bluuebunny/crossref_metadata_2025 huggingface dataset:
Different nuclease requirements for exosome-mediated degradation of normal and nonstop mRNAs
Authors: Schaeffer Daneen , van Hoof Ambro
Published: January 2011

Two general pathways of mRNA decay have been characterized in yeast. In one pathway, the mRNA is degraded by the cytoplasmic form of the exosome. The exosome has both 3′ to 5′ exoribonuclease and endoribonuclease activity, and the available evidence suggests that the exonuclease activity is required for the degradation of mRNAs. We confirm here that this is true for normal mRNAs, but that aberrant mRNAs that lack a stop codon can be efficiently degraded in the absence of the exonuclease activity of the exosome. Specifically, we show that the endo- and exonuclease activities of the exosome are both capable of rapidly degrading nonstop mRNAs and ribozyme-cleaved mRNAs. Additionally, the endonuclease activity of the exosome is not required for endonucleolytic cleavage in no-go decay. In vitro, the endonuclease domain of the exosome is active only under nonphysiological conditions, but our findings show that the in vivo activity is sufficient for the rapid degradation of nonstop mRNAs. Thus, whereas normal mRNAs are degraded by two exonucleases (Xrn1p and Rrp44p), several endonucleases contribute to the decay of many aberrant mRNAs, including transcripts subject to nonstop and no-go decay. Our findings suggest that the nuclease requirements for general and nonstop mRNA decay are different, and describe a molecular function of the core exosome that is not disrupted by inactivating its exonuclease activity.
NogoA restricts synaptic plasticity in the adult hippocampus on a fast time scale
Authors: Delekate Andrea , Zagrebelsky Marta , Kramer Stella , Schwab Martin E. , Korte Martin
Published: January 2011

Whereas the role of NogoA in limiting axonal fiber growth and regeneration following an injury of the mammalian central nervous system (CNS) is well known, its physiological functions in the mature uninjured CNS are less well characterized. NogoA is mainly expressed by oligodendrocytes, but also by subpopulations of neurons, in particular in plastic regions of the CNS, e.g., in the hippocampus where it is found at synaptic sites. We analyzed synaptic transmission as well as long-term synaptic plasticity (long-term potentiation, LTP) in the presence of function blocking anti-NogoA or anti-Nogo receptor (NgR) antibodies and in NogoA KO mice. Whereas baseline synaptic transmission, short-term plasticity and long-term depression were not affected by either approach, long-term potentiation was significantly increased following NogoA or NgR1 neutralization. Synaptic potentiation thus seems to be restricted by NogoA. Surprisingly, synaptic weakening was not affected by interfering with NogoA signaling. Mechanistically of interest is the observation that by blockade of the GABA
A
receptors normal synaptic strengthening reoccurred in the absence of NogoA signaling. The present results show a unique role of NogoA expressed in the adult hippocampus in restricting physiological synaptic plasticity on a very fast time scale. NogoA could thus serve as an important negative regulator of functional and structural plasticity in mature neuronal networks.
Predicting and optimizing asymmetric catalyst performance using the principles of experimental design and steric parameters
Authors: Harper Kaid C. , Sigman Matthew S.
Published: January 2011

Using a modular amino acid based chiral ligand motif, a library of ligands was synthesized systematically varying the substituents at two positions. The effects of these changes on ligand structure were probed in the enantioselective allylation of benzaldehyde, acetophenone, and methylethyl ketone under Nozaki-Hiyama-Kishi conditions. The resulting three-dimensional datasets allowed for the construction of mathematical surface models which describe the interplay of substituent effects on enantioselectivity for a given reaction. The surface models were both extrapolated and manipulated to predict the enantioselective outcomes of several previously untested ligands. Analyses were also used to predict optimal ligand structure of a minimal dataset. Within the dataset, a linear free energy relationship was also discovered and a direct comparison of both the linear prediction as well as the three-dimensional prediction illustrates the potential predictive power of using a three-dimensional model approach to asymmetric catalyst development.
Evaporation kinetics and phase of laboratory and ambient secondary organic aerosol
Authors: Vaden Timothy D. , Imre Dan , Beránek Josef , Shrivastava Manish , Zelenyuk Alla
Published: January 2011

Field measurements of secondary organic aerosol (SOA) find significantly higher mass loads than predicted by models, sparking intense effort focused on finding additional SOA sources but leaving the fundamental assumptions used by models unchallenged. Current air-quality models use absorptive partitioning theory assuming SOA particles are liquid droplets, forming instantaneous reversible equilibrium with gas phase. Further, they ignore the effects of adsorption of spectator organic species during SOA formation on SOA properties and fate. Using accurate and highly sensitive experimental approach for studying evaporation kinetics of size-selected single SOA particles, we characterized room-temperature evaporation kinetics of laboratory-generated α-pinene SOA and ambient atmospheric SOA. We found that even when gas phase organics are removed, it takes ∼24 h for pure α-pinene SOA particles to evaporate 75% of their mass, which is in sharp contrast to the ∼10 min time scale predicted by current kinetic models. Adsorption of “spectator” organic vapors during SOA formation, and aging of these coated SOA particles, dramatically reduced the evaporation rate, and in some cases nearly stopped it. Ambient SOA was found to exhibit evaporation behavior very similar to that of laboratory-generated coated and aged SOA. For all cases studied in this work, SOA evaporation behavior is nearly size-independent and does not follow the evaporation kinetics of liquid droplets, in sharp contrast with model assumptions. The findings about SOA phase, evaporation rates, and the importance of spectator gases and aging all indicate that there is need to reformulate the way SOA formation and evaporation are treated by models.
Cognitive dysfunction and prefrontal synaptic abnormalities in a mouse model of fragile X syndrome
Authors: Krueger Dilja D. , Osterweil Emily K. , Chen Stephanie P. , Tye Lynne D. , Bear Mark F.
Published: January 2011

Among the hallmark phenotypes reported in individuals with fragile X syndrome (FXS) are deficits in attentional function, inhibitory control, and cognitive flexibility, a set of cognitive skills thought to be associated with the prefrontal cortex (PFC). However, despite substantial clinical research into these core deficits, the PFC has received surprisingly little attention in preclinical research, particularly in animal models of FXS. In this study, we sought to investigate the molecular, cellular, and behavioral consequences of the loss of the fragile X mental retardation protein in the PFC of
Fmr1
KO mice, a mouse model of FXS. We identify a robust cognitive impairment in these mice that may be related to the deficits in cognitive flexibility observed in individuals with FXS. In addition, we report that levels of proteins involved in synaptic function, including the NMDA receptor subunits NR1, NR2A, and NR2B; the scaffolding proteins PSD-95 and SAPAP3; and the plasticity-related gene Arc, are decreased in the prefrontal cortex of
Fmr1
KO mice and are partly correlated with behavioral performance. Finally, we report that expression of c-Fos, a marker of neuronal activity, is decreased in the PFC of
Fmr1
KO mice. Together, these data suggest that
Fmr1
KO mice may represent a valuable animal model for the PFC-associated molecular, cellular, and behavioral abnormalities in FXS and that this model may be useful for testing the efficacy of therapeutic strategies aimed at treating the cognitive impairments in FXS.
Lack of the endosomal SNAREs vti1a and vti1b led to significant impairments in neuronal development
Authors: Kunwar Ajaya J. , Rickmann Michael , Backofen Bianca , Browski Sascha M. , Rosenbusch Joachim , Schöning Susanne , Fleischmann Thomas , Krieglstein Kerstin , Fischer von Mollard Gabriele
Published: January 2011

Fusion between membranes is mediated by specific SNARE complexes. Here we report that fibroblasts survive the absence of the trans-Golgi network/early endosomal SNARE vti1a and the late endosomal SNARE vti1b with intact organelle morphology and minor trafficking defects. Because vti1a and vti1b are the only members of their SNARE subclass and the yeast homolog Vti1p is essential for cell survival, these data suggest that more distantly related SNAREs acquired the ability to function in endosomal traffic during evolution. However, absence of vti1a and vti1b resulted in perinatal lethality. Major axon tracts were missing, reduced in size, or misrouted in

Vti1a
−/−
Vti1b
−/−

embryos. Progressive neurodegeneration was observed in most

Vti1a
−/−
Vti1b
−/−

peripheral ganglia. Neurons were reduced by more than 95% in

Vti1a
−/−
Vti1b
−/−

dorsal root and geniculate ganglia at embryonic day 18.5. These data suggest that special demands for endosomal membrane traffic could not be met in

Vti1a
−/−
Vti1b
−/−

neurons.

Vti1a
−/−

and

Vti1b
−/−

single deficient mice were viable without these neuronal defects, indicating that they can substitute for each other in these processes.
Barhl2 limits growth of the diencephalic primordium through Caspase3 inhibition of β-catenin activation
Authors: Juraver-Geslin Hugo A. , Ausseil Jérome J. , Wassef Marion , Durand Béatrice C.
Published: January 2011

Little is known about the respective contributions of cell proliferation and cell death to the control of vertebrate forebrain growth. The homeodomain protein
barhl2
is expressed in the diencephalons of
Xenopus
, zebrafish, and mouse embryos, and we previously showed that Barhl2 overexpression in
Xenopus
neuroepithelial cells induces Caspase3-dependent apoptosis. Here,
barhl2
is shown to act as a brake on diencephalic proliferation through an unconventional function of Caspase3. Depletion of Barhl2 or Caspase3 causes an increase in diencephalic cell number, a disruption of the neuroepithelium architecture, and an increase in Wnt activity. Surprisingly, these changes are not caused by decreased apoptosis but instead, are because of an increase in the amount and activation of β-catenin, which stimulates excessive neuroepithelial cell proliferation and induces defects in β-catenin intracellular localization and an up-regulation of
axin2
and
cyclinD1
, two downstream targets of β-catenin/T-cell factor/lymphoïd enhancer factor signaling. Using two different sets of complementation experiments, we showed that, in the developing diencephalon, Caspase3 acts downstream of Barhl2 in limiting neuroepithelial cell proliferation by inhibiting β-catenin activation. Our data argue that Bar homeodomain proteins share a conserved function as cell type-specific regulators of Caspase3 activities.
Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8
+
T cells and reduces chronic retroviral set points
Authors: Dietze Kirsten K. , Zelinskyy Gennadiy , Gibbert Kathrin , Schimmer Simone , Francois Sandra , Myers Lara , Sparwasser Tim , Hasenkrug Kim J. , Dittmer Ulf
Published: January 2011

Although chronic infections with viruses such as HIV and hepatitis C virus have been associated with regulatory T cell (Treg)-mediated suppression of virus-specific CD8
+
T-cell activity, no causal relationship between Tregs and chronic viral set points has been established. Using transgenic mice in which Tregs can be selectively ablated, we now show that transient depletion of Tregs during a chronic retroviral infection allows exhausted CD8
+
T cells to regain antiviral functions, including secretion of cytokines, production of cytotoxic molecules, and virus-specific cytolytic activity. Furthermore, short-term Treg ablation resulted in long-term reductions in chronic virus loads. These results demonstrate that Treg-mediated immunosuppression can be a significant factor in the maintenance of chronic viral infections and that Treg-targeted immunotherapy could be a valuable component in therapeutic strategies to treat chronic infectious diseases.
Crystal structure of a γδ T-cell receptor specific for the human MHC class I homolog MICA
Authors: Xu Bin , Pizarro Juan C. , Holmes Margaret A. , McBeth Christine , Groh Veronika , Spies Thomas , Strong Roland K.
Published: January 2011

γδ T cells play important roles in bridging innate and adaptive immunity, but their recognition mechanisms remain poorly understood. Human γδ T cells of the V
δ
1 subset predominate in intestinal epithelia and respond to MICA and MICB (MHC class I chain-related, A and B; MIC) self-antigens, mediating responses to tumorigenesis or viral infection. The crystal structure of an MIC-reactive V
δ
1 γδ T-cell receptor (TCR) showed expected overall structural homology to antibodies, αβ, and other γδ TCRs, but complementary determining region conformations and conservation of V
δ
1 use revealed an uncharacteristically flat potential binding surface. MIC, likewise, serves as a ligand for the activating immunoreceptor natural killer group 2, D (NKG2D), also expressed on γδ T cells. Although MIC recognition drives both the TCR-dependent stimulatory and NKG2D-dependent costimulatory signals necessary for activation, interaction analyses showed that MIC binding by the two receptors was mutually exclusive. Analysis of relative binding kinetics suggested sequential recognition, defining constraints for the temporal organization of γδ T-cell/target cell interfaces.
Optical probing of a dynamic membrane interaction that regulates the TREK1 channel
Authors: Sandoz Guillaume , Bell Sarah C. , Isacoff Ehud Y.
Published: January 2011

TREK channels produce background currents that regulate cell excitability. These channels are sensitive to a wide variety of stimuli including polyunsaturated fatty acids (PUFAs), phospholipids, mechanical stretch, and intracellular acidification. They are inhibited by neurotransmitters, hormones, and pharmacological agents such as the antidepressant fluoxetine. TREK1 knockout mice have impaired PUFA-mediated neuroprotection to ischemia, reduced sensitivity to volatile anesthetics, altered perception of pain, and a depression-resistant phenotype. Here, we investigate TREK1 regulation by Gq-coupled receptors (GqPCR) and phospholipids. Several reports indicate that the C-terminal domain of TREK1 is a key regulatory domain. We developed a fluorescent-based technique that monitors the plasma membrane association of the C terminus of TREK1 in real time. Our fluorescence and functional experiments link the modulation of TREK1 channel function by internal pH, phospholipid, and GqPCRs to TREK1–C-terminal domain association to the plasma membrane, where increased association results in greater activity. In keeping with this relation, inhibition of TREK1 current by fluoxetine is found to be accompanied by dissociation of the C-terminal domain from the membrane.
Transdifferentiation of glioblastoma cells into vascular endothelial cells
Authors: Soda Yasushi , Marumoto Tomotoshi , Friedmann-Morvinski Dinorah , Soda Mie , Liu Fei , Michiue Hiroyuki , Pastorino Sandra , Yang Meng , Hoffman Robert M. , Kesari Santosh , Verma Inder M.
Published: January 2011

Glioblastoma (GBM) is the most malignant brain tumor and is highly resistant to intensive combination therapies and anti-VEGF therapies. To assess the resistance mechanism to anti-VEGF therapy, we examined the vessels of GBMs in tumors that were induced by the transduction of p53
+/−
heterozygous mice with lentiviral vectors containing oncogenes and the marker GFP in the hippocampus of GFAP-Cre recombinase (Cre) mice. We were surprised to observe GFP
+
vascular endothelial cells (ECs). Transplantation of mouse GBM cells revealed that the tumor-derived endothelial cells (TDECs) originated from tumor-initiating cells and did not result from cell fusion of ECs and tumor cells. An in vitro differentiation assay suggested that hypoxia is an important factor in the differentiation of tumor cells to ECs and is independent of VEGF. TDEC formation was not only resistant to an anti-VEGF receptor inhibitor in mouse GBMs but it led to an increase in their frequency. A xenograft model of human GBM spheres from clinical specimens and direct clinical samples from patients with GBM also showed the presence of TDECs. We suggest that the TDEC is an important player in the resistance to anti-VEGF therapy, and hence a potential target for GBM therapy.
Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3′ to 5′ exonuclease activity essential for immune suppression
Authors: Hastie Kathryn M. , Kimberlin Christopher R. , Zandonatti Michelle A. , MacRae Ian J. , Saphire Erica Ollmann
Published: January 2011

Lassa fever virus, a member of the family Arenaviridae, is a highly endemic category A pathogen that causes 300,000–500,000 infections per year in Western Africa. The arenaviral nucleoprotein NP has been implicated in suppression of the host innate immune system, but the mechanism by which this occurs has remained elusive. Here we present the crystal structure at 1.5 Å of the immunosuppressive C-terminal portion of Lassa virus NP and illustrate that, unexpectedly, its 3D fold closely mimics that of the DEDDh family of exonucleases. Accompanying biochemical experiments illustrate that NP indeed has a previously unknown, bona fide exonuclease activity, with strict specificity for double-stranded RNA substrates. We further demonstrate that this exonuclease activity is essential for the ability of NP to suppress translocation of IFN regulatory factor 3 and block activation of the innate immune system. Thus, the nucleoprotein is a viral exonuclease with anti-immune activity, and this work provides a unique opportunity to combat arenaviral infections.
Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus–host recombinant
Authors: Shukla Priyanka , Nguyen Hanh T. , Torian Udana , Engle Ronald E. , Faulk Kristina , Dalton Harry R. , Bendall Richard P. , Keane Frances E. , Purcell Robert H. , Emerson Suzanne U.
Published: January 2011

The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20–30%. Until recently, hepatitis E was rarely identified in industrialized countries, but Hepatitis E now is reported increasingly throughout Western Europe, some Eastern European countries, and Japan. Most of these cases are caused by genotype 3, which is endemic in swine, and these cases are thought to be zoonotically acquired. However, transmission routes are not well understood. HEV that infect humans are divided into nonzoonotic (types 1, 2) and zoonotic (types 3, 4) genotypes. HEV cell culture is inefficient and limited, and thus far HEV has been cultured only in human cell lines. The HEV strain Kernow-C1 (genotype 3) isolated from a chronically infected patient was used to identify human, pig, and deer cell lines permissive for infection. Cross-species infections by genotypes 1 and 3 were studied with this set of cultures. Adaptation of the Kernow-C1 strain to growth in human hepatoma cells selected for a rare virus recombinant that contained an insertion of 174 ribonucleotides (58 amino acids) of a human ribosomal protein gene.
Activation of the plasma membrane Na/H antiporter Salt-Overly-Sensitive 1 (SOS1) by phosphorylation of an auto-inhibitory C-terminal domain
Authors: Quintero Francisco J. , Martinez-Atienza Juliana , Villalta Irene , Jiang Xingyu , Kim Woe-Yeon , Ali Zhair , Fujii Hiroaki , Mendoza Imelda , Yun Dae-Jin , Zhu Jian-Kang , Pardo Jose M.
Published: January 2011

The plasma membrane sodium/proton exchanger Salt-Overly-Sensitive 1 (SOS1) is a critical salt tolerance determinant in plants. The SOS2–SOS3 calcium-dependent protein kinase complex up-regulates SOS1 activity, but the mechanistic details of this crucial event remain unresolved. Here we show that SOS1 is maintained in a resting state by a C-terminal auto-inhibitory domain that is the target of SOS2–SOS3. The auto-inhibitory domain interacts intramolecularly with an adjacent domain of SOS1 that is essential for activity. SOS1 is relieved from auto-inhibition upon phosphorylation of the auto-inhibitory domain by SOS2–SOS3. Mutation of the SOS2 phosphorylation and recognition site impeded the activation of SOS1 in vivo and in vitro. Additional amino acid residues critically important for SOS1 activity and regulation were identified in a genetic screen for hypermorphic alleles.
Major global radiation of corvoid birds originated in the proto-Papuan archipelago
Authors: Jønsson Knud A. , Fabre Pierre-Henri , Ricklefs Robert E. , Fjeldså Jon
Published: January 2011

A central paradigm in island biogeography has been the unidirectional “downstream” colonization of islands from continents (source to sink) based on the idea that less-diverse island communities are easier to invade than biologically more-diverse continental communities. Recently, several cases of “upstream” colonization (from islands to continents) have been documented, challenging the traditional view. However, all these cases have involved individual island species that have colonized mainland regions. Here, using molecular phylogenetic data, divergence time estimates, lineage diversity distributions, and ancestral area analyses, we reconstruct the spread of a species-rich (>700 species) passerine bird radiation (core Corvoidea) from its late Eocene/Oligocene origin in the emerging proto-Papuan archipelago north of Australia, including multiple colonizations from the archipelago to Southeast Asia. Thus, islands apparently provided the setting for the initiation of a major songbird radiation that subsequently invaded all other continents. Morphological and behavioral adaptations of the core Corvoidea as generalist feeders in open habitats, which facilitated dispersal and colonization, apparently evolved in the descendants of sedentary forest birds that invaded the proto-Papuan archipelago. The archipelago evidently provided islands of the right size, number, and proximity to continental areas to support the adaptation and diversification of vagile colonizers that went on to increase avian diversity on a global scale.
De novo-engineered transcription activator-like effector (TALE) hybrid nuclease with novel DNA binding specificity creates double-strand breaks
Authors: Mahfouz Magdy M. , Li Lixin , Shamimuzzaman Md. , Wibowo Anjar , Fang Xiaoyun , Zhu Jian-Kang
Published: January 2011

Site-specific and rare cutting nucleases are valuable tools for genome engineering. The generation of double-strand DNA breaks (DSBs) promotes homologous recombination in eukaryotes and can facilitate gene targeting, additions, deletions, and inactivation. Zinc finger nucleases have been used to generate DSBs and subsequently, for genome editing but with low efficiency and reproducibility. The transcription activator-like family of type III effectors (TALEs) contains a central domain of tandem repeats that could be engineered to bind specific DNA targets. Here, we report the generation of a Hax3-based hybrid TALE nuclease with a user-selected DNA binding specificity. We show that the engineered TALE nuclease can bind to its target sequence in vitro and that the homodimeric TALE nuclease can cleave double-stranded DNA in vitro if the DNA binding sites have the proper spacing and orientation. Transient expression assays in tobacco leaves suggest that the hybrid nuclease creates DSB in its target sequence, which is subsequently repaired by nonhomologous end-joining repair. Taken together, our data show the feasibility of engineering TALE-based hybrid nucleases capable of generating site-specific DSBs and the great potential for site-specific genome modification in plants and eukaryotes in general.
Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A
Authors: Idoyaga Juliana , Lubkin Ashira , Fiorese Christopher , Lahoud Mireille H. , Caminschi Irina , Huang Yaoxing , Rodriguez Anthony , Clausen Björn E. , Park Chae Gyu , Trumpfheller Christine , Steinman Ralph M.
Published: January 2011

Improved protein-based vaccines should facilitate the goal of effective vaccines against HIV and other pathogens. With respect to T cells, the efficiency of immunization, or “immunogenicity,” is improved by targeting vaccine proteins to maturing dendritic cells (DCs) within mAbs to DC receptors. Here, we compared the capacity of Langerin/CD207, DEC205/CD205, and Clec9A receptors, each expressed on the CD8+DC subset in mice, to bring about immunization of microbial-specific T cells from the polyclonal repertoire, using HIV gag-p24 protein as an antigen. α-Langerin mAb targeted splenic CD8+DCs selectively in vivo, whereas α-DEC205 and α-Clec9A mAbs targeted additional cell types. When the mAb heavy chains were engineered to express gag-p24, the α-Langerin, α-DEC205, and α-Clec9A fusion mAbs given along with a maturation stimulus induced comparable levels of gag-specific T helper 1 (Th1) and CD8+T cells in BALB/c × C57BL/6 F1 mice. These immune T cells were more numerous than targeting the CD8−DC subset with α-DCIR2-gag-p24. In an in vivo assay in which gag-primed T cells were used to report the early stages of T-cell responses, α-Langerin, α-DEC205, and α-Clec9A also mediated cross-presentation to primed CD8+T cells if, in parallel to antigen uptake, the DCs were stimulated with α-CD40. α-Langerin, α-DEC205, and α-Clec9A targeting greatly enhanced T-cell immunization relative to nonbinding control mAb or nontargeted HIV gag-p24 protein. Therefore, when the appropriate subset of DCs is targeted with a vaccine protein, several different receptors expressed by that subset are able to initiate combined Th1 and CD8+immunity.
The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins
Authors: Bolliger Marc F. , Martinelli David C. , Südhof Thomas C.
Published: January 2011

C1q-like genes (C1ql1–C1ql4) encode small, secreted proteins that are expressed in differential patterns in the brain but whose receptors and functions remain unknown. BAI3 protein, in contrast, is a member of the cell-adhesion class of G protein-coupled receptors that are expressed at high levels in the brain but whose ligands have thus far escaped identification. Using a biochemical approach, we show that all four C1ql proteins bind to the extracellular thrombospondin-repeat domain of BAI3 with high affinity, and that this binding is mediated by the globular C1q domains of the C1ql proteins. Moreover, we demonstrate that addition of submicromolar concentrations of C1ql proteins to cultured neurons causes a significant decrease in synapse density, and that this decrease was prevented by simultaneous addition of the thrombospondin-repeat fragment of BAI3, which binds to C1ql proteins. Our data suggest that C1ql proteins are secreted signaling molecules that bind to BAI3 and act, at least in part, to regulate synapse formation and/or maintenance.
The malaria circumsporozoite protein has two functional domains, each with distinct roles as sporozoites journey from mosquito to mammalian host
Authors: Coppi Alida , Natarajan Ramya , Pradel Gabriele , Bennett Brandy L. , James Eric R. , Roggero Mario A. , Corradin Giampietro , Persson Cathrine , Tewari Rita , Sinnis Photini
Published: January 2011

Plasmodium sporozoites make a remarkable journey from the mosquito midgut to the mammalian liver. The sporozoite’s major surface protein, circumsporozoite protein (CSP), is a multifunctional protein required for sporozoite development and likely mediates several steps of this journey. In this study, we show that CSP has two conformational states, an adhesive conformation in which the C-terminal cell-adhesive domain is exposed and a nonadhesive conformation in which the N terminus masks this domain. We demonstrate that the cell-adhesive domain functions in sporozoite development and hepatocyte invasion. Between these two events, the sporozoite must travel from the mosquito midgut to the mammalian liver, and N-terminal masking of the cell-adhesive domain maintains the sporozoite in a migratory state. In the mammalian host, proteolytic cleavage of CSP regulates the switch to an adhesive conformation, and the highly conserved region I plays a critical role in this process. If the CSP domain architecture is altered such that the cell-adhesive domain is constitutively exposed, the majority of sporozoites do not reach their target organs, and in the mammalian host, they initiate a blood stage infection directly from the inoculation site. These data provide structure–function information relevant to malaria vaccine development.
First-wall erosion in fusion reactors
Authors: Behrisch R.
Published: January 2011

The subject of sputtering by ions and neutrons has been reviewed, and yields for various ions on Nb in the energy range of 100 eV to 100 keV have been assembled. Furthermore, evaporation rates of Nb for stationary conditions and for short time energy pulses are calculated, and a brief summary is given of the blistering phenomena.

For a Tokamak or Stellarator-type CTR first-wall bombardment is estimated from the a-energy released in the plasma. First-wall-erosion data as well as the flux of sputtered and evaporated Nb-atoms back to the plasma are calculated for two CTR reactors with a difference of a factor of 10 in first-wall load. It is shown that sputtering can account for wall deterioration at a rate of more than 1 mm per year.
Cross-section sensitivity of tritium breeding in a fusion reactor blanket: effects of uncertainties in cross-sections of6Li,7Li, and93Nb
Authors: Steiner D. , Tobias M.
Published: January 2011

The authors have examined the cross-section sensitivity of the tritium-breeding ratio in a fusion reactor blanket model which is representative of a large class of blanket configurations under current investigation. This blanket model exhibits the following tritium-breeding and neutronic characteristics: (1) liquid lithium of natural isotopic abundance is used for breeding; (2) the tritium-breeding ratio is in the “high” range, ∼ 1. 5; (3) graphite is employed for neutron moderation; and (4) the neutron leakage from the blanket is relatively low, ∼4% of the source neutrons. The sensitivity of the breeding ratio was evaluated by altering reference cross-section sets to reflect estimates of the uncertainties in the cross-section of the6Li(n, α)t, the7Li(n, n′α)t, and the93Nb(n,2n) reactions. Our analysis leads to the following observations:

The status of the6Li(n,α)t cross-section data appears adequate for accurate (of the order of ∼1%) tritium-breeding calculations. We emphasize that this observation applies to the class of blanket configurations considered here and that other classes must be examined to determine the generality of the observation.

Uncertainties in the cross-section and secondary-neutron energy distribution of the7Li(n, n′α)t reaction attach uncertainties in excess of 5% to the tritium-breeding ratio. A re-evaluation of the relevant data in the energy range above ∼ 10 MeV might provide a smaller uncertainty, and we recommend that such a re-evaluation be undertaken. Additional measurements may be required to reduce the uncertainty in the tritium-breeding ratio to the order of 1 to 2%.

Uncertainties in the (n, 2n) cross-section of93Nb attach uncertainties of ∼ 2.4% to the tritium-breeding ratio. New experimental data on the93Nb(n, 2n) cross-section are available, and a recent evaluation of this data suggests that the variations adopted here may reflect too pessimistic an estimate of the uncertainty. This point will be pursued in future studies

When the cross-sections of the6Li(n, α)t, the7Li(n, n′α) t, and the93Nb(n, 2n) reactions are varied simultaneously, the calculated uncertainty in the tritium-breeding ratio is ∼ 7 to 8%. This uncertainty approaches 10% when uncertainties in the secondary-neutron energy distribution of the7Li(n, n′α)t reaction are included.
Powerful relativistic electron beams in a plasma and in a vacuum (theory)
Authors: Brejzman B.N. , Ryutov D.D.
Published: January 2011

The possibility of using intense relativistic electron beams (REBs) for heating plasmas in open systems is discussed. Within this context the following three sets of problems are discussed:

REB transport in a vacuum with a strong magnetic field; beam equilibrium, stability and critical currents in a vacuum.

Beam transport in a plasma; charge and current neutralization of the beam; reverse-current heating of the plasma, and macroscopic REB instabilities in the plasma.

The theory of collective relaxation of REBs in a plasma, including quasi-linear and non-linear relaxation models; the role of plasma non-uniformity, and macroscopic effects during REB relaxation.
Density limit of tokamak experiments
Authors: Lehnert B.
Published: January 2011

Neutral gas which penetrates into a hot plasma body, of characteristic dimension
Lb, average density n̄ and temperature T, consists mainly of a slow and
a fast component, of densities nns, nnf and temperatures
Tns≪T, Tnf≃T, respectively. These components have the
penetration lengths Lns = l/σcsn̄ and Lnf=
1/σcfn̄, corresponding to the critical densities
ncs=1/σcsLb and
ncf=l/σcfLb where
l/σcf≃lOO/σcs≃5 × 1018 m−2 for
hydrogen in the range 106 < T < 107 K. Thus, hot plasmas
can be divided into the classes of permeable dilute, permeable non-dilute, and
impermeable systems defined by n̄⪅ncs≪ncf,
ncs≪n̄⪅ncf, and ncs ≪ ncf ≪ n̄,
respectively.

Concerning tokamaks, an analysis of the plasma-neutral gas interaction leads to the
following conclusions:

So far, all reported tokamak experiments have been conducted in the permeable
density range and have been limited by instabilities in the transition region
close to n̄ = ncf. Full-scale tokamak reactors should, on the other
hand, operate far inside the impermeable density range.

The driving force of instabilities due to the pressure gradient is expected to
reach its maximum value when n̄ approachesthe density limit ncf from below,
i.e. at the transition to the impermeable state.

The experimentally observed parameter values at the instability limit agree
with those calculated from the theory on collisionless ballooning modes driven
by the pressure gradient.
Confinement of a dense plasma by a static magnetic and stationary electromagnetic fields
Authors: Consoli Térenzio , Le Gardeur René , Slama Lucien
Published: January 2011

The confinement of a plasma by the radiation pressure of a stationary electromagnetic wave has been proposed and made the subject of experiments by different authors.

In these various projects and devices, the HF field creates and confines the plasma.

In the device described here one starts with a cavity containing a plasma that is pre-formed and pre-heated in order to fix the mode, to facilitate the tuning of the oscillators exciting the cavity and to permit investigation of the reduction in frequency resulting from the evolution of the plasma.

The initial plasma in the form of a spindle is strongly ionized (>> 50%) and of high density (> 1013e/cm3). The spherical cavity, in the absence of plasma, is resonant at ∼1130 MHz in the mode H101. The depth of penetration (< 2 mm) is a small fraction of the diameter of the plasma (∼6 cm). The plasma behaves like a metallic conductor.

Use of two H101modes perpendicular to one another in space gives a confinement with no gap.

The initial plasma is created by means of a pulsed reflex discharge (pulse length ∼100 μsec) of which the cavity constitutes the interanode section. Controllable densities from 1012to 1014e/cm3are readily obtained. The portion of the discharge situated outside the cavity allows the determination of the parameters of the discharge.

A system of eight pulsed auto-oscillators (total power 200 kW, pulse length ∼100 μsec) are coupled to the cavity and regulated in such a manner that oscillation frequency will be near the theoretical resonance frequency of the cavity containing the plasma.

In this way the radiation pressure is maintained in spite of the variations in diameter and form of the plasma. The power delivered increases progressively as the resistivity of the plasma diminishes.

The couplings of the oscillators to the cavity are capable of being oriented in an arbitrary manner. One can thus either fix the axis of the mode or choose an operational regime with one or two modes.

Windows are provided for the application of various diagnostic techniques:

ultra-fast cinematography and image convertor for the study of the evolution of the plasma

optical interferometry with time resolution (Perrot-Fabry) for the measurement of ion temperature

UHF interferometry at 8 and 4 mm for the determination of the electron density

Langmuir probes placed in the wall thickness and along the axis of a mode for the measurement of radial leakage flux.
Influence of the initial conditions on the adiabatic
compression of a column of plasma
Authors: Consoli Térenzio , Geller Richard , Le Gardeur René
Published: January 2011

In the CIRCE experimental apparatus we have chosen as a medium undergoing adiabatic
compression the plasma created by a pulsed reflex discharge, which is preheated by
oscillating electromagnetic fields. We have been able to realize the following
conditions necessary for an effective compression:

a quasi-thermalized medium, for which the ionic and electronic temperatures,
which can be measured and calculated, are of the order of a few electron volts

low pressure of neutrals outside the discharge with ionization greater than
70% in the plasma column

high initial charge density in order to have rapid thermalization;
ne = 1014 electrons/cm3

purity of the initial plasma

magnetic field trapped in the discharge uniform, reversable in direction and
well determined before the compression

finally, the possibility of varying at will the parameters electronic
temperature, ionic temperature, density of neutrals, electronic density, level
of ionization, compression magnetic field and mirror ratio.

Thanks to a battery of 28 capacitors of 2.5 μF and 25 kV, the compression apparatus
enables the production of a 70-kG magnetic field in a volume of 280 cm3.
The rise time is some 1.5 μsec. Provision is made for a short circuit permitting one
to prolong the duration of this field to 100 μsec.

Magnetic compression is thus applied to the ionized medium under well defined,
controlable and reproducible conditions, which can be made very close to the
hypotheses used in the theory of the phenomenon. The comparison of this theory with
experiment thus becomes particularly favorable.
The physics of DT ignition in small fusion targets
Authors: Kirkpatrick R.C. , Wheeler J.A.
Published: January 2011

Ignition of sub-milligram fusion targets is critically dependent on DT temperature, density, radius, radiation temperature, implosion velocity, and other parameters that characterize the target and its implosion. This paper discusses the interplay of such major physical processes as bremsstrahlung, Compton scattering, DT fusion, hydrodynamics, and thermal conduction during the implosion and especially near turnaround where the potential for ignition or failure most critically depends on the small differences between large rates of energy loss and gain. The phase plane analysis presented here proves to be most advantageous in understanding the DT ignition problem. Four examples are discussed in order to illustrate the interplay of the various physical processes.
Drift wave transport and origin of the disruption phenomenon – a theoretical model
Authors: Hasselberg G. , Rogister A.
Published: January 2011

