bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Party Effects on Local Policies: A Quarter Century of Progress or Eternal Recurrence?
Authors: Boyne George A.
Published: December 2006

Fifty studies which test the impact of political parties on local policy variation in the UK are evaluated. A major feature of these studies over the last twenty-five years is the recurrence of the same conceptual and methodological problems. It appears that there has been little progress towards a better understanding of the impact of parties. The results suggest that party political variables are insignificant in a majority of cases. However, problems in the evidence suggest that party effects have been substantially underestimated: the measurement of party politics is weak and the conceptualization of the impact of parties is shallow. Thus progress can be discerned, despite the recurrence of these problems.
Towards a ‘Third Level’ in Europe? The German Länder in the European Union
Authors: Jeffery Charlie
Published: December 2006

Since 1990 the German Länder have enjoyed unprecedented success in their longstanding quest to influence the European policy process. They were able to leave a clear stamp on the text of the Maastricht Treaty, to achieve domestic constitutional changes which secured for them a continuing and, in some fields, decisive role in the German European policy process, and to make significant progress in attracting regional ‘allies' from other federal or decentralized member states. The effects have been to reduce the freedom of manoeuvre of the German central government in Europe, to deepen the complexity of European policy-making in both Germany and ‘Brussels’, and, arguably, to give fuller meaning to a ‘third’, sub-national level in EU affairs.
No Exit: ‘Nation-Stateness' and Democratization in the German Democratic Republic
Authors: Thompson Mark R.
Published: December 2006

A variable affecting the chances of regime exit – weak ‘nation-stateness' – has often been overlooked. If a country enjoys no single, exclusive national identity, then democratic transition poses a threat to the survival of the state and the interests connected with it. The Honecker regime was unwilling to exit from communism–unlike Polish and Hungarian parties which negotiated democratic transition with the opposition – because it (rightly) feared for the survival of the German Democratic Republic. The GDR's ‘national problem’ also explains why the opposition did not demand power after the fall of the hardliners. Opposed to dictatorship, they nonetheless believed in many of the ideals upon which the state had been founded. These dissidents found they had more in common with reform communists trying to preserve the GDR than the majority of the population favouring unification.
Rawls on Respect and Self-respect: An Israeli Perspective
Authors: Brunner José , Peled Yoav
Published: December 2006

This essay provides a detailed and critical analysis of Rawls' notions of respect and self-respect from the vantage point of the Israeli-Palestinian conflict. It demonstrates that Rawls' empirical and normative claims concerning respect and self-respect are pivotal to his theorizing on psychology and politics. It considers the extent to which processes and developments in Israeli-Palestinian relations can be said to be compatible with – or even corroborate – some of Rawls' empirical hypotheses concerning the interdependence of respect and self-respect. It establishes where the values entailed in Rawls' perspective on respect and self-respect would place a Rawlsian vis-à-vis some aspects of the Israeli-Palestinian question.
Enfranchising the Earth, and its Alternatives
Authors: Goodin Robert E.
Published: December 2006

Greens have always favoured grass-roots participatory democracy, but it has never been clear in terms of their fundamental environmental ethic why they should. An argument for doing so is developed in familiar liberal terms of equal protection of interests. First it is shown that nature has ‘interests' as deserving of protection as anyone else's. Then it is shown that notions of ‘encapsulated interests’, discredited in other connections, are the appropriate way of conceptualizing those interests politically. Finally, it is argued that discursive participatory democratic practices are most likely to evoke such encapsulated natural interests and secure representation for them in political deliberations.
In Defence of Arms Control
Authors: Croft Stuart
Published: December 2006

Arms control has been strongly attacked from two quarters since the end of the Cold War. Some argue that it is flawed in essence, elaborating a conservative critique developed over 25 years. Others argue that arms control was a Cold War institution, and therefore its time has passed. Both are wrong, fundamentally because arms control is defined too narrowly. A typology of arms control is proposed with five distinct forms: the traditional interpretation, focusing on strategic stability; arms control at the end of major conflicts; arms control to develop the laws of war; controls on proliferation; and arms control by international organization. Arms control has a long history, and when seen in this broader perspective, it is clear that it has a future.
Democracy and Dynamite: The Peoples' Right to Self-Determination
Authors: Freeman Michael
Published: December 2006

The right to self-determination is a potent and paradoxical political concept. It is associated with democracy, xenophobia and anarchy. Its explosive potential was more or less held in check during the Cold War by an international consensus that restricted it to the context of decolonization. The unravelling of the Soviet Union and the break-up of Yugoslavia have demonstrated the inadequacy of the available theory and practice. Various recent approaches to self-determination are reviewed. These may be roughly classified as realist, liberal and communitarian. Although no approach is wholly satisfactory, the key issues can now be more clearly stated, an emerging consensus identified, and the agenda for further theoretical work proposed.
Reviews
Authors: Pumfrey P.D. , Popp Helen M.
Published: December 2006

Moseley, D. and Moseley, C. (1977) Language and Reading among Under achievers: a practical review of research.

Pumfrey, P. D. (1977) Measuring Reading Abilities: Concepts, Sources and Applications.
Reviews
Authors: Hydes Jack , Humphries E. V. , Shipstone Nadine
Published: December 2006

Peet, M. C. and Robinson, D. (1978) The Critical Examination.

Morris, Helen (1979). Where's That Poem?

Swatridge, C. and S. (1979) The Biblio File: an Index of prose Passages.

Raggett, Michael, Tutt, Christine, qnd Raggett, Patricia (Editors), (1979) Assessment and Testing of Reading: Problems and Practices.
Tumor Suppression by p53 Is Mediated in Part by the Antiangiogenic Activity of Endostatin and Tumstatin
Authors: Folkman Judah
Published: December 2006

Recent research shows that p53 suppresses tumor angiogenesis by transcriptionally activating the α(II) collagen prolyl-4-hydroxylase gene. This results in the extracellular release of the potent endogenous angiogenesis inhibitors endostatin and tumstatin from collagens 18 and 4, respectively. The involvement of these inhibitors elucidates a molecular mechanism. By simultaneously repressing a multitude of proangiogenic pathways and by inducing antiangiogenic pathways, a tumor suppressor protein can prevent an incipient tumor from switching to the angiogenic phenotype. Thus, p53 guards the genome from cancer by controlling the three fundamental processes that are critical for growth of a primary tumor and its metastases—tumor cell proliferation, apoptosis, and tumor angiogenesis.
Advances in Understanding Brassinosteroid Signaling
Authors: Karlova Rumyana , de Vries Sacco C.
Published: December 2006

Brassinosteroids (BRs) function as signaling molecules in plants and are involved in processes such as stem elongation, vascular differentiation, male fertility, timing of senescence and flowering, leaf development, and resistance to biotic and abiotic stresses. Unlike animal steroids that are perceived by nuclear receptors, BRs are perceived by transmembrane receptor kinase complexes that initiate a phosphorylation-mediated signaling cascade to transduce the steroid signal. BR binding to the extracellular domain of the receptor BRI1 induces kinase activation and hetero-oligomerization with the second transmembrane kinase BAK1. Activated BRI1 then dissociates from the BRI1-interacting protein BKI1, a newly identified negative regulator of BR signaling. In the presence of BR, the kinase BIN2, which is the
Arabidopsis
homolog of GSK3 (glycogen synthase kinase 3), is inhibited by an unknown mechanism, leading to dephosphorylation of BES1 and BZR1 inside the nucleus. This allows BES1 and BZR1 to homodimerize or combine with other transcription factors to bind to promoters of BR-responsive genes. These studies of BR signaling in plants have revealed signaling pathways that are distinctly different from related ones operating in animal cells.
Muscle Building
Authors: Kelner Katrina L.
Published: December 2006

When neurons innervate muscles, they secrete a protein, agrin, which causes neurotransmitter receptors to cluster on the muscle and form a synapse at the point of nerve contact. A muscle-specific kinase is necessary for synapse development, as is the recently described protein Dok-7. Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission that lead to muscle weakness. Beeson
et al
. now find that a group of patients with CMS have mutations in Dok-7. These mutations result in the formation of small, abnormal synapses at the neuromuscular junction and help account for the symptoms of the disease.

D. Beeson, O. Higuchi, J. Palace, J. Cossins, H. Spearman, S. Maxwell, J. Newsom-Davis, G. Burke, P. Fawcett, M. Motomura, J. S. Müller, H. Lochmüller, C. Slater, A. Vincent, Y. Yamanashi, Dok-7 mutations underlie a neuromuscular junction synaptopathy.
Science
313
, 1975-1978 (2006).
[Abstract]
[Full Text]
A Unified Model of the Presynaptic and Postsynaptic Changes During LTP at CA1 Synapses
Authors: Lisman John , Raghavachari Sridhar
Published: December 2006

Long-term potentiation (LTP) has been studied extensively at CA1 synapses of the hippocampus, and there is evidence implicating both postsynaptic and presynaptic changes in this process. These changes include (i) addition of AMPA channels to the extrasynaptic membrane and diffusional equilibrium of extrasynaptic receptors with synaptic receptors, (ii) sudden addition of AMPA channels to the synapse in large groups, (iii) a change in the mode of glutamate release (presumably from kiss-and-run to full fusion), and (iv) a delayed increase in the number of vesicles released. However, it remains unclear whether (or how) these changes work together. We have incorporated all of these processes into a structural model of the synapse. We propose that the synapse is composed of transsynaptic modules that function quasi-independently in AMPA-mediated transmission. Under basal conditions, synapses are partially silent; some modules are AMPA-silent (but contribute to NMDA-mediated transmission), whereas others are functional (and contribute to both AMPA- and NMDA-mediated transmission). During LTP, there is both a rapid change in the mode of vesicle fusion and a rapid insertion of a postsynaptic complex (a hyperslot) containing many proteins (slots) capable of binding AMPA channels. The combined effect of these pre- and postsynaptic changes is to convert AMPA-silent modules into functional modules. Slot filling is transiently enhanced by a rapid increase in extrasynaptic GluR1, a form of the AMPA-type receptor. A slower transsynaptic growth process adds AMPA-silent modules to the synapse, enhancing the number of vesicles released and thereby enhancing the NMDA response. This model accounts for a broad range of data, including the LTP-induced changes in quantal parameters. The model also provides a coherent explanation for the diverse effects of GluR1 knockout on basal transmission, LTP, and distance-dependent scaling.
Molecular Signaling Mechanisms Underlying Epileptogenesis
Authors: McNamara James O. , Huang Yang Zhong , Leonard A. Soren
Published: December 2006

Epilepsy, a disorder of recurrent seizures, is a common and frequently devastating neurological condition. Available therapy is only symptomatic and often ineffective. Understanding epileptogenesis, the process by which a normal brain becomes epileptic, may help identify molecular targets for drugs that could prevent epilepsy. A number of acquired and genetic causes of this disorder have been identified, and various in vivo and in vitro models of epileptogenesis have been established. Here, we review current insights into the molecular signaling mechanisms underlying epileptogenesis, focusing on limbic epileptogenesis. Study of different models reveals that activation of various receptors on the surface of neurons can promote epileptogenesis; these receptors include ionotropic and metabotropic glutamate receptors as well as the TrkB neurotrophin receptor. These receptors are all found in the membrane of a discrete signaling domain within a particular type of cortical neuron—the dendritic spine of principal neurons. Activation of any of these receptors results in an increase Ca2+concentration within the spine. Various Ca2+-regulated enzymes found in spines have been implicated in epileptogenesis; these include the nonreceptor protein tyrosine kinases Src and Fyn and a serine-threonine kinase [Ca2+-calmodulin–dependent protein kinase II (CaMKII)] and phosphatase (calcineurin). Cross-talk between astrocytes and neurons promotes increased dendritic Ca2+and synchronous firing of neurons, a hallmark of epileptiform activity. The hypothesis is proposed that limbic epilepsy is a maladaptive consequence of homeostatic responses to increases of Ca2+concentration within dendritic spines induced by abnormal neuronal activity.
Anxious Mice and Men
Authors: Stern Peter
Published: December 2006

