bluuebunny/crossref_metadata_2025 huggingface dataset:
Ground states of the Mo2, W2, and CrMo molecules: A second and third order multireference perturbation theory study
Authors: Angeli Celestino , Cavallini Alex , Cimiraglia Renzo
Published: August 2007

The potential energy curves of the molecules Mo2, W2, and CrMo have been studied ab initio using large basis sets and the “n-electron valence state perturbation theory” up to the third order in the energy. The third order results for Mo2 and W2 reproduce the equilibrium distances re and the harmonic frequencies ωe in fairly good accordance with the experimental values but tend to underestimate the dissociation energy. The CrMo molecule, for which experimental dissociation energy data do not exist yet, is predicted to have a value for De of ≈2.5eV.
Electron-acoustic solitary waves in dense quantum electron-ion plasmas
Authors: Misra A. P. , Shukla P. K. , Bhowmik C.
Published: August 2007

A quantum hydrodynamic (QHD) model is used to investigate the propagation characteristics of nonlinear electron-acoustic solitary waves (EASWs) in a dense quantum plasma whose constituents are two groups of electrons: one inertial cold electrons and other inertialess hot electrons, and the stationary ions which form the neutralizing background. By using the standard reductive perturbation technique, a Kadomtsev-Petviashvili (KP) equation, which governs the dynamics of EASWs, is derived in both spherical and cylindrical geometry. The effects of cold electrons and the density correlations due to quantum fluctuations on the profiles of the amplitudes and widths of the solitary structures are examined numerically. The nondimensional parameter δ=nc0∕nh0, which is the equilibrium density ratio of the cold to hot electron component, is shown to play a vital role in the formation of both bright and dark solitons. It is also found that the angular dependence of the physical quantities and the presence of cold electrons in a quantum plasma lead to the coexistence of some new interesting novel solitary structures quite distinctive from the classical ones.
Polarization-dependent photoinduced mechanical deformations in covalent chalcogenide glasses
Authors: Asao Hideaki , Tanaka Keiji
Published: August 2007

The optomechanical effect and photoinduced anisotropic deformation induced by illumination of linearly polarized light have been comparatively studied for glassy As2S3 and Se films. The two materials show qualitatively the same behaviors in the mechanical effect and the deformation, which suggests that these photoinduced phenomena are inherent to the covalent chalcogenide glass. But, the two phenomena show different dependences upon intensity, spectrum and exposure time of excitation light, which imply different underlying mechanisms.
High-gain pentacene-based inverter achieved through high and low energy ultraviolet treatments
Authors: Choi Jeong-M. , Kim Jae Hoon , Im Seongil
Published: August 2007

The authors report on the fabrication of pentacene-based inverter with two p-channel thin-film transistors (TFTs) on polymer∕AlOx bilayer dielectric, which has been patterned by high energy ultraviolet (UV) (254nm) illumination. After pentacene channel growth on the dielectric, the inverter showed a high voltage gain of ∼10 under −6V supply voltage (VDD) but at a transition voltage of −1V which is too marginal to guarantee a desirable inverter operation between 0 and −6V. When low energy UV (352nm) was applied onto one of the two p TFTs, which plays as a load in the inverter circuit, the transition voltage shifted to an adequate value (−3V) because the UV changes the threshold voltage of the load TFT to be lower. The UV-treated inverter demonstrated a high voltage gain of ∼150 under a VDD of −30V.
Coherent terahertz detection with a large-area photoconductive antenna
Authors: Peter F. , Winnerl S. , Nitsche S. , Dreyhaupt A. , Schneider H. , Helm M.
Published: August 2007

We present a nonresonant photoconductive terahertz detection antenna suitable for detection of both focused and unfocused terahertz radiations. Our system consists of a scalable terahertz emitter based on an interdigitated electrode structure and a detection antenna with similar electrode geometry. While the emitter is fabricated on semi-insulating GaAs we compare different ion-implanted GaAs-based detection antennas. We studied the dependence of the measured terahertz signal on the power and spot size of the gating laser pulse. In addition we compare the performance of our antenna with that of electro-optical sampling.
Correlation between local structure of melts and glass forming ability for Al-based alloys: A first-principles study
Authors: Gu T. K. , Qin J. Y. , Bian X. F.
Published: August 2007

The structures of several well-selected Al70Fe20EM10 (EM=Ti, Zr, Hf, V, and Cr) melts are investigated by first-principles method. The structural and dynamical properties of these melts, which change evidently with the addition of different EM elements, are closely correlated with the ease of their glass formation as observed in experiment. The interaction among EM, Al, and Fe plays an important role in their glass forming ability. Based on these results, the authors suggest that it should be possible to select energetic additive elements ahead of experiment for multicomponent metallic glasses by first-principles simulation on their molten structures.
Epitaxial growth by pulsed laser deposition of Er-doped Sc2O3 films on sesquioxides monitored in situ by reflection high energy electron diffraction
Authors: Gün Teoman , Kuzminykh Yury , Petermann Klaus , Scheife Hanno , Huber Günter
Published: August 2007

