bluuebunny/crossref_metadata_2025 huggingface dataset:
Connecting GPCRs to NF-κB
Authors: Gough Nancy R.
Published: March 2007

Many different kinds of receptors can activate the proinflammatory transcriptional regulator NF-κB. NF-κB is maintained in an inactive state in the cytosol through its interaction with the protein IκB, and activation involves stimulation of the IκB kinase (IKK). In T and B cells, a signaling adaptor complex consisting of CARMA1 [caspase recruitment domain (CARD) 11], Bcl10, and MALT1 connects the receptor-induced activation of protein kinase C (PKC) to activation of IKK and NF-κB. Three groups report a similar signaling adaptor complex in the transmission of signals from G protein-coupled receptors (GPCRs) to NF-κB activation. NF-κB activation plays a pathophysiological role in many types of liver disease and appears to be mediated by the increased activity of angiotensin II (Ang II) at the type I Ang II receptor. McAllister-Lucas
et al
. show that the CARMA3 [caspase recruitment domain (CARD) 10], a scaffolding protein related to CARMA1, which is found in immune cells, is present in many tissues, including liver, along with Bcl10 and MALT1. Through the analysis of dominant-negative mutants, knockout mouse cells, and RNA interference studies, McAllister-Lucas
et al
. show that, similar to activation by immune receptors, Ang II stimulates NF-κB activation by signaling through a CARMA3-Bcl10-MALT1 complex. In each study, activation of NF-κB by tumor necrosis factor α, which acts through a different type of receptor, was unaffected. Two additional groups report that the GPCRs activated by lysophosphatidic acid (LPA) (Wang
et al
. and Klemm
et al
.) or endothelin-1 (Wang
et al
.) also signal through Bcl10 and MALT1 to activate NF-κB. Experiments with mouse embryo fibroblasts from mice deficient in Bcl10 (Wang
et al
. and Klemm
et al
.) or MALT1 (Klemm
et al
.) show that these two proteins were essential for the activation of NF-κB by LPA. From the combined studies, Bcl10 and MALT1 were not required for activation of various members of the mitogen-activated protein kinase family, including p38, JNK, and ERK, nor were they required for activation of the kinase Akt. Both groups showed that pharmacological studies suggested that PKC activation was required for GPCR-mediated NF-κB activation, whereas phosphatidylinositol 3-kinase activity was not.

L. M. McAllister-Lucas, J. Ruland, K. Siu, X. Jin. S. Gu, D. S. L. Kim, P. Kuffa, D. Kohrt, T. W. Mak, G. Nuñez, P. C. Lucas, CARMA3/Bcl10/MALT1-dependent NF-κB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells.
Proc. Natl. Acad. Sci. U.S.A.
104
, 139-144 (2007).
[Abstract]
[Full Text]

D. Wang, Y. You, P.-C. Lin, L. Xue, S. W. Morris, H. Zeng, R. Wen, X. Lin, Bcl10 plays a critical role in NF-κB activation induced by G protein-coupled receptors.
Proc. Natl. Acad. Sci. U.S.A.
104
, 145-150 (2007).
[Abstract]
[Full Text]

S. Klemm, S. Zimmermann, C. Peschel, T. W. Mak, J. Ruland, Bcl10 and Malt1 control lysophosphatidic acid-induced NF-κB activation and cytokine production.
Proc. Natl. Acad. Sci. U.S.A.
104
, 134-138 (2007).
[Abstract]
[Full Text]
How Do TrkA and p75 Interact?
Authors: Adler Elizabeth M.
Published: March 2007

Nerve growth factor (NGF) binds to two structurally unrelated cell surface receptors, the p75 neurotrophin receptor (p75) and the receptor tyrosine kinase TrkA. p75 increases TrkA’s responsiveness to NGF, and coexpression of the two receptors appears to lead to the formation of binding sites with higher affinity for NGF than that of either receptor alone. This suggests that the high-affinity NGF-binding site may involve a complex containing both p75 and TrkA. Wehrmann
et al
. determined the crystal structure of the complete TrkA extracellular domain in complex with NGF and found that this structure was not incompatible with the existence of a 1:2:1 TrkA-NGF-p75 ternary complex. To investigate this possibility in a cellular context, the authors determined interactions between proteins (p75 and a truncated form of TrkA) fused to fragments of β-galactosidase (which become functional when brought together) that were expressed in C2C12 myoblasts. NGF promoted formation of TrkA homodimers but not that of TrkA-p75 heterodimers (which also did not exist in untreated cells); p75 formed oligomers in the absence of ligand, and NGF did not affect this oligomerization. When corrected for background binding, Scatchard analysis of
125
I-NGF binding in both PC12 cells and C2C12 cells expressing TrkA and p75 constructs failed to reveal the higher-affinity NGF binding site. Thus, the authors conclude that functional interactions between p75 and TrkA likely depend on downstream signaling rather than physical complexes involving the two receptors. In discussing this research, Barker suggests that p75 could pass NGF to TrkA in a ternary complex that exists too briefly to be detected by the β-galactosidase complementation assay.

T. Wehrman, X. He, B. Raab, A. Dukipatti, H. Blau, K. C. Garcia, Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors.
Neuron
53
, 25-38 (2007).
[PubMed]

P. A. Barker, High affinity not in the vicinity?
Neuron
53
, 1-4 (2007).
[PubMed]
Cellular Accounting
Authors: Szuromi Philip D.
Published: March 2007

Fluorescent labeling has allowed quantification of proteins in single cells, but potential problems arise from interference between reporter molecules themselves and interactions with other molecules within the cell. Huang
et al
. have devised a microfluidic chip for counting fluorescent proteins within a cell. Single cells are captured and lysed, and their contents are separated by electrophoresis and quantified by single-molecule fluorescence detection. This method was applied to natively fluorescent compounds (the phycobiliprotein subcomplexes in individual cyanobacterial cells grown under nitrogen-limited conditions), and proteins were labeled with fluorescent antibodies (β
2
adrenergic receptor) present in low copy numbers.