The genes that contribute to depression and anxiety disorders are still unknown, but the recently discovered single-nucleotide polymorphism (Val66Met) in the brain-derived neurotrophic factor (BDNF) gene may be related to mood and anxiety disorders common in human populations. Chen
et al
. report that, in transgenic mice expressing the variant BDNFMet version, there are alterations in brain anatomy and memory as has been described in humans. This allelic variant also reproduces the phenotypic hallmarks of anxiety in humans, but these mutant mice did not respond to a common, widely used antidepressant.

Z.-Y. Chen, D. Jing, K. G. Bath, A. Ieraci, T. Khan, C.-J. Siao, D. G. Herrera, M. Toth, C. Yang, B. S. McEwen, B. L. Hempstead, F. S. Lee, Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior.
Science
314
, 140-143 (2006).
[Abstract]
[Full Text]
Dual Cleavage Events Activate TGF-β
Authors: Gough Nancy R.
Published: December 2006

Growth factors of the transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) families are synthesized and maintained in inactive complexes, which are then cleaved into action by various proteinases. TGF-β interacts with the cleaved prodomain, called latency-associated peptide (LAP), which is disulfide linked to latent TGF-β-binding protein (LTBP), which then interacts with the extracellular matrix. The TGF-β-LAP-LTBP complex is called a large latent complex (LLC). Ge and Greenspan show that LTBP of the TGF-β1 LLC, but not LAP, is cleaved by the proteinase BMP1, which is a member of a family of proteinases, not BMP ligands, that are also known to process extracellular matrix proteins, chordin (a BMP antagonist), and the inhibitory prodomains of GDFs (growth and differentiation factors). By comparing mouse embryo fibroblasts (MEFs) from wild-type and
bmp1
knockout mice, the authors showed that the
bmp1
cells had increased deposition of LTBP (detected by immunofluorescence) but decreased processing of TGF-β to the active form (based on the TGF-β activity in cultured medium). Although in vitro LAP was not a substrate for BMP1, in vivo LAP cleavage was impaired in the
bmp1
knockouts, suggesting that BMP1 cleavage of LTBP precedes LAP cleavage, which is required to release active TGF-β. Using pharmacological inhibitors and RNAi experiments, the authors demonstrated that matrix metalloproteinase 2 (MMP2) was required for LAP processing. In embryonic mice, the
bmp1
knockouts displayed increased staining for fibrillar LTBP but decreased phosphorylation of Smad2 and 3, which are downstream of TGF-β, which is consistent with BMP1 contributing to activation of TGF-β. Thus, TGF-β activation appears to involve sequential cleavage events: First BMP1 cleavage of LTBP releases the LLC from the extracellular matrix, and then MMP2 cleavage of LAP releases TGF-β from the LLC.

G, Ge, D. S. Greenspan, BMP1 controls TGFβ1 activation via cleavage of latent TGFβ-binding protein.
J. Cell Biol.
175
, 111-120 (2006).
[Abstract]
[Full Text]
Protein Degradation and Growth Regulation
Authors: Ray L. Bryan
Published: December 2006

Controlled protein degradation is a fundamentally important cellular regulatory mechanism. Dorrello
et al
. searched for binding partners of the ubiquitin ligase SCF
βTRCP
and detected programmed cell death protein 4 (PDCD4). The growth factor-stimulated protein kinase, S6K1, phosphorylated PDCD4 and promoted its ubiquitination by SCF
βTRCP
and consequent degradation. The degradation of PDCD4 relieved its inhibitory effect on a translation initiation factor and enhanced protein synthesis. Thus, regulated destruction of PDCD4 appears to regulate cell proliferation and cell size.

N. V. Dorrello, A. Peschiaroli, D. Guardavaccaro, N. H. Colburn, N. E. Sherman, M. Pagano, S6K1- and βTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth.
Science
314
, 467-471 (2006).
[Abstract]
[Full Text]

N. Sonenberg, A. Pause, Protein synthesis and oncogenesis meet again.
Science
314
, 428-429 (2006).
[Summary]
[Full Text]
Fungal Gib2, an Atypical Gβ Subunit
Authors: Gough Nancy R.
Published: December 2006

The genome of
Cryptococcus neoformans
, which causes meningoencephalitis, has been sequenced, revealing three Gα subunits (Gpa1, Gpa2, and Gpa3) and a single Gβ subunit (Gbp1). Palmer
et al
. used a yeast two-hybrid screen to identify Gib2 (Gpa1-interacting protein-β) as a partner for Gpa1, and this interaction was confirmed by protein pull-down assay. Although sequence comparisons indicated that Gib2 was more similar to proteins of the RACK1 (receptor for activated protein kinase C1) family than to Gβ proteins, modeling of the protein structure revealed a seven-bladed β propeller structure like that of Gβ proteins. Yeast two-hybrid assays and pull-down assays confirmed that Gib2 interacted with
C. neoformans
Gγ proteins (Gpg1 and Gpg2). Overexpression or suppression of
Gib2
expression did not alter responsiveness to mating pheromone. However, the
Gib2
gene was essential, and analysis of
gpa1
-deficient strains overexpressing
Gib2
showed that Gib2 restored melanin production and capsule formation, two virulence factors. Gib2 also restored cyclic adenosine monophosphate (cAMP) production in
gpa1
-deficient strains. Thus, Gib2 appears to serve as an atypical Gβ in a cAMP pathway that contributes to virulence in
C. neoformans
.

D. A. Palmer, J. K. Thompson, L. Li, A. Prat, P. Wang, Gib2, a novel Gβ-like/RACK1 homolog, functions as a Gβ subunit in cAMP signaling and is essential in
Cryptococcus neoformans
.
J. Biol. Chem.
281
, 32596-32605 (2006).
[Abstract]
[Full Text]
Diacylglycerol Kinase in T Cell Anergy
Authors: Gough Nancy R.
Published: December 2006

Defective Ras signaling contributes to T cell anergy, which occurs when T cells are presented with antigens in the absence of costimulatory signals and leads to T cells’ unresponsiveness to subsequent stimulation. T cell anergy is a key mechanism by which inappropriate immune responses are prevented. Previous work had shown that diacylglycerol (DAG)-mediated signaling was defective in anergic T cells and that abundance of the transcript encoding diacylglycerol kinase α (DGK-α) was decreased in activated T cells and increased in anergic T cells. Two groups (Zha
et al
. and Olenchock
et al
.) extend these observations and show that DGK-α, an enzyme that converts DAG to phosphatic acid, contributes to T cell anergy. Zha
et al
. showed that introduction of constitutively active Ras, one of the components downstream of DAG, restored T cell responsiveness [interleukin-2 (IL-2) production and mitogen-activated protein kinase (MAPK) phosphorylation] to cells previously rendered anergic. Expression of the
Dgka
gene was increased in anergic T cells in the system used by Zha
et al
., and overexpression of DGK-α in resting T cells diminished recruitment of the Ras guanine nucleotide exchange factor RasGRP1 to the plasma membrane, decreased IL-2 production, and decreased MAPK activation in response to stimulation. Olenchock
et al
. used cells from
Dgka
−/−
mice to show that T cells from these animals failed to undergo anergy in response to T cell receptor activation in the absence of costimulatory signals. Together, these two reports demonstrate a key role in DAG metabolism in promoting T cell anergy (see Mueller). What remains to be determined is how DGK activity is regulated to prevent excessive activity in cells that receive an activating signal and to promote activity in cells that receive a signal that produces anergy.

Y. Zha, R. Marks, A. W. Ho, A. C. Peterson, S. Janardhan, I. Brown, K. Praveen, S. Stang, J. C. Stone, T. F. Gajewski, T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-α.
Nat. Immunol.
7
, 1166-1173 (2006).
[PubMed]

B. A. Olenchock, R. Guo, J. H. Carpenter, M. Jordan, M. K. Topham, G. A. Koretzky, X.-P. Zhong, Disruption of diacylglycerol metabolism impairs the induction of T cell anergy.
Nat. Immunol.
7
, 1174-1181 (2006).
[PubMed]

D. L. Mueller, Linking diacylglycerol kinase to T cell anergy.
Nat. Immunol.
7
, 1132-1134 (2006).
[PubMed]
Ring Around the Spindle Checkpoint
Authors: Hurtley Stella M.
Published: December 2006

The molecular role of the centrosome in the spindle checkpoint has been debated for some time. Müller
et al
. have now identified a function for a subset of core centrosomal proteins, namely their involvement in the spindle checkpoint. γ-tubulin ring proteins are functionally and biochemically integrated into checkpoint control, together with two of the major players in this pathway, BubR1 and Cdc20. However, the function of the γ-tubulin ring components was not linked to centrosome integrity, nor did it require localization to this organelle.

H. Müller, M.-L. Fogeron, V. Lehmann, H. Lehrach, B. M. H. Lange, A centrosome-independent role for γ-TuRC proteins in the spindle assembly checkpoint.
Science
314
, 654-657 (2006).
[Abstract]
[Full Text]
Probed Isoelectric Focusing for Quantifying Phosphorylated Proteins
Authors: Gough Nancy R.
Published: December 2006

O'Neill
et al
. report a new highly sensitive method that they call probed isoelectric focusing (PIF) for quantifying phosphorylated proteins based on capillary isoelectric focusing. Cell lysates from as few as 25 cells were subjected to isoelectric focusing in capillary tubes along with standards. The proteins were then covalently attached to photoactivatable groups on the capillary walls and probed with specific antibodies that detected the complete spectrum of phosphorylated and unphosphorylated, or only phosphorylated forms of the proteins of interest. The bound antibodies were then detected with horseradish peroxidase and chemiluminescence. Experiments were performed to detect the relative amounts of phosphorylated forms of extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2), Akt, and Bcl-2. In the experiments monitoring ERK phosphorylation, PIF allowed single and multiply phosphorylated forms of ERK1 and ERK2 to be detected and quantified as a percentage of the total abundance of each ERK isoform. Western blotting using the same panel of antibodies did not resolve the different phosphorylated individual species. PIF is very sensitive, detecting as little as 2 pg/μl of protein or endogenous ERK from as few as 25 cells. This method may be useful in diagnostic assays or experiments where sample size may be limited.

R. A. O'Neill, A. Bhamidipati, X. Bi, D. Deb-Basu, L. Cahill, J. Ferrante, E. Gentalen, M. Glazer, J. Gossett, K. Hacker, C. Kirby, J. Knittle, R. Loder, C. Mastroieni, M. MacLaren, T. Mills, U. Nguyen, N. Parker, A. Rice, D. Roach, D. Suich, D. Voehringer, K. Voss, J. Yang, T. Yang, P. B. Vander Horn, Isoelectric focusing technology quantifies protein signaling in 25 cells.
Proc. Natl. Acad. Sci. U.S.A.
103
, 16153-16158 (2006).
[Abstract]
[Full Text]
Focus Issue: Spiky Signalers from the Sea
Authors: Ray L. Bryan
Published: December 2006

This week’s issue of
Science
’s STKE complements the special issue of
Science
featuring the Sea Urchin Genome. With new insights gleaned from the 814-Mb genome of the California purple sea urchin
Strongylocentrotus purpuratus
and its estimated 23,000 genes, this organism holds many secrets to help us understand cell signaling and the evolution of regulatory systems in biology. Two STKE Perspectives discuss signal transduction during early development in the sea urchin.
Sympathetic to Osteoporosis
Authors: Adler Elizabeth M.
Published: December 2006

Major depression is associated with decreased bone mineral density (indicative of osteoporosis) and an increased risk for osteoporotic fractures. The precise relationship between depression and osteoporosis, however, has been unclear, leading Yirmiya
et al
. to investigate the effects on mouse skeleton of chronic mild stress (CMS), a rodent model of depression. Mice subjected to CMS experienced decreased bone mass and a reduced rate of bone formation in parallel with behavioral effects such as decreased preference for sucrose (comparable to human anhedonia) and reduced social exploration. Treatment with the tricyclic antidepressant imipramine attenuated both the behavioral effects of CMS and bone loss. Moreover, mice that failed to respond to imipramine behaviorally also failed to show an attenuation of bone loss. Body weight, locomotor activity, and serum testosterone were unaffected by CMS. Serum corticosterone was higher in mice exposed to CMS; however, adrenalectomized mice failed to show either behavioral responses to CMS or bone loss, making the role of corticosteroids in mediating depression-induced loss of bone mass difficult to evaluate. The content of sympathetically derived norepinephrine in trabecular bone was increased in CMS mice, and treatment with the β-adrenergic receptor propanolol, which failed to affect the behavioral response to CMS, markedly attenuated the CMS-induced decrease in bone mass and inhibition of bone formation. Thus, the authors conclude that depression leads to bone loss through sympathetic release of norepinephrine and that, in individuals at risk for both, antidepressants could be used to combat not only depression but also osteoporosis.

R. Yirmiya, I. Goshen, A. Bajayo, T. Kreisel, S. Feldman, J. Tam, V. Trembovler, V. Csernus, E. Shohami, I. Bab, Depression induces bone loss through stimulation of the sympathetic nervous system.
Proc. Natl. Acad. Sci. U.S.A.
103
, 16876-16881 (2006).
[Abstract]
[Full Text]
Nitrated Fatty Acids as Signaling Molecules
Authors: Ray L. Bryan
Published: December 2006

Some fatty acid derivatives, like prostaglandins and thromboxanes, are well known signaling molecules. A more recently recognized, related class of molecules that could have similar functions includes the nitration products of unsaturated fatty acids (nitroalkenes) formed in nitric oxide (NO)-dependent oxidative reactions. In particular, the nitroalkene derivatives of linoleic acid (LNO
2
) and oleic acid (OA-NO
2
) are found in human plasma and are thought to regulate physiological functions in multiple cell types. Rather than binding to receptors, though, these molecules are proposed to act by mediating reversible nitroalkylation of glutathione or of Cys or His residues of proteins. Cui
et al
. now report experiments indicating that LNO
2
and OA-NO
2
may function as antiinflammatory agents. The authors applied concentrations of LNO
2
and OA-NO
2
similar to those found in human blood to cultured mouse macrophages and observed dose-dependent decreases in lipopolysaccharide (LPS)-induced cytokine secretion by the cells. The transcription factor NF-κB has a central role in inflammatory responses, and treatment of macrophages with LNO
2
or OA-NO
2
decreased activation of the transcription factor in response to LPS. Experiments with biotinylated LNO
2
, OA-NO
2
, LA (linoleic acid), and OA indicated that LNO
2
and OA-NO
2
, but not LA or OA, associated with the p65 subunit of NF-κB and appeared to modify p65 by covalent nitroalkylation. The nitroalkenes also inhibited adhesion of monocytes to endothelial cells in culture. The authors propose that nitroalkenes like LNO
2
and OA-NO
2
may prove to be an important class of signaling molecules influencing inflammatory processes.

T. Cui, F. J. Schopfer, J. Zhang, K. Chen, T. Ichikawa, P. R. S. Baker, C. Batthyany, B. K. Chacko, X. Feng, R. P. Patel, A. Agarwal, B. A. Freeman, Y. E. Chen, Nitrated fatty acids: Endogenous anti-inflammatory signaling mediators.
J. Biol. Chem.
281
, 35686-35698 (2006).
[Abstract]
[Full Text]
Channel Activated by Histidine Phosphorylation
Authors: Gough Nancy R.
Published: December 2006

Previous work had indicated that the calcium-activated K
+
channel KCa3.1, which is important for T and B cell activation, was indirectly activated by phosphatidylinositol 3-phosphate [PI(3)P]. Srivastava
et al
. now show that KCa3.1 interacts with and is stimulated by nucleoside diphosphate kinase B (NDPK-B), which is a histidine kinase. A 14-amino-acid sequence in the C-terminal region of KCa3.1 was known to mediate the regulation by PI(3)P, and using this region in a yeast two-hybrid assay, the authors identified NDPK-B as an interacting partner. KCa3.1 and NDPK-B were also coimmunoprecipitated from transfected cells, and the endogenous proteins were coimmunoprecipitated from T cells. Overexpression of active NDPK-B, but not a kinase inactive mutant or the related protein NDPK-A, stimulated KCa3.1 channel activity in whole cells and inside-out patches. Furthermore, depletion of PI(3)P from the cells with wortmannin inhibited the KCa3.1 channel activity, and full activation by NDPK-B required the addition of PI(3)P in these patches from the PI(3)P-depleted cells. KCa3.1 has a histidine at position 358 within the C-terminal 14-amino-acid sequence that is required for PI(3)P regulation. The related channels KCa2.1, KCa2.2, and KCa2.3 have an aspartic acid, and these channels are not regulated by PI(3)P (previous work), nor were they stimulated by NDPK-B. The C-terminal domain of KCa3.1 was phosphorylated in vitro by NDPK-B. Mutation of the His
358
eliminated the stimulation of channel activity by NDPK-B, and these mutant channels were resistant to the inhibitory effects of PI(3)P depletion. Finally, mRNA analysis of activated CD4
+
T cells showed that the transcription of gene encoding NDPK-B, as was already known for gene encoding KCa3.1, was increased. Down-regulation of NDPK-B activity with siRNA reduced KCa3.1 channel activity in stimulated T cells without altering the activity of an unrelated K
+
channel. Because KCa3.1 hyperpolarizes the membrane potential to maintain a driving force for Ca
2+
entry, siRNA-mediated down-regulation of NDPK-B also decreased Ca
2+
influx in stimulated T cells, thus confirming the biological importance of NDPK-B activity in regulation of T cell function.

S. Srivastava, Z. Li, K. Ko, P. Choudhury, M. Albaqumi, A. K. Johnson, Y. Yan, J. M. Backer, D. Unutmaz, W. A. Coetzee, E. Y. Skolnik, Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells.
Mol. Cell
24
, 665-675 (2006).
[Online Journal]
From Fluctuations to Phenotypes: The Physiology of Noise
Authors: Samoilov Michael S. , Price Gavin , Arkin Adam P.
Published: December 2006

There are fundamental physical reasons why biochemical processes might be subject to noise and stochastic fluctuations. Indeed, it has long been understood that random molecular-scale mechanisms, such as those that drive genetic mutation, lie at the heart of population-scale evolutionary dynamics. What we can now appreciate is how stochastic fluctuations inherent in biochemical processes contribute to cellular and organismal phenotypes. Advancements in techniques for empirically measuring single cells and in corresponding theoretical methods have enabled the rigorous design and interpretation of experiments that provide incontrovertible proof that there are important endogenous sources of stochasticity that drive biological processes at the scale of individual organisms. Recently, some studies have progressed beyond merely ascertaining the presence of noise in biological systems; they trace its role in cellular physiology as it is passed through and processed by the biomolecular pathways—from the underlying origins of stochastic fluctuations in random biomolecular interactions to their ultimate manifestations in characteristic species phenotypes. These emerging results suggest new biological network design principles that account for a constructive role played by noise in defining the structure, function, and fitness of biological systems. They further show that stochastic mechanisms open novel classes of regulatory, signaling, and organizational choices that can serve as efficient and effective biological solutions to problems that are more complex, less robust, or otherwise suboptimal to deal with in the context of purely deterministic systems. Research in
Drosophila melanogaster
eye color-vision development and
Bacillus subtilis
competence induction has elegantly traced the role of noise in vital physiological processes from fluctuations to phenotypes, and is used here to highlight these developments.
Quieting the Brain at Birth
Authors: Hines Pamela J.
Published: December 2006

Birth entails a multitude of transitions. Studying rats, Tyzio
et al
. have identified yet one more, a link between oxytocin exposure and the switch in how certain brain neurons fire. The neurotransmitter GABA (γ-aminobutyric acid) is usually excitatory in fetal brain neurons but inhibitory once they mature. Exposure to oxytocin during parturition causes a switch from excitation to inhibition in GABA signaling. This quieting of neuronal activity may serve to protect the brain against transient hypoxia during birth.

R. Tyzio, R. Cossart, I. Khalilov, M. Minlebaev, C. A. Hübner, A. Represa, Y. Ben-Ari, R. Khazipov, Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery.
Science
314
, 1788-1792 (2006).
[Abstract]
[Full Text]
Development and Evaluation of Methods To Detect Nucleopolyhedroviruses in Larvae of the Douglas-Fir Tussock Moth,
Orgyia pseudotsugata
(McDunnough)
Authors: Thorne Christine M. , Otvos Imre S. , Conder Nicholas , Levin David B.
Published: December 2006

Various molecular methods are used to detect pathogenic microorganisms and viruses within their hosts, but these methods are rarely validated by direct comparison. Southern hybridization, enzyme-linked immunosorbent assay (ELISA), and a novel DNA extraction/PCR assay were used to detect
Orgyia pseudotsugata
multiple nucleopolyhedrovirus (OpMNPV) in Douglas-fir tussock moth larvae. PCR was more sensitive than Southern hybridization and ELISA at detecting semipurified virus. ELISA, however, was the most accurate method for detecting virus within larvae, given that Southern hybridization and PCR produced false-negative results (31% and 2.5%, respectively). ELISA may be preferable in some applications because virus infections can be quantified (
r
2
= 0.995). These results may be applicable to both applied and academic research that seeks to accurately identify the incidence of viruses and microorganisms that regulate insect populations.
Identification and Cultivation of Anaerobic, Syntrophic Long-Chain Fatty Acid-Degrading Microbes from Mesophilic and Thermophilic Methanogenic Sludges
Authors: Hatamoto Masashi , Imachi Hiroyuki , Ohashi Akiyoshi , Harada Hideki
Published: December 2006

We investigated long-chain fatty acid (LCFA)-degrading anaerobic microbes by enrichment, isolation, and RNA-based stable isotope probing (SIP). Primary enrichment cultures were made with each of four LCFA substrates (palmitate, stearate, oleate, or linoleate, as the sole energy source) at 55°C or 37°C with two sources of anaerobic granular sludge as the inoculum. After several transfers, we obtained seven stable enrichment cultures in which LCFAs were converted to methane. The bacterial populations in these cultures were then subjected to 16S rRNA gene-based cloning, in situ hybridization, and RNA-SIP. In five of seven enrichment cultures, the predominant bacteria were affiliated with the familySyntrophomonadaceae. The other two enrichment cultures contained different bacterial populations in which the majority of members belonged to the phylumFirmicutesand the classDeltaproteobacteria. After several attempts to isolate these dominant bacteria, strain MPA, belonging to the familySyntrophomonadaceae, and strain TOL, affiliated with the phylumFirmicutes, were successfully isolated. Strain MPA converts palmitate to acetate and methane in syntrophic association withMethanospirillum hungatei. Even though strain TOL assimilated [13C]palmitate in the original enrichment culture, strain TOL has not shown the ability to degrade LCFAs after isolation. These results suggest that microbes involved in the degradation of LCFAs under methanogenic conditions might not belong only to the familySyntrophomonadaceae, as most anaerobic LCFA-degrading microbes do, but may also be found in phylogenetically diverse bacterial groups.
Saccharomyces cerevisiae
Multidrug Resistance Transporter Qdr2 Is Implicated in Potassium Uptake, Providing a Physiological Advantage to Quinidine-Stressed Cells
Authors: Vargas Rita C. , García-Salcedo Raúl , Tenreiro Sandra , Teixeira Miguel C. , Fernandes Alexandra R. , Ramos José , Sá-Correia Isabel
Published: December 2006

The
QDR2
gene of
Saccharomyces cerevisiae
encodes a putative plasma membrane drug:H
+
antiporter that confers resistance against quinidine, barban, bleomycin, and cisplatin. This work provides experimental evidence of defective K
+
(Rb
+
) uptake in the absence of
QDR2
. The direct involvement of Qdr2p in K
+
uptake is reinforced by the fact that increased K
+
(Rb
+
) uptake due to
QDR2
expression is independent of the Trk1p/Trk2p system.
QDR2
expression confers a physiological advantage for the yeast cell during the onset of K
+
limited growth, due either to a limiting level of K
+
in the growth medium or to the presence of quinidine. This drug decreases the K
+
uptake rate and K
+
accumulation in the yeast cell, especially in the Δ
qdr2
mutant. Qdr2p also helps to sustain the decrease of intracellular pH in quinidine-stressed cells in growth medium at pH 5.5 by indirectly promoting H
+
extrusion affected by the drug. The results are consistent with the hypothesis that Qdr2p may also couple K
+
movement with substrate export, presumably with quinidine. Other clues to the biological role of
QDR2
in the yeast cell come from two additional lines of experimental evidence. First,
QDR2
transcription is activated under nitrogen (NH
4
+
) limitation or when the auxotrophic strain examined enters stationary phase due to leucine limitation, this regulation being dependent on general amino acid control by Gcn4p. Second, the amino acid pool is higher in Δ
qdr2
cells than in wild-type cells, indicating that
QDR2
expression is, directly or indirectly, involved in amino acid homeostasis.
A Novel Protein, TtpC, Is a Required Component of the TonB2 Complex for Specific Iron Transport in the Pathogens
Vibrio anguillarum
and
Vibrio cholerae
Authors: Stork Michiel , Otto Ben R. , Crosa Jorge H.
Published: December 2006

Active transport across the outer membrane in gram-negative bacteria requires the energy that is generated by the proton motive force in the inner membrane. This energy is transduced to the outer membrane by the TonB protein in complex with the proteins ExbB and ExbD. In the pathogen
Vibrio anguillarum
we have identified two TonB systems, TonB1 and TonB2, the latter is used for ferric-anguibactin transport and is transcribed as part of an operon that consists of
orf2
,
exbB2
,
exbD2
, and
tonB2
. This cluster was identified by a polar transposon insertion in
orf2
that resulted in a strain deficient for ferric-anguibactin transport. Only the entire cluster (
orf2
,
exbB2
,
exbD2
and
tonB2
) could complement for ferric-anguibactin transport, while just the
exbB2
,
exbD2
, and
tonB2
genes were unable to restore transport. This suggests an essential role for this Orf2, designated TtpC, in TonB2-mediated transport in
V. anguillarum.
A similar gene cluster exists in
V. cholerae
, i.e., with the homologues of
ttpC-exbB2-exbD2-tonB2
, and we demonstrate that TtpC from
V. cholerae
also plays a role in the TonB2-mediated transport of enterobactin in this human pathogen. Furthermore, we also show that in
V. anguillarum
the TtpC protein is found as part of a complex that might also contain the TonB2, ExbB2, and ExbD2 proteins. This novel component of the TonB2 system found in
V. anguillarum
and
V. cholerae
is perhaps a general feature in bacteria harboring the
Vibrio
-like TonB2 system.
The
fox
Operon from
Rhodobacter
Strain SW2 Promotes Phototrophic Fe(II) Oxidation in
Rhodobacter capsulatus
SB1003
Authors: Croal Laura R. , Jiao Yongqin , Newman Dianne K.
Published: December 2006