In this letter, the authors report on the epitaxial growth by pulsed laser deposition of Sc2O3 and Er(5%):Sc2O3 films on {100} and {111} oriented Sc2O3. They observed layer-by-layer growth in the orientation defined by the substrate. This was indicated by reflection high energy electron diffraction as intensity oscillations of the specularly reflected electron beam. A monolayer-smooth film surface was observed by atomic force microscopy. Such a growth behavior was also achieved during initial growth of Sc2O3 on {100} oriented Y2O3. Additional x-ray diffraction analysis shows good agreement with the growth behavior mentioned above.
NS3 helicase actively separates RNA strands and senses sequence barriers ahead of the opening fork
Authors: Cheng Wei , Dumont Sophie , Tinoco Ignacio , Bustamante Carlos
Published: August 2007

RNA helicases regulate virtually all RNA-dependent cellular processes. Although much is known about helicase structures, very little is known about how they deal with barriers in RNA and the factors that affect their processivity. The hepatitis C virus encodes NS3, an RNA helicase that is essential for viral RNA replication. We have used optical tweezers to determine at the single-molecule level how the local stability of the RNA substrate affects the enzyme rate of strand separation, whether separation occurs by an active or a passive mechanism, and whether processivity is affected. We show that sequence barriers in RNA modulate NS3 activity. NS3 processivity depends on barriers ahead of the opening fork. Our results rule out a model where NS3 passively waits for the thermal fraying of double-stranded RNA. Instead, we find that NS3 destabilizes the duplex before separating the strands. Failure to do so before a strong barrier leads to helicase dissociation and limits the processivity of the enzyme.
Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter
Authors: Wang Baiping , Yang Li , Wang Zilai , Zheng Hui
Published: August 2007

The key pathological features of Alzheimer's disease include synaptic dysfunction, profound changes in the cholinergic system, and deposition of β-amyloid peptides generated by proteolytic processing of the amyloid-β precursor protein (APP). However, the pathways linking APP with synaptic activity and cholinergic neuronal function are poorly understood. We report here that APP is essential in regulating the presynaptic expression and activity of the high-affinity choline transporter (CHT), a molecule that mediates the rate-limiting step of cholinergic synaptic transmission in both the neuromuscular junction and central cholinergic neurons. Loss of APP leads to aberrant localization of CHT at the neuromuscular synapses and reduced CHT activity at cholinergic projections. At the cellular level, we show that APP and CHT can be found in Rab5-positive endosomal compartments and that APP affects CHT endocytosis. Furthermore, we demonstrate that APP interacts with CHT through the C-terminal domain, providing support for a specific and direct regulation of CHT by APP through protein–protein interactions. These results identify a physiological activity of APP in cholinergic neurons, and our data indicate that deregulation of APP function may contribute to cholinergic impairment and AD pathogenesis.
Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells
Authors: Maréchal Yoann , Pesesse Xavier , Jia Yonghui , Pouillon Valérie , Pérez-Morga David , Daniel Julien , Izui Shozo , Cullen Peter J. , Leo Oberdan , Luo Hongbo R. , Erneux Christophe , Schurmans Stéphane
Published: August 2007

The contribution of the B isoform of inositol 1,4,5-trisphosphate [Ins(1,4,5)
P
3
] 3-kinase (or Itpkb) and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)
P
4
], its reaction product, to B cell function and development remains unknown. Here, we show that mice deficient in Itpkb have defects in B cell survival leading to specific and intrinsic developmental alterations in the B cell lineage and antigen unresponsiveness
in vivo
. The decreased B cell survival is associated with a decreased phosphorylation of Erk1/2 and increased Bim gene expression. B cell survival, development, and antigen responsiveness are normalized in parallel to reduced expression of Bim in
Itpkb
−/−
Bim
+/−
mice. Analysis of the signaling pathway downstream of Itpkb revealed that Ins(1,3,4,5)
P
4
regulates subcellular distribution of Rasa3, a Ras GTPase-activating protein acting as an Ins(1,3,4,5)
P
4
receptor. Together, our results indicate that Itpkb and Ins(1,3,4,5)
P
4
mediate a survival signal in B cells via a Rasa3–Erk signaling pathway controlling proapoptotic Bim gene expression.
High-throughput fluorescent-based optimization of eukaryotic membrane protein overexpression and purification in
Saccharomyces cerevisiae
Authors: Newstead Simon , Kim Hyun , von Heijne Gunnar , Iwata So , Drew David
Published: August 2007

Eukaryotic membrane proteins are often difficult to produce in large quantities, which is a significant obstacle for further structural and biochemical investigation. Based on the analysis of 43 eukaryotic membrane proteins, we present a cost-effective high-throughput approach for rapidly screening membrane proteins that can be overproduced to levels of >1 mg per liter in
Saccharomyces cerevisiae
. We find that 70% of the well expressed membrane proteins tested in this system are stable, targeted to the correct organelle, and monodisperse in either Fos-choline 12 (FC-12) or
n
-dodecyl-β-
d
-maltoside. We illustrate the advantage of such an approach, with the purification of monodisperse human and yeast nucleotide-sugar transporters to unprecedented levels. We estimate that our approach should be able to provide milligram quantities for at least one-quarter of all membrane proteins from both yeast and higher eukaryotic organisms.
Aberrant infection and persistence of varicella-zoster virus in human dorsal root ganglia
in vivo
in the absence of glycoprotein I
Authors: Zerboni Leigh , Reichelt Mike , Jones Carol D. , Zehnder James L. , Ito Hideki , Arvin Ann M.
Published: August 2007

Varicella-zoster virus (VZV) causes varicella, establishes latency in sensory ganglia, and reactivates as herpes zoster. Human dorsal root ganglia (DRGs) xenografts in immunodeficient mice provide a model for evaluating VZV neuropathogenesis. Our investigation of the role of glycoprotein I (gI), which is dispensable
in vitro
, examines the functions of a VZV gene product during infection of human neural cells
in vivo
. Whereas intact recombinant Oka (rOka) initiated a short replicative phase followed by persistence in DRGs, the gI deletion mutant, rOkaΔgI, showed prolonged replication with no transition to persistence up to 70 days after infection. Only a few varicella-zoster nucleocapsids and cytoplasmic virions were observed in neurons, and the major VZV glycoprotein, gE, was retained in the rough endoplasmic reticulum in the absence of gI. VZV neurotropism was not disrupted when DRG xenografts were infected with rOka mutants lacking gI promoter elements that bind cellular transactivators, specificity factor 1 (Sp1) and upstream stimulatory factor (USF). Because gI is essential and Sp1 and USF contribute to VZV pathogenesis in skin and T cells
in vivo
, these DRG experiments indicate that the genetic requirements for VZV infection are less stringent in neural cells
in vivo
. The observations demonstrate that gI is important for VZV neurotropism and suggest that a strategy to reduce neurovirulence by deleting gI could prolong active infection in human DRGs.
Characterization of the role of the Synaptotagmin family as calcium sensors in facilitation and asynchronous neurotransmitter release
Authors: Saraswati Sudipta , Adolfsen Bill , Littleton J. Troy
Published: August 2007

Ca
2+
influx into presynaptic nerve terminals activates synaptic vesicle exocytosis by triggering fast synchronous fusion and a slower asynchronous release pathway. In addition, a brief rise in Ca
2+
after consecutive action potentials has been correlated with a form of short-term synaptic plasticity with enhanced vesicle fusion termed facilitation. Although the synaptic vesicle protein Synaptotagmin 1 (Syt1) has been implicated as the Ca
2+
sensor for synchronous fusion, the molecular identity of the Ca
2+
sensors that mediate facilitation and asynchronous release is unknown. To test whether the synchronous Ca
2+
sensor, Syt1, or the asynchronous Ca
2+
sensor is involved in facilitation, we analyzed whether genetic elimination of Syt1 in
Drosophila
results in a concomitant impairment in facilitation. Our results indicate that Syt1 acts as a redundant Ca
2+
sensor for facilitation, with the asynchronous Ca
2+
sensor contributing significantly to this form of short-term plasticity. We next examined whether other members of the
Drosophila
Syt family functioned in Ca
2+
-dependent asynchronous release or facilitation
in vivo
. Genetic elimination of other panneuronally expressed Syt proteins did not alter these forms of exocytosis, indicating a non-Syt Ca
2+
sensor functions for both facilitation and asynchronous release. In light of these findings, the presence of two presynaptic Ca
2+
sensors can be placed in a biological context, a Syt1-based Ca
2+
sensor devoted primarily to baseline synaptic transmission and a second non-Syt Ca
2+
sensor for short-term synaptic plasticity and asynchronous release.
BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment
Authors: Zhang Jiayin , Ahmad Sana , Mao Yinghui
Published: August 2007

The accurate segregation of chromosomes in mitosis requires the stable attachment of microtubules to kinetochores. The details of this complex and dynamic process are poorly understood. In this study, we report the interaction of a kinetochore-associated mitotic checkpoint kinase, BubR1, with two microtubule plus end–associated proteins, adenomatous polyposis coli (APC) and EB1, providing a potential link in stable kinetochore microtubule attachment. Using immunodepletion from and antibody addition to Xenopus laevis egg extracts, we show that BubR1 and its kinase activity are essential for positioning chromosomes at the metaphase plate. BubR1 associates with APC and EB1 in egg extracts, and the complex formation is necessary for metaphase chromosome alignment. Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules. These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.
Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage
Authors: Griparic Lorena , Kanazawa Takayuki , van der Bliek Alexander M.
Published: August 2007

The dynamin-related protein Opa1 is localized to the mitochondrial intermembrane space, where it facilitates fusion between mitochondria. Apoptosis causes Opa1 release into the cytosol and causes mitochondria to fragment. Loss of mitochondrial membrane potential also causes mitochondrial fragmentation but not Opa1 release into the cytosol. Both conditions induce the proteolytic cleavage of Opa1, suggesting that mitochondrial fragmentation is triggered by Opa1 inactivation. The opposite effect was observed with knockdown of the mitochondrial intermembrane space protease Yme1. Knockdown of Yme1 prevents the constitutive cleavage of a subset of Opa1 splice variants but does not affect carbonyl cyanide m-chlorophenyl hydrazone or apoptosis-induced cleavage. Knockdown of Yme1 also increases mitochondrial connectivity, but this effect is independent of Opa1 because it also occurs in Opa1 knockdown cells. We conclude that Yme1 constitutively regulates a subset of Opa1 isoforms and an unknown mitochondrial morphology protein, whereas the loss of membrane potential induces the further proteolysis of Opa1.
Neurofascin assembles a specialized extracellular matrix at the axon initial segment
Authors: Hedstrom Kristian L. , Xu Xiaorong , Ogawa Yasuhiro , Frischknecht Renato , Seidenbecher Constanze I. , Shrager Peter , Rasband Matthew N.
Published: August 2007

Action potential initiation and propagation requires clustered Na+ (voltage-gated Na+ [Nav]) channels at axon initial segments (AIS) and nodes of Ranvier. In addition to ion channels, these domains are characterized by cell adhesion molecules (CAMs; neurofascin-186 [NF-186] and neuron glia–related CAM [NrCAM]), cytoskeletal proteins (ankyrinG and βIV spectrin), and the extracellular chondroitin-sulfate proteoglycan brevican. Schwann cells initiate peripheral nervous system node formation by clustering NF-186, which then recruits ankyrinG and Nav channels. However, AIS assembly of this protein complex does not require glial contact. To determine the AIS assembly mechanism, we silenced expression of AIS proteins by RNA interference. AnkyrinG knockdown prevented AIS localization of all other AIS proteins. Loss of NF-186, NrCAM, Nav channels, or βIV spectrin did not affect other neuronal AIS proteins. However, loss of NF-186 blocked assembly of the brevican-based AIS extracellular matrix, and NF-186 overexpression caused somatodendritic brevican clustering. Thus, NF-186 assembles and links the specialized brevican-containing AIS extracellular matrix to the intracellular cytoskeleton.
Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis
Authors: Scott-Browne James P. , Shafiani Shahin , Tucker-Heard Glady's , Ishida-Tsubota Kumiko , Fontenot Jason D. , Rudensky Alexander Y. , Bevan Michael J. , Urdahl Kevin B.
Published: August 2007

Mycobacterium tuberculosis (Mtb) frequently establishes persistent infections that may be facilitated by mechanisms that dampen immunity. T regulatory (T reg) cells, a subset of CD4+ T cells that are essential for preventing autoimmunity, can also suppress antimicrobial immune responses. We use Foxp3-GFP mice to track the activity of T reg cells after aerosol infection with Mtb. We report that during tuberculosis, T reg cells proliferate in the pulmonary lymph nodes (pLNs), change their cell surface phenotype, and accumulate in the pLNs and lung at a rate parallel to the accumulation of effector T cells. In the Mtb-infected lung, T reg cells accumulate in high numbers in all sites where CD4+ T cells are found, including perivascular/peribronchiolar regions and within lymphoid aggregates of granulomas. To determine the role of T reg cells in the immune response to tuberculosis, we generated mixed bone marrow chimeric mice in which all cells capable of expressing Foxp3 expressed Thy1.1. When T reg cells were depleted by administration of anti-Thy1.1 before aerosol infection with Mtb, we observed ∼1 log less of colony-forming units of Mtb in the lungs. Thus, after aerosol infection, T reg cells proliferate and accumulate at sites of infection, and have the capacity to suppress immune responses that contribute to the control of Mtb.
Mutations of the Igβ gene cause agammaglobulinemia in man
Authors: Ferrari Simona , Lougaris Vassilios , Caraffi Stefano , Zuntini Roberta , Yang Jianying , Soresina Annarosa , Meini Antonella , Cazzola Giantonio , Rossi Cesare , Reth Michael , Plebani Alessandro
Published: August 2007

Agammaglobulinemia is a rare primary immunodeficiency characterized by an early block of B cell development in the bone marrow, resulting in the absence of peripheral B cells and low/absent immunoglobulin serum levels. So far, mutations in Btk, μ heavy chain, surrogate light chain, Igα, and B cell linker have been found in 85–90% of patients with agammaglobulinemia. We report on the first patient with agammaglobulinemia caused by a homozygous nonsense mutation in Igβ, which is a transmembrane protein that associates with Igα as part of the preBCR complex. Transfection experiments using Drosophila melanogaster S2 Schneider cells showed that the mutant Igβ is no longer able to associate with Igα, and that assembly of the BCR complex on the cell surface is abrogated. The essential role of Igβ for human B cell development was further demonstrated by immunofluorescence analysis of the patient's bone marrow, which showed a complete block of B cell development at the pro-B to preB transition. These results indicate that mutations in Igβ can cause agammaglobulinemia in man.
Methods of remote homology detection can be combined to increase coverage by 10% in the midnight zone
Authors: Reid Adam James , Yeats Corin , Orengo Christine Anne
Published: August 2007

Motivation: A recent development in sequence-based remote homologue detection is the introduction of profile–profile comparison methods. These are more powerful than previous technologies and can detect potentially homologous relationships missed by structural classifications such as CATH and SCOP. As structural classifications traditionally act as the gold standard of homology this poses a challenge in benchmarking them.

Results: We present a novel approach which allows an accurate benchmark of these methods against the CATH structural classification. We then apply this approach to assess the accuracy of a range of publicly available methods for remote homology detection including several profile–profile methods (COMPASS, HHSearch, PRC) from two perspectives. First, in distinguishing homologous domains from non-homologues and second, in annotating proteomes with structural domain families. PRC is shown to be the best method for distinguishing homologues. We show that SAM is the best practical method for annotating genomes, whilst using COMPASS for the most remote homologues would increase coverage. Finally, we introduce a simple approach to increase the sensitivity of remote homologue detection by up to 10 %. This is achieved by combining multiple methods with a jury vote.

Contact:  reid@bioichem.ucl.ac.uk

Supplementary information: Supplementary data are available at Bioinformatics online.
Effects of Topical Application of Clonidine Cream on Pain Behaviors and Spinal Fos Protein Expression in Rat Models of Neuropathic Pain, Postoperative Pain, and Inflammatory Pain
Authors: Li Chi , Sekiyama Hiroshi , Hayashida Masakazu , Takeda Kenji , Sumida Toshinobu , Sawamura Shigehito , Yamada Yoshitsugu , Arita Hideko , Hanaoka Kazuo
Published: August 2007

Background

Clonidine can effectively reduce pain and/or hypersensitivity. However, the antihypersensitivity effects of clonidine topically applied in cream (CC) have not been investigated. The authors evaluated effects of topical application of CC on pain behaviors and spinal Fos-like immunoreactivity in rats with hypersensitivity.

Methods

Clonidine (30, 100, and 300 microg/g) was prepared in a cream base. In rat models of neuropathic pain, inflammatory pain, and postoperative pain, the authors evaluated effects of CC (0.1 g), topically applied onto the plantar surface of the injured or uninjured paw, on thermal hyperalgesia and mechanical allodynia to von Frey filaments. The authors also evaluated effects of CC on lumbar spinal Fos-like immunoreactivity.

Results

In neuropathic rats, CC applied onto the injured paw reduced thermal hyperalgesia and mechanical allodynia dose dependently, whereas CC applied onto the uninjured paw had no effect. The antihypersensitivity effects of CC were antagonized by intraperitoneal yohimbine (10 mg/kg). Further, CC reduced Fos-like immunoreactivity in neuropathic rats. In contrast, CC in a single dose had no effects on hyperalgesia, allodynia, or Fos-like immunoreactivity in rats with inflammatory or postoperative pain. In rats with postoperative pain, CC repeatedly applied for 6 days reduced thermal hyperalgesia, but not mechanical allodynia, in the postoperative days, whereas it had no effects on hyperalgesia or allodynia in those with inflammatory pain.

Conclusions

Topical CC in concentrations examined significantly reduced hypersensitivity and lumbar spinal Fos-like immunoreactivity in rats with neuropathic pain, probably through activation of peripherally located alpha2 adrenoceptors. However, CC was only partially effective and totally ineffective in rats with postoperative pain and inflammatory pain, respectively.
A Conserved Tyrosine in the β2Subunit M4 Segment Is a Determinant of γ-Aminobutyric Acid Type A Receptor Sensitivity to Propofol
Authors: Richardson James E. , Garcia Paul S. , O'Toole Kate K. , Derry Jason M. C. , Bell Shannon V. , Jenkins Andrew
Published: August 2007

Background

The gamma-aminobutyric acid type A receptor (GABAA-R) beta subunits are critical targets for the actions for several intravenous general anesthetics, but the precise nature of the anesthetic binding sites are unknown. In addition, little is known about the role the fourth transmembrane (M4) segment of the receptor plays in receptor function. The aim of this study was to better define the propofol binding site on the GABAA-R by conducting a tryptophan scan in the M4 segment of the beta2 subunit.

Methods

Seven tryptophan mutations were introduced into the C-terminal end of the M4 segment of the GABAA-R beta2 subunit. GABAA-R subunit complementary DNAs were transfected into human embryonic kidney 293 cells grown on glass coverslips. After transfection (36-72 h), coverslips were transferred to a perfusion chamber to assay receptor function. Cells were whole cell patch clamped and exposed to GABA, propofol, etomidate, and pregnenolone. Chemicals were delivered to the cells using two 10-channel infusion pumps and a rapid solution exchanger.

Results

All tryptophan mutations were well tolerated, and with one exception, all resulted in minimal changes in receptor activation by GABA. One mutation, beta2(Y444W), selectively suppressed the ability of propofol to enhance receptor function while retaining normal sensitivity to etomidate and pregnenolone.

Conclusions

This is the first report of a mutation that selectively reduces propofol sensitivity without altering the action of etomidate. The reduction in propofol sensitivity is consistent with the loss of a hydrogen bond within the propofol binding site. These results also suggest a possible orientation of the propofol molecule within its binding site.
Effects of Butorphanol on Morphine-induced Itch and Analgesia in Primates
Authors: Lee Heeseung , Naughton Norah N. , Woods James H. , Ko Mei-Chuan
Published: August 2007

Background

Butorphanol is an opioid analgesic with partial agonist actions at micro- and kappa-opioid receptors (MOR and KOR). Previous studies have demonstrated that both MOR antagonists and KOR agonists are effective in alleviating intrathecal morphine-induced itch in primates. The aim of the study was to investigate the effectiveness of butorphanol as an antipruritic and to elucidate the receptor mechanisms underlying butorphanol's antipruritic effect in primates.

Methods

Adult rhesus monkeys were used in the behavioral assays for measuring itch/scratching and analgesia. The dose-response curves of butorphanol were studied using selective MOR and KOR antagonists. In addition, the effect of butorphanol as an antipruritic was studied on subcutaneous and intrathecal morphine-induced itch and analgesia. KOR-selective antagonists were further used to compare the degrees of MOR and KOR activation underlying the antipruritic effect of butorphanol.

Results

Butorphanol alone produced analgesia with slight itch responses, and both effects were blocked by a MOR antagonist, clocinnamox (0.1 mg/kg). In contrast, a KOR antagonist, 5'-guanidinylnaltrindole (1 mg/kg), increased butorphanol-elicited itch. Systemic butorphanol (0.0032-0.032 mg/kg) dose-dependently attenuated systemic or intrathecal morphine-induced itch. In addition, butorphanol either potentiated or maintained morphine-induced analgesia without producing sedation. KOR-selective antagonists, 5'-guanidinylnaltrindole (1 mg/kg) and nor-binaltorphimine (3.2 mg/kg), only partially reversed the antipruritic effect of butorphanol with different durations of KOR antagonism.

