bluuebunny/crossref_metadata_2025 huggingface dataset:
Commercializing Conservation in South Africa
Authors: King Brian
Published: October 2008

The field of development studies has produced a number of institutional ethnographies in recent years that evaluate the internal workings of development agencies such as the World Bank or grassroots social organizations. Although within the social sciences research on conservation often emphasizes the power of international conservation institutions, there have been few comparable studies assessing the internal workings of these organizations. In addition, less is known about the specific activities of national and provincial conservation agencies operating in the Global South. Ethnographies of these institutions are also needed in order to examine how conservation is variously understood and executed by organizations within different contexts. This paper presents an institutional ethnography of the Mpumalanga Parks Board, which is the chief conservation agency operating in Mpumalanga Province, South Africa. Following the 1994 democratic elections, the Mpumalanga Parks Board pursued a neoliberal commercialized conservation mandate that reflected the position of natural resource management in relation to other national priorities. This paper traces out the construction of the commercialization discourse in order to understand the internal and external factors that produced it while assessing its implications for nature preservation. Although the commercialization drive emulated a general trend towards neoliberal decentralization in the Global South, I argue that its particular manifestations were deeply embedded in South Africa's particular spatial economy and history of racial segregation. In tracing out the commercialization discourse from within the conservation agency itself, this paper assists in an understanding of how neoliberalism shapes natural resource management and can become hegemonic at the expense of other possibilities.
Belonging as a Resource: The Case of Ralphs Bay, Tasmania, and the Local Politics of Place
Authors: Stratford Elaine
Published: October 2008

This paper seeks to contribute to the theorization of belonging as a resource on which people draw in the local politics of place—especially in contestations over ecological space and decisions about land use that resonate at many scales and across many domains. The task is advanced with reference to a controversial development proposal to build a marina and residential subdivision on estuarine mudflats near a seaside dormitory suburb in the capital city of Hobart on the island state of Tasmania, Australia. Particular attention is paid to story lines generated in three discourse coalitions which have formed around the controversy over the proposal: a multimillion dollar mainland company known as the Walker Corporation, the Tasmanian state government, and a community action group known as Save Ralphs Bay Inc. Techniques of narrative and discourse analysis are used to read these story lines for evidence of belonging. In this analysis of ‘text, talk, and practice’, opportunities arise to consider the wider salience of the case to geographers, among them connection and attachment to place, and counterpoints of belonging such as social and ecological dispossession and displacement.
Fostering Environment Efficiency through Transnational Linkages? Trajectories of CO2 and SO2, 1980–2000
Authors: Perkins Richard , Neumayer Eric
Published: October 2008

Recent optimism about sustainability has centred on the opportunities for improvements in environment efficiency through the international diffusion of environmentally beneficial innovations. This paper investigates two claims about the conditions under which countries are most likely to realise these gains. First, ‘dirtier’ economies should improve their environment efficiency faster as they adopt environmentally sound technologies and policies similar to those in ‘cleaner’ countries, resulting in catch-up and convergence over time. Second, transnational linkages accelerate the international spread of environmentally beneficial innovations and, therefore, improvements in environment efficiency. To test these claims, we use econometric techniques to examine the dynamics and determinants of two pollutants—CO2 and SO2—using a panel comprising up to 114 countries over the period 1980–2000. Our empirical findings broadly support both claims. Applying tests of unconditional convergence, we find robust evidence for convergence in levels of CO2 and SO2 efficiency, indicating catch-up by less pollution-efficient economies over time. Similarly, confirming claims about transnational linkages, we find that imports from more pollution-efficient countries and telecommunications connectivity are associated with faster improvements in domestic CO2 and SO2 efficiency. Results also suggest that inward foreign direct investment is positively associated with CO2 efficiency. Yet we find that exports to countries with high levels of pollution efficiency have no discernable effect on domestic pollution efficiency.
Biomechanical ordering of dense cell populations
Authors: Volfson Dmitri , Cookson Scott , Hasty Jeff , Tsimring Lev S.
Published: October 2008

The structure of bacterial populations is governed by the interplay of many physical and biological factors, ranging from properties of surrounding aqueous media and substrates to cell–cell communication and gene expression in individual cells. The biomechanical interactions arising from the growth and division of individual cells in confined environments are ubiquitous, yet little work has focused on this fundamental aspect of colony formation. We analyze the spatial organization ofEscherichia coligrowing in a microfluidic chemostat. We find that growth and expansion of a dense colony of cells leads to a dynamical transition from an isotropic disordered phase to a nematic phase characterized by orientational alignment of rod-like cells. We develop a continuum model of collective cell dynamics based on equations for local cell density, velocity, and the tensor order parameter. We use this model and discrete element simulations to elucidate the mechanism of cell ordering and quantify the relationship between the dynamics of cell proliferation and the spatial structure of the population.
Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses
Authors: Kerr Angharad M. , Reisinger Ellen , Jonas Peter
Published: October 2008

