bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of the hypocretin 1 receptor antagonist SB 334867 on high‐fat food self‐administration and reinstatement of food seeking in rats
Authors: Nair S G , Golden S A , Shaham Y 
Published: January 2008

Background and purpose:Many studies have demonstrated a role of hypocretin 1 (orexin 1) receptors in home‐cage food consumption in rodents. However, the role of these receptors in operant food self‐administration or relapse to food seeking in animal models is unknown.Experimental approach:In Experiment 1, we trained food‐restricted rats (16–20 g per day) to lever press for high‐fat (35%) pellets (3–6 h per day, every other day). We then tested the effect of the hypocretin 1 receptor antagonist SB 334867 (10, 20 mg kg−1, i.p) on pellet self‐administration. In Experiment 2, we trained rats to self‐administer the food pellets, and following extinction of the food‐reinforced responding, we tested the effect of hypocretin 1 (3 and 6 μg, i.c.v) on reinstatement of food‐seeking and the effect of SB 334867 on this reinstatement. In Experiment 3, we tested the effect of SB 334867 on reinstatement induced by non‐contingent pellet exposure (pellet‐priming) or the pharmacological stressor yohimbine (2 mg kg−1, i.p).Key results:SB 334867 attenuated high‐fat pellet self‐administration. In contrast, SB 334867 had no effect on reinstatement of lever presses induced by hypocretin 1, pellet‐priming or yohimbine.Conclusions and implications:These data indicate that during dieting, hypocretin 1 receptors contribute to operant high‐fat pellet self‐administration, but not to relapse to food seeking induced by acute re‐exposure to the food itself or by the induction of a stress‐like state.British Journal of Pharmacology (2008) 154, 406–416; doi:10.1038/bjp.2008.3; published online 28 January 2008
The cholinergic mesopontine tegmentum is a relatively neglected nicotinic master modulator of the dopaminergic system: relevance to drugs of abuse and pathology
Authors: Maskos U 
Published: January 2008

The mammalian mesopontine tegmentum (MPT) contains two cholinergic nuclei, the pedunculopontine tegmental nucleus (PPTg) and the laterodorsal tegmental nucleus (LDTg). These provide the cholinergic innervation of, among other brain areas, the dopaminergic A9 and A10 cell groups. Their axons are thus the source of endogenous acetylcholine (ACh) acting on somato‐dendritic acetylcholine receptors in the substantia nigra (SN) and ventral tegmental area (VTA). The anatomy, physiology, functional and pathological implications of these interactions with the nicotinic subtype of acetylcholine receptors (nAChRs) are discussed with a view of the important role of the MPT as a master regulator of nicotinic dopaminergic signalling in the brain, including for nicotine addiction.British Journal of Pharmacology (2008) 153, S438–S445; doi:10.1038/bjp.2008.5; published online 28 January 2008
Procoagulant signalling mechanisms in lung inflammation and fibrosis: novel opportunities for pharmacological intervention?
Authors: Chambers R C 
Published: January 2008

There is compelling evidence that uncontrolled activation of the coagulation cascade following lung injury contributes to the development of lung inflammation and fibrosis in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and fibrotic lung disease. This article reviews our current understanding of the mechanisms leading to the activation of the coagulation cascade in response to lung injury and the evidence that excessive procoagulant activity is of pathophysiological significance in these disease settings. Current evidence suggests that the tissue factor‐dependent extrinsic pathway is the predominant mechanism by which the coagulation cascade is locally activated in the lungs of patients with ALI/ARDS and pulmonary fibrosis. Whilst, fibrin deposition might contribute to the pathophysiology of ALI/ARDS following systemic insult; current evidence suggests that the cellular effects mediated via activation of proteinase‐activated receptors (PARs) may be of particular importance in influencing inflammatory and fibroproliferative responses in experimental models involving direct injury to the lung. In this regard, studies in PAR1 knockout mice have shown that this receptor plays a major role in orchestrating the interplay between coagulation, inflammation and lung fibrosis. This review will focus on our current understanding of excessive procoagulant signalling in acute and chronic lung injury and will highlight the novel opportunities that this may present for therapeutic intervention.British Journal of Pharmacology (2008) 153, S367–S378; doi:10.1038/sj.bjp.0707603; published online 28 January 2008
Comparative study on transduction and toxicity of protein transduction domains
Authors: Sugita T , Yoshikawa T , Mukai Y , Yamanada N , Imai S , Nagano K , Yoshida Y , Shibata H , Yoshioka Y , Nakagawa S , Kamada H , Tsunoda S‐i , Tsutsumi Y 
Published: January 2008

Background and purpose:Protein transduction domains (PTDs), such as Tat, antennapedia homeoprotein (Antp), Rev and VP22, have been extensively utilized for intracellular delivery of biologically active macromolecules in vitro and in vivo. There is little known, however, about the relative transduction efficacy, cytotoxicity and internalization mechanism of individual PTDs.Experimental approach:We examined the cargo delivery efficacies of four major PTDs (Tat, Antp, Rev and VP22) and evaluated their toxicities and cell internalizing pathways in various cell lines.Key results:The relative order of the transduction efficacy of these PTDs conjugated to fluorescein was Rev>Antp>Tat>VP22, independent of cell type (HeLa, HaCaT, A431, Jurkat, MOLT‐4 and HL60 cells). Antp produced significant toxicity in HeLa and Jurkat cells, and Rev produced significant toxicity in Jurkat cells. Flow cytometric analysis demonstrated that the uptake of PTD–fluorescein conjugate was dose‐dependently inhibited by methyl‐β‐cyclodextrin, cytochalasin D and amiloride, indicating that all four PTDs were internalized by the macropinocytotic pathway. Accordingly, in cells co‐treated with ‘Tat‐fused’ endosome‐disruptive HA2 peptides (HA2‐Tat) and independent PTD‐fluorescent protein conjugates, fluorescence spread throughout the cytosol, indicating that all four PTDs were internalized into the same vesicles as Tat.Conclusions and implications:These findings suggest that macropinocytosis‐dependent internalization is a crucial step in PTD‐mediated molecular transduction. From the viewpoint of developing effective and safe protein transduction technology, although Tat was the most versatile carrier among the peptides studied, PTDs should be selected based on their individual characteristics.British Journal of Pharmacology (2008) 153, 1143–1152; doi:10.1038/sj.bjp.0707678; published online 28 January 2008
Effect of CCR5 receptor antagonists on endocytosis of the human CCR5 receptor in CHO‐K1 cells
Authors: Longden J , Cooke E‐L , Hill S J 
Published: January 2008

Background and purpose:The CCR5 chemokine receptor is a member of the G protein‐coupled receptor (GPCR) family that is expressed by macrophages, memory T‐lymphocytes and dendritic cells and is activated by chemotactic proteins (e.g. MIP‐1α [CCL3], MIP‐1β [CCL4] and RANTES [CCL5]). CCR5 is also the principal co‐receptor for macrophage‐tropic strains of human immunodeficiency virus‐1 (HIV‐1) and some chemokines can inhibit HIV‐1 infection by stimulating CCR5 receptor endocytosis. The aim of this study was to evaluate the effect of CCR5 antagonists on CCR5 endocytosis.Experimental approach:The effects of CCR5 agonists and antagonists on receptor internalization in CHