bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient frequency doubling in femtosecond laser-written waveguides in lithium niobate
Authors: Burghoff Jonas , Grebing Christian , Nolte Stefan , Tünnermann Andreas
Published: August 2006

Optical waveguides in lithium niobate have been fabricated with a femtosecond laser. Different types of modifications depending on the laser parameters were observed and discussed. In these waveguides, frequency doubling of 1064nm radiation was demonstrated utilizing birefringent phase matching. A conversion efficiency of 49% was obtained in a 9.3mm long sample.
Multilayer buffer for high-temperature superconductor devices on MgO
Authors: Faley M. I. , Mi S. B. , Petraru A. , Jia C. L. , Poppe U. , Urban K.
Published: August 2006

A multilayer thin film epitaxial passivation of single crystal MgO substrates was developed. YBa2Cu3O7−x films on the buffered MgO substrates demonstrate pure c-axis orientation, absence of in-plane disoriented grains, transition temperature Tc>91K, and critical current density Jc∼5MA∕cm2 at 77.4K and were deposited in thicknesses of up to several micrometers without cracks. High-temperature superconductor multilayer flux transformers of 2μm thickness on the buffered MgO substrates demonstrated improved insulation between the superconducting layers and an increased dynamic range compared to flux transformers on SrTiO3 substrates.
Five-cross microfluidic network design free of coupling between electrophoretic motion and electro-osmotic flow
Authors: Hu Xin , Wang Shengnian , Juang Yi-Je , Lee L. James
Published: August 2006

Electro-osmotic and electrophoretic interactions are a major concern in the electrokinetic-based microfluidics, in particular, when the electrophoretic mobility of charged particles is greater than the surface electro-osmotic mobility. In this letter, a microfluidic device without surface charge patterning on the channel walls is introduced. Unlike the previous microfluidic devices, the charged particle movements in this five-cross design are largely independent of their charge density and polarity. Different flow patterns (i.e., extensional, mixed shear, and rotational flows) can be generated in this single design and can be quickly switched by just changing the external voltage inputs. The observed flow patterns of charged polystyrene microspheres and λ-DNA molecules in buffer solutions agree well with simulation results.
Comments on ‘‘Stability of shear flow in a magnetized plasma’’
Authors: Shivamoggi Bhimsen K.
Published: August 2006

A comment is made on ‘‘Stability of Shear Flow in a Magnetized Plasma’’ by Y. Y. Lau and C. S. Liu. (AIP)
An Expansion of the Role of the Corey - Link Reaction for the Synthesis of α-Substituted Carboxylic Acid Esters
Authors: Scaffidi Adrian , Skelton Brian W. , Stick Robert V. , White Allan H.
Published: August 2006

The treatment of 1,2:5,6-di-O-isopropylidene-α-d-ribo-hexos-3-ulose with chloroform under basic conditions has yielded the normal 3-C-trichloromethyl-α-d-allofuranose derivative. Under the conditions of the modified Corey–Link reaction but with a nucleophile different from the usual azide, a range of α-substituted carboxylic acid esters (and one amide) has been obtained. A similar addition of bromoform to the ulose has formed the α-bromo methyl ester. Two attempts at forming an ‘inositol α-amino acid’ from a polyhydroxylated cyclohexanone failed.
Single-crystal X-ray structure determinations are reported for (3S)-1,2:5,6-di-O-isopropylidene-3-C-methoxycarbonyl-3-S-phenyl-3-thio-α-d-ribo-hexose, (3S)-1,2:5,6-di-O-isopropylidene-3-S-phenyl-3-C-(phenylthio)carbonyl-3-thio-α-d-ribo-hexose, 3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-methoxycarbonyl-α-d-erythro-hex-3-enofuranose, 4,6-di-O-benzyl-2-C-trichloromethyl-scyllo-inositol 1,3,5-orthoformate, 2,2'-anhydro-4,6-di-O-benzyl-2-C-dichlorohydroxymethyl-scyllo-inositol 1,3,5-orthoformate, 1,3,4,5,6-penta-O-benzyl-2-C-trichloromethyl-myo-inositol, and 2-amino-1,3,4,5,6-penta-O-benzyl-2-C-cyano-2-deoxy-myo-inositol.
Determination of the Anomeric Configurations of 2,3,4,6-Tetra-O-Acetyl-D-Mannopyranosyl Azide
Authors: Cosgrove Kelly L. , Bernhardt Paul V. , Ross Benjamin P. , McGeary Ross P.
Published: August 2006

The structures of 2,3,4,6-tetra-O-acetyl-α-d-mannopyranosyl azide and 2,3,4,6-tetra-O-acetyl-β-d-mannopyranosyl azide were determined using X-ray crystallographic and one-dimensional NOESY techniques.
Synthesis and Biological Activity of Allosteric Modulators of GABAB Receptors, Part 2. 3-(2,6-Bis-tert-butyl-4-hydroxyphenyl)propanols
Authors: Kerr David I. B. , Khalafy Jabbar , Ong Jennifer , Perkins Michael V. , Prager Rolf H. , Puspawati Ni Made , Rimaz Mehdi
Published: August 2006