B. Huang, H. Wu, D. Bhaya, A. Grossman, S. Granier, B. K. Kobilka, R. N. Zare, Counting low-copy number proteins in a single cell.
Science
315
, 81-84 (2007).
[Abstract]
[Full Text]
Choosing the Right Path
Authors: Simpson Stephen
Published: March 2007

Dendritic cells of the immune system present antigen to T cells in the context of either class I or class II molecules of the major histocompatibility complex (MHC) as a means of generating two distinct arms of T cell immunity: Class I-restricted CD8
+
T cell responses and CD4
+
T cell help. Dudziak
et al
. present evidence that each pathway dominates in distinct subsets of dendritic cells. Using chimeric antibodies specific for cell surface markers present on each specific subtype of dendritic cell, it was possible to target antigens to the class I or class II MHC pathways and so elicit CD8 or CD4 responses, respectively.

D. Dudziak, A. O. Kamphorst, G. F. Heidkamp, V. R. Buchholz, C. Trumpfheller, S. Yamazaki, C. Cheong, K. Liu, H.-W. Lee, C. G. Park, R. M. Steinman, M. C. Nussenzweig, Differential antigen processing by dendritic cell subsets in vivo.
Science
315
, 107-111 (2007).
[Abstract]
[Full Text]
Subverting the Histone Code
Authors: Gough Nancy R.
Published: March 2007

The bacteria
Shigella flexneri
causes dysentery as a consequence of its infection of colonic epithelial cells. Arbibe
et al
. show that the mitogen-activated protein kinase kinase MEK1 was activated (phosphorylated) in HeKa cells infected with Shigella; however, activation (phosphorylation) of the downstream MEK target extracellular signal-regulated kinase (ERK) did not occur. Inactive, dephosphorylated ERK accumulated in the nucleus in shigella-infected cells, which suggests that shigella may trigger ERK dephosphorylation. Shigella delivers bacterial proteins to the infected cell using a type III secretion system. Bacterial supernatants were assayed for an ERK2 dephosphorylating activity, and OspF was determined to have such an activity. Purified OspF was a dual-specificity phosphatase that dephosphorylated ERK2 at both threonine and tyrosine residues. Infection of Caco-2 cells (a human intestinal epithelial cell line) with wild-type or an
ospF
mutant strain showed that in the absence of active OspF, shigella infection stimulated ERK and p38 phosphorylation. Microarray analysis of infected cells showed that 46 genes were specifically up-regulated in response to infection with the
ospF
mutant. These included mitogen-activated protein kinase target genes, immediate early genes, and a subset of nuclear factor κB (NF-κB)-regulated genes. Because interleukin 8 (IL-8) is a critical chemoattractant signal for polymorphonuclear leukocytes that clear shigella infection and is also regulated by NF-κB, the authors focused on the gene encoding this chemokine, which was up-regulated in cells infected with the
ospF
mutant compared with those infected with wild-type shigella. Wild-type and the
ospF
mutant both activated NF-κB to the same extent; however, only in the
ospF
mutant-infected cells was there a transient increase in the phosphorylation of histone H3 at Ser
10
, a site known to be involved in increasing the accessibility of the promoter to NF-κB. Analysis of the
IL8
promoter by chromatin immunoprecipitation showed that when OspF was inactivated, there was substantial phosphorylation of H3 at Ser
10
and recruitment of NF-κB upon shigella infection, whereas cells infected with wild-type shigella did not exhibit this response. The importance of OspF in vivo was assessed in a rabbit model of infection and showed that the ospF strain caused more extensive lesions and massive recruitment of polymorphonuclear leukocytes into the intestinal lumen. Thus, by dephosphorylating nuclear ERK, shigella fine-tunes the host gene expression profile to dampen the immune response and promote infection (see Grassl and Finlay for discussion).

L. Arbibe, D. W. Kim, E. Batsche, T. Pedron, B. Mateescu, C. Muchardt, C. Parsot, P. J. Sansonetti, An injected bacterial effector targets chromatin access for transcription factor NF-κB to alter transcription of host genes involved in immune responses.
Nat. Immunol.
8
, 47-56 (2007).
[PubMed]

G. A. Grassl, B. B. Finlay, Shigella rewrites host transcriptional responses.
Nat. Immunol.
8
, 15-16 (2007).
[PubMed]
Proline-Rich Regions in Transcriptional Complexes: Heading in Many Directions
Authors: Neduva Victor , Russell Robert B.
Published: March 2007

Although many protein complexes are now known, the precise details of how each component operates are rarely understood. Through a combination of bioinformatics and analysis of gene-trapped mouse clones, Enkhmandakh
et al
. were able to deduce the modular function for a part of Ssdp1, a crucial component of the Ldb1 transcriptional complex, which plays a central role in mammalian head development. A proline-rich module from Ssdp1 is likely responsible for transactivation, and this region is curiously mobile, occurring in different proteins in different species. The results underscore the importance of protein modularity in complex organization, as well as the role of irregular or disordered parts of proteins in crucial biological processes.
Describing Delicate Interactions
Authors: Vinson Valda
Published: March 2007

Quantifying the affinities of interactions in biological networks, particularly transient ones, remains a challenge. Maerkl and Quake describe a high-throughput microfluidic platform that allows the measurement of transient and low-affinity interactions and characterize the DNA binding energy landscapes for four eukaryotic transcription factors. In two cases, the binding specificities were used to predict which genes the transcription factors would bind and likely regulate.

S. J. Maerkl, S. R. Quake, A systems approach to measuring the binding energy landscapes of transcription factors.
Science
315
, 233-237 (2007).
[Abstract]
[Full Text]
Interference in the Secondary
Authors: Riddihough Guy
Published: March 2007

The effector molecules in RNA interference (RNAi) are small interfering RNAs (siRNAs). The initial population of "primary" siRNAs, ~22 nucleotides in length with 5′-monophosphates groups, is generated by the Dicer nuclease. Amplification and "spreading" of the initial trigger population are thought to contribute to strength of the RNAi response in a number of systems and involve an RNA-dependent RNA polymerase (RDRP) (see the Perspective by Baulcombe). To investigate the nature of this secondary response, Pak and Fire and Sijen
et al
. analyzed the course of an experimentally induced RNAi reaction in the nematode worm
Caenorhabditis elegans
and also examined endogenous small RNAs. They found distinct populations of "secondary" siRNAs that are antisense to the messenger RNA target, that have a di- or triphosphate moiety at their 5′ ends, and that may map both upstream and downstream of the original dsRNA trigger. Primary siRNAs do not appear to act as primers for RdRP but rather guide RdRP to targeted messages for the de novo synthesis of secondary siRNAs that further boost the RNAi response.

J. Pak, A. Fire, Distinct populations of primary and secondary effectors during RNAi in
C. elegans
.
Science
315
, 241-244 (2007).
[Abstract]
[Full Text]

T. Sijen, F. A. Steiner, K. L. Thijssen, R. H. A. Plasterk, Secondary siRNAs result from unprimed RNA synthesis and form a distinct class.
Science
315
, 244-247 (2007).
[Abstract]
[Full Text]

D. C. Baulcombe, Amplified silencing.
Science
315
, 199-200 (2007).
[Summary]
[Full Text]
One Ubiquitin, Two Ubiquitin, Three Ubiquitin, Four
Authors: Hurtley Stella M.
Published: March 2007

The role of protein ubiquitination is well known in promoting regulated protein degradation. Mukhopadhyay and Riezman review what is known about the contribution of protein ubiquitination in other cellular pathways, including intracellular signaling, endocytosis, and protein sorting.

D. Mukhopadhyay, H. Riezman, Proteasome-independent functions of ubiquitin in endocytosis and signaling.
Science
315
, 201-205 (2007).
[Abstract]
[Full Text]
Propping Up Our Knowledge of G Protein Signaling Pathways: Diverse Functions of Putative Noncanonical Gβ Subunits in Fungi
Authors: Hoffman Charles S.
Published: March 2007

Heterotrimeric guanine nucleotide–binding proteins, composed of Gα, Gβ, and Gγ subunits, are important mediators of fungal pheromone and nutrient signaling pathways. Most fungal genomes encode two or three functionally distinct Gα subunits but only a single canonical Gβ subunit, which does not bind multiple Gα subunits. Studies inSaccharomyces cerevisiae,Cryptococcus neoformans, andSchizosaccharomyces pombehave identified binding partners for Gα subunits, which are proposed to be "noncanonical Gβ subunits." This Perspective reviews these studies, summarizing the strengths and weaknesses of the claims to this designation for these four fungal proteins.
Finding Redox-Active Cysteines
Authors: Jasny Barbara R.
Published: March 2007

Cysteine residues are found in a wide variety of proteins, in which they serve many functions. Identifying particular functions has required laborious individual characterization. Fomenko
et al
. present and experimentally verify an algorithm that can identify which cysteines act in redox reactions by searching for sporadic selenocysteine-Cys pairs in sequence databases. This methodology should assist in metagenomic analyses to identify oxidoreductase families.

D. E. Fomenko, W. Xing, B. M. Adair, D. J. Thomas, V. N. Gladyshev, High-throughput identification of catalytic redox-active cysteine residues.
Science
315
, 387-389 (2007).
[Abstract]
[Full Text]
Inside B Cell Central
Authors: Simpson Stephen
Published: March 2007

B cells become effective factories for antibody production only after they have gone through a series of maturation steps that select clones of B cells carrying somatic mutations for high-affinity antibody. This process takes place in the germinal center, where B cells are also thought to compete vigorously for available antigen. Using intravital microscopy, Allen
et al
. observed that the behavior of germinal center B cells is more consistent with a competition for the attention of helper T cells than for scarce antigen. This finding could prove useful in considering how best to stimulate robust immune responses with vaccines.

C. D. C. Allen, T. Okada, H. L. Tang, J. G. Cyster, Imaging of germinal center selection events during affinity maturation.
Science
315
, 528-531 (2007).
[Abstract]
[Full Text]
Neuronal Polarity and the Kinesin Superfamily Proteins
Authors: Nakata Takao , Hirokawa Nobutaka
Published: March 2007

Neurons are highly polarized cells, typically with a long axon and relatively short dendrites. A wealth of recent data has identified a number of signaling molecules that are involved in neuronal polarization. Kinesin superfamily proteins (KIFs) contribute to the establishment and maintenance of neuronal polarity by selectively transporting various proteins and vesicles to either the axon or dendrites. Now evidence is emerging that KIFs also play an important role in axonal formation, the initial event of neuronal polarization. In particular, KIF13B transports phosphatidylinositol (3,4,5)-trisphosphate, which, based on current hypotheses, is one of the most upstream molecules in the intracellular signaling cascades involved in axonal formation.
Diversifying Role for β-Arrestin
Authors: Ray L. Bryan
Published: March 2007

Intense investigation is focused on understanding mechanisms that control signaling through G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs), because they are known to be productive targets for therapeutic drugs. Nelson
et al
. show that β-arrestins, which limit signaling by GPCRs coupled to G proteins of the G
s
class, serve a very similar function in control of signaling by M1 muscarinic receptors. The muscarinic receptors use a different class of G protein linked to distinct signaling machinery.