The purpose of this paper is to demonstrate that the turbulence spectra and the electron heat fluxes derived from the theory of drift wave saturation presented recently are consistent with the discharge data from two tokamaks. It is shown that the calculated rapid increase in transport with increasing linear growth rate explains the observed relaxation of the profiles towards a weakly unstable state with respect to the trappedelectron instability. It is further suggested that the occurrence of sawtooth oscillations of the core can be interpreted in terms of drift instability quenching and anomalous heat flux clamping in the surrounding gradient layer. The high-density limit derived from this assumption agrees well with the observations.
The kinetics of nuclear processes in hot D6Li and DD plasmas
Authors: Voronchev V.T , Kukulin V.I , Krasnopol'Skij V.M
Published: January 2011

The paper is devoted to a detailed analysis of hot non-relativistic D6Li and DD plasmas. Non-isothermic processes in hot DD plasmas and their effect on energy release, loss, etc. are studied. The nonconventional D6Li plasma is investigated as a promising thermonuclear fuel. The presence of lithium in the deuterium plasma is shown to be an active factor increasing the energy release, as compared with the catalytic DD reaction, and to change the energy generation mechanism.
Tandem mirror experiments at the Lawrence Livermore National Laboratory
Authors: Simonen T.C.
Published: January 2011

The paper summarizes results from the-TMX and TMX-U tandem mirror experiments at the Lawrence Livermore National Laboratory.
Fusion Reactor Design IV (Report on the 4th IAEA Technical Committee Meeting and Workshop, Yalta, USSR, 26 May – 6 June 1986)
Authors: Abdou M.A. , Bertolini E. , Hancox R. , Hogan W.J. , Kostenko A.I. , Kulcinski G.L. , Miller R.L. , Orlov V.V. , Rau F. , Sviatoslavsky I.N. , Kupitz J.
Published: January 2011

The International Atomic Energy Agency convened, in the framework of its Fusion Technology and Engineering Programme, the 4th Technical Committee and Workshop on Fusion Reactor Design and Technology at Yalta, USSR, from 26 May – 6 June 1986. This report contains all summaries of sessions that were organized during the workshop. The papers presented at the meeting are being published by the Agency in its Proceedings Series.
Field reversed configurations
Authors: Tuszewski M.
Published: January 2011

The review is devoted to field reversed configurations and to the related field reversed mirrors; both are compact toroids with little or no toroidal magnetic field. Experimental and theoretical results on the formation, equilibrium, stability and confinement properties of these plasmas are presented. Although they have been known for about three decades, field reversed configurations have been studied intensively only in recent years. This renewed interest is due to the unusual fusion reactor potential of these high beta plasmas and also to their surprising macroscopic stability. At the present time, field reversed configurations appear to be completely free of gross instabilities and show relatively good confinement. The primary research goal for the near future is to retain these favourable properties in a less kinetic regime. Other important issues include the development of techniques for slow formation and stability, and a clearer assessment of the confinement scaling laws.
New density diagnostic method based on emission line intensity ratio of neutral hydrogen in an ionizing phase plasma
Authors: Fujimoto T. , Miyachi S. , Sawada K.
Published: January 2011

For high temperature hydrogen plasmas in the ionizing phase, the population density of the excited levels has been calculated for a wide range of electron densities and temperatures. In the calculation we employed the most recent and reliable cross-section data for excitation between discrete levels and the ionization cross-section data from these levels. The line intensity ratios calculated under conditions of optical thinness are presented graphically for the Lyman and Balmer series lines. The intensity ratios are found to be rather insensitive to the electron temperature for temperatures higher than 10 eV. These values may be used for determining the electron density in the region of 1017⪅ ne⪅ 1021m−3, which is relevant to fusion research plasmas. Radiation loss from the plasma and energy loss from the plasma electrons are also presented for a wide range of electron densities and temperatures.
Penetration of energetic neutral beams into fusion plasmas
Authors: Janev R.K. , Boley C.D. , Post D.E.
Published: January 2011

The efficiency of neutral beam heating and current drive depends crucially on the deposition of the energy and momentum of the beam in the plasma. This deposition is determined by the atomic processes involved in the stopping (or effective ionization) of the neutral beam atoms. These processes have been studied in detail for the energy range from 10 keV/u to 10 MeV/u. The processes considered include both the ground state and the excited state of the beam atoms, thus allowing for the multistep ionization of the beam in collisions with the plasma constituents and impurities. The effective beam stopping cross-section has been calculated for a wide variety of beam and plasma parameters. The atomic database necessary for these calculations has been documented using the best data available at present. The stopping cross-section data are also given in terms of a convenient analytic fit, which can be used either in computer calculations or for simpler analytic estimates of neutral beam penetration.
Bifurcating equilibria and hydromagnetic stability
Authors: Laval G. , Pellat R. , Rebut P. H.
Published: January 2011

The bifurcating equilibria of a family of hydromagnetic equilibria are defined and studied. It is shown that if the laws of motion satisfy certain very general conditions, the results of this study permit the formulation of a criterion necessary for stability.

A formalism independent of geometry is introduced and a variation principle is found from which the equilibrium equations are derived.

The method proposed is used to study the stability of plane, cylindrical and rotational equilibria, and the results are compared with those obtained with explicit laws of motion.

In cases of tubular configurations, a stricter criterion is obtained than that derived from classical magnetohydrodynamics since new possibilities of instability are taken into account corresponding to changes in topology of the magnetic surfaces.