Conclusions

Butorphanol is effective in attenuating systemic or spinal morphine-induced itch without reducing morphine analgesia. This study provides functional evidence that both partial MOR and KOR agonist actions contribute to the effectiveness of butorphanol as an antipruritic in primates.
Impact of the C2/C6 Ratio of High-molecular-weight Hydroxyethyl Starch on Pharmacokinetics and Blood Coagulation in Pigs
Authors: Schramm Sebastian , Thyes Caroline , Frascarolo Philippe , Buclin Thierry , Burki Marco , Fisch Andreas , Burmeister Marc-Alexander , Asmis Lars , Spahn Donat R.
Published: August 2007

Background

High-molecular-weight, low-substituted hydroxyethyl starch (HES) may not affect blood coagulation more than low-molecular-weight, low-substituted HES. The authors assessed in vivo the effect of a lowered C2/C6 ratio on pharmacokinetic characteristics and the impact on blood coagulation of high-molecular-weight, low-substituted HES.

Methods

A prospective, randomized, parallel study in 30 pigs compared HES 650/0.42/2.8 with HES 650/0.42/5.6. Before, during, and after infusion of 30 ml/kg body weight HES, blood samples were collected over 630 min to measure HES concentrations and plasmatic coagulation and to assess blood coagulation in whole blood by Thrombelastography (TEG; Haemoscope Corporation, Niles, IL). Pharmacokinetic parameters were estimated using a two-compartment model.

Results

The elimination constant was 0.009 +/- 0.001 min(-1) for HES 650/0.42/2.8 and 0.007 +/- 0.001 min(-1) for HES 650/0.42/5.6 (P < 0.001); the area under the plasma concentration-time curve was 1,374 +/- 340 min x g/l for HES 650/0.42/2.8 and 1,697 +/- 411 min x g/l for HES 650/0.42/5.6 (P = 0.026). The measured plasma HES concentrations were not different between HES 650/0.42/2.8 and HES 650/0.42/5.6. Both HES solutions equally affected blood coagulation: Thrombelastographic coagulation index decreased similarly at the end of infusion of HES 650/0.42/2.8 and at the end of infusion of HES 650/0.42/5.6 (P = 0.293). Also, activated partial thromboplastin and prothrombin times increased similarly for HES 650/0.42/2.8 and HES 650/0.42/5.6 (P = 0.831).

Conclusion

Reducing the C2/C6 ratio in high-molecular, low-substituted HES solutions results in a slightly faster HES elimination. However, the blood coagulation compromising effect was unaffected.
Influence of Administration Rate on Propofol Plasma–Effect Site Equilibration
Authors: Struys Michel M. R. F. , Coppens Marc J. , De Neve Nikolaas , Mortier Eric P. , Doufas Anthony G. , Van Bocxlaer Jan F. P. , Shafer Steven L.
Published: August 2007

Background

The authors hypothesized a difference in plasma-effect site equilibration, depicted by a first-order constant k(e0), depending on the injection rate of propofol.

Methods

Sixty-one patients received 2.5 mg/kg propofol given as a bolus or as a 1-, 2-, or 3-min infusion. The Bispectral Index was used to monitor drug effect. Propofol predicted plasma concentration was calculated using a three-compartment model and the effect site concentration over time as the convolution between the predicted plasma concentration and the disposition function of the effect site concentration. The authors evaluated the influence of the infusion rate on the k(e0) by comparing the model with one k(e0) for all groups with models estimating different k(e0) values for each group. The authors also assessed the accuracy of two pharmacokinetic models after bolus injection.

Results

The best model based was a fixed (Bispectral Index > or = 90) plus sigmoidal model (Bispectral Index < 90) with two values of k(e0), one for the bolus (t(1/2) k(e0) = 1.2 min) and one for the infusions (t(1/2) k(e0) = 2.2 min). However, the tested pharmacokinetic models poorly predicted the arterial concentrations in the first minutes after bolus injection. Simulations showed the requirement for two k(e0) values for bolus and infusion was mostly a compensation for the inaccurate prediction of arterial concentrations after a bolus.

Conclusion

Propofol plasma-effect site equilibration occurs more rapidly after a bolus than after rapid infusion, based on the electroencephalogram as a drug effect measure, mostly because of misspecification of the pharmacokinetic model in the first minutes after bolus.
Continuous Preperitoneal Infusion of Ropivacaine Provides Effective Analgesia and Accelerates Recovery after Colorectal Surgery
Authors: Beaussier Marc , El’Ayoubi Hanna , Schiffer Eduardo , Rollin Maxime , Parc Yann , Mazoit Jean-Xavier , Azizi Louisa , Gervaz Pascal , Rohr Serge , Biermann Celine , Lienhart André , Eledjam Jean-Jacques
Published: August 2007

Background

Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial.

Methods

After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia.

Results

Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 +/- 19 vs. 105 +/- 54 h; P = 0.02) and duration of hospital stay (115 +/- 25 vs. 147 +/- 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed.

