bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic morphine produce antinociception mediated by spinal 5‐HT7, but not 5‐HT1A and 5‐HT2 receptors in the spinal cord
Authors: Dogrul A , Seyrek M
Published: August 2006

Background and purpose:

The serotonergic system within the spinal cord have been proposed to play an important role in the analgesic effects of systemic morphine. Currently, seven groups of 5‐HT receptors (5‐HT1–7) have been characterized. One of the most recently identified subtypes of 5 HT receptor is the 5‐HT7 receptor. We aimed to examine the role of spinal 5‐HT7 receptors in the antinociceptive effects of systemic morphine.

Experimental approach:

The involvement of spinal 5‐HT7 receptor in systemic morphine antinociception was compared to that of the 5‐HT1A and 5‐HT2 receptors by using the selective 5‐HT7 receptor antagonist, SB‐269970, the selective 5‐HT1A receptor antagonist, WAY 100635, the selective 5‐HT2 antagonist ketanserin as well as the non‐selective 5‐HT1,2,7 receptor antagonist, metergoline. Nociception was evaluated by the radiant heat tail‐flick test.

Key results:

I.t. administration of SB‐269970 (10 μg) and metergoline (20 μg) completely blocked the s.c. administered morphine‐induced (1, 3, 5 and 10 mg kg−1) antinociception in a time‐dependent manner. Additionally, i.t. administration of SB‐269970 (1, 3, 10 and 20 μg) and metergoline (1, 5, 10 and 20 μg) dose dependently inhibited the antinociceptive effects of a maximal dose of morphine (10 mg kg−1, s.c.). I.t. administration of WAY 100635 (20 μg) or ketanserine (20 μg) did not alter morphine‐induced (1, 3, 5 and 10 mg kg−1, s.c.) antinociception.

Conclusion and implications:

These findings indicate that the involvement of spinal 5‐HT7, but not of 5‐HT1A or of 5‐HT2 receptors in the antinociceptive effects of systemic morphine.

British Journal of Pharmacology (2006) 149, 498–505. doi:10.1038/sj.bjp.0706854
An ab initio study of the low-lying electronic states of S3
Authors: Peterson Kirk A. , Lyons James R. , Francisco Joseph S.
Published: August 2006

Accurate calculations of the low-lying singlet and triplet electronic states of thiozone, S3, have been carried out using large multireference configuration interaction wave functions. Cuts of the full potential energy surfaces along the stretching and bending coordinates have been presented, together with the vertical excitation spectra. The strong experimentally observed absorption around 395nm is assigned to the 1B21 state, which correlates to ground state products. Absorption at wavelengths shorter than 260nm is predicted to lead to singlet excited state products, S2 (aΔg1)+S(D1). The spectroscopic properties of the XΣg−3, aΔg1, and bΣg+1 electronic states of the S2 radical have also been accurately characterized in this work. The investigations of the low-lying electronic states were accompanied by accurate ground state coupled cluster calculations of the thermochemistry of both S2 and S3 using large correlation consistent basis sets with corrections for core-valence correlation, scalar relativity, and atomic spin-orbit effects. Resulting values for D0(S2+S) and ∑D0 for S3 are predicted to be 61.3 and 162.7kcal∕mol, respectively, with conservative uncertainties of ±1kcal∕mol. Analogous calculations predict the C2v-D3h (open-cyclic) isomerization energy of S3 to be 4.4±0.5kcal∕mol.
On Miura transformations among nonlinear partial differential equations
Authors: Cao Xifang , Wu Hongyou , Xu Chuanyou
Published: August 2006

In this paper, we study Miura transformations u↦v from partial differential equations uxxx=F(u,ux,ut) to nonlinear partial differential equations G(v,vx,vt,…,∂xlv,…,∂t1v)=0 defined using integrable systems on v. We classify all such Miura transformations under some restrictions, and hence generalize the classical Miura transformation to a large class of nonlinear partial differential equations. For some examples, by applying Miura transformations found in this paper, we derive exact solutions v from known solutions u. In particular, kink and soliton-kink solutions of vt=32vxsin2v+12vx3+vxxx are obtained from constant solutions and soliton solutions of the MKdV equation. As another application of Miura transformations of this paper, we deduce a new Bäcklund transformation for each of vt=32vxsin2v+12vx3+vxxx and vt=−32vxsinh2v−12vx3+vxxx from the known Bäcklund transformations for the MKdV equations.
Plasma-focus-based tabletop hard x-ray source for 50ns resolution introspective imaging of metallic objects through metallic walls
Authors: Moreno C. , Raspa V. , Sigaut L. , Vieytes R. , Clausse A.
Published: August 2006

A tabletop 4.7kJ, 30kV plasma focus device was used as a pulsed hard x-ray source for fast radiography (50ns exposure time) of metallic pieces even through several millimeter thick metallic walls. An experimental estimation of the effective average energy of the x-ray beam (found to be around 100keV) and a numerical estimation of the induced voltage on the focus during the compressional stage of a plasma focus are briefly discussed.
Theoretical model of infrared spectra of hydrogen bonds in molecular crystals and its application to interpretation of infrared spectra of 1-methylthymine
Authors: Boczar Marek , Boda Łukasz , Wójcik Marek J.
Published: August 2006

A theoretical model for vibrational interactions in the hydrogen bonds in molecular crystals with four molecules forming two centrosymmetric dimers in the unit cell is presented. The model takes into account anharmonic-type couplings between the high-frequency N–H(D) and the low-frequency N⋯O stretching vibrations in each hydrogen bond, resonance interactions (Davydov coupling) between equivalent hydrogen bonds in each dimer, resonance interdimer interactions within a unit cell, and Fermi resonance between the N–H(D) stretching fundamental and the first overtone of the N–H(D) in-plane bending vibrations. The vibrational Hamiltonian, selection rules, and expressions for the integral properties of an absorption spectrum are derived. The model is used for theoretical simulation of the NH stretching bands of 1-methylthymine and its ND derivative at 300K. The effect of deuteration is successfully reproduced by our model. Infrared, far-infrared, Raman, and low-frequency Raman spectra of 1-methylthymine and its deuterated derivative have been measured. Experimental geometry and frequencies are compared with the results of density functional theory calculations performed at the B3LYP∕6-311++G**, B3LYP/cc-pVTZ, B3PW91∕6-311++G**, and B3PW91/cc-pVTZ levels.
Impedance spectroscopy of TiO2 thin films showing resistive switching
Authors: Jeong Doo Seok , Schroeder Herbert , Waser Rainer
Published: August 2006

Impedance characteristics of 27nm thick anatase TiO2 films showing bistable resistive switching were investigated in the frequency domain (100Hz–10MHz) in various resistance states, a fresh state (before electroforming), a high resistive state (HRS), and a low resistive state (LRS). dc conductance in the film becomes dominent in HRS and LRS and the capacitances in the various states are almost identical. Numerical calculations using finite element analysis were performed for the localized filament and homogeneous model, whose results suggest that the filament model is consistent with the experimental results.
Effective thermal conductivity of two-scale porous media
Authors: Zhang H.-F. , Ge X.-S. , Ye H.
Published: August 2006

A two-scale model is developed for predicting the effective thermal conductivity of porous media. To account for the effects of the microstructure on the macroscopic conductivity, predictions from the one- and two-scale models are comparatively investigated. The results show that the microstructure can strongly affect the macroscopic conductivity, and the degree of the effects is related to the total porosity and the conductivity ratio of the components.
Mechanism of eliminating basal plane dislocations in SiC thin films by epitaxy on an etched substrate
Authors: Zhang Z. , Moulton E. , Sudarshan T. S.
Published: August 2006

Homoepitaxial growth is performed on 8° off-axis SiC substrates that are molten KOH etched. The shape of a basal plane dislocation (BPD) etch pit at different stages of epitaxial growth is studied by atomic force microscopy. It is found that the growth steps covering a BPD etch pit are curved, and both the usual step-flow growth and lateral growth perpendicular to the step-flow direction will take place in the pit simultaneously during epitaxy. The lateral growth is usually dominant and “blocks” the path for the BPD to propagate, and thus the conversion of BPDs to threading edge dislocations is enhanced.
The electronic spectrum of jet-cooled copper hydrosulfide (CuSH)
Authors: Sunahori Fumie X. , Zhang Xiaopeng , Clouthier Dennis J.
Published: August 2006

The electronic spectrum of copper hydrosulfide (CuSH) has been observed for the first time. CuSH and CuSD were produced in a pulsed discharge jet by the reaction of sputtered copper atoms with H2S or D2S. Strong laser-induced fluorescence bands observed in the 515–470nm region were assigned as the ÃA″1−X̃A′1 band system based on detailed rotational analysis and the correspondence with the predictions of our CCSD(T)∕6-311++G(3df,3pd) ab initio calculations. The laser-induced fluorescence and single vibronic level emission spectra consist primarily of a short progression in ν3, the Cu–S stretching mode, indicative of only modest structural changes on electronic excitation. The rotational constants of four isotopomers of CuSH were used to determine effective zero-point structures in the combining states as r″(CuS)=2.0916(3)Å, r″(SH)=1.364(3)Å, θ″=93.5(3)°, r′(CuS)=2.172(3)Å, r′(SH)=1.408(23)Å, and θ′=93.5(24)°. A comparison of the ground state structures of the known metal hydrosulfides shows that they can be considered to be metal-substituted hydrogen sulfides. The electronic spectra and molecular structures of CuOH and CuSH are compared and contrasted.
Thermal stability of Ti∕Pt∕Cu Schottky contact on InAlAs layer
Authors: Lien Yi-Chung , Chang Edward Yi , Chen Szu-Hung , Chu Li-Hsin , Chen Po-Chou , Hsieh Yen-Chang
Published: August 2006

Electrical characteristics and thermal stability of the Ti∕Pt∕Cu Schottky contact on InAlAs were investigated. The Ti∕Pt∕Cu Schottky contact had comparable electrical properties compared to the conventional Ti∕Pt∕Au contact after annealing. As judged from the material analysis, the Ti∕Pt∕Cu on InAlAs after 350°C annealing showed no diffusion sign into the InAlAs. After 400°C annealing, the interfacial mixing of Cu and the underlying layers occurred and resulted in the formation of Cu4Ti. The results show that Ti∕Pt∕Cu Schottky contact using platinum as the diffusion barrier is very stable up to 350°C annealing and can be used for InAlAs∕InGaAs high-electron mobility transistors and monolithic microwave integrated circuits.
Local magnetic field detector made by microscale ion irradiation on high temperature superconducting films
Authors: Laviano Francesco , Gerbaldo Roberto , Ghigo Gianluca , Gozzelino Laura , Minetti Bruno , Mezzetti Enrica
Published: August 2006

Microscale modulations of the crystal structure in a continuous superconductor turn out to be effective for the spatial focusing of the energy dissipation induced by unpinned vortices. High-energy heavy-ion irradiation allowed the authors to finely control the defect density in order to study the properties of interfaces between pristine and irradiated parts of high temperature superconductors. In particular, strip-shaped samples were locally irradiated to create microscale modulations across their whole width. Magneto-optical imaging under electrical transport and magnetoresistive measurements imply that such tailored modulation in a superconducting strip can be exploited to develop a fully planar, single-compound, local magnetoresistive sensor.
Coupling of waveguide and surface modes in enhanced transmission through stacking gratings
Authors: Fong King-Yan , Hui P. M.
Published: August 2006

The physics of enhanced transmission through two metallic gratings stacked one on top of another with a lateral shift is studied. Full electromagnetic calculations via the method of rigorous coupled-wave analysis show that enhanced transmission may result even when the slits in one grating are covered by the other. Despite the channel of waveguide mode is blocked, the coupling of strongly excited surface modes in one grating to the waveguide mode in another leads to an enhanced transmission which could even be larger than that in the case of two stacking gratings unshifted with respect to one another.
Charge trapping in nitrided HfSiO gate dielectric layers
Authors: Vellianitis G. , Rittersma Z. M. , Pétry J.
Published: August 2006

The effects of HfSiO nitridation on charge trapping and long-term dielectric reliability are investigated. A comparison between decoupled plasma nitridation, annealing in NH3, and no nitridation is made. It was found that thinner HfSiO layers show less trapped charge. Decoupled plasma nitridation resulted always in a larger hysteresis in the characteristics. A common behavior in all samples was seen at elevated temperatures, which corresponds to lower trapped charge and higher leakage current. Dependence between the trapped charge and the leakage current changes with temperature was established.
Critical conditions for the wetting of soils
Authors: Shirtcliffe Neil J. , McHale Glen , Newton Michael I. , Pyatt F. Brian , Doerr Stefan H.
Published: August 2006

The wettability of soil is of great importance for plants and soil biota and in determining whether flooding and soil erosion will occur. The analysis used in common measurements of soil hydrophobicity makes the assumption that water always enters soils if the average contact angle between the soil and water is 90° or lower; these tests have been used for decades. The authors show theoretically and experimentally that water cannot enter many soils unless the contact angle is considerably lower than this, down to approximately 50°. This difference generates serious errors in determining and modeling soil wetting behavior.
Single crystal x-ray diffraction of lead magnesium niobate-lead titanate in the transmission mode
Authors: Sehirlioglu Alp , Payne David A. , Wilson Scott R. , Han Pengdi
Published: August 2006

0.7 Pb ( Mg 1 ∕ 3 Nb 2 ∕ 3 ) O 3 – 0.3 Pb Ti O 3 single crystals were examined by single crystal x-ray diffraction in the transmission mode, and a superlattice was revealed with a doubling of the unit cell in all three directions, giving a cell volume eight times that of a traditional perovskite unit cell. The significance of the superlattice peaks increased with poling, indicating a structural contribution to ordering. Lack of such observations by electron diffraction in the transmission electron microscope examinations suggests the presence of a bulk effect.
Influence of the local adsorption environment on the intramolecular contrast of organic molecules in noncontact atomic force microscopy
Authors: Such Bartosz , Weiner Domenique , Schirmeisen André , Fuchs Harald
Published: August 2006

Thin epitaxial layers of the organic molecule 3,4,9,10-perylenetetracarboxylic dianhydrite on a Cu(111) surface were imaged using noncontact atomic force microscopy in ultrahigh vacuum. The second layer molecules show a distinct intramolecular structure, which is compared to the internal charge distribution of the molecule. The molecules in the first layer, though, exhibit no detectable intramolecular features. This effect is discussed with respect to the presence of the metallic substrate for the first layer molecules, which demonstrates the strong influence of the local adsorption environment on the internal electronic properties of organic molecules.
Systematics of the Protohermes davidi species-group (Megaloptera:Corydalidae) with notes on phylogeny and biogeography
Authors: Liu Xingyue , Yang Ding
Published: August 2006

A new species-group, the Protohermes davidi species-group, of the dobsonfly genus Protohermes van der Weele is recognised. Five species belonging to the P. davidi species-group from China are described and illustrated, including one new species. The cladistic analysis infers that this species-group appears monophyletic and is divided into two subgroups. The distribution pattern of this species-group is presented, and its biogeography is also discussed.
Psyllid communication: acoustic diversity, mate recognition and phylogenetic signal
Authors: Percy Diana M. , Taylor Gary S. , Kennedy Martyn
Published: August 2006

Acoustic signals play an important role in mate selection and speciation in diverse groups of insects. We report reciprocal acoustic mate signalling, often as highly synchronised duetting, for several species of psyllid (Hemiptera : Psylloidea). We reveal that considerable acoustic diversity is present in Australian psyllids belonging to the family Triozidae. The acoustic signals are species and gender specific. Our acoustic analysis and observations suggest that acoustic signals are important in both species recognition and mate selection in psyllids. We found a significant level of phylogenetic signal in the acoustic data when we compared divergence in genetic data (obtained from mitochondrial DNA sequences of the small subunit rRNA) with divergence in acoustic signals in two groups of Australian psyllids. Phylogenetic reconstruction based on DNA sequence data supports the monophyly of the Eucalyptus-feeding genus Schedotrioza Tuthill & Taylor, 1955, whereas a diverse but little known group on Casuarinaceae hosts appears to be paraphyletic. These two psyllid groups also differ in amounts of geographical and ecological sympatry. We found a significant positive correlation between acoustic distance and genetic distance using pairwise comparisons for all taxa, but the trends within the two groups differ due to a negative association between acoustic and genetic divergence among the sympatric taxa. Phylogenetic information in acoustic data may be greatest in recently speciating and allopatric groups because of increased acoustic divergence in sympatric taxa and greater acoustic convergence in more distantly related species.
Phylogeny of the Oxycoryninae sensu lato (Coleoptera:Belidae) and evolution of host-plant associations
Authors: Marvaldi A. E. , Oberprieler R. G. , Lyal C. H. C. , Bradbury T. , Anderson R. S.
Published: August 2006

Phylogenetic relationships among the genera of the subfamily Oxycoryninae and other belids (Curculionoidea) were reconstructed by cladistic analysis using 21 terminals and 98 characters: 62 from imaginal morphology, 33 from larval morphology and three biological characters relating to host plants and larval feeding habits. Terminal taxa represent all extant genera of Oxycoryninae, two genera of each of the three tribes of Belinae plus two outgroup taxa used to root the tree. New information on the larvae and biology of the metrioxenines is used in phylogenetic reconstruction. In accord with the single optimal cladogram obtained, a revised classification of the Oxycoryninae is proposed. The subfamily is classified into three tribes (Oxycorynini, Metrioxenini and Aglycyderini), with the tribe Oxycorynini further classified into three subtribes (Oxycraspedina Marvaldi & Oberprieler, subtr. nov., Oxycorynina and Allocorynina) and the tribe Metrioxenini into two subtribes (Metrioxenina and Afrocorynina ( = Hispodini, syn. nov.)). Larval and adult unambiguous synapomorphies defining each clade are identified. Tracing the evolution of biological traits from the phylogenetic estimate indicates that drastic shifts to phylogenetically distant host plants occurred from the ancestral belid association with conifers. Structural, chemical and/or ecological similarities of the plant organs consumed apparently had a major influence in the colonisation of different plant taxa by this group of weevils.
The vaginal ring and transdermal patch: new methods of contraception
Authors: McNamee Kathleen
Published: August 2006

The most common method of reversible contraception used worldwide is the intrauterine device. However, in the Asia–Pacific the combined oral contraceptive pill and condoms, methods of contraception that require a high degree of day-to-day user compliance, are more popular. The combined vaginal ring and transdermal patch have been developed to overcome the need for daily compliance associated with combined pill use. They have the added advantages of non-oral delivery, thus avoiding gastro-intestinal interference with absorption, and in addition there is no hepatic first-pass effect. Both have been available internationally for some years and offer an alternative to the combined pill. This article reviews and summarises published data on these new methods.
The SLAPPA (Significance of Lower Abdominal/Periumbilical Piercing as a predictor of acute Appendicitis) audit
Authors: Ahmed Irfan , Boulter Matthew K. , Lobo Dileep N.
Published: August 2006

Background: Anecdotal observations among medical staff suggest that young women with periumbilical piercing presenting with right iliac fossa pain are more likely to have pelvic inflammatory disease than acute appendicitis because of an unconventional lifestyle. This audit was performed to test the validity of this prejudice. Methods: The clinical data of all female patients aged 16–45 years admitted to a teaching hospital with suspected acute appendicitis were collected prospectively over six months. Patients who had undergone previous appendicectomy or gynaecological surgery, those with known Crohn’s disease, or those on antibiotics at the time of admission were excluded. Results: 107 patients with a median age of 29.7 years (range 15–45 years) were studied. Thirty-two patients had periumbilical piercing (Group A) and 75 patients did not (Group B). Fifty-nine out of 107 (55.14%) were operated upon. Ten (31.2%) patients in Group A had histologically confirmed acute appendicitis compared with 25 (33.3%) in Group B. Other diagnoses in Group A included non-specific abdominal pain (n = 13, 40.6%), urinary tract infection (4, 12.5%), pelvic inflammatory disease (4, 12.5%) and ovarian cyst (1, 3.1%). Corresponding figures for patients in Group B were 30 (40.0%), 8 (10.7%), 7 (9.3%) and 4 (5.3%) respectively. None of the differences between the two groups were statistically significant. Conclusions: There was no difference in the frequency of a final diagnosis of acute appendicitis or pelvic inflammatory disease in female patients with and without periumbilical piercing. Health care professionals should not allow their clinical judgment to be prejudiced by the presence of body piercing.
Changes in the diagnosis and management of bacterial vaginosis following clinical research
Authors: Morton Anna N. , Bradshaw Catriona S. , Fairley Christopher K.
Published: August 2006

Background: It has become common practice to offer patients attending public sexual health clinics participation in research studies. We investigated the premise that clinician involvement in research leads to improvements in clinical practice within a sexual health service in Melbourne, Australia. Methods: Retrospective case note reviews were conducted of 100 cases of bacterial vaginosis (BV) during three time periods; 2000, 2002 and 2004. The first and second reviews were conducted 2 years before and immediately prior to a cross-sectional study of BV at Melbourne Sexual Health Centre. The third review was conducted immediately after study completion. Diagnostic criteria and treatment for BV were recorded. Clinicians were divided into high and low recruiters, according to the percentage of eligible patients that they recruited into the cross-sectional study. No audited cases were enrolled in the study. Results: Significant improvements in the use of Amsel’s criteria occurred between the second and third audit periods (51 to 65%, P = 0.04) but not between the first and second audits (51% for both, P = 1.0). The improvement was seen in high-recruiting clinicians (P = 0.02) but not low-recruiting clinicians (P = 0.75). Although treatment with 7 days of metronidazole or vaginal clindamycin increased for all clinicians between the first and second audit periods (8 to 18%, P = 0.04), it was greater between the second and third audit periods (18 to 72%, P < 0.01). No difference was observed between high- and low-recruiting clinicians. Conclusion: Introduction of research was temporally associated with improved clinical practice in high-recruiting clinicians only.
Anorectal lymphogranuloma venereum in a Melbourne man
Authors: Morton Anna N. , Fairley Christopher K. , Zaia Angelo M. , Chen Marcus Y.
Published: August 2006

We report the first case of anorectal lymphogranuloma venereum (LGV) in a man who has sex with men (MSM) in Australia in the setting of the recent emergence of LGV among MSM in Europe and the USA. A 33-year-old man presented with a 2 month history of mild external anal discomfort. He gave a history of unprotected receptive and insertive anal intercourse with one partner in Europe during the preceding 6 months. No symptoms suggested proctitis and examination revealed two small anal fissures. An anal swab was positive for Chlamydia trachomatis; investigation for other STIs including HIV were negative. On review 6 days later, he was investigated and treated presumptively for LGV. The LGV diagnosis was confirmed by identifying the L2 serovar of C. trachomatis using a genotype test on the original anal specimen. This case is in keeping with the more recent reports of LGV from Europe, and has demonstrated the need for a high index of suspicion for asymptomatic or minimally symptomatic anorectal LGV.
Inactivation of JNK1 enhances innate IL-10 production and dampens autoimmune inflammation in the brain
Authors: Tran Elise H. , Azuma Yasu-Taka , Chen Manchuan , Weston Claire , Davis Roger J. , Flavell Richard A.
Published: August 2006

Environmental insults such as microbial pathogens can contribute to the activation of autoreactive T cells, leading to inflammation of target organs and, ultimately, autoimmune disease. Various infections have been linked to multiple sclerosis and its animal counterpart, autoimmune encephalomyelitis. The molecular process by which innate immunity triggers autoreactivity is not currently understood. By using a mouse model of multiple sclerosis, we found that the genetic loss of the MAPK, c-Jun N-terminal kinase 1 (JNK1), enhances IL-10 production, rendering innate myeloid cells unresponsive to certain microbes and less capable of generating IL-17–producing, encephalitogenic T cells. Moreover, JNK1-deficient central nervous system myeloid cells are unable to respond to effector T cell inflammatory cytokines, preventing further progression to neuroinflammation. Thus, we have identified the JNK1 signal transduction pathway in myeloid cells to be a critical component of a regulatory circuit mediating inflammatory responses in autoimmune disease. Our findings provide further insights into the pivotal MAPK-regulated network of innate and adaptive cytokines in the progression to autoimmunity.
A functional SNP in the promoter of the
SERPINH1
gene increases risk of preterm premature rupture of membranes in African Americans
Authors: Wang Hongyan , Parry Samuel , Macones George , Sammel Mary D. , Kuivaniemi Helena , Tromp Gerard , Argyropoulos George , Halder Indrani , Shriver Mark D. , Romero Roberto , Strauss Jerome F.
Published: August 2006

Prematurity is more prevalent in African Americans than in European Americans. We investigated the contribution of a functional SNP in the promoter of the
SERPINH1
gene, enriched among those of African ancestry, to preterm premature rupture of membranes (PPROM), the leading identifiable cause of preterm birth.
SERPINH1
encodes heat-shock protein 47, a chaperone essential for collagen synthesis. The
SERPINH1
−656 minor T allele had a greater frequency in African populations and African Americans than in European Americans (12.4% vs. 4.1%). The −656 T allele displayed significantly reduced promoter activity compared to the major −656 C allele in amnion fibroblasts, which lay down the fibrillar collagen that gives tensile strength to the amnion. An initial case-control study demonstrated that the −656 T allele is significantly more frequent in African-American neonates (
P
< 0.0009) born from pregnancies complicated by PPROM compared with controls (odds ratio of 3.22, 95% confidence interval 1.50, 7.22). There was no significant difference in ancestry among cases and controls using a dihybrid model based on 29 ancestry-informative markers. Adjusting the results of the case-control study for admixture still yielded a statistically significant association between the −656 T allele and PPROM (
P
< 0.002). A follow-up case-control study gave similar results. The combined case-control findings showed a highly significant (
P
< 0.0000045) association between the −656 T allele and PPROM. The
SERPINH1
−656 T allele is the first example of an ancestry-informative marker associated with preterm birth in African Americans.
Structural mechanism for the carriage and release of thyroxine in the blood
Authors: Zhou Aiwu , Wei Zhenquan , Read Randy J. , Carrell Robin W.
Published: August 2006