Anoxygenic photosynthesis based on Fe(II) is thought to be one of the most ancient forms of metabolism and is hypothesized to represent a transition step in the evolution of oxygenic photosynthesis. However, little is known about the molecular basis of this process because, until recently (Y. Jiao and D. K. Newman, J. Bacteriol. 189:1765-1773, 2007), most phototrophic Fe(II)-oxidizing bacteria have been genetically intractable. In this study, we circumvented this problem by taking a heterologous-complementation approach to identify a three-gene operon (the
foxEYZ
operon) from
Rhodobacter
sp. strain SW2 that confers enhanced light-dependent Fe(II) oxidation activity when expressed in its genetically tractable relative
Rhodobacter capsulatus
SB1003. The first gene in this operon,
foxE
, encodes a
c
-type cytochrome with no significant similarity to other known proteins. Expression of
foxE
alone confers significant light-dependent Fe(II) oxidation activity on SB1003, but maximal activity is achieved when
foxE
is expressed with the two downstream genes
foxY
and
foxZ
. In SW2, the
foxE
and
foxY
genes are cotranscribed in the presence of Fe(II) and/or hydrogen, with
foxZ
being transcribed only in the presence of Fe(II). Sequence analysis predicts that
foxY
encodes a protein containing the redox cofactor pyrroloquinoline quinone and that
foxZ
encodes a protein with a transport function. Future biochemical studies will permit the localization and function of the Fox proteins in SW2 to be determined.
Biosynthetic Analysis of the Petrobactin Siderophore Pathway from
Bacillusanthracis
Authors: Lee Jung Yeop , Janes Brian K. , Passalacqua Karla D. , Pfleger Brian F. , Bergman Nicholas H. , Liu Haichuan , Håkansson Kristina , Somu Ravindranadh V. , Aldrich Courtney C. , Cendrowski Stephen , Hanna Philip C. , Sherman David H.
Published: December 2006

The
asbABCDEF
gene cluster from
Bacillus anthracis
is
responsible for biosynthesis of petrobactin, a catecholate siderophore
that functions in both iron acquisition and virulence in a murine model
of anthrax. We initiated studies to determine the biosynthetic details
of petrobactin assembly based on mutational analysis of the
asb
operon, identification of accumulated intermediates, and
addition of exogenous siderophores to
asb
mutant strains. As a
starting point, in-frame deletions of each of the genes in the
asb
locus (
asbABCDEF
) were constructed. The
individual mutations resulted in complete abrogation of petrobactin
biosynthesis when strains were grown on iron-depleted medium. However,
in vitro analysis showed that each
asb
mutant grew to a very
limited extent as vegetative cells in iron-depleted medium. In
contrast, none of the
B. anthracis asb
mutant strains were
able to outgrow from spores under the same culture conditions.
Provision of exogenous petrobactin was able to rescue the growth defect
in each
asb
mutant strain. Taken together, these data provide
compelling evidence that AsbA performs the penultimate step in the
biosynthesis of petrobactin, involving condensation of
3,4-dihydroxybenzoyl spermidine with citrate to form
3,4-dihydroxybenzoyl spermidinyl citrate. As a final step, the
data reveal that AsbB catalyzes condensation of a second molecule of
3,4-dihydroxybenzoyl spermidine with 3,4-dihydroxybenzoyl spermidinyl
citrate to form the mature siderophore. This work sets the stage for
detailed biochemical studies with this unique acyl carrier
protein-dependent, nonribosomal peptide synthetase-independent
biosynthetic
system.
Fabrication of Nanodispersed Pt–Sn/SBA-16 Catalysts and Their Catalytic Applications
Authors: Hwang Young Kyu , Kim Deok-Kyu , Mamman Ajit Singh , Park Sang-Eon , Chang Jong-San
Published: December 2006

Monodispersed bimetallic Pt–Sn/SBA-16 catalysts prepared by coimpregnation technique and microwave-drying method showed enhanced catalytic activities for selective dehydrogenation of n-dodecane to its corresponding mono-olefins and preferential oxidation (PROX) of CO in the presence of excess H2.
Alkyl Phosphinites: Versatile Synthetic Intermediates for Dehydration Condensation Reactions
Authors: Mukaiyama Teruaki , Yamabe Hokuto
Published: December 2006

Recent advances in the oxidation–reduction condensation reaction of alkyl phosphinites are described. The carbon–sulfur, carbon–carbon, or carbon–nitrogen bond forming reactions and cyanation, isocyanation reactions are established. These reactions proceed through inversion of configuration even when tertiary alkyl phosphinites are employed, providing thus, a novel route to chiral hydrosulfides, amines, nitriles, and isocyanides from easily available chiral alcohols.
Highly Diastereoselective Conjugate Addition of Aryllithium to Chiral β-Nitrostyrene Derivative: An Application to the Asymmetric Synthesis of 4-Aryl-1,2,3,4-tetrahydroisoquinoline
Authors: Asami Masatoshi , Taketoshi Ayako , Miyoshi Keita , Hoshino Hayato , Sakakibara Kazuhisa
Published: December 2006

Highly diastereoselective conjugate addition of aryllithium to β-nitrostyrene derivative, having chiral acetal moiety derived from (S,S)-1,2-bis(1-hydroxypropyl)benzene, was achieved. The adduct was transformed to 4-aryl-1,2,3,4-tetrahydroisoquinoline in high enantiomeric excess (ee).
W(CO)5(L)-catalyzed Cyclization of ω-Acetylenic Silyl Enol Ethers for the Preparation of Nitrogen-containing Cyclic Compounds
Authors: Grandmarre Antoine , Kusama Hiroyuki , Iwasawa Nobuharu
Published: December 2006

Electrophilic alkyne activation of nitrogen-containing 7-siloxy-6-en-1-ynes by W(CO)5(L) allows the preparation of synthetically useful heterocycles. Two types of cyclized products, 5-exo and 6-endo, could be obtained selectively under the appropriate conditions.
Ultracentrifuge-mediated Diels–Alder Reaction in a Two-phase System of Water and Chloroform
Authors: Hayashi Yujiro , Takeda Mitsuhiro , Shoji Mitsuru , Morita Masataka
Published: December 2006

Dramatic acceleration of the Diels–Alder reaction of acrylate ester or methacrolein with cyclopentadiene has been observed under ultracentrifugation conditions in the presence of water, when water–CHCl3 two-phase system was employed. The Diels–Alder reaction proceeds in the lower organic phase under ultracentrifugation-induced high pressure with the upper water phase acting like a weight.