process can serve as a mechanism to “filter out” aberrations at the chromosome level. Our reinterpretation of data from the literature strongly supports this hypothesis. Thus, the principal consequence of sexual reproduction is the reduction of drastic genetic diversity at the genome or chromosome level, resulting in the preservation of species identity rather than the provision of evolutionary diversity for future environmental challenges. Genetic recombination does contribute to genetic diversity, but it does so secondarily and within the framework of the chromosomally defined genome.
Normalization of the calcineurin pathway underlies the regression of hypertensive hypertrophy induced by Na+/H+exchanger-1 (NHE-1) inhibitionThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Ennis Irene L. , Garciarena Carolina D. , Escudero Eduardo M. , Pérez Néstor G. , Dulce Raúl A. , Camilión de Hurtado María C. , Cingolani Horacio E.
Published: July 2007

Na+/H+exchanger-1 (NHE-1) inhibition induces cardiac hypertrophy regression and (or) prevention in several experimental models, although the intracellular events involved remain unclarified. We aimed to determine whether the calcineurin/NFAT pathway mediates this effect of NHE-1 inhibitors. Spontaneously hypertensive rats (SHR) with cardiac hypertrophy were treated with the NHE-1 inhibitors cariporide and BIIB723 for 30 days. Wistar rats served as normotensive controls. Their hearts were studied by echocardiography, immunoblotting, and real-time RT-PCR. Cytoplasmic Ca2+and calcineurin Aβ expression were measured in cultured neonatal rat ventricular myocytes (NRVM) stimulated with endothelin-1 for 24 h. NHE-1 blockade induced cardiac hypertrophy regression (heart mass/body mass = 3.63 ± 0.07 vs. 3.06 ± 0.05 and 3.02 ± 0.13 for untreated vs. cariporide- and BIIB723-treated SHR, respectively; p < 0.05) and decreased myocardial brain natriuretic peptide, calcineurin Aβ, and nuclear NFAT expressions. Echocardiographic evaluation demonstrated a reduction in left ventricular wall thickness without changes in cavity dimensions or a significant decrease in blood pressure. NHE-1-inhibitor treatment did not affect myocardial stiffness or endocardial shortening, but increased mid-wall shortening, suggesting that a positive inotropic effect develops after hypertrophy regression. Cariporide normalized the increased diastolic Ca2+and calcineurin Aβ expression observed in ET-1-stimulated NRVM. In conclusion, our data suggest that inactivation of calcineurin/NFAT pathway may underlie the regression of cardiac hyper-trophy induced by NHE-1 inhibition.
Vascular dysfunction in type 2 diabetic TallyHo mice: role for an increase in the contribution of PGH2/TxA2 receptor activation and cytochrome p450 productsThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Cheng Zhong Jian , Jiang Yan-Fen , Ding Hong , Severson David , Triggle Chris R.
Published: July 2007

In this study, we tested the hypothesis that spontaneously diabetic TallyHo (TH) mice, a novel polygenic model for type 2 diabetes, will exhibit endothelial dysfunction associated with an increased contribution from endothelium-derived contractile factors (EDCF). The cellular mechanisms underlying the increased contribution of EDCF were explored in 16 and 30-week-old male TH and age-matched male C57BL/6J mice (n = 4–9). Blood glucose and serum lipid profiles were markedly increased in the TH mice. Superoxide generation, assessed with a lucigenin chemiluminescence assay, was markedly increased in the aortae of TH mice. Endothelium-dependent vascular relaxations and contractions to acetylcholine (ACh), but not endothelium-independent relaxations to sodium nitroprusside, were impaired and vascular contractions to phenylephrine were significantly enhanced in aortae from TH mice. Nω-nitro-l-arginine methyl ester markedly increased the ACh-induced contractions in TH mice, whereas SQ29548, a thromboxane receptor antagonist, and cytochrome P450 (CYP) inhibitors 17-octadecynoic acid and sulfaphenazole, the latter being specific for CYP2C6 and 2C9, decreased and (or) normalized the contractile response to ACh in TH mice. The present study indicates that enhanced contribution of prostaglandin H2/thromboxane A2 receptor and CYP, likely CYP2C6 and 2C9, play a critical role in the pathogenesis of increased EDCF in the aortae of type 2 diabetic TH mice.
Visualization and grading of regional ischemia in pigs in vivo using near-infrared and thermal imagingThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Manley Darren M. , Xiang Bo , Kupriyanov Valery V.
Published: July 2007