C. D. Nelson, S. J. Perry, D. S. Regier, S. M. Prescott, M. K. Topham, R. J. Lefkowitz, Targeting of diacylglycerol degradation to M1 muscarinic receptors by β-arrestins.
Science
315
, 663-666 (2007).
[Abstract]
[Full Text]

E. F. Grady, β-Arrestin, a two-fisted terminator.
Science
315
, 605-606 (2007).
[Summary]
[Full Text]
MicroRNA May Link Inflammation and Cancer
Authors: Ray L. Bryan
Published: March 2007

For mammals, inflammatory responses of the innate immune system provide an indispensable protective mechanism against infection. But these signaling mechanisms may also contribute to certain diseases, including cancer. O’Connell
et al
. investigated the role of microRNAs (noncoding RNAs that regulate gene expression through interaction with cellular mRNAs) in the inflammatory response to viral infection and may have unearthed a molecular link between inflammation and cancer. The authors used microarrays to monitor expression of a panel of 200 microRNAs in response to polyriboinosinic:polyribocytidylic acid [poly(I:C)], a synthetic double-stranded RNA used to mimic viral infection, or the antiviral cytokine interferon-β (IFN-β). They identified one microRNA, miR-155, that showed increased expression in macrophages in response to both stimuli. Expression of miR-155 was regulated through multiple signaling pathways. The response to poly(I:C) required signaling through Toll receptors and the MyD88 or TRIF adaptor proteins. Interferons, on the other hand, stimulated expression of miR-155 through a slower mechanism that required autocrine signals mediated by tumor necrosis factor α. Both pathways appeared to converge on regulation of an AP-1 transcription factor binding site, and an inhibitor of the JNK mitogen-activated protein kinase inhibited the response to poly(I:C) or interferon. The miR-155 microRNA is also an oncogene, and its overexpression can cause B cell lymphoma. Thus, the authors note that the finding of miR-155 as a common target of pathways activated by viral infection presents a potential link between inflammatory responses and cancer.

R. M. O’Connell, K. D. Taganov, M. P. Boldin, G. Cheng, D. Baltimore, MicroRNA-155 is induced during the macrophage inflammatory response.
Proc. Natl. Acad. Sci. U.S.A.
104
, 1604-1609 (2007).
[Abstract]
[Full Text]
A Motor for Netrin Receptors
Authors: Gough Nancy R.
Published: March 2007

Netrin receptors include neogenin and DCC (deleted in colorectal cancer). These receptors function in axon guidance, with neogenin implicated in the response to repulsive guidance cues and DCC in the response to attractive guidance cues. Myosin X (Myo X) is an unconventional myosin implicated in the formation of cellular projections. Zhu
et al
. found that Myo X interacted with neogenin and DCC in a manner that required the FERM domain of Myo X and the P3 region of the netrin receptor. Neogenin interacted more strongly with Myo X lacking the motor domain, whereas DCC showed a preference for full-length Myo X. (A motorless form of Myo X generated by alternative splicing has been reported in brain.) Overexpression studies in COS7 cells, rat cortical neurons, and the neuronal cell line NLT suggested that Myo X and DCC colocalized at the tips of filopodia and that Myo X increased the delivery of DCC to these structures. RNA interference studies to knock down Myo X in NLT cells showed that, in the absence of endogenous Myo X, DCC targeting to neurites was decreased (based on immunofluorescence analysis). NLT cells exhibited opposing responses to netrin depending on whether MyoX was coexpresssed with neogenin or DCC. Netrin treatment of the DCC- and Myo X-expressing cells resulted in the formation of neurites and a neuronal-like morphology, whereas the neogenin- and Myo X-expressing cells adopted a spread morphology lacking filopodia or neurites. The motorless Myo X was overexpressed in mouse embryos using in utero electroporation, and the response of cortical explants from these mice to netrin was analyzed. The neurons expressing the motorless Myo X showed shorter neurites in the absence of netrin and reduced outgrowth in response to netrin. In ovo electroporation of the motorless Myo X allowed the effect of Myo X on commissural axon guidance to be analyzed in chicken embryos. Neurons expressing the motorless Myo X failed to cross the midline. This study demonstrates a direct association between a motor protein, Myo X, and the plasma membrane netrin receptors. Furthermore, the differential interaction of neogenin with a motorless form of Myo X, which appears to inhibit neurite extension and axon guidance, provides a potential mechanism for repulsive signaling by neogenin.

X.-J. Zhu, C.-Z. Wang, P.-G. Dai, Y. Xie, N.-N. Song, Y. Liu, Q.-S. Du, L. Mei, Y.-Q. Ding, W.-C. Xiong, Myosin X regulates netrin receptors and functions in axonal path-finding.
Nat. Cell Biol.
9
, 184-192 (2007).
[PubMed]
Activating Cytokinin in the Meristem
Authors: Gough Nancy R.
Published: March 2007

Cytokinin is a plant hormone synthesized from adenine that is important in controlling plant development and in meristem signaling. The meristem is a source of cells that differentiate to produce various parts of the plant, including stems, flowers, leaves, and roots. Kurakawa
et al
. characterized the rice mutant called
lonely guy
(
log
), which they found in a screen for plants defective in shoot meristem maintenance. These plants show defects in reproductive organ formation that result from premature termination of organ differentiation. Analysis of meristem markers revealed that the meristem pool was not maintained in the
log
mutants. Cloning and genome analysis of rice and Arabidopsis indicated that LOG belongs to a large gene family (11 members in rice). Analysis of the mRNA expression of LOG indicated that the gene was expressed in a small region of the floral meristem that included the stem cells. LOG had phosphoribohydrolase activity that converted a cytokinin nucleotide precursor into active cytokinin in a one-step process. This was unexpected, because cytokinin production was proposed to require a two-step activation by a nucleotidase and a nucleosidase. Analysis of the phenotypes of the
log
mutants was consistent with a cytokinin-activating activity for LOG--alleles with weak activity had weak phenotypes, whereas those completely lacking activity had a strong phenotype. Furthermore, the decrease in expression of cytokinin-induced genes in the meristem of
log
mutants supported the hypothesis that LOG activity in the meristem increases cytokinin activity.