The hormones that most directly control tissue activities in health and disease are delivered by two noninhibitory members of the serpin family of protease inhibitors, thyroxine-binding globulin (TBG) and corticosteroid-binding globulin. The structure of TBG bound to tetra-iodo thyroxine, solved here at 2.8 Å, shows how the thyroxine is carried in a surface pocket on the molecule. This unexpected binding site is confirmed by mutations associated with a loss of hormone binding in both TBG and also homologously in corticosteroid-binding globulin. TBG strikingly differs from other serpins in having the upper half of its main β-sheet fully opened, so its reactive center peptide loop can readily move in and out of the sheet to give an equilibrated binding and release of thyroxine. The entry of the loop triggers a conformational change, with a linked contraction of the binding pocket and release of the bound thyroxine. The ready reversibility of this change is due to the unique presence in the reactive loop of TBG of a proline that impedes the full and irreversible entry of the loop that occurs in other serpins. Thus, TBG has adapted the serpin inhibitory mechanism to give a reversible flip-flop transition, from a high-affinity to a low-affinity form. The complexity and ready triggering of this conformational mechanism strongly indicates that TBG has evolved to allow a modulated and targeted delivery of thyroxine to the tissues.
Matefin/SUN-1 is a nuclear envelope receptor for CED-4 during
Caenorhabditis elegans
apoptosis
Authors: Tzur Yonatan B. , Margalit Ayelet , Melamed-Book Naomi , Gruenbaum Yosef
Published: August 2006

In
Caenorhabditis elegans
, the antiapoptotic protein CED-9 is localized at the mitochondria, where it binds the proapoptotic protein CED-4. Induction of apoptosis begins when the proapoptotic protein EGL-1 is expressed and binds CED-9. The binding of EGL-1 to CED-9 releases CED-4 from CED-9 and causes the activation of the caspase CED-3. Upon its release from CED-9, CED-4 rapidly translocates to the nuclear envelope (NE) in a CED-3-independent manner. However, the identity of the NE receptor for CED-4 and its possible role in the execution of apoptosis has remained unknown. Here, we show that the inner nuclear membrane SUN-domain protein matefin/SUN-1 is the NE receptor for CED-4. Our data demonstrate that matefin/SUN-1 binds CED-4 and is specifically required for CED-4 translocation and maintenance at the NE. The role of matefin/SUN-1 in the execution of apoptosis is further suggested by the significant reduction in the number of apoptotic cells in the organism after matefin/SUN-1 down-regulation by RNAi. The finding that matefin/SUN-1 is required for the execution of apoptosis adds an important link between cytoplasmic and nuclear apoptotic events.
Monitoring of heparin and its low-molecular-weight analogs by silicon field effect
Authors: Milović Nebojša M. , Behr Jonathan R. , Godin Michel , Hou Chih-Sheng Johnson , Payer Kristofor R. , Chandrasekaran Aarthi , Russo Peter R. , Sasisekharan Ram , Manalis Scott R.
Published: August 2006

Heparin is a highly sulfated glycosaminoglycan that is used as an important clinical anticoagulant. Monitoring and control of the heparin level in a patient's blood during and after surgery is essential, but current clinical methods are limited to indirect and off-line assays. We have developed a silicon field-effect sensor for direct detection of heparin by its intrinsic negative charge. The sensor consists of a simple microfabricated electrolyte-insulator-silicon structure encapsulated within microfluidic channels. As heparin-specific surface probes the clinical heparin antagonist protamine or the physiological partner antithrombin III were used. The dose–response curves in 10% PBS revealed a detection limit of 0.001 units/ml, which is orders of magnitude lower than clinically relevant concentrations. We also detected heparin-based drugs such as the low-molecular-weight heparin enoxaparin (Lovenox) and the synthetic pentasaccharide heparin analog fondaparinux (Arixtra), which cannot be monitored by the existing near-patient clinical methods. We demonstrated the specificity of the antithrombin III functionalized sensor for the physiologically active pentasaccharide sequence. As a validation, we showed correlation of our measurements to those from a colorimetric assay for heparin-mediated anti-Xa activity. These results demonstrate that silicon field-effect sensors could be used in the clinic for routine monitoring and maintenance of therapeutic levels of heparin and heparin-based drugs and in the laboratory for quantitation of total amount and specific epitopes of heparin and other glycosaminoglycans.
Fluorogenic metabolic probes for direct activity readout of redox enzymes: Selective measurement of human AKR1C2 in living cells
Authors: Yee Dominic J. , Balsanek Vojtech , Bauman David R. , Penning Trevor M. , Sames Dalibor
Published: August 2006

The current arsenal of tools and methods for the continuous monitoring and imaging of redox metabolic pathways in the context of intact cells is limited. Fluorogenic substrates allow for direct measurement of enzyme activity
in situ
; however, in contrast to proteases and exo-glycosidases, there are no simple guidelines for the design of selective probes for redox metabolic enzymes. Here, we introduce redox probe 1 and demonstrate its high selectivity in living cells for human hydroxysteroid dehydrogenases (HSDs) of the aldo-keto reductase (AKR) superfamily. AKR1C isoforms perform multiple functions among which the metabolism of potent steroid hormones is well documented. Moreover, expression of these enzymes is responsive to cellular stress and pathogenesis, including cancer. Our probe design is based on redox-sensitive optical switches, which couple a ketone–alcohol redox event to a profound change in fluorescence. The high selectivity of phenyl ketone 1 for AKR1C2 over the many endogenous reductases present in mammalian cells was established by a quantitative comparison of the metabolic rates between null control cells (COS-1) and AKR1C2-transfected cells. Phenyl ketone 1 is a cell-permeable fluorogenic probe that permits a direct, real-time, and operationally simple readout of AKR1C2 enzyme activity in intact mammalian cells. Furthermore, it was demonstrated that probe 1 enables the quantitative examination of physiological substrate 5α-dihydrotestosterone (“dark substrate”)
in situ
by means of a two-substrate competitive assay. Similarly, inhibitor potency of physiological (ursodeoxycholate) and synthetic inhibitors (flufenamic acid, ibuprofen, and naproxen) was also readily evaluated.
Evolution of increased glia–neuron ratios in the human frontal cortex
Authors: Sherwood Chet C. , Stimpson Cheryl D. , Raghanti Mary Ann , Wildman Derek E. , Uddin Monica , Grossman Lawrence I. , Goodman Morris , Redmond John C. , Bonar Christopher J. , Erwin Joseph M. , Hof Patrick R.
Published: August 2006

Evidence from comparative studies of gene expression and evolution suggest that human neocortical neurons may be characterized by unusually high levels of energy metabolism. The current study examined whether there is a disproportionate increase in glial cell density in the human frontal cortex in comparison with other anthropoid primate species (New World monkeys, Old World monkeys, and hominoids) to support greater metabolic demands. Among 18 species of anthropoids, humans displayed the greatest departure from allometric scaling expectations for the density of glia relative to neurons in layer II/III of dorsolateral prefrontal cortex (area 9L). However, the human glia–neuron ratio in this prefrontal region did not differ significantly from allometric predictions based on brain size. Further analyses of glia–neuron ratios across frontal areas 4, 9L, 32, and 44 in a sample of humans, chimpanzees, and macaque monkeys showed that regions involved in specialized human cognitive functions, such as “theory of mind” (area 32) and language (area 44) have not evolved differentially higher requirements for metabolic support. Taken together, these findings suggest that greater metabolic consumption of human neocortical neurons relates to the energetic costs of maintaining expansive dendritic arbors and long-range projecting axons in the context of an enlarged brain.
A
Drosophila
model for age-associated changes in sleep:wake cycles
Authors: Koh Kyunghee , Evans Joshua M. , Hendricks Joan C. , Sehgal Amita
Published: August 2006

One of the most consistent behavioral changes that occurs with age in humans is the loss of sleep consolidation. This can be quite disruptive and yet little is known about its underlying basis. To better understand the effects of aging on sleep:wake cycles, we sought to study this problem in
Drosophila melanogaster
, a powerful system for research on aging and behavior. By assaying flies of different ages as well as monitoring individual flies constantly over the course of their lifetime, we found that the strength of sleep:wake cycles decreased and that sleep became more fragmented with age in
Drosophila
. These changes in sleep:wake cycles became faster or slower with manipulations of ambient temperature that decreased or increased lifespan, respectively, demonstrating that they are a function of physiological rather than chronological age. The effect of temperature on lifespan was not mediated by changes in overall activity level or sleep amount. Flies treated with the oxidative stress-producing reagent paraquat showed a breakdown of sleep:wake cycles similar to that seen with aging, leading us to propose that the accumulation of oxidative damage with age contributes to the changes in rhythm and sleep. Together, these findings establish
Drosophila
as a valuable model for studying age-associated sleep fragmentation and breakdown of rhythm strength, and indicate that these changes in sleep:wake cycles are an integral part of the physiological aging process.
Energy analysis of chemistry for correct insertion by DNA polymerase β
Authors: Lin Ping , Pedersen Lars C. , Batra Vinod K. , Beard William A. , Wilson Samuel H. , Pedersen Lee G.
Published: August 2006

X-ray crystallographic structures of human DNA polymerase β with nonhydrolyzable analogs containing all atoms in the active site required for catalysis provide a secure starting point for a theoretical analysis (quantum mechanics/molecular mechanics) of the mechanism of chemistry without biasing of modeling assumptions as required in previous studies. These structures provide the basis for a detailed quantum mechanics/molecular mechanics study of the path for the complete transfer of a monophosphate nucleoside donor to the sugar acceptor in the active site. The reaction is largely associative with the main energetic step preceded by proton transfer from the terminal primer deoxyribose O3′ to Asp-256. The key residues that provide electrostatic stabilization of the transition state are identified and compared with those identified by mutational studies.
Faithful replication of foraging techniques along cultural transmission chains by chimpanzees and children
Authors: Horner Victoria , Whiten Andrew , Flynn Emma , de Waal Frans B. M.
Published: August 2006