Conclusions

Continuous preperitoneal administration of 0.2% ropivacaine at 10 ml/h during 48 h after open colorectal resection reduced morphine consumption, improved pain relief, and accelerated postoperative recovery.
Effects of the Antimicrobial Peptide LL-37 and Hyperthermic Preconditioning in Septic Rats
Authors: Torossian Alexander , Gurschi Eugeniu , Bals Robert , Vassiliou Timon , Wulf Hinnerk F. , Bauhofer Artur
Published: August 2007

Background

The authors tested the effects of LL-37 prophylaxis or therapy on the outcome after intraabdominal sepsis and examined whether hyperthermic preconditioning plus LL-37 therapy augments host immune response and improves survival.

Methods

A rat model of peritoneal contamination and infection (PCI) with human stool was used to simulate clinical conditions. In trial 1, the authors compared (1) PCI, (2) LL-37 prophylaxis (0.5 mg/kg, 12 h before PCI), and (3) LL-37 therapy (0.5 mg/kg, 1 h after PCI). In trial 2, the authors compared (1) PCI, (2) LL-37 therapy, (3) hyperthermic preconditioning (41 degrees C for 1 h, 24 h before PCI), and (4) LL-37 therapy and hyperthermic preconditioning. The primary endpoint was mortality at 120 h. In trial 2, secondary endpoints were systemic levels of tumor necrosis factor alpha, interleukin 6, macrophage inflammatory protein 2, and heat shock protein 70; leukocyte counts; and neutrophil granulocyte phagocytosis.

Results

In trial 1, 30% of the control group compared with 70% of the LL-37 therapy group survived, but 55% after LL-37 prophylaxis survived (P = 0.038). In trial 2, 38% of the controls, 67% of the LL-37 therapy, 59% of the hyperthermic preconditioned, and 90% of the hyperthermic preconditioned plus LL-37 therapy group survived (P = 0.01). LL-37 therapy plus hyperthermic preconditioning reduced proinflammatory cytokine concentrations after sepsis; specifically compared with controls, macrophage inflammatory protein-2 and interleukin-6 levels were 1.5 +/- 1.5 versus 11 +/- 6 pg/ml (P = 0.028) and 13 +/- 8 versus 86 +/- 31 pg/ml, (P = 0.015), respectively.

Conclusions

In this model of intraabdominal sepsis, LL-37 therapy improved outcome. Hyperthermic preconditioning per se was not successful, but in combination with LL-37 therapy, the survival rate after sepsis was increased and the proinflammatory cytokine response was downgraded.
Systemic Antiinflammatory Corticosteroid Reduces Mechanical Pain Behavior, Sympathetic Sprouting, and Elevation of Proinflammatory Cytokines in a Rat Model of Neuropathic Pain
Authors: Li Huiqing , Xie Wenrui , Strong Judith A. , Zhang Jun-Ming
Published: August 2007

Background

Chronic pain models are commonly defined as either nerve-injury or inflammation models, but recent work suggests inflammatory processes are important in nerve injury-induced pain.

Methods

In the rat spinal nerve ligation model, the authors examined effects of systemic corticosteroid triamcinolone acetonide (TA) on the cytokine protein profile and sympathetic sprouting in the axotomized sensory ganglia, excitability of sensory neurons, and mechanical sensitivity.

Results

By postoperative day 3, marked increases (5- to 16-fold) in monocyte chemoattractant protein-1, growth-related oncogene (GRO/KC or CXCL1), and interleukin (IL)-6 were observed, whereas IL-4 and IL-2 levels fell more than fourfold. The increased cytokines and number of sympathetic basket formations in the sensory ganglia were reduced toward normal values by TA given starting at the time of injury. Interleukin-4 and IL-2 levels were not restored by TA. Systemic TA also reduced the firing rate and incidence of bursting activity, but not the overall incidence of spontaneous activity, in large- and medium-sized neurons. Mechanical hypersensitivity on postoperative day 3 was reduced by TA, and some effect could still be observed 4 days after cessation of TA. However, starting TA at day 7 was ineffective.

Conclusions

Several components of the spinal nerve injury model are responsive to corticosteroid, suggesting inflammatory processes are important in the development of neuropathic pain. The observation that TA was effective when given starting at the time of injury suggests that steroid treatment might alter the development of chronic pain after surgical procedures that involve nerve injury, such as amputation or hernia repair.
Sedation and Anesthesia Care for Ophthalmologic Surgery during Local/Regional Anesthesia
Authors: Vann Mary Ann , Ogunnaike Babatunde O. , Joshi Girish P. , Warltier David C.
Published: August 2007

Anesthesia care for the patients undergoing ophthalmologic surgical procedures during local/regional anesthesia balances goals of patient comfort with safety and an optimal outcome in a highly cost-conscious environment. This article discusses current practices and trends in anesthesia care with respect to sedation for eye surgery during local/regional anesthesia. Although there is no evidence that one local/regional anesthesia technique or sedation analgesia regimen is superior to the others, this review highlights important differences between these varied approaches. The type of block used for the ophthalmologic surgery alters the sedation requirements. Changes in surgical techniques have increased the popularity of topical anesthesia, which reduces the need for sedation analgesia and may lessen the need for an anesthesia practitioner. The involvement of an anesthesia practitioner in eye surgery varies from facility to facility based on costs, anesthesiologist availability, and local standards. Anesthesia care choices are often made based on surgeon skill and anesthesiologist comfort, as well as the expectations and needs of the patient.
Interspecies physiological variation as a tool for cross-species assessments of global warming-induced endangerment: validation of an intrinsic determinant of macroecological and phylogeographic structure
Authors: Bernardo Joseph , Ossola Ryan J , Spotila James , Crandall Keith A
Published: August 2007