A series of 13 2,2-disubstituted 3-(3,5-di-t-butyl-4-hydroxyphenyl)propan-1-ol derivatives have been prepared for evaluation as allosteric modulators of GABAB receptors. The activity (EC50, 4–7 μM) was greatest for the cyclohexyl and cyclopentyl analogues.
Assembly of the 1-Azaspiro[5.5]undecane Framework Associated with Perhydrohistrionicotoxin via Electrocyclic Ring-Opening of a Ring-Fused gem-Dichlorocyclopropane and Trapping of the Resulting π-Allyl Cation by a Tethered, Nitrogen-Centered Nucleophile
Authors: Banwell Martin G. , Vogt Florian , Wu Angela W.
Published: August 2006

The carbamate-tethered gem-dichlorocyclopropane 27 was prepared, as a mixture of epimers, in ten steps from commercially available β,γ-unsaturated nitrile 9. Upon treatment with silver acetate under a range of reaction conditions, compound 27 underwent electrocyclic ring opening to give the corresponding π-allyl cation that was then trapped by the reaction solvent, chloride ion, and/or acetate ion, and so affording varying mixtures of the chlorocyclohexenes 28, 29, 30, and/or 31. Sequential treatment of the same substrate with LiHMDS (to generate the conjugate base of this carbamate) then silver tetrafluoroborate afforded the chlorocyclohexadiene 32 as the exclusive product of reaction. No spirocyclization product of the type 3 arising from trapping of the intermediate π-allyl cation by the tethered carbamate was observed under any of the reaction conditions examined. In contrast, analogous treatment of the more rigid system 38 afforded compound 39 incorporating the 1-azaspiro[5.5]undecane framework associated with the potent neurotoxin perhydrohistrionicotoxin (2).
Kelch-repeat proteins interacting with the G
α
protein Gpa2 bypass adenylate cyclase for direct regulation of protein kinase A in yeast
Authors: Peeters Tom , Louwet Wendy , Geladé Ruud , Nauwelaers David , Thevelein Johan M. , Versele Matthias
Published: August 2006

The cAMP–PKA pathway consists of an extracellular ligand-sensitive G protein-coupled receptor, a G protein signal transmitter, and the effector, adenylate cyclase, of which the product, cAMP, acts as an intracellular second messenger. cAMP activates PKA by dissociating the regulatory subunit from the catalytic subunit. Yeast cells (
Saccharomyces cerevisiae
) contain a glucose/sucrose-sensitive seven-transmembrane domain receptor, Gpr1, that was proposed to activate adenylate cyclase through the G
α
protein Gpa2. Consistently, we show here that adenylate cyclase binds only to active, GTP-bound Gpa2. Two related kelch-repeat proteins, Krh1/Gpb2 and Krh2/Gpb1, are associated with Gpa2 and were suggested to act as G
β
mimics for Gpa2, based on their predicted seven-bladed β-propeller structure. However, we find that although Krh1 associates with both GDP and GTP-bound Gpa2, it displays a preference for GTP-Gpa2. The strong down-regulation of PKA targets by Krh1 and Krh2 does not require Gpa2 but is strictly dependent on both the catalytic and the regulatory subunits of PKA. Krh1 directly interacts with PKA by means of the catalytic subunits, and Krh1/2 stimulate the association between the catalytic and regulatory subunits
in vivo
. Indeed, both a constitutively active
GPA2
allele and deletion of
KRH1/2
lower the cAMP requirement of PKA for growth. We propose that active Gpa2 relieves the inhibition imposed by the kelch-repeat proteins on PKA, thereby bypassing adenylate cyclase for direct regulation of PKA. Importantly, we show that Krh1/2 also enhance the association between mouse R and C subunits, suggesting that Krh control of PKA has been evolutionarily conserved.
Surface-modulated motion switch: Capture and release of iron–sulfur protein in the cytochrome
bc
1
complex
Authors: Esser Lothar , Gong Xing , Yang Shaoqing , Yu Linda , Yu Chang-An , Xia Di
Published: August 2006

In the cytochrome
bc
1
complex, the swivel motion of the iron–sulfur protein (ISP) between two redox sites constitutes a key component of the mechanism that achieves the separation of the two electrons in a substrate molecule at the quinol oxidation (Q
o
) site. The question remaining is how the motion of ISP is controlled so that only one electron enters the thermodynamically favorable chain via ISP. An analysis of eight structures of mitochondrial
bc
1
with bound Q
o
site inhibitors revealed that the presence of inhibitors causes a bidirectional repositioning of the cd1 helix in the cytochrome
b
subunit. As the cd1 helix forms a major part of the ISP binding crater, any positional shift of this helix modulates the ability of cytochrome
b
to bind ISP. The analysis also suggests a mechanism for reversal of the ISP fixation when the shape complementarity is significantly reduced after a positional reorientation of the reaction product quinone. The importance of shape complementarity in this mechanism was confirmed by functional studies of
bc
1
mutants and by a structure determination of the bacterial form of
bc
1
. A mechanism for the high fidelity of the bifurcated electron transfer is proposed.
A climate-change risk analysis for world ecosystems
Authors: Scholze Marko , Knorr Wolfgang , Arnell Nigel W. , Prentice I. Colin
Published: August 2006