Reductions in regional coronary flow result in tissue deoxygenation and decrease in surface temperature, changes detectable by near-infrared spectroscopic (NIRS) and thermal imaging, respectively. In anesthetized open-chest pigs, an inflatable occluder and flow probe were placed around the left anterior descending artery. Gated NIRS and nongated thermal images were acquired at baseline, partial (17% and 50%), and complete occlusion and reflow. At each step, dobutamine was infused (10 μg·min–1·kg–1) for 7–9 min to increase blood pressure and flow. Changes in the oxygen saturation parameter, rate of indocyanine green flow tracer passage, and the surface temperature were correlated with the measured left anterior descending artery flow. Location and sizes of the areas of reduced oxygenation, indocyanine green uptake, and temperature were similar. Decrease in the coronary flow to 50% and 17% of baseline resulted in progressive decrease in the above parameters, whereas increase in flow from 75% to ~250% achieved by dobutamine and reactive hyperemia did not significantly change them. Dobutamine increased total and epicardial flow in ischemic areas and increased subepicardial oxygenation. NIRS and thermal imaging provide epicardial maps of oxygen saturation and perfusion that reveal ischemic areas. Combination of these techniques may be useful in the coronary artery bypass graft (CABG) surgery setting.
OPTICAL PROPERTIES OF GaInN/GaN MULTI-QUANTUM WELL STRUCTURE AND LIGHT EMITTING DIODE GROWN BY METALORGANIC CHEMICAL VAPOR PHASE EPITAXY
Authors: Senawiratne J. , Zhu M. , Zhao W. , Xia Y. , Li Y. , Detchprohm T. , Wetzel C.
Published: July 2007

Optical properties of green emission Ga 0.80 In 0.20 N/GaN multi-quantum well and light emitting diode have been investigated by using photoluminescence, cathodoluminescence, electroluminescence, and photoconductivity. The temperature dependent photoluminescence and cathodoluminescence studies show three emission bands including GaInN/GaN quantum well emission centered at 2.38 eV (~ 520 nm). The activation energy of the non-radiative recombination centers was found to be ~ 60 meV. The comparison of photoconductivity with luminescence spectroscopy revealed that optical properties of quantum well layers are strongly affected by the quantum-confined Stark effect.
BALLISTIC ELECTRON ACCELERATION NEGATIVE-DIFFERENTIAL-CONDUCTIVITY DEVICES
Authors: ASLAN BARBAROS , EASTMAN LESTER F. , SCHAFF WILLIAM J. , CHEN XIAODONG , SPENCER MICHAEL G. , CHA HO-YOUNG , DYSON ANGELA , RIDLEY BRIAN K.
Published: July 2007

We present the experimental development and characterization of GaN ballistic diodes for THz operation. Fabricated devices have been described and gathered experimental data is discussed. The major problem addressed is the domination of the parasitic resistances which significantly reduce the accelerating electric field across the ballistic region (intrinsic layer).
UNDERSTANDING ULTRAVIOLET EMITTER PERFORMANCE USING INTENSITY DEPENDENT TIME-RESOLVED PHOTOLUMINESCENCE
Authors: WRABACK MICHAEL , GARRETT GREGORY A. , SAMPATH ANAND V. , SHEN PAUL H.
Published: July 2007

Time-resolved photoluminescence studies of nitride semiconductors and ultraviolet light emitters comprised of these materials are performed as a function of pump intensity as a means of understanding and evaluating device performance. Comparison of time-resolved photoluminescence (TRPL) on UV LED wafers prior to fabrication with subsequent device testing indicate that the best performance is attained from active regions that exhibit both reduced nonradiative recombination due to saturation of traps associated with point and extended defects and concomitant lowering of radiative lifetime with increasing carrier density. Similar behavior is observed in optically pumped UV lasers. Temperature and intensity dependent TRPL measurements on a new material, AlGaN containing nanoscale compositional inhomogeneities (NCI), show that it inherently combines inhibition of nonradiative recombination with reduction of radiative lifetime, providing a potentially higher efficiency UV emitter active region.
PHOTOCAPACITANCE OF SELECTIVELY DOPED AlGaAs/GaAs HETEROSTRUCTURES CONTAINING DEEP TRAPS
Authors: GOREV NIKOLAI B. , KODZHESPIROVA INNA F. , PRIVALOV EVGENY N. , KHUCHUA NINA , KHVEDELIDZE LEVAN , SHUR MICHAEL S.
Published: July 2007

The results of calculations of the low-frequency and the high-frequency barrier capacitance of selectively doped AlGaAs/GaAs heterostructures containing deep traps in the AlGaAs layer are presented. The calculations are done for the samples in the dark and under extrinsic illumination. It is shown that the high-frequency photocapacitance of these structures exhibits a positive peak, and the low-frequency photocapacitance has a positive peak followed by a negative valley. The underlying physical mechanisms are discussed.
THE ADSORPTION AND BONDING OF H2S ON THE α-FeOOH(110) SURFACE
Authors: SIMONETTI S. , DAMIANI D. , JUAN A. , BRIZUELA G.
Published: July 2007

The electronic structure of H 2 S adsorbed on the goethite (110) surface has been studied by ASED-MO cluster calculations. We have studied both the perpendicular and the parallel H 2 S molecular adsorption on the FeOOH (110) surface. We have analyzed the adsorption configuration energies including rotation. The parallel species does not rotate during adsorption and corresponds to the most stable configuration. We have also studied the bonding contributions for the minimum energy configuration and the density of states plots.
SEPARATED CuInSe2 QUANTUM DOTS ON ZnO THIN FILM BY ICP-ASSISTED MAGNETRON SPUTTERING
Authors: HUANG S. Y. , XU S. , LONG J. D. , CHENG Q. J. , XU X. B. , CHU J. B.
Published: July 2007

Uniformly hemispherical separated CuInSe 2 (CIS) quantum dots (QDs) were fabricated by low-frequency inductivity coupled plasma (LF-ICP) assisted radio-frequency (RF) magnetron sputtering technique from a ternary compound target on Si (100) and glass substrate with ZnO film serving as buffer layer. The average lateral size and densities of the QDs could be controlled by appropriate deposition parameters. The distribution scope of diameters was from 40 to 120 nm, density was from 4.5E9 to 2.1E11/cm2. Field-emission scanning electron microscope (FE-SEM) and energy-dispersive X-ray (EDX) spectrometer were adopted to measure the properties of CIS QDs.
STOCHASTIC AVERAGING NEAR LONG HETEROCLINIC ORBITS
Authors: SOWERS RICHARD B.
Published: July 2007

We refine some of the bounds of [10]. There, we considered the effect of diffusive perturbations on a two-dimensional ODE with a heteroclinic cycle. We constructed corrector functions for asymptotically "glueing" together behavior of periodic orbits in the boundary layer near the heteroclinic cycle. Here, we adapt the analysis of [10] to allow for "long" heteroclinic cycles.
CONSTRAINED OPINION LEADER INFLUENCE IN AN ELECTORAL CAMPAIGN SEASON: REVISITING THE TWO-STEP FLOW THEORY WITH MULTI-AGENT SIMULATION
Authors: LIU FRANK C. S.
Published: July 2007

The conventional wisdom derived from the two-step flow theory suggests that opinion leaders have great influence on their followers. However, it has been difficult for social scientists to measure and describe the extent to which political opinion leaders influence voters, especially when voters today access multiple information sources like communication networks and self-selected news media. This paper fills this gap by using agent-based modeling to represent what the two-step flow theory describes about opinion leader influence and refines the theory based on the findings. First, opinion leader influence does not diffuse to the public without homogeneous communication networks. Second, opinion leader influence usually does not diffuse widely to the public because it inevitably faces resistance from self-strengthening communication networks.
POSITION-DEPENDENT LAGRANGE INTERPOLATING MULTIRESOLUTIONS
Authors: BACCOU J. , LIANDRAT J.
Published: July 2007

This paper is devoted to the construction of interpolating multiresolutions using Lagrange polynomials and incorporating a position dependency. It uses the Harten's framework21 and its connection to subdivision schemes. Convergence is first emphasized. Then, plugging the various ingredients into the wavelet multiresolution analysis machinery, the construction leads to position-dependent interpolating bases and multi-scale decompositions that are useful in many instances where classical translation-invariant frameworks fail. A multivariate generalization is proposed and analyzed. We investigate applications to the reduction of the so-called Gibbs phenomenon for the approximation of locally discontinuous functions and to the improvement of the compression of locally discontinuous 1D signals. Some applications to image decomposition are finally presented.
STEREO MATCHING USING THE DISCRETE WAVELET TRANSFORM
Authors: LIU HAIYING , BHATTACHARYA PRABIR
Published: July 2007

This paper presents a hierarchical stereo matching strategy using the Discrete Wavelet Transform. Both area- and feature-based methods are combined into a single process by the discrete wavelet decomposition. Experiments show that the method is accurate, fast, and robust to noise.
CONSTRUCTION FOR A CLASS OF SMOOTH TIGHT FRAMES IN L2(ℝ2)
Authors: WANG HAIHUI , PENG LIZHONG
Published: July 2007

We generalize the inequality |P(z)|2 + |P(-z)|2 ≤ 1 (Ref. 1) to the inequality |P(z1, z2)|2 + |P(-z1, z2)|2 + |P(z1, -z2)|2 + |P(-z1, -z2)|2 ≤ 1 in L2(ℝ2); and construct compactly supported tight frames with good symmetry and dilation matrix 2I under the condition that both the low-pass filter and high-pass filters are unknown.