Observational studies of wild chimpanzees (Pan troglodytes) have revealed population-specific differences in behavior, thought to represent cultural variation. Field studies have also reported behaviors indicative of cultural learning, such as close observation of adult skills by infants, and the use of similar foraging techniques within a population over many generations. Although experimental studies have shown that chimpanzees are able to learn complex behaviors by observation, it is unclear how closely these studies simulate the learning environment found in the wild. In the present study we have used a diffusion chain paradigm, whereby a behavior is passed from one individual to the next in a linear sequence in an attempt to simulate intergenerational transmission of a foraging skill. Using a powerful three-group, two-action methodology, we found that alternative methods used to obtain food from a foraging device (“lift door” versus “slide door”) were accurately transmitted along two chains of six and five chimpanzees, respectively, such that the last chimpanzee in the chain used the same method as the original trained model. The fidelity of transmission within each chain is remarkable given that several individuals in the no-model control group were able to discover either method by individual exploration. A comparative study with human children revealed similar results. This study is the first to experimentally demonstrate the linear transmission of alternative foraging techniques by non-human primates. Our results show that chimpanzees have a capacity to sustain local traditions across multiple simulated generations.
Structure of aminopeptidase N from
Escherichia coli
suggests a compartmentalized, gated active site
Authors: Addlagatta Anthony , Gay Leslie , Matthews Brian W.
Published: August 2006

Aminopeptidase N from
Escherichia coli
is a major metalloprotease that participates in the controlled hydrolysis of peptides in the proteolytic pathway. Determination of the 870-aa structure reveals that it has four domains similar to the tricorn-interacting factor F3. The thermolysin-like active site is enclosed within a large cavity with a volume of 2,200 Å
3
, which is inaccessible to substrates except for a small opening of approximately 8–10 Å. The substrate-based inhibitor bestatin binds to the protein with minimal changes, suggesting that this is the active form of the enzyme. The previously described structure of F3 had three distinct conformations that were described as “closed,” “intermediate,” and “open.” The structure of aminopeptidase N from
E. coli
, however, is substantially more closed than any of these. Taken together, the results suggest that these proteases, which are involved in intracellular peptide degradation, prevent inadvertent hydrolysis of inappropriate substrates by enclosing the active site within a large cavity. There is also some evidence that the open form of the enzyme, which admits substrates, remains inactive until it adopts the closed form.
Anisotropic network model: systematic evaluation and a new web interface
Authors: Eyal Eran , Yang Lee-Wei , Bahar Ivet
Published: August 2006

Motivation: The Anisotropic Network Model (ANM) is a simple yet powerful model for normal mode analysis of proteins. Despite its broad use for exploring biomolecular collective motions, ANM has not been systematically evaluated to date. A lack of a convenient interface has been an additional obstacle for easy usage.

Results: ANM has been evaluated on a large set of proteins to establish the optimal model parameters that achieve the highest correlation with experimental data and its limits of accuracy and applicability. Residue fluctuations in globular proteins are shown to be more accurately predicted than those in nonglobular proteins, and core residues are more accurately described than solvent-exposed ones. Significant improvement in agreement with experiments is observed with increase in the resolution of the examined structure. A new server for ANM calculations is presented, which offers flexible options for controlling model parameters and output formats, interactive animation of collective modes and advanced graphical features.

Availability: ANM server ()

Contact:  bahar@ccbb.pitt.edu
Retrograde Blood Flow in the Brachial and Axillary Arteries during Routine Radial Arterial Catheter Flushing
Authors: Murphy Glenn S. , Szokol Joseph W. , Marymont Jesse H. , Avram Michael J. , Vender Jeffery S. , Kubasiak John
Published: August 2006

Background

Flushing of radial arterial catheters may be associated with retrograde embolization of air or thrombus into the cerebral circulation. For embolization into the central circulation to occur, sufficient pressure must be generated during the flushing process to reverse antegrade blood flow in the arterial blood vessels of the upper extremity. This ultrasound study was designed to examine whether routine radial catheter flushing practices produce retrograde blood flow patterns in the brachial and proximal axillary arteries.

Methods

Duplex ultrasound examinations of the brachial and axillary arteries were conducted in 100 surgical patients to quantify direction and velocity of blood flow during catheter flushing. After obtaining Doppler spectral images of brachial and axillary arterial flow patterns, manual flushing was performed by injecting 10 ml flush solution using a syringe at a rate reflecting standard clinical practices. The flow-regulating device on the pressurized (300 mmHg) arterial flushing-sampling system was then opened for 10 s to deliver a rapid bolus of fluid (flush valve opening).

Results

The rate of manual flush solution injection through the radial arterial catheter was related to the probability of retrograde flow in the axillary artery (P < 0.001). Reversed arterial flow was noted in the majority of subjects (33 of 51) at a manual flush rate of less than 9 s and in no subjects (0 of 48) at a rate 9 s or greater. Retrograde flow was observed less frequently during flush valve opening (2 of 99 patients; P < 0.001 vs. manual flushing).

Conclusions

Rapid manual flushing of radial arterial catheters at rates faster than 1 ml/s produces retrograde flow in the proximal axillary artery.