We quantify the risks of climate-induced changes in key ecosystem processes during the 21st century by forcing a dynamic global vegetation model with multiple scenarios from 16 climate models and mapping the proportions of model runs showing forest/nonforest shifts or exceedance of natural variability in wildfire frequency and freshwater supply. Our analysis does not assign probabilities to scenarios or weights to models. Instead, we consider distribution of outcomes within three sets of model runs grouped by the amount of global warming they simulate: <2°C (including simulations in which atmospheric composition is held constant, i.e., in which the only climate change is due to greenhouse gases already emitted), 2–3°C, and >3°C. High risk of forest loss is shown for Eurasia, eastern China, Canada, Central America, and Amazonia, with forest extensions into the Arctic and semiarid savannas; more frequent wildfire in Amazonia, the far north, and many semiarid regions; more runoff north of 50°N and in tropical Africa and northwestern South America; and less runoff in West Africa, Central America, southern Europe, and the eastern U.S. Substantially larger areas are affected for global warming >3°C than for <2°C; some features appear only at higher warming levels. A land carbon sink of ≈1 Pg of C per yr is simulated for the late 20th century, but for >3°C this sink converts to a carbon source during the 21st century (implying a positive climate feedback) in 44% of cases. The risks continue increasing over the following 200 years, even with atmospheric composition held constant.
A repressor complex, AP4 transcription factor and geminin, negatively regulates expression of target genes in nonneuronal cells
Authors: Kim Mi-Young , Jeong Byung Chul , Lee Ji Hee , Kee Hae Jin , Kook Hyun , Kim Nack Sung , Kim Yoon Ha , Kim Jong-Keun , Ahn Kyu Youn , Kim Kyung Keun
Published: August 2006

The transcription of neuron-specific genes must be repressed in nonneuronal cells. REST/NRSF is a transcription factor that restricts the expression of many neuronal genes through interaction with the neuron-restrictive silencer element at the promoter level. PAHX-AP1 is a neuronal gene that is developmentally up-regulated in the adult mouse brain but that has no functional NRSE motif in its 5′ upstream sequence. Here, we report that the transcription factor AP4 and the corepressor geminin form a functional complex in which SMRT and histone deacetylase 3 are recruited. The functional complex represses PAHX-AP1 expression in nonneuronal cells and participates in regulating the developmental expression of PAHX-AP1 in the brain. This complex also serves as a transcriptional repressor of DYRK1A, a candidate gene for Down’s syndrome. Furthermore, compared with that in normal fetal brain, the expression of AP4 and geminin is reduced in Down’s syndrome fetal brain at 20 weeks of gestation age, at which time premature overexpression of dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A) is observed. Our findings indicate that AP4 and geminin act as a previously undescribed repressor complex distinct from REST/NRSF to negatively regulate the expression of target genes in nonneuronal cells and suggest that the AP4–geminin complex may contribute to suppressing the precocious expression of target genes in fetal brain.
Direct stimulation of T lymphocytes by immunosomes: Virus-like particles decorated with T cell receptor/CD3 ligands plus costimulatory molecules
Authors: Derdak Sophia V. , Kueng Hans J. , Leb Victoria M. , Neunkirchner Alina , Schmetterer Klaus G. , Bielek Edith , Majdic Otto , Knapp Walter , Seed Brian , Pickl Winfried F.
Published: August 2006

Many infectious viruses coevolved with the vertebrate immune system. During the assembly of enveloped viruses, lipid ordered domains of the host cell plasma membrane, called lipid rafts, frequently function as a natural meeting point for viral proteins. The role of lipid rafts in the organization of complex combinations of immune receptors during antigen presentation and T cell signaling is widely recognized. In our studies, we determined whether lipid rafts, virus budding, and molecular interactions during T cell activation could be brought into a novel context to create artificial antigen-presenting particles. We show here that cell-free virus-like particles (VLP) expressing a surrogate TCR/CD3 ligand (OKT3scFv) and the costimulator CD80 polyclonally activate human T cells independently of accessory cells. VLP expressing the glycoprotein epitope 33–41 of the lymphocytic choriomeningitis virus in the context of H-2D
b
activate and expand naïve, antigen-specific CD8
+
T lymphocytes and differentiate them into cytotoxic effector cells. Efficient targeting of T cell ligands to lipid rafts and ultimately to VLP is achieved by C-terminal introduction of glycosyl phosphatidyl inositol acceptor sequences, replacing transmembrane and intracellular domains. In this work, basic functions of immunostimulatory molecules meet virus biology and translate into a reductionist antigen-specific T lymphocyte-stimulating vehicle, which we refer to as immunosomes. A large variety of agonistic and antagonistic accessory molecules on genuine antigen-presenting cells may complicate the predictable manipulation of T cells as well as the analysis of selected receptor combinations, making immunosomes potentially useful reagents for such purposes in the future.
Plague dynamics are driven by climate variation
Authors: Stenseth Nils Chr. , Samia Noelle I. , Viljugrein Hildegunn , Kausrud Kyrre Linné , Begon Mike , Davis Stephen , Leirs Herwig , Dubyanskiy V. M. , Esper Jan , Ageyev Vladimir S. , Klassovskiy Nikolay L. , Pole Sergey B. , Chan Kung-Sik
Published: August 2006

The bacteriumYersinia pestiscauses bubonic plague. In Central Asia, where human plague is still reported regularly, the bacterium is common in natural populations of great gerbils. By using field data from 1949–1995 and previously undescribed statistical techniques, we show thatY. pestisprevalence in gerbils increases with warmer springs and wetter summers: A 1°C increase in spring is predicted to lead to a >50% increase in prevalence. Climatic conditions favoring plague apparently existed in this region at the onset of the Black Death as well as when the most recent plague pandemic arose in the same region, and they are expected to continue or become more favorable as a result of climate change. Threats of outbreaks may thus be increasing where humans live in close contact with rodents and fleas (or other wildlife) harboring endemic plague.
OX40 ligand shuts down IL-10-producing regulatory T cells
Authors: Ito Tomoki , Wang Yui-Hsi , Duramad Omar , Hanabuchi Shino , Perng Olivia A. , Gilliet Michel , Qin F. Xiao-Feng , Liu Yong-Jun
Published: August 2006