Global warming is now recognized as the dominant threat to biodiversity because even protected populations and habitats are susceptible. Nonetheless, current criteria for evaluating species' relative endangerment remain purely ecological, and the accepted conservation strategies of habitat preservation and population management assume that species can mount ecological responses if afforded protection. The insidious threat from climate change is that it will attenuate or preclude ecological responses by species that are physiologically constrained; yet, quantitative, objective criteria for assessing relative susceptibility of diverse taxa to warming-induced stress are wanting. We explored the utility of using interspecies physiological variation for this purpose by relating species' physiological phenotypes to landscape patterns of ecological and genetic exchange. Using a salamander model system in which ecological, genetic and physiological diversity are well characterized, we found strong quantitative relationships of basal metabolic rates (BMRs) to both macroecological and phylogeographic patterns, with decreasing BMR leading to dispersal limitation (small contemporary ranges with marked phylogeographic structure). Measures of intrinsic physiological tolerance, which vary systematically with macroecological and phylogeographic patterns, afford objective criteria for assessing endangerment across a wide range of species and should be incorporated into conservation assessment criteria that currently rely exclusively upon ecological predictors.
Function of weaponry in females: the use of horns in intrasexual competition for resources in female Soay sheep
Authors: Robinson Matthew R , Kruuk Loeske E.B
Published: August 2007

In many species, females show reduced expression of a trait that is under sexual selection in males, and this expression is thought to be maintained through genetic associations with the male phenotype. However, there is also the potential for the female trait to convey an advantage in intrasexual conflicts over resources. We tested this hypothesis in a feral population of Soay sheep, in which males and females have a polymorphism for horn development, producing either full (normal horned), reduced (scurred) or no (polled, females only) horns. During the lambing period, females who possessed horns were more likely to initiate and win aggressive interactions, independent of age, weight and birthing status. The occurrence of aggression was also context dependent, decreasing over the lambing period and associated with local density. Our results demonstrate that a trait that confers benefits to males during intrasexual competition for mates may also be used by females in intrasexual competition over resources: males use weaponry to gain mates, whereas females use weaponry to gain food.
Larval rearing environment affects several post-copulatory traits in
Drosophila melanogaster
Authors: McGraw Lisa A , Fiumera Anthony C , Ramakrishnan Meera , Madhavarapu Swetha , Clark Andrew G , Wolfner Mariana F
Published: August 2007

In
Drosophila melanogaster
, accessory gland proteins (Acps) that a male transfers during mating affect his reproductive success by altering the female's behaviour and physiology. To test the role of male condition in the expression of Acps, we manipulated the pre-adult environment and examined adult males for relative transcript abundance of nine Acps, and for post-copulatory traits that Acps influence. Larval culture density had no effect on any measured trait. Larval nutrient availability impacted the number of sperm transferred and stored, the male's ability to induce refractoriness in his mate, but relative transcript abundance of only a single Acp (
Acp36DE
). Reduced male body size due to low yeast levels affected sperm competition. Our data indicate that some female-mediated post-copulatory traits (induced refractoriness and sperm transfer and storage) might be influenced by the male's developmental environment, but relative expression of most Acps and some traits they influence (
P1
′) are not.
On subsystem codes beating the quantum Hamming or Singleton bound
Authors: Klappenecker Andreas , Sarvepalli Pradeep Kiran
Published: August 2007

Subsystem codes are a generalization of noiseless subsystems, decoherence-free subspaces and stabilizer codes. We generalize the quantum Singleton bound to

q

-linear subsystem codes. It follows that no subsystem code over a prime field can beat the quantum Singleton bound. On the other hand, we show the remarkable fact that there exist impure subsystem codes beating the quantum Hamming bound. A number of open problems concern the comparison in the performance of stabilizer and subsystem codes. One of the open problems suggested by Poulin's work asks whether a subsystem code can use fewer syndrome measurements than an optimal

q

-linear maximum distance separable stabilizer code while encoding the same number of qudits and having the same distance. We prove that linear subsystem codes cannot offer such an improvement under complete decoding.
Probabilistic participation in public goods games
Authors: Sasaki Tatsuya , Okada Isamu , Unemi Tatsuo
Published: August 2007

Voluntary participation in public goods games (PGGs) has turned out to be a simple but effective mechanism for promoting cooperation under full anonymity. Voluntary participation allows individuals to adopt a risk-aversion strategy, termed loner. A loner refuses to participate in unpromising public enterprises and instead relies on a small but fixed pay-off. This system leads to a cyclic dominance of three pure strategies, cooperators, defectors and loners, but at the same time, there remain two considerable restrictions: the addition of loners cannot stabilize the dynamics and the time average pay-off for each strategy remains equal to the pay-off of loners. Here, we introduce probabilistic participation in PGGs from the standpoint of diversification of risk, namely simple mixed strategies with loners, and prove the existence of a dynamical regime in which the restrictions no longer hold. Considering two kinds of mixed strategies associated with participants (cooperators or defectors) and non-participants (loners), we can recover all basic evolutionary dynamics of the two strategies: dominance; coexistence; bistability; and neutrality, as special cases depending on pairs of probabilities. Of special interest is that the expected pay-off of each mixed strategy exceeds the pay-off of loners at some interior equilibrium in the coexistence region.