Previous studies revealed that synaptotagmin 1 is the major Ca
2+
sensor for fast synchronous transmitter release at excitatory synapses. However, the molecular identity of the Ca
2+
sensor at hippocampal inhibitory synapses has not been determined. To address the functional role of synaptotagmin 1 at identified inhibitory terminals, we made paired recordings from synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus in organotypic slice cultures from wild-type and synaptotagmin 1-deficient mice. As expected, genetic elimination of synaptotagmin 1 abolished synchronous transmitter release at excitatory GC–BC synapses. However, synchronous release at inhibitory BC–GC synapses was maintained. Quantitative analysis revealed that elimination of synaptotagmin 1 reduced release probability and depression but maintained the synchrony of transmitter release at BC–GC synapses. Elimination of synaptotagmin 1 also increased the frequency of both miniature excitatory postsynaptic currents (measured in BCs) and miniature inhibitory postsynaptic currents (recorded in GCs), consistent with a clamping function of synaptotagmin 1 at both excitatory and inhibitory terminals. Single-cell reverse-transcription quantitative PCR analysis revealed that single BCs coexpressed multiple synaptotagmin isoforms, including synaptotagmin 1–5, 7, and 11–13. Our results indicate that, in contrast to excitatory synapses, synaptotagmin 1 is not absolutely required for synchronous release at inhibitory BC–GC synapses. Thus, alternative fast Ca
2+
sensors contribute to synchronous release of the inhibitory transmitter GABA in cortical circuits.
The splicing-factor oncoprotein SF2/ASF activates mTORC1
Authors: Karni Rotem , Hippo Yoshitaka , Lowe Scott W. , Krainer Adrian R.
Published: October 2008

The splicing factor SF2/ASF is an oncoprotein that is up-regulated in many cancers and can transform immortal rodent fibroblasts when slightly overexpressed. The mTOR signaling pathway is activated in many cancers, and pharmacological blockers of this pathway are in clinical trials as anticancer drugs. We examined the activity of the mTOR pathway in cells transformed by SF2/ASF and found that this splicing factor activates the mTORC1 branch of the pathway, as measured by S6K and eIF4EBP1 phosphorylation. This activation is specific to mTORC1 because no activation of Akt, an mTORC2 substrate, was detected. mTORC1 activation by SF2/ASF bypasses upstream PI3K/Akt signaling and is essential for SF2/ASF-mediated transformation, as inhibition of mTOR by rapamycin blocked transformation by SF2/ASF
in vitro
and
in vivo
. Moreover, shRNA-mediated knockdown of mTOR, or of the specific mTORC1 and mTORC2 components Raptor and Rictor, abolished the tumorigenic potential of cells overexpressing SF2/ASF. These results suggest that clinical tumors with SF2/ASF up-regulation could be especially sensitive to mTOR inhibitors.
From particles to spins: Eulerian formulation of supercooled liquids and glasses
Authors: Chamon Claudio , Cugliandolo Leticia F. , Fabricius Gabriel , Iguain José Luis , Weeks Eric R.
Published: October 2008

The dynamics of supercooled liquid and glassy systems are usually studied within the Lagrangian representation, in which the positions and velocities of distinguishable interacting particles are followed. Within this representation, however, it is difficult to define measures of spatial heterogeneities in the dynamics, as particles move in and out of any one given region within long enough times. It is also nontransparent how to make connections between the structural glass and the spin glass problems within the Lagrangian formulation. We propose an Eulerian formulation of supercooled liquids and glasses that allows for a simple connection between particle and spin systems, and that permits the study of dynamical heterogeneities within a fixed frame of reference similar to the one used for spin glasses. We apply this framework to the study of the dynamics of colloidal particle suspensions for packing fractions corresponding to the supercooled and glassy regimes, which are probed via confocal microscopy.
Loss of
Rb1
in the gastrointestinal tract of

Apc
1638N

mice promotes tumors of the cecum and proximal colon
Authors: Kucherlapati Melanie H. , Yang Kan , Fan Kunhua , Kuraguchi Mari , Sonkin Dmitriy , Rosulek Andrew , Lipkin Martin , Bronson Roderick T. , Aronow Bruce J. , Kucherlapati Raju
Published: October 2008

To examine the role of
Rb1
in gastrointestinal (GI) tumors, we generated mice with an

Apc
1638N

allele,

Rb
tm2brn

floxed alleles, and a villin-cre transgene (RBVCA). These animals had exon 19 deleted from
Rb1
throughout the GI tract. We have shown previously that
Rb1
deficiency is insufficient for GI tumor initiation, with inactivation of an
Apc
allele capable of overcoming the insufficiency. In this study we demonstrate that RBVCA mice have reduced median survival because of an increase in tumor incidence and multiplicity in the cecum and the proximal colon. Large intestinal tumors are predominantly adenomas, whereas the tumors of the small intestine are a mixture of adenomas and adenocarcinomas. We find truncation mutations to the second
Apc
allele in tumors of both the large and small intestine. Expression profiles of duodenal and cecal tumors relative to each other show unique gene subsets up and down regulated. Substantial expression patterns compare to human colorectal cancer, including recapitulation of embryonic genes. Our results indicate that
Rb1
has significant influence over tumor location in the GI tract, and that both cecal and duodenal tumors initiate through inactivation of
Apc
. Expression profile analysis indicates the two tumor types differentially regulate distinct sets of genes that are over-expressed in a majority of human colorectal carcinomas.
Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior
Authors: Bergami Matteo , Rimondini Roberto , Santi Spartaco , Blum Robert , Götz Magdalena , Canossa Marco
Published: October 2008

New neurons in the adult dentate gyrus are widely held to incorporate into hippocampal circuitry via a stereotypical sequence of morphological and physiological transitions, yet the molecular control over this process remains unclear. We studied the role of brain-derived neurotrophic factor (BDNF)/TrkB signaling in adult neurogenesis by deleting the full-length TrkB via Cre expression within adult progenitors in TrkB
lox/lox
mice. By 4 weeks after deletion, the growth of dendrites and spines is reduced in adult-born neurons demonstrating that TrkB is required to create the basic organization of synaptic connections. Later, when new neurons normally display facilitated synaptic plasticity and become preferentially recruited into functional networks, lack of TrkB results in impaired neurogenesis-dependent long-term potentiation and cell survival becomes compromised. Because of the specific lack of TrkB signaling in recently generated neurons a remarkably increased anxiety-like behavior was observed in mice carrying the mutation, emphasizing the contribution of adult neurogenesis in regulating mood-related behavior.
Structure elucidation and biosynthesis of fuscachelins, peptide siderophores from the moderate thermophile
Thermobifida fusca
Authors: Dimise Eric J. , Widboom Paul F. , Bruner Steven D.
Published: October 2008

Bacteria belonging to the order Actinomycetales have proven to be an important source of biologically active and often therapeutically useful natural products. The characterization of orphan biosynthetic gene clusters is an emerging and valuable approach to the discovery of novel small molecules. Analysis of the recently sequenced genome of the thermophilic actinomycete
Thermobifida fusca
revealed an orphan nonribosomal peptide biosynthetic gene cluster coding for an unknown siderophore natural product.
T. fusca
is a model organism for the study of thermostable cellulases and is a major degrader of plant cell walls. Here, we report the isolation and structure elucidation of the fuscachelins, siderophore natural products produced by
T. fusca
. In addition, we report the purification and biochemical characterization of the termination module of the nonribosomal peptide synthetase. Biochemical analysis of adenylation domain specificity supports the assignment of this gene cluster as the producer of the fuscachelin siderophores. The proposed nonribosomal peptide biosynthetic pathway exhibits several atypical features, including a macrocyclizing thioesterase that produces a 10-membered cyclic depsipeptide and a nonlinear assembly line, resulting in the unique heterodimeric architecture of the siderophore natural product.
Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease
Authors: Le Scouarnec Solena , Bhasin Naina , Vieyres Claude , Hund Thomas J. , Cunha Shane R. , Koval Olha , Marionneau Celine , Chen Biyi , Wu Yuejin , Demolombe Sophie , Song Long-Sheng , Le Marec Hervé , Probst Vincent , Schott Jean-Jacques , Anderson Mark E. , Mohler Peter J.
Published: October 2008

The identification of nearly a dozen ion channel genes involved in the genesis of human atrial and ventricular arrhythmias has been critical for the diagnosis and treatment of fatal cardiovascular diseases. In contrast, very little is known about the genetic and molecular mechanisms underlying human sinus node dysfunction (SND). Here, we report a genetic and molecular mechanism for human SND. We mapped two families with highly penetrant and severe SND to the human
ANK2
(ankyrin-B/AnkB) locus. Mice heterozygous for AnkB phenocopy human SND displayed severe bradycardia and rate variability. AnkB is essential for normal membrane organization of sinoatrial node cell channels and transporters, and AnkB is required for physiological cardiac pacing. Finally, dysfunction in AnkB-based trafficking pathways causes abnormal sinoatrial node (SAN) electrical activity and SND. Together, our findings associate abnormal channel targeting with human SND and highlight the critical role of local membrane organization for sinoatrial node excitability.
Evolution of vertebrate opioid receptors
Authors: Dreborg Susanne , Sundström Görel , Larsson Tomas A. , Larhammar Dan
Published: October 2008

The opioid peptides and receptors have prominent roles in pain transmission and reward mechanisms in mammals. The evolution of the opioid receptors has so far been little studied, with only a few reports on species other than tetrapods. We have investigated species representing a broader range of vertebrates and found that the four opioid receptor types (delta, kappa, mu, and NOP) are present in most of the species. The gene relationships were deduced by using both phylogenetic analyses and chromosomal location relative to 20 neighboring gene families in databases of assembled genomes. The combined results show that the vertebrate opioid receptor gene family arose by quadruplication of a large chromosomal block containing at least 14 other gene families. The quadruplication seems to coincide with, and, therefore, probably resulted from, the two proposed genome duplications in early vertebrate evolution. We conclude that the quartet of opioid receptors was already present at the origin of jawed vertebrates ≈450 million years ago. A few additional opioid receptor gene duplications have occurred in bony fishes. Interestingly, the ancestral receptor gene duplications coincide with the origin of the four opioid peptide precursor genes. Thus, the complete vertebrate opioid system was already established in the first jawed vertebrates.
Synthesis of heterogeneous catalysts with well shaped platinum particles to control reaction selectivity
Authors: Lee Ilkeun , Morales Ricardo , Albiter Manuel A. , Zaera Francisco
Published: October 2008

Colloidal and sol-gel procedures have been used to prepare heterogeneous catalysts consisting of platinum metal particles with narrow size distributions and well defined shapes dispersed on high-surface-area silica supports. The overall procedure was developed in three stages. First, tetrahedral and cubic colloidal metal particles were prepared in solution by using a procedure derived from that reported by El-Sayed and coworkers [Ahmadi TS, Wang ZL, Green TC, Henglein A, El-Sayed MA (1996)Science272:1924–1926]. This method allowed size and shape to be controlled independently. Next, the colloidal particles were dispersed onto high-surface-area solids. Three approaches were attempted: (i)in situreduction of the colloidal mixture in the presence of the support, (ii)in situsol-gel synthesis of the support in the presence of the colloidal particles, and (iii) direct impregnation of the particles onto the support. Finally, the resulting catalysts were activated and tested for the promotion of carbon–carbon double-bondcis-transisomerization reactions in olefins. Our results indicate that the selectivity of the reaction may be controlled by using supported catalysts with appropriate metal particle shapes.
Sustained retrotransposition is mediated by nucleotide deletions and interelement recombinations
Authors: Sharma Anupma , Schneider Kevin L. , Presting Gernot G.
Published: October 2008