IL-10-producing CD4
+
type 1 regulatory T (Tr1) cells play a critical role in the maintenance of peripheral tolerance. Although immunosuppressive drugs, cytokines, costimulatory molecules, and immature dendritic cells are implicated in the induction of Tr1 cells, the signals that negatively regulate the generation and function of Tr1 cells have been elusive. We report that OX40 ligand (OX40L) completely inhibited the generation of IL-10-producing Tr1 cells from naïve and memory CD4
+
T cells induced by the immunosuppressive drugs dexamethasone and vitamin D3. This unique function of OX40L was not shared by two costimulatory TNF family members, GITR ligand and 4-1BB ligand. OX40L strongly inhibited the generation of IL-10-producing Tr1 cells induced by two physiologic stimuli, the inducible costimulatory ligand and immature dendritic cells. In addition, OX40L strongly inhibited IL-10 production and suppressive function of differentiated IL-10-producing Tr1 cells. These two novel functions of OX40L shed light on the mechanism by which OX40/OX40L regulates immunity and tolerance.
Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival inToxoplasma gondii
Authors: Mazumdar Jolly , H. Wilson Emma , Masek Kate , A. Hunter Christopher , Striepen Boris
Published: August 2006

Apicomplexan parasites are the cause of numerous important human diseases including malaria and AIDS-associated opportunistic infections. Drug treatment for these diseases is not satisfactory and is threatened by resistance. The discovery of the apicoplast, a chloroplast-like organelle, presents drug targets unique to these parasites. The apicoplast-localized fatty acid synthesis (FAS II) pathway, a metabolic process fundamentally divergent from the analogous FAS I pathway in humans, represents one such target. However, the specific biological roles of apicoplast FAS II remain elusive. Furthermore, the parasite genome encodes additional and potentially redundant pathways for the synthesis of fatty acids. We have constructed a conditional null mutant of acyl carrier protein, a central component of the FAS II pathway inToxoplasma gondii. Loss of FAS II severely compromises parasite growth in culture. We show FAS II to be required for the activation of pyruvate dehydrogenase, an important source of the metabolic precursor acetyl-CoA. Interestingly, acyl carrier protein knockout also leads to defects in apicoplast biogenesis and a consequent loss of the organelle. Most importantly,in vivoknockdown of apicoplast FAS II in a mouse model results in cure from a lethal challenge infection. In conclusion, our study demonstrates a direct link between apicoplast FAS II functions and parasite survival and pathogenesis. Our genetic model also offers a platform to dissect the integration of the apicoplast into parasite metabolism, especially its postulated interaction with the mitochondrion.
Evidence for stroke-induced neurogenesis in the human brain
Authors: Jin Kunlin , Wang Xiaomei , Xie Lin , Mao Xiao Ou , Zhu Wei , Wang Yin , Shen Jianfeng , Mao Ying , Banwait Surita , Greenberg David A.
Published: August 2006

Experimental stroke in rodents stimulates neurogenesis and migration of newborn neurons from their sites of origin into ischemic brain regions. We report that in patients with stroke, cells that express markers associated with newborn neurons are present in the ischemic penumbra surrounding cerebral cortical infarcts, where these cells are preferentially localized in the vicinity of blood vessels. These findings suggest that stroke-induced compensatory neurogenesis may occur in the human brain, where it could contribute to postischemic recovery and represent a target for stroke therapy.
Spontaneous and evoked synaptic rewiring in the neonatal neocortex
Authors: Le Bé Jean-Vincent , Markram Henry
Published: August 2006

The local microcircuitry of the neocortex is structurally a tabula rasa, with the axon of each pyramidal neuron having numerous submicrometer appositions with the dendrites of all neighboring pyramidal neurons, but is functionally highly selective, with synapses formed onto only a small proportion of these targets. This design leaves a vast potential for the microcircuit to rewire without extensive axonal or dendritic growth. To examine whether rewiring does take place, we used multineuron patch-clamp recordings on 12- to 14-day-old rat neocortical slices and studied long-term changes in synaptic connectivity within clusters of neurons. We found pyramidal neurons spontaneously connecting and disconnecting from each other and that exciting the slice with glutamate greatly increases the number of new connections established. Evoked emergence of new synaptic connections requires action potential activity and activation of metabotropic glutamate receptor 5, but not NMDA receptor or group II or group III metabotropic glutamate receptor activation. We also found that it is the weaker connections that are selectively eliminated. These results provide direct evidence for spontaneous and evoked rewiring of the neocortical microcircuitry involving entire functional multisynaptic connections. We speculate that this form of microcircuit plasticity enables an evolution of the microcircuit connectivity by natural selection as a function of experience.
Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects
Authors: Govindarajan Arvind , Rao B. S. Shankaranarayana , Nair Deepti , Trinh Mimi , Mawjee Nadya , Tonegawa Susumu , Chattarji Sumantra
Published: August 2006

Although neurotrophins have been postulated to have antidepressant properties, their effect on anxiety is not clear. We find that transgenic overexpression of the neurotrophin BDNF has an unexpected facilitatory effect on anxiety-like behavior, concomitant with increased spinogenesis in the basolateral amygdala. Moreover, anxiogenesis and amygdalar spinogenesis are also triggered by chronic stress in control mice but are occluded by BDNF overexpression, thereby suggesting a role for BDNF signaling in stress-induced plasticity in the amygdala. BDNF overexpression also causes antidepressant effects, because transgenic mice exhibit improved performance on the Porsolt forced-swim test and an absence of chronic stress-induced hippocampal atrophy. Thus, structural changes in the amygdala and hippocampus, caused by genetic manipulation of the same molecule BDNF, give rise to contrasting effects on anxiety and depressive symptoms, both of which are major behavioral correlates of stress disorders.
ETHYLENE-INSENSITIVE5
encodes a 5′→3′ exoribonuclease required for regulation of the EIN3-targeting F-box proteins EBF1/2
Authors: Olmedo Gabriela , Guo Hongwei , Gregory Brian D. , Nourizadeh Saeid D. , Aguilar-Henonin Laura , Li Hongjiang , An Fengying , Guzman Plinio , Ecker Joseph R.
Published: August 2006

Ethylene is a gaseous plant growth regulator that controls a multitude of developmental and stress responses. Recently, the levels of
Arabidopsis
EIN3 protein, a key transcription factor mediating ethylene-regulated gene expression, have been demonstrated to increase in response to the presence of ethylene gas. Furthermore, in the absence of ethylene, EIN3 is quickly degraded through a ubiquitin/proteasome pathway mediated by two F-box proteins, EBF1 and EBF2. Here we report the identification of
ETHYLENE-INSENSITIVE5
as the 5′→3′ exoribonuclease
XRN4
. Specifically, we demonstrate that EIN5 is a component of the ethylene signal transduction cascade acting downstream of CTR1 that is required for ethylene-mediated gene expression changes. Furthermore, we find that the ethylene insensitivity of
ein5
mutant plants is a consequence of the over-accumulation of
EBF1
and
EBF2
mRNAs resulting in the under-accumulation of EIN3 even in the presence of ethylene gas. Together, our results suggest that the role of EIN5 in ethylene perception is to antagonize the negative feedback regulation on EIN3 by promoting
EBF1
and
EBF2
mRNA decay, which consequently allows the accumulation of EIN3 protein to trigger the ethylene response.
Partially redundant functions of two SET-domain polycomb-group proteins in controlling initiation of seed development in
Arabidopsis
Authors: Wang Dongfang , Tyson Mark D. , Jackson Shawn S. , Yadegari Ramin
Published: August 2006

In
Arabidopsis
, a complex of Polycomb-group (PcG) proteins functions in the female gametophyte to control the initiation of seed development. Mutations in the PcG genes, including
MEDEA
(
MEA
) and
FERTILIZATION-INDEPENDENT SEED 2
(
FIS2
), produce autonomous seeds where endosperm proliferation occurs in the absence of fertilization. By using a yeast two-hybrid screen, we identified MEA and a related protein, SWINGER (SWN), as SET-domain partners of FIS2. Localization data indicated that all three proteins are present in the female gametophyte. Although single-mutant
swn
plants did not show any defects,
swn
mutations enhanced the
mea
mutant phenotype in producing autonomous seeds. Thus, MEA and SWN perform partially redundant functions in controlling the initiation of endosperm development before fertilization in
Arabidopsis
.
The cyanobacterial genome core and the origin of photosynthesis
Authors: Mulkidjanian Armen Y. , Koonin Eugene V. , Makarova Kira S. , Mekhedov Sergey L. , Sorokin Alexander , Wolf Yuri I. , Dufresne Alexis , Partensky Frédéric , Burd Henry , Kaznadzey Denis , Haselkorn Robert , Galperin Michael Y.
Published: August 2006

Comparative analysis of 15 complete cyanobacterial genome sequences, including “near minimal” genomes of five strains of
Prochlorococcus
spp., revealed 1,054 protein families [core cyanobacterial clusters of orthologous groups of proteins (core CyOGs)] encoded in at least 14 of them. The majority of the core CyOGs are involved in central cellular functions that are shared with other bacteria; 50 core CyOGs are specific for cyanobacteria, whereas 84 are exclusively shared by cyanobacteria and plants and/or other plastid-carrying eukaryotes, such as diatoms or apicomplexans. The latter group includes 35 families of uncharacterized proteins, which could also be involved in photosynthesis. Only a few components of cyanobacterial photosynthetic machinery are represented in the genomes of the anoxygenic phototrophic bacteria
Chlorobium tepidum, Rhodopseudomonas palustris, Chloroflexus aurantiacus
, or
Heliobacillus mobilis
. These observations, coupled with recent geological data on the properties of the ancient phototrophs, suggest that photosynthesis originated in the cyanobacterial lineage under the selective pressures of UV light and depletion of electron donors. We propose that the first phototrophs were anaerobic ancestors of cyanobacteria (“procyanobacteria”) that conducted anoxygenic photosynthesis using a photosystem I-like reaction center, somewhat similar to the heterocysts of modern filamentous cyanobacteria. From procyanobacteria, photosynthesis spread to other phyla by way of lateral gene transfer.
Neural correlate of subjective sensory experience gradually builds up across cortical areas
Authors: de Lafuente Victor , Romo Ranulfo
Published: August 2006

When a sensory stimulus is presented, many cortical areas are activated, but how does the representation of a sensory stimulus evolve in time and across cortical areas during a perceptual judgment? We investigated this question by analyzing the responses from single neurons, recorded in several cortical areas of parietal and frontal lobes, while trained monkeys reported the presence or absence of a mechanical vibration of varying amplitude applied to the skin of one fingertip. Here we show that the strength of the covariations between neuronal activity and perceptual judgments progressively increases across cortical areas as the activity is transmitted from the primary somatosensory cortex to the premotor areas of the frontal lobe. This finding suggests that the neuronal correlates of subjective sensory experience gradually build up across somatosensory areas of the parietal lobe and premotor cortices of the frontal lobe.
Tripodal saltren Al(iBu)(Cl)3
Authors: Mitra Amitabha , Wei Pingrong , Atwood David A.
Published: August 2006

The compound saltren[AliBuCl]3 (1) has been prepared by the reaction of the tripodal ligand saltrenH3 (tris(((2-hydroxybenzyl)amino)ethyl)amine) and di-isobutyl aluminum chloride. It has been characterized by physical (mp, EA), spectroscopic (1H NMR, IR) and structural (single crystal X-ray diffraction) studies. 1 crystallizes in the trigonal space group P-3. The structure is a trimetallic monomer. Each aluminum atom is four-coordinate with a distorted tetrahedral geometry. It is the first main group halide compound of the saltren ligand.
The shapes of hypoelectronic six-vertex anionic bare boron clusters: Effects of the countercations
Authors: King R. B. , Silaghi-Dumitrescu I. , Lupan A. , Kun A.
Published: August 2006

RHF/6-31G(d) calculations have been carried out on the hypoelectronic six-vertex boron cluster anions B6z− (z = 6 and 4) as well as the corresponding alkali metal derivatives B6Mz (z = 6 and 4; M = Na and Li) and the isoelectronic B6H6 and B6H62+. Using such computational methods, the introduction of alkali metal counterions was found to have relatively little effect on the general structural patterns of the lowest lying structures for these clusters. However, introduction of external hydrogen atoms (i.e., protonation of B66− to B6H6 and B64− to B6H62+) was found to lead to more open structures in the boron network relative to the corresponding alkali metal derivatives because of the need to divert boron valence orbitals from skeletal bonding to covalent bonds to the external hydrogens. The preferred structures of a bicapped tetrahedron for 12 skeletal electron systems derived from B66− and a planar network of four fused triangles for 10 skeletal electron systems derived from B64− can be rationalized both by localized and delocalized chemical bonding models.
Characterization, kinetics of thermal decomposition and molecular modeling studies on mercury (II) complexes of biologically active glutathione
Authors: Singh Bibhesh K. , Sharma Rakesh K. , Garg Bhagwan S.
Published: August 2006

Mercury (II) complexes of reduced glutathione (GSH) of general composition [Hg(L)(X)]H2O (where HL = GSH; X = NO3−, SCN−, CH3CO2−, Cl−) have been synthesized and characterized by elemental analysis, infrared spectra and electronic spectral studies. The stability constant of the mercury complex has been evaluated potentiometrically, and thermogravimetric (TG) and differential thermal analytical (DTA) studies have also been carried out for these complexes. Infrared spectra indicate deprotonation and coordination of cysteinyl sulfur with the metal ions. It indicates the presence of water molecules in all the complexes which has been supported by TG and DTA studies. The thermal behavior of complexes shows that the water molecule is removed in first step, followed by the removal of anions and then decomposition of the ligand molecule in subsequent steps. General mechanisms describing the decomposition of the solid complexes are suggested. Kinetic and thermodynamic parameters were computed from the thermal decomposition data. The geometry of the metal complexes has been optimized with the help of molecular modeling.
Metacognitive inferences in source memory judgements: The role of perceived differences in item recognition
Authors: Meiser Thorsten , Sattler Christine , Von Hecker Ulrich
Published: August 2006

This research investigated the hypothesis that metacognitive inferences in source memory judgements are based on the recognition or nonrecognition of an event together with perceived or expected differences in the recognizability of events from different sources. The hypothesis was tested with a multinomial source-monitoring model that allowed separation of source-guessing tendencies for recognized and unrecognized items. Experiments 1A and 1B manipulated the number of item presentations as relevant source information and revealed differential guessing tendencies for recognized and unrecognized items, with a bias to attribute unrecognized items to the source associated with poor item recognition. Experiments 2A and 2B replicated the findings with a manipulation of presentation time and extended the analysis to subjective differences in item recognition. Experiments 3A and 3B used more natural source information by varying type of acoustic signal and demonstrated that subjective theories about differences in item recognition are sufficient to elicit differential source-guessing biases for recognized and unrecognized items. Together the findings provide new insights into the cognitive processes underlying source memory decisions, which involve episodic memory and reconstructive tendencies based on metacognitive beliefs and general world knowledge.
Specificity in reactive oxidant signaling: think globally, act locally
Authors: Terada Lance S.
Published: August 2006

Although reactive oxidants have long been stigmatized as unwanted metabolic byproducts, the expression of oxidases specifically functioning to produce these same molecules in a regulated fashion is surprisingly pervasive throughout metazoan and plant evolution. Although the involvement of oxidants in many signaling pathways is well documented, the cellular strategies for conferring pathway specificity to such reactive molecules have remained more recondite. Recent studies now suggest that cells may spatially restrict oxidant production to allow microdomain-specific signaling.
Membrane binding of the bacterial signal recognition particle receptor involves two distinct binding sites
Authors: Angelini Sandra , Boy Diana , Schiltz Emile , Koch Hans-Georg
Published: August 2006

Cotranslational protein targeting in bacteria is mediated by the signal recognition particle (SRP) and FtsY, the bacterial SRP receptor (SR). FtsY is homologous to the SRα subunit of eukaryotes, which is tethered to the membrane via its interaction with the membrane-integral SRβ subunit. Despite the lack of a membrane-anchoring subunit, 30% of FtsY in Escherichia coli are found stably associated with the cytoplasmic membrane. However, the mechanisms that are involved in this membrane association are only poorly understood. Our data indicate that membrane association of FtsY involves two distinct binding sites and that binding to both sites is stabilized by blocking its GTPase activity. Binding to the first site requires only the NG-domain of FtsY and confers protease protection to FtsY. Importantly, the SecY translocon provides the second binding site, to which FtsY binds to form a carbonate-resistant 400-kD FtsY–SecY translocon complex. This interaction is stabilized by the N-terminal A-domain of FtsY, which probably serves as a transient lipid anchor.
The nuclear receptor LRH-1 critically regulates extra-adrenal glucocorticoid synthesis in the intestine
Authors: Mueller Matthias , Cima Igor , Noti Mario , Fuhrer Andrea , Jakob Sabine , Dubuquoy Laurent , Schoonjans Kristina , Brunner Thomas
Published: August 2006

The nuclear receptor liver receptor homologue-1 (LRH-1, NR5A2) is a crucial transcriptional regulator of many metabolic pathways. In addition, LRH-1 is expressed in intestinal crypt cells where it regulates the epithelial cell renewal and contributes to tumorigenesis through the induction of cell cycle proteins. We have recently identified the intestinal epithelium as an important extra-adrenal source of immunoregulatory glucocorticoids. We show here that LRH-1 promotes the expression of the steroidogenic enzymes and the synthesis of corticosterone in murine intestinal epithelial cells in vitro. Interestingly, LRH-1 is also essential for intestinal glucocorticoid synthesis in vivo, as LRH-1 haplo-insufficiency strongly reduces the intestinal expression of steroidogenic enzymes and glucocorticoid synthesis upon immunological stress. These results demonstrate for the first time a novel role for LRH-1 in the regulation of intestinal glucocorticoid synthesis and propose LRH-1 as an important regulator of intestinal tissue integrity and immune homeostasis.
Elimination of chronic viral infection by blocking CD27 signaling
Authors: Matter Matthias , Odermatt Bernhard , Yagita Hideo , Nuoffer Jean-Marc , Ochsenbein Adrian F.
Published: August 2006

Neutralizing antibody (nAb) responses to lymphocytic choriomeningitis virus (LCMV) in mice and immunodeficiency virus and hepatitis C virus in humans are usually weak and slow to develop. This may be the result of structural properties of the surface glycoprotein, a low frequency of B cells with neutralizing specificity, and the necessity of prolonged affinity maturation of specific nAbs. In this study, we show that during LCMV infection, CD27 signaling on CD4+ T cells enhances the secretion of interferon-γ and tumor necrosis factor-α. These inflammatory cytokines lead to the destruction of splenic architecture and immunodeficiency with reduced and delayed virus-specific nAb responses. Consequently, infection with the otherwise persistent LCMV strain Docile was eliminated after CD27 signaling was blocked. Our data provide a novel mechanism by which LCMV avoids nAb responses and suggest that blocking the CD27–CD70 interaction may be an attractive strategy to prevent chronic viral infection.
Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction
Authors: Girardi Guillermina , Yarilin Dmitry , Thurman Joshua M. , Holers V. Michael , Salmon Jane E.
Published: August 2006

Immune mechanisms have been implicated in placental dysfunction in patients with recurrent miscarriages and intrauterine growth restriction (IUGR), but the mediators are undefined. Here we show that complement activation, particularly C5a, is a required intermediary event in the pathogenesis of placental and fetal injury in an antibody-independent mouse model of spontaneous miscarriage and IUGR, and that complement activation causes dysregulation of the angiogenic factors required for normal placental development. Pregnancies complicated by miscarriage or growth restriction were characterized by inflammatory infiltrates in placentas, functional deficiency of free vascular endothelial growth factor (VEGF), elevated levels of soluble VEGF receptor 1 (sVEGFR-1, also known as sFlt-1; a potent anti-angiogenic molecule), and defective placental development. Inhibition of complement activation in vivo blocked the increase in sVEGFR-1 and rescued pregnancies. In vitro stimulation of monocytes with products of the complement cascade directly triggered release of sVEGFR-1, which sequesters VEGF. These studies provide the first evidence linking the complement system to angiogenic factor imbalance associated with placental dysfunction, and identify a new effector of immune-triggered pregnancy complications.
On the dynamics of the McMullen family 𝑅(𝑧)=𝑧^{𝑚}+𝜆/𝑧^{ℓ}
Authors: Steinmetz Norbert
Published: August 2006

In this note we discuss the parameter plane and the dynamics of the rational family

R
(
z
)
=

z
m

+
λ

/

z

ℓ

R(z)=z^m+\lambda /z^{\ell }

, with

m
≥
2

m\ge 2

,

ℓ
≥
1

\ell \ge 1

, and

0
>

|

λ

|

>
∞

0>|\lambda |>\infty

.
GenePro: a cytoscape plug-in for advanced visualization and analysis of interaction networks
Authors: Vlasblom James , Wu Samuel , Pu Shuye , Superina Mark , Liu Gina , Orsi Chris , Wodak Shoshana J.
Published: August 2006

Motivation: Analyzing the networks of interactions between genes and proteins has become a central theme in systems biology. Versatile software tools for interactively displaying and analyzing these networks are therefore very much in demand. The public-domain open software environment Cytoscape has been developed with the goal of facilitating the design and development of such software tools by the scientific community.

Results: We present GenePro, a plugin to Cytoscape featuring a set of versatile tools that greatly facilitates the visualization and analysis of protein networks derived from high-throughput interactions data and the validation of various methods for parsing these networks into meaningful functional modules.

Availability: The GenePro plugin is available at the website

contact:  shuyepu@sickkids.ca
Electro‐Acupuncture at Acupoint ST36 Reduces Inflammation and Regulates Immune Activity in Collagen‐Induced Arthritic Mice
Authors: Yim Yun-Kyoung , Lee Hyun , Hong Kwon-Eui , Kim Young-Il , Lee Byung-Ryul , Son Chang-Gue , Kim Jung-Eun
Published: August 2006

This study aimed to investigate the anti‐inflammatory, anti‐arthritic and immuno‐regulatory effects of electro‐acupuncture (EA) at ST36 on Collagen‐induced arthritis (CIA) in mice. Male DBA/1J mice were divided into five groups: Normal, Control, NR (needle retention), EAI and EAII. All mice except those in the normal group were immunized with Collagen II for arthritis induction. Acupuncture needles were inserted into mice ST36 and electrical currents at a frequency of 2 Hz in a continuous rectangular wave form were conducted through the needles for 15 min, 3 times a week. EA treatments were administered for 5 weeks in the EAI group and for 9 weeks in the EAII group. The mice in the NR group were acupunctured in the same manner as the EA groups and the needles were retained for 15 min without electrical stimulation. CIA incidence analysis, ELISA, histological analysis and FACS analysis were performed to evaluate the effect of EA on CIA. EA at ST36 significantly reduced CIA incidence, IL‐6, TNF‐a, INF‐γ, collagen II antibody, IgG and IgM levels in CIA mice serum and prevented knee joint destruction. EA at ST36 also reduced CD69+/CD3e+ cells and CD11a+/CD19+ cells in CIA mice lymph nodes, and CD11b+/Gr1+ cells in CIA mice knee joints. The ratios of CD3e+ cells to CD19+ cells, and CD8+ cells to CD4+ cells were maintained closer to the normal range in the EA groups as compared with the control group or the NR group. EAII was more effective than EAI throughout all the measurements. The NR was effective as well, though less effective than EA. EA at ST36 may have an anti‐inflammatory, anti‐arthritic and immuno‐regulatory effects on CIA in mice. The effectiveness is stronger when EA starts earlier and is applied longer. Needle retention without electrical stimulation may be effective on CIA as well, however less effective than EA. Electrical stimulation and acupoint ST36 may have synergistic effects on CIA.
The role of modelling in identifying drug targets for diseases of the cell cycle
Authors: Clyde Robert G , Bown James L , Hupp Ted R , Zhelev Nikolai , Crawford John W
Published: August 2006

The cell cycle is implicated in diseases that are the leading cause of mortality and morbidity in the developed world. Until recently, the search for drug targets has focused on relatively small parts of the regulatory network under the assumption that key events can be controlled by targeting single pathways. This is valid provided the impact of couplings to the wider scale context of the network can be ignored. The resulting depth of study has revealed many new insights; however, these have been won at the expense of breadth and a proper understanding of the consequences of links between the different parts of the network. Since it is now becoming clear that these early assumptions may not hold and successful treatments are likely to employ drugs that simultaneously target a number of different sites in the regulatory network, it is timely to redress this imbalance. However, the substantial increase in complexity presents new challenges and necessitates parallel theoretical and experimental approaches. We review the current status of theoretical models for the cell cycle in light of these new challenges. Many of the existing approaches are not sufficiently comprehensive to simultaneously incorporate the required extent of couplings. Where more appropriate levels of complexity are incorporated, the models are difficult to link directly to currently available data. Further progress requires a better integration of experiment and theory. New kinds of data are required that are quantitative, have a higher temporal resolution and that allow simultaneous quantitative comparison of the concentration of larger numbers of different proteins. More comprehensive models are required and must accommodate not only substantial uncertainties in the structure and kinetic parameters of the networks, but also high levels of ignorance. The most recent results relating network complexity to robustness of the dynamics provide clues that suggest progress is possible.
The ideal free pike: 50 years of fitness-maximizing dispersal in Windermere
Authors: Haugen Thrond O , Winfield Ian J , Vøllestad L. Asbjørn , Fletcher Janice M , James J. Ben , Stenseth Nils Chr
Published: August 2006

The ideal free distribution (IFD) theory is one of the most influential theories in evolutionary ecology. It predicts how animals ought to distribute themselves within a heterogeneous habitat in order to maximize lifetime fitness. We test the population level consequence of the IFD theory using 40-year worth data on pike (Esox lucius) living in a natural lake divided into two basins. We do so by employing empirically derived density-dependent survival, dispersal and fecundity functions in the estimation of basin-specific density-dependent fitness surfaces. The intersection of the fitness surfaces for the two basins is used for deriving expected spatial distributions of pike. Comparing the derived expected spatial distributions with 50 years data of the actual spatial distribution demonstrated that pike is ideal free distributed within the lake. In general, there was a net migration from the less productive north basin to the more productive south basin. However, a pike density-manipulation experiment imposing shifting pike density gradients between the two basins managed to switch the net migration direction and hence clearly demonstrated that the Windermere pike choose their habitat in an ideal free manner. Demonstration of ideal free habitat selection on an operational field scale like this has never been undertaken before.