T. Kurakawa, N. Ueda, M. Maekawa, K. Kobayashi, M. Kojima, Y. Nagato, H. Sakakibara, J. Kyozuka, Direct control of shoot meristem activity by a cytokinin-activating enzyme.
Nature
445
, 652-655 (2007).
[PubMed]
Mobile mRNA Makes Potatoes
Authors: Ray L. Bryan
Published: March 2007

Tuber formation in potato plants is promoted when plants are exposed to short-day photoperiods and inhibited in plants that experience summerlike long periods of daylight. This process requires that a signal be passed from the leaves to the growing tuber underground. Banerjee
et al
. report a series of experiments that implicate specific mRNAs as the molecules that carry the signal. The mRNA encodes a transcription factor called St BEL5 that acts with another transcription factor, POTH1, to control hormone concentrations in the tuber that regulate growth. The authors used laser microdissection of specific cell types and reverse transcription polymerase chain reaction amplification to pinpoint specific mRNAs in phloem and other cell types. When a leaf-specific promoter was used to drive expression of St BEL5 RNA, exposure to short days enhanced mobility of the RNA to the root region. Overexpression of the St BEL5 transcript enabled transgenic plants to undertake tuber formation even when exposed to long photoperiods. The authors propose that the mRNA transport reflects light-dependent changes in the abundance of RNA-binding proteins that facilitate transport and targeting of mRNA to specific cells.

A. K. Banerjee, M. Chatterjee, Y. Yu, S.-G. Suh, W. A. Miller, D. J. Hannapel, Dynamics of a mobile RNA of potato involved in a long-distance signaling pathway.
Plant Cell
18
, 3443-3457 (2006).
[Abstract]
[Full Text]
Integrating Cell Signaling Pathways in Development
Authors: Purnell Beverly
Published: March 2007

During development, signaling by the fibroblast growth factor (FGF) receptor tyrosine kinase enhances mesoderm induction by transforming growth factor-β (TGF-β) and Activin-like growth factors. Cordenonsi
et al
. combine Xenopus embryology with biochemical analyses to show that FGF signaling promotes phosphorylation of the N-terminal region of the tumor-suppressor protein p53. This modification enables the formation of a complex between p53 and TGF-β-activated Smad, which regulates gene expression and promotes Xenopus mesoderm induction.

M. Cordenonsi, M. Montagner, M. Adorno, L. Zacchigna, G. Martello, A. Mamidi, S. Soligo, S. Dupont, S. Piccolo, Integration of TGF-β and Ras/MAPK signaling through p53 phosphorylation.
Science
315
, 840-843 (2007).
[Abstract]
[Full Text]
Shifting the Balance
Authors: Gough Nancy R.
Published: March 2007

The striatum controls motor activity through the balance of the activity of a direct and indirect pathway. Kreitzer and Malenka used mice engineered to express green fluorescent protein in neurons of the direct pathway or indirect pathway to show that the cells of the indirect pathway exhibited (i) higher probability of neurotransmitter release, (ii) increased ratios of NMDA- to AMPA-type glutamate receptors, and (iii) increased rate of synaptic activity compared with cells of the direct pathway. High-frequency afferent stimulation only triggered long-term depression (LTD) in the indirect pathway, and application of an antagonist of the endocannabinoid receptor CB1 or the D2 dopamine receptor blocked this response. However, this difference was not caused by a lack of CB1 receptors in the direct pathway, because application of CB1 agonist increased both direct and indirect pathway excitatory postsynaptic potentials. Instead, endocannabinoid release or synthesis in response to synaptic activity appeared to be limited to the indirect pathway. Mouse models of Parkinson's disease showed a lack of an indirect pathway LTD response that was restored if the slices were exposed to a D2 agonist or an inhibitor of endocannabinoid degradation. In the Parkinson's model mice, treatment with both a D2 agonist and the endocannabinoid degradation inhibitor reduced catalepsy and improved motor activity compared to treatment with the D2 agonist alone.

A. C. Kreitzer, R. C. Malenka, Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models.
Nature
445
, 643-647 (2007).
[PubMed]
Two Wings Good, Four Wings Better
Authors: Chin Gilbert
Published: March 2007

Some flying insects have two wings, whereas others have four. The common housefly, which possesses two wings, makes use of the vestigial hindwing (the pendulum-shaped haltere) as a source of mechanosensory input to the neural centers that support stable flight. Sane
et al
. have asked whether moths, which have four wings, possess a similar kind of flight control mechanism. Instead, the antennae appear to serve a haltere-like function by providing mechanosensory input through hairs or bristles located at their base, whose deflections are translated into afferent neural signals.