The term “C-value paradox” was coined by C. A. Thomas, Jr. in 1971 [Thomas CA (1971)
Ann Rev Genetics
5:237–256] to describe the initially puzzling lack of correlation between an organism's genome size and its morphological complexity. Polyploidy and the expansion of repetitive DNA, primarily transposable elements, are two mechanisms that have since been found to account for this differential. While the inactivation of retrotransposons by methylation and their removal from the genome by illegitimate recombination have been well documented, the cause of the apparently periodic bursts of retrotranposon expansion is as yet unknown. We show that the expansion of the CRM1 retrotransposon subfamily in the ancient allotetraploid crop plant corn is linked to the repeated formation of novel recombinant elements derived from two parental retrotransposon genotypes, which may have been brought together during the hybridization of two sympatric species that make up the present day corn genome, thus revealing a unique mechanism linking polyploidy and retrotransposition.
Light-induced chromophore activity and signal transduction in phytochromes observed by
13
C and
15
N magic-angle spinning NMR
Authors: Rohmer Thierry , Lang Christina , Hughes Jon , Essen Lars-Oliver , Gärtner Wolfgang , Matysik Jörg
Published: October 2008

Both thermally stable states of phytochrome, Pr and Pfr, have been studied by
13
C and
15
N cross-polarization (CP) magic-angle spinning (MAS) NMR using cyanobacterial (Cph1) and plant (
phyA
) phytochrome sensory modules containing uniformly
13
C- and
15
N-labeled bilin chromophores. Two-dimensional homo- and heteronuclear experiments allowed most of the
13
C chemical shifts to be assigned in both states. Chemical shift differences reflect changes of the electronic structure of the cofactor at the atomic level as well as its interactions with the chromophore-binding pocket. The chromophore in cyanobacterial and plant phytochromes shows very similar features in the respective Pr and Pfr states. The data are interpreted in terms of a strengthened hydrogen bond at the ring
D
carbonyl. The red shift in the Pfr state is explained by the increasing length of the conjugation network beyond ring
C
including the entire ring
D
. Enhanced conjugation within the π-system stabilizes the more tensed chromophore in the Pfr state. Concomitant changes at the ring
C
propionate carboxylate and the ring
D
carbonyl are explained by a loss of hydrogen bonding to Cph1-His-290 and transmittance of conformational changes to the ring
C
propionate via a water network. These and other conformational changes may lead to modified surface interactions, e.g., along the tongue region contacting the bilin chromophore.
Neuregulin-1 regulates LTP at CA1 hippocampal synapses through activation of dopamine D4 receptors
Authors: Kwon Oh Bin , Paredes Daniel , Gonzalez Carmen M. , Neddens Jörg , Hernandez Luis , Vullhorst Detlef , Buonanno Andres
Published: October 2008

Neuregulin-1 (NRG-1) is genetically linked with schizophrenia, a neurodevelopmental cognitive disorder characterized by imbalances in glutamatergic and dopaminergic function. NRG-1 regulates numerous neurodevelopmental processes and, in the adult, suppresses or reverses long-term potentiation (LTP) at hippocampal glutamatergic synapses. Here we show that NRG-1 stimulates dopamine release in the hippocampus and reverses early-phase LTP via activation of D4 dopamine receptors (D4R). NRG-1 fails to depotentiate LTP in hippocampal slices treated with the antipsychotic clozapine and other more selective D4R antagonists. Moreover, LTP is not depotentiated in D4R null mice by either NRG-1 or theta-pulse stimuli. Conversely, direct D4R activation mimics NRG-1 and reduces AMPA receptor currents and surface expression. These findings demonstrate that NRG-1 mediates its unique role in counteracting LTP via dopamine signaling and opens future directions to study new aspects of NRG function. The novel functional link between NRG-1, dopamine, and glutamate has important implications for understanding how imbalances in Neuregulin-ErbB signaling can impinge on dopaminergic and glutamatergic function, neurotransmitter pathways associated with schizophrenia.
Jellyfish vision starts with cAMP signaling mediated by opsin-G
s
cascade
Authors: Koyanagi Mitsumasa , Takano Kosuke , Tsukamoto Hisao , Ohtsu Kohzoh , Tokunaga Fumio , Terakita Akihisa
Published: October 2008

Light sensing starts with phototransduction in photoreceptor cells. The phototransduction cascade has diverged in different species, such as those mediated by transducin in vertebrate rods and cones, by G
q
-type G protein in insect and molluscan rhabdomeric-type visual cells and vertebrate photosensitive retinal ganglion cells, and by G
o
-type G protein in scallop ciliary-type visual cells. Here, we investigated the phototransduction cascade of a prebilaterian box jellyfish, the most basal animal having eyes containing lens and ciliary-type visual cells similar to vertebrate eyes, to examine the similarity at the molecular level and to obtain an implication of the origin of the vertebrate phototransduction cascade. We showed that the opsin-based pigment functions as a green-sensitive visual pigment and triggers the G
s
-type G protein-mediated phototransduction cascade in the ciliary-type visual cells of the box jellyfish lens eyes. We also demonstrated the light-dependent cAMP increase in the jellyfish visual cells and HEK293S cells expressing the jellyfish opsin. The first identified prebilaterian cascade was distinct from known phototransduction cascades but exhibited significant partial similarity with those in vertebrate and molluscan ciliary-type visual cells, because all involved cyclic nucleotide signaling. These similarities imply a monophyletic origin of ciliary phototransduction cascades distributed from prebilaterian to vertebrate.
The remarkable influence of M
2
δ to thienyl π conjugation in oligothiophenes incorporating MM quadruple bonds
Authors: Burdzinski G. T. , Chisholm M. H. , Chou P.-T. , Chou Y.-H. , Feil F. , Gallucci J. C. , Ghosh Y. , Gustafson T. L. , Ho M.-L. , Liu Y. , Ramnauth R. , Turro C.
Published: October 2008

Oligothiophenes incorporating MM quadruple bonds have been prepared from the reactions between Mo
2
(TiPB)
4
(TiPB = 2,4,6-triisopropyl benzoate) and 3′,4′-dihexyl-2,2′-:5′,2″-terthiophene-5,5″-dicarboxylic acid. The oligomers of empirical formula Mo
2
(TiPB)
2
(O
2
C(Th)-C
4
(
n
-hexyl)
2
S-(Th)CO
2
) are soluble in THF and form thin films with spin-coating (Th = thiophene). The reactions between Mo
2
(TiPB)
4
and 2-thienylcarboxylic acid (Th-H), 2,2′-bithiophene-5-carboxylic acid (BTh-H), and (2,2′:5′,2″-terthiophene)-5-carboxylic acid (TTh-H) yield compounds of formula
trans
-Mo
2
(TiPB)
2
L
2
, where L = Th, BTh, and TTh (the corresponding thienylcarboxylate), and these compounds are considered as models for the aforementioned oligomers. In all cases, the thienyl groups are substituted or coupled at the 2,5 positions. Based on the x-ray analysis, the molecular structure of
trans
-Mo
2
(TiPB)
2
(BTh)
2
reveals an extended Lπ-M
2
δ-Lπ conjugation. Calculations of the electronic structures on model compounds, in which the TiPB are substituted by formate ligands, reveal that the HOMO is mainly attributed to the M
2
δ orbital, which is stabilized by back-bonding to one of the thienylcarboxylate π* combinations, and the LUMO is an in-phase combination of the thienylcarboxylate π* orbitals. The compounds and the oligomers are intensely colored due to M
2
δ–thienyl carboxylate π* charge transfer transitions that fall in the visible region of the spectrum. For the molybdenum complexes and their oligomers, the photophysical properties have been studied by steady-state absorption spectroscopy and emission spectroscopy, together with time-resolved emission and transient absorption for the determination of relaxation dynamics. Remarkably, THF solutions the molybdenum complexes show room-temperature dual emission, fluorescence and phosphorescence, originating mainly from
1
MLCT and
3
MM(δδ*) states, respectively. With increasing number of thienyl rings from 1 to 3, the observed lifetimes of the
1
MLCT state increase from 4 to 12 ps, while the phosphorescence lifetimes are ≈80 μs. The oligomers show similar photophysical properties as the corresponding monomers in THF but have notably longer-lived triplet states, ≈200 μs in thin films. These results, when compared with metallated oligothiophenes of the later transition elements, reveal that M
2
δ–thienyl π conjugation leads to a very small energy gap between the
1
MLCT and
3
MLCT states of <0.6 eV.
Cohesin subunit SMC1 associates with mitotic microtubules at the spindle pole
Authors: Wong Richard W. , Blobel Günter
Published: October 2008

Accurate mitotic chromosome segregation depends on the formation of a microtubule-based bipolar spindle apparatus. We report that the cohesin subunit structural maintenance of chromosomes subunit
1
(SMC1) is recruited to microtubule-bound RNA export factor
1
(Rae1) at the mitotic spindle pole. We locate the Rae1-binding site to a 21-residue-long region, SMC1
947-967
and provide several lines of evidence that phosphorylation of Ser
957
and Ser
966
of SMC1 stimulates binding to Rae1. Imbalances in these assembly pathways caused formation of multipolar spindles. Our data suggest that cohesin's known bundling function for chromatids in mitotic and interphase cells extends to microtubules at the spindle pole.
BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact
Authors: Scholz Jean L. , Crowley Jenni E. , Tomayko Mary M. , Steinel Natalie , O'Neill Patrick J. , Quinn William J. , Goenka Radhika , Miller Juli P. , Cho Yun Hee , Long Vatana , Ward Chris , Migone Thi-Sau , Shlomchik Mark J. , Cancro Michael P.
Published: October 2008

We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereasin vivoBLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells were not, although both were more resistant than naïve cells. There was also heterogeneity within B1 pools, as splenic but not peritoneal B1 cells were diminished by anti-BLyS treatment, yet the number of natural antibody-secreting cells remained constant. Together, these findings show that memory B cells and natural antibody-secreting cells are BLyS-independent and suggest that these pools can be separately manipulated.
Structure of the human voltage-dependent anion channel
Authors: Bayrhuber Monika , Meins Thomas , Habeck Michael , Becker Stefan , Giller Karin , Villinger Saskia , Vonrhein Clemens , Griesinger Christian , Zweckstetter Markus , Zeth Kornelius
Published: October 2008

The voltage-dependent anion channel (VDAC), also known as mitochondrial porin, is the most abundant protein in the mitochondrial outer membrane (MOM). VDAC is the channel known to guide the metabolic flux across the MOM and plays a key role in mitochondrially induced apoptosis. Here, we present the 3D structure of human VDAC1, which was solved conjointly by NMR spectroscopy and x-ray crystallography. Human VDAC1 (hVDAC1) adopts a β-barrel architecture composed of 19 β-strands with an α-helix located horizontally midway within the pore. Bioinformatic analysis indicates that this channel architecture is common to all VDAC proteins and is adopted by the general import pore TOM40 of mammals, which is also located in the MOM.
Hippocampal-dependent learning requires a functional circadian system
Authors: Ruby Norman F. , Hwang Calvin E. , Wessells Colin , Fernandez Fabian , Zhang Pei , Sapolsky Robert , Heller H. Craig
Published: October 2008

Decades of studies have shown that eliminating circadian rhythms of mammals does not compromise their health or longevity in the laboratory in any obvious way. These observations have raised questions about the functional significance of the mammalian circadian system, but have been difficult to address for lack of an appropriate animal model. Surgical ablation of the suprachiasmatic nucleus (SCN) and clock gene knockouts eliminate rhythms, but also damage adjacent brain regions or cause developmental effects that may impair cognitive or other physiological functions. We developed a method that avoids these problems and eliminates rhythms by noninvasive means in Siberian hamsters (
Phodopus sungorus
). The present study evaluated cognitive function in arrhythmic animals by using a hippocampal-dependent learning task. Control hamsters exhibited normal circadian modulation of performance in a delayed novel-object recognition task. By contrast, arrhythmic animals could not discriminate a novel object from a familiar one only 20 or 60 min after training. Memory performance was not related to prior sleep history as sleep manipulations had no effect on performance. The GABA antagonist pentylenetetrazol restored learning without restoring circadian rhythms. We conclude that the circadian system is involved in memory function in a manner that is independent of sleep. Circadian influence on learning may be exerted via cyclic GABA output from the SCN to target sites involved in learning. Arrhythmic hamsters may have failed to perform this task because of chronic inhibitory signaling from the SCN that interfered with the plastic mechanisms that encode learning in the hippocampus.
Bioinformatics identification of MurJ (MviN) as the peptidoglycan lipid II flippase in
Escherichia coli
Authors: Ruiz Natividad
Published: October 2008

Peptidoglycan is a cell-wall glycopeptide polymer that protects bacteria from osmotic lysis. Whereas in Gram-positive bacteria it also serves as scaffold for many virulence factors, in Gram-negative bacteria, peptidoglycan is an anchor for the outer membrane. For years, we have known the enzymes required for the biosynthesis of peptidoglycan; what was missing was the flippase that translocates the lipid-anchored precursors across the cytoplasmic membrane before their polymerization into mature peptidoglycan. Using a reductionist bioinformatics approach, I have identified the essential inner-membrane protein MviN (renamed MurJ) as a likely candidate for the peptidoglycan flippase in
Escherichia coli
. Here, I present genetic and biochemical data that confirm the requirement of MurJ for peptidoglycan biosynthesis and that are in agreement with a role of MurJ as a flippase. Because of its essential nature, MurJ could serve as a target in the continuing search for antimicrobial compounds.
RETRACTED: Notch1 regulates the fate of cardiac progenitor cells
Authors: Boni Alessandro , Urbanek Konrad , Nascimbene Angelo , Hosoda Toru , Zheng Hanqiao , Delucchi Francesca , Amano Katsuya , Gonzalez Arantxa , Vitale Serena , Ojaimi Caroline , Rizzi Roberto , Bolli Roberto , Yutzey Katherine E. , Rota Marcello , Kajstura Jan , Anversa Piero , Leri Annarosa
Published: October 2008

The Notch receptor mediates cell fate decision in multiple organs. In the current work we tested the hypothesis that Nkx2.5 is a target gene of Notch1 and raised the possibility that Notch1 regulates myocyte commitment in the adult heart. Cardiac progenitor cells (CPCs) in the niches express Notch1 receptor, and the supporting cells exhibit the Notch ligand Jagged1. The nuclear translocation of Notch1 intracellular domain (N1ICD) up-regulates Nkx2.5 in CPCs and promotes the formation of cycling myocytes
in vitro
. N1ICD and RBP-Jk form a protein complex, which in turn binds to the Nkx2.5 promoter initiating transcription and myocyte differentiation. In contrast, transcription factors of vascular cells are down-regulated by Jagged1 activation of the Notch1 pathway. Importantly, inhibition of Notch1 in infarcted mice impairs the commitment of resident CPCs to the myocyte lineage opposing cardiomyogenesis. These observations indicate that Notch1 favors the early specification of CPCs to the myocyte phenotype but maintains the newly formed cells in a highly proliferative state. Dividing Nkx2.5-positive myocytes correspond to transit amplifying cells, which condition the replicative capacity of the heart. In conclusion, Notch1 may have critical implications in the control of heart homeostasis and its adaptation to pathologic states.
The control of Ca
2+
influx and NFATc3 signaling in arterial smooth muscle during hypertension
Authors: Nieves-Cintrón Madeline , Amberg Gregory C. , Navedo Manuel F. , Molkentin Jeffery D. , Santana Luis F.
Published: October 2008

Many excitable cells express L-type Ca
2+
channels (LTCCs), which participate in physiological and pathophysiological processes ranging from memory, secretion, and contraction to epilepsy, heart failure, and hypertension. Clusters of LTCCs can operate in a PKCα-dependent, high open probability mode that generates sites of sustained Ca
2+
influx called “persistent Ca
2+
sparklets.” Although increased LTCC activity is necessary for the development of vascular dysfunction during hypertension, the mechanisms leading to increased LTCC function are unclear. Here, we tested the hypothesis that increased PKCα and persistent Ca
2+
sparklet activity contributes to arterial dysfunction during hypertension. We found that PKCα and persistent Ca
2+
sparklet activity is indeed increased in arterial myocytes during hypertension. Furthermore, in human arterial myocytes, PKCα-dependent persistent Ca
2+
sparklets activated the prohypertensive calcineurin/NFATc3 signaling cascade. These events culminated in three hallmark signs of hypertension-associated vascular dysfunction: increased Ca
2+
entry, elevated arterial [Ca
2+
]
i
, and enhanced myogenic tone. Consistent with these observations, we show that PKCα ablation is protective against the development of angiotensin II-induced hypertension. These data support a model in which persistent Ca
2+
sparklets, PKCα, and calcineurin form a subcellular signaling triad controlling NFATc3-dependent gene expression, arterial function, and blood pressure. Because of the ubiquity of these proteins, this model may represent a general signaling pathway controlling gene expression and cellular function.
Speech Perception by 6‐to 8‐Month‐Olds in the Presence of Distracting Sounds
Authors: Polka Linda , Rvachew Susan , Molnar Monika
Published: October 2008

The role of selective attention in infant phonetic perception was examined using a distraction masker paradigm. We compared perception of /bu/ versus /gu/ in 6‐ to 8‐month‐olds using a visual fixation procedure. Infants were habituated to multiple natural productions of 1 syllable type and then presented 4 test trials (old‐new‐old‐new). Perception of the new syllable (indexed as novelty preference) was compared across 3 groups: habituated and tested on syllables in quiet (Group 1), habituated and tested on syllables mixed with a nonspeech signal (Group 2), and habituated with syllables mixed with a non‐speech signal and tested on syllables in quiet (Group 3). In Groups 2 and 3, each syllable was mixed with a segment spliced from a recording of bird and cricket songs. This nonspeech signal has no overlapping frequencies with the syllable; it is not expected to alter the sensory structure or perceptual coherence of the syllable. Perception was negatively affected by the presence of the auditory distracter during habituation; individual performance levels also varied more in these groups. The findings show that perceiving speech in the presence of irrelevant sounds poses a cognitive challenge for young infants. We conclude that selective attention is an important skill that supports speech perception in infants; the significance of this skill for language learning during infancy deserves investigation.
Clause Segmentation by 6‐Month‐Old Infants: A Crosslinguistic Perspective
Authors: Johnson Elizabeth K. , Seidl Amanda
Published: October 2008

Each clause and phrase boundary necessarily aligns with a word boundary. Thus, infants' attention to the edges of clauses and phrases may help them learn some of the language‐specific cues defining word boundaries. Attention to prosodically well‐formed clauses and phrases may also help infants begin to extract information important for learning the grammatical structure of their language. Despite the potentially important role that the perception of large prosodic units may play in early language acquisition, there has been little work investigating the extraction of these units from fluent speech by infants learning languages other than English. We report 2 experiments investigating Dutch learners' clause segmentation abilities. In these studies, Dutch‐learning 6‐month‐olds readily extract clauses from speech. However, Dutch learners differ from English learners in that they seem to be more reliant on pauses to detect clause boundaries. Two closely related explanations for this finding are considered, both of which stem from the acoustic differences in clause boundary realizations in Dutch versus English.
The Microstructure of Infants' Gaze as They View Adult Shifts in Overt Attention
Authors: Gredebäck Gustaf , Theuring Carolin , Hauf Petra , Kenward Ben
Published: October 2008

We presented infants (5, 6, 9, and 12 months old) with movies in which a female model turned toward and fixated 1 of 2 toys placed on a table. Infants' gaze was measured using a Tobii 1750 eye tracker. Six‐, 9‐, and 12‐month‐olds' first gaze shift from the model's face (after the model started turning) was directed to the attended toy. The 5‐month‐olds performed at random. Following this initial response, 5‐, 6‐, and 9‐month‐olds performed more gaze shifts to the attended target; 12‐month‐olds performed at random. Infants at all ages displayed longer looking times to the attended toy. We discuss a number of explanations for 5‐month‐olds' ability to follow a shift in overt attention by an adult after an initially random response, including the possibility that infants' initial gaze response strengthens the representation of the objects in the peripheral visual field.
Infants' Sensitivity to the Depth Cue of Height‐in‐the‐Picture‐Plane
Authors: Arterberry Martha E.
Published: October 2008

Five‐ and 7‐month‐old infants' sensitivity to the pictorial depth cue of height‐in‐the‐picture‐plane was assessed. Infants were presented with 2 objects, 1 higher than the other, and their reaching was recorded under monocular and binocular viewing conditions. The results showed that both age groups reached significantly more to the lower, apparently closer object under monocular view and that they reached equally to the 2 objects under binocular view. The results suggest that both 5‐ and 7‐month‐old infants are sensitive to the depth information provided by height‐in‐the‐picture‐plane. Demonstration of pictorial depth sensitivity at 5 months has implications for the mechanism underlying the onset of sensitivity to this type of depth information.
Notch1 signaling stimulates proliferation of immature cardiomyocytes
Authors: Collesi Chiara , Zentilin Lorena , Sinagra Gianfranco , Giacca Mauro
Published: October 2008

The identification of the molecular mechanisms controlling cardiomyocyte proliferation during the embryonic, fetal, and early neonatal life appears of paramount interest in regard to exploiting this information to promote cardiac regeneration. Here, we show that the proliferative potential of neonatal rat cardiomyocytes is powerfully stimulated by the sustained activation of the Notch pathway. We found that Notch1 is expressed in proliferating ventricular immature cardiac myocytes (ICMs) both in vitro and in vivo, and that the number of Notch1-positive cells in the heart declines with age. Notch1 expression in ICMs paralleled the expression of its Jagged1 ligand on non-myocyte supporting cells. The inhibition of Notch signaling in ICMs blocked their proliferation and induced apoptosis; in contrast, its activation by Jagged1 or by the constitutive expression of its activated form using an adeno-associated virus markedly stimulated proliferative signaling and promoted ICM expansion. Maintenance or reactivation of Notch signaling in cardiac myocytes might represent an interesting target for innovative regenerative therapy.
Growth and characterization of co-evaporated Cu2ZnSnSe4thin films for photovoltaic applications
Authors: Suresh Babu G , Kishore Kumar Y B , Uday Bhaskar P , Sundara Raja V
Published: October 2008

Cu2ZnSnSe4thin films are deposited using the four-source co-evaporation technique onto glass substrates held at 523, 573, 623 and 673 K andin situannealed at 723 K for 1 h in a selenium atmosphere. XRD studies revealed that the films deposited at 523 and 573 K and annealed at 723 K contain ZnSe as a secondary phase. However, films deposited at 673 K and annealed at 723 K have Cu2−xSe as a secondary phase along with Cu2ZnSnSe4. Single phase, polycrystalline Cu2ZnSnSe4films are obtained at a substrate temperature (Ts) of 623 K onin situannealing at 723 K. The structure is found to be kesterite and the lattice parameters area= 0.569 nm,c= 1.141 nm. The direct optical band gap of the films is found to lie between 1.42 and 1.57 eV for films deposited at different substrate temperatures. Electrical resistivity of the films is in the range 0.1–0.8 Ω cm depending onTs.
Counting faces of randomly projected polytopes when the projection radically lowers dimension
Authors: Donoho David , Tanner Jared
Published: October 2008

Let

Q
=

Q
N

Q = Q_N

denote either the

N
N

-dimensional cross-polytope

C
N

C^N

or the

N
−
1

N-1

-dimensional simplex

T

N
−
1

T^{N-1}

. Let

A
=

A

n
,
N

A = A_{n,N}

denote a random orthogonal projector

A
:

R

N

↦
b

R
n

A: \mathbf {R}^{N} \mapsto bR^n

. We compare the number of faces

f
k

(
A
Q
)

f_k(AQ)

of the projected polytope

A
Q

AQ

to the number of faces of

f
k

(
Q
)

f_k(Q)

of the original polytope

Q
Q

. We concentrate on the case where

n
n

and

N
N

are both large, but

n
n

is much smaller than

N
N

; in this case the projection dramatically lowers dimension.

We consider sequences of triples

(
k
,
n
,
N
)

(k,n,N)

where

N
=

N
n

N = N_n

is not exponentially larger than

n
n

. We identify thresholds of the form

c
o
n
s
t
⋅
n
log
⁡
(
n

/

N
)

const \cdot n \log (n/N)

where the relationship of

f
k

(
A
Q
)

f_k(AQ)

and

f
k

(
Q
)

f_k(Q)

changes abruptly.

These properties of polytopes have significant implications for neighborliness of convex hulls of Gaussian point clouds, for efficient sparse solution of underdetermined linear systems, for efficient decoding of random error correcting codes and for determining the allowable rate of undersampling in the theory of compressed sensing.

The thresholds are characterized precisely using tools from polytope theory, convex integral geometry, and large deviations. Asymptotics developed for these thresholds yield the following, for fixed

ϵ
>
0

\epsilon > 0

.

With probability tending to 1 as

n
n

,

N
N

tend to infinity:

(1a) for

k
>
(
1
−
ϵ
)
⋅
n
[
2
e
ln
⁡
(
N

/

n
)

]

−
1

k > (1-\epsilon ) \cdot n [2e\ln (N/n)]^{-1}

we have

f
k

(
A
Q
)
=

f
k

(
Q
)

f_k(AQ) = f_k(Q)

,

(1b) for

k
>
(
1
+
ϵ
)
⋅
n
[
2
e
ln
⁡
(
N

/

n
)

]

−
1

k > (1 +\epsilon ) \cdot n [2e\ln (N/n)]^{-1}

we have

f
k

(
A
Q
)
>

f
k

(
Q
)

f_k(AQ) > f_k(Q)

,

with

E

{\mathcal E}

denoting expectation,

(2a) for

k
>
(
1
−
ϵ
)
⋅
n
[
2
ln
⁡
(
N

/

n
)

]

−
1

k > (1-\epsilon ) \cdot n [2\ln (N/n)]^{-1}

we have

E

f
k

(
A
Q
)
>
(
1
−
ϵ
)

f
k

(
Q
)

{\mathcal E} f_k(AQ) > (1-\epsilon ) f_k(Q)

,

(2b) for

k
>
(
1
+
ϵ
)
⋅
n
[
2
ln
⁡
(
N

/

n
)

]

−
1

k > (1 +\epsilon ) \cdot n [2\ln (N/n)]^{-1}

we have

E

f
k

(
A
Q
)
>
ϵ

f
k

(
Q
)

{\mathcal E} f_k(AQ) > \epsilon f_k(Q)

.

These asymptotically sharp transitions in the behavior of face numbers as

k
k

varies relative to

n
log
⁡
(
N

/

n
)

n \log (N/n)

are proven, interpreted, and related to the above-mentioned applications.