S. P. Sane, A. Dieudonné, M. A. Willis, T. L. Daniel, Antennal mechanosensors mediate flight control in moths.
Science
315
, 863-866 (2007).
[Abstract]
[Full Text]

R. M. Alexander, Antennae as gyroscopes.
Science
315
, 771-772 (2007).
[Summary]
[Full Text]
Patched Polymorphisms in Skin Cancer
Authors: Gough Nancy R.
Published: March 2007

Activation of the sonic hedgehog (SHH) pathway has been implicated in basal cell carcinoma (BCC), and one mechanism to achieve aberrant SHH signaling is through loss of the function of Patched (Ptch, also sometimes abbreviated Ptc), a receptor that inhibits the pathway in the absence of SHH. Wakabayashi
et al
. now implicate aberrant Ptc function in susceptibility to squamous cell carcinoma (SCC) caused by H-Ras. They mapped the difference in susceptibility of two strains of mice to H-Ras-induced SCC: C57BL/6 mice are resistant to SCC, and FVB/N mice are susceptible to SCC compared with a control mouse strain. They found a polymorphism in the
Ptch
gene that resulted in the appearance of either a Thr (resistant mice Ptch
B6
) or an Asn (susceptible mice Ptch
FVB
) at position 1267 in the C-terminal region. Comparison with the human protein revealed that humans have an Asn in that position. This polymorphism affected the interaction of Ptch with Tid1, with the Ptch
B6
version interacting with the short form of this protein, which has been implicated in Ras-induced apoptosis and senescence. In contrast, Ptch
FVB
did not interact with Tid1 by coimmunoprecipitation when expressed in transfected cells. When coexpressed in NIH 3T3 cells or C5N keratinocytes with H-Ras, only the Ptc
FVB
inhibited apoptosis. In mice transgenic for Ptc
FVB
in the skin,
Ptc
and
Gli
transcripts were present in normal skin, whereas these two transcripts were repressed in the SCC tumors. This implies that the altered Ptch function may be required at a very early stage in tumor initiation but is not required or is actively silenced in the tumors. This contrasts with the situation in BCC in which increased SHH signaling is present. The authors propose a mechanism for SHH in cell fate determination that may contribute to the two different forms of cancer, with Ptch activity contributing to SCC and Ptch loss contributing to BCC.

Y. Wakabayashi, J.-H. Mao, K. Brown, M. Girardi, A. Balmain, Promotion of Hras-induced squamous carcinomas by a polymorphic variant of the
Patched
gene in FVB mice.
Nature
445
, 761-765 (2007).
[PubMed]
Customizing MicroRNAs
Authors: Riddihough Guy
Published: March 2007

MicroRNAs (miRNAs) are ubiquitous small noncoding RNAs that regulate gene expression in eukaryotes. Because of the double-stranded nature of intermediates in their synthesis, miRNAs are potential targets for RNA editing. Kawahara
et al
. now show that members of a related mammalian miRNA cluster are edited in their seed regions, the region that determines their target specificity. The editing, which is tissue specific, changes the potential target range of the miRNAs.

Y. Kawahara, B. Zinshteyn, P. Sethupathy, H. Iizasa, A. G. Hatzigeorgiou, K. Nishikura, Redirection of silencing targets by adenosine-to-inosine editing of miRNAs.
Science
315
, 1137-1140 (2007).
[Abstract]
[Full Text]
Coordinating Plant Defenses
Authors: Hines Pamela J.
Published: March 2007

Plants respond to pathogen attack by recognizing molecular signals from the invaders and instigating their own cellular responses to limit damage. Shen
et al
. now show that two of the plant’s defense systems themselves interact at the level of gene transcription. Studying barley’s MLA proteins, part of one of the plant pathogen response pathways, the authors show how these proteins are localized to the nucleus, where they alter transcription of factors that regulate the other plant pathogen response pathway. The plant’s response to pathogenic attack is thus coordinated and tuned to be appropriate to the challenge.

Q.-H. Shen, Y. Saijo, S. Mauch, C. Biskup, S. Bieri, B. Keller, H. Seki, B. Ülker, I. E. Somssich, P. Schulze-Lefert, Nuclear activity of MLA immune receptors links isolate-specific and basal disease-resistance responses.
Science
315
, 1098-1103 (2007).
[Abstract]
[Full Text]

J. L. Dangl, Nibbling at the plant cell nucleus.
Science
315
, 1088-1089 (2007).
[Summary]
[Full Text]
Signaling the Way Home
Authors: Adler Elizabeth M.
Published: March 2007

T cells "home" to extralymphoid tissues that correspond to the regions in which they were initially activated; for instance, effector T cells initially activated in gut-associated lymphoid tissue home to the gut, whereas T cells activated in lymph nodes associated with the skin return to the skin. This preferential migration depends on the induction by dendritic cells (DCs) of receptors on T cells that recognize ligands found in distinct regions (see Mebius). Sigmundsdottir
et al
. found that exposure to the active form of vitamin D3 [1,25(OH)
2
D
3
] stimulated the expression of the CC chemokine receptor 10 (CCR10) on T cells activated in vitro, allowing them to migrate toward the CCR10 ligand CCL27 (a chemokine secreted by epidermal keratinocytes). The expression of receptors involved in homing to the gut, however, was inhibited. Induction of CCR10 expression by 1,25(OH)
2
D
3
depended on interleukin-12 in naïve T cells but not in those activated before 1,25(OH)
2
D
3
exposure. Microarray analysis revealed that monocyte-derived DCs expressed the enzymes required to process inactive vitamin D3 (cholecalciferol, which is produced in skin exposed to sunlight) into 1,25(OH)
2
D
3
; moreover, T cell-DC cocultures, monocyte-derived DCs, and DCs isolated from lymph vessels draining skin all converted inactive vitamin D3 to 1,25(OH)
2
D
3
. When T cells were activated by cocultured DCs, cholecalciferol stimulated expression of CCR10; it was ineffective during activation by antibodies directed against CD3 and CD28. Thus, the authors propose that DCs process epidermally derived vitamin D3 into a form that can be used to direct T cell homing to skin.

H. Sigmundsdottir, J. Pan, G. F. Debes, C. Alt, A. Habtezion, D. Soler, E. C. Butcher, DCs metabolize sunlight-induced vitamin D3 to "program" T cell attraction to the epidermal chemokine CCL27.
Nat. Immunol.
8
, 285-293 (2007).
[PubMed]

R. E. Mebius, Vitamins in control of lymphocyte migration.
Nat. Immunol.
8
, 229-230 (2007).
[PubMed]
Variation on Synaptic Potentiation
Authors: Stern Peter
Published: March 2007

Synaptic changes linked to associative learning are well known. Lamsa
et al
. examined long-term synaptic plasticity in different types of interneurons in rat hippocampal slices. They discovered an induction rule for long-term potentiation (LTP) that shows unusual characteristics. In contrast to known forms of plasticity, pairing synaptic input with hyperpolarization resulted in LTP, whereas pairing it with depolarization prevented it.

K. P. Lamsa, J. H. Heeroma, P. Somogyi, D. A. Rusakov, D. M. Kullmann, Anti-Hebbian long-term potentiation in the hippocampal feedback inhibitory circuit.
Science
315
, 1262-1266 (2007).
[Abstract]
[Full Text]
Interfering with Interferon
Authors: Simpson Stephen
Published: March 2007

The early host response to viral infection is regulated by the type I interferons (IFNα/β), which are induced after detection of virus-specific products. The subsequent transcriptional response is mediated via the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, which controls transcription of a range of interferon-stimulated genes (ISGs). The IKK-related kinases TBK and IKKε (an inhibitor of nuclear factor κB kinase) are also integral components of the IFNβ pathway. However, tenOever
et al
. reveal that, although mice deficient in IKKε are susceptible to viral infection, this susceptibility is not because of a loss of IFNβ expression. Rather, the deficiency resulted from an unanticipated downstream effect in which IKKε prevents homodimerization of STAT-1 by its phosphorylation. Instead, STAT-1 was incorporated into a heterotrimeric complex transcribing a distinct set of ISGs.

B. R. tenOever, S.-L. Ng, M. A. Chua, S. M. McWhirter, A. García-Sastre, T. Maniatis, Multiple functions of the IKK-related kinase IKKε in interferon-mediated antiviral immunity.
Science
315
, 1274-1278 (2007).
[Abstract]
[Full Text]
Another Mechanism for p53-Mediated Protection
Authors: Adler Elizabeth M.
Published: March 2007

Ultraviolet (UV) radiation of the skin stimulates production of melanin, which absorbs UV and free radicals and helps protect the skin from UV-induced DNA damage and skin cancers. This process of tanning depends on activation of the melanocortin-1 receptor by α-melanocyte-stimulating hormone, a product of the pro-opiomelanocortin (
POMC
) gene. Noting that mice lacking the tumor suppressor p53 are extremely susceptible to UV-induced skin cancers, Cui
et al
. investigated the role of p53 in tanning. After determining that the
POMC
promoter contains a p53 consensus element, the authors exposed primary human keratinocytes and mouse PAM212 keratinocytes to UV and saw an increase in POMC mRNA and protein, with a peak increase in p53 protein preceding the POMC peak. p53 overexpression in PAM212 cells increased POMC mRNA and protein, whereas a dominant-negative
p53
allele inhibited the UV-dependent increase in POMC. Mice lacking p53 failed to show a UV-dependent increase in POMC mRNA or protein, and their ears and tails failed to tan (although basal expression of POMC persisted and fur pigmentation resembled that of wild-type mice). UV stimulated the expression of gene reporters containing the
POMC
p53-binding site, an effect blocked by site-specific mutation. Electrophoretic mobility shift assay indicated that UV stimulated p53 binding to keratinocyte DNA, and chromatin immunoprecipitation showed that UV stimulated p53 binding to the
POMC
promoter. The topoisomerase inhibitor etoposide also stimulated p53 and POMC expression, and topical 5-fluorouracil, which is known to induce hyperpigmentation, failed to do so in the skin of mice lacking p53. Thus, the authors propose that p53 acts as a UV sensor to mediate the protective tanning response through transcriptional activation of
POMC
. Oren and Bartek discuss implications of the research in a Preview.

R. Cui, H. R. Widlund, E. Feige, J. Y. Lin, D. L. Wilensky, V. E. Igras, J. D'Orazio, C. Y. Fung, C. F. Schanbacher, S. R. Granter, D. E. Fisher, Central role of p53 in the suntan response and pathologic hyperpigmentation.
Cell
128
, 853-864 (2007).
[Online Journal]

M. Oren, J. Bartek, The sunny side of p53.
Cell
128
, 826-828 (2007).
[Online Journal]
A Simulation Environment for Directional Sensing as a Phase Separation Process
Authors: de Candia Antonio , Gamba Andrea , Cavalli Fausto , Coniglio Antonio , Di Talia Stefano , Bussolino Federico , Serini Guido
Published: March 2007

The ability of eukaryotic cells to navigate along spatial gradients of extracellular guidance cues is crucial for embryonic development, tissue regeneration, and cancer progression. One proposed model for chemotaxis is a phosphoinositide-based phase separation process, which takes place at the plasma membrane upon chemoattractant stimulation and triggers directional motility of eukaryotic cells. Here, we make available virtual-cell software that allows the execution and spatiotemporal analysis of in silico chemotaxis experiments, in which the user can control physical and chemical parameters as well as the number and position of chemoattractant sources.
Buried object approach for solving scattering problems related to rough surfaces
Authors: Altuncu Yasemin , Yapar Ali , Akduman Ibrahim
Published: March 2007

A new method for the scattering of electromagnetic waves from a locally rough interface between two dielectric half-spaces is addressed. The method is based on the assumption that the perturbations of the rough surface from the planar interface are objects buried in a two-half spaces media with a planar boundary, which allows one to reduce the problem to the scattering of electromagnetic waves by cylindrical bodies of arbitrary cross section. Then through the Green's function of the background medium one obtains a Fredholm integral equation of the second kind, which is solved via an application of the Method of Moments. The present formulation permits one to get the near and far field expressions of the scattered wave. The method is effective for surfaces having a local roughness and arbitrary root mean square heights but does not work in the case of a highly conductive background medium.PACS Nos.: 41.20.–q, 41.20.Jb, 03.50.De
Electron capture branching ratios for the odd–odd intermediate nuclei in double-beta decay using the TITAN ion trap facility
Authors: Frekers D , Dilling J , Tanihata I
Published: March 2007

We suggest a measurement of the electron capture (EC) branching ratios for the odd–odd intermediate nuclei in double-beta (β– β–) decay using the new ion trap facility TITAN at the TRIUMF radioactive beam facility. The EC branching ratios are important for evaluating the nuclear matrix elements involved in the β– β– -decay for both, the 2ν and the 0ν-decay mode. Especially the neutrinoless (0νββ) mode is presently at the center of attention, as it probes the Majorana character of the neutrino, and if observed unambiguously, knowledge of the nuclear matrix elements are the key for determining the neutrino mass. The EC branches are in most cases suppressed by several orders of magnitude relative to their β– -counterparts owing to much lower decay energies, and are, therefore, either poorly known or not known at all. Here, the traditional methods of producing the radioactive isotope through irradiation of a suitable target and then measuring the K-shell X-rays have reached a limit of sensitivity. In this note, we will describe a novel technique to measure the EC branching ratios, where the TITAN ion traps and the ISAC radioactive beam facility at TRIUMF are the central components. This approach will increase the sensitivity limit because of significantly reduced background levels. Seven cases will be discussed in detail and connections to hadronic charge-exchange reactions will be made. For most of these, the daughter isotopes are β– β– -decay nuclei that are presently under intense experimental investigations. These are

[Formula: see text]PACS Nos.: 23.40.–s, 23.40.Hc, 29.30.Kv, 29.25.Rm, 14.60.Pq
Loading of a far off-resonance dipole force trap for stable 39K
Authors: Prime E J , Behr J A , Pearson M R
Published: March 2007

A useful tool that can achieve a high level of spin polarization is a circularly polarized far off-resonance dipole force trap (CFORT). This work is the first step in its development; building the necessary components to successfully load stable 39K into a linearly polarized far off-resonance trap (FORT) from a magneto-optical trap, where the atoms are precooled to a temperature of 400 μK. The FORT consists of 700 mW of light from a titanium–sapphire ring laser, focused with a 200 mm achromatic lens to a waist of 35 μm. The light is detuned between 1 and 20 nm to the red of the D1 transition and this gives rise to trap depths in the region of a few milliKelvin. A characterization of the FORT's loading efficiency and lifetime as a function of FORT beam detuning, power, and ellipticity are studied. PACS Nos.: 32.80.Pj, 23.40.–s, 39.25.+k
Perturbation and variational-perturbation method for the free energy of anharmonic oscillators
Authors: Vlachos K , Papatheou V , Okopińska A
Published: March 2007

The perturbation and the variational-perturbation methods are applied for calculating the partition function of one-dimensional oscillators with anharmonicity x2n. New formally simple expressions for the free energy and for the Rayleigh–Schrodinger energy corrections are derived. It is shown that the variational-perturbation method overcomes all the deficiencies of the conventional perturbation method. The results of fifth-order numerical calculations for the free energy of the quartic, quartic–sextic, and octic anharmonic oscillator are highly accurate in the whole range of temperatures. PACS Nos.: 03.65.–w, 05.30.–d
ON WEIGHTED BÜCHI AUTOMATA WITH ORDER-COMPLETE WEIGHTS
Authors: DROSTE MANFRED , PÜSCHMANN ULRIKE
Published: March 2007

We investigate Büchi automata with weights for the transitions. Assuming that the weights are taken in a suitable ordered semiring, we show how to define the behaviors of these automata on infinite words. Our main result shows that the formal power series arising in this way are precisely the ones which can be constructed using ω-rational operations. This extends the classical Kleene–Schützenberger result for weighted finite automata to the case of infinite words and generalizes Büchi's theorem on languages of infinite words. We also derive versions of our main result for non-complete semirings and for other automata models.
Drug Abuse in African American and Hispanic Adolescents: Culture, Development, and Behavior
Authors: Szapocznik José , Prado Guillermo , Burlew Ann Kathleen , Williams Robert A. , Santisteban Daniel A.
Published: March 2007

An understanding of African American and Hispanic adolescent drug abuse occurs at the intersection of context, development, and behavior. The focus of this review is on the impact of racial/ethnic culture as one of the important contexts that influence adolescent development toward or away from prosocial behaviors. Because family plays a major role in both African American and Hispanic cultures, it is also a centerpiece of any discussion of adolescent development in these groups. This review on the state of the science in drug abuse for African American and Hispanic adolescents focuses on epidemiology, culturally specific risk and protective processes, and prevention and treatment research. From the perspective of a broad lens, specific minority groups such as African Americans and Hispanics would appear to have more in common than not. However, each of these groups encompasses considerable genetic, historical, social, and cultural heterogeneity. Investigation across such diversity will yield a more complete picture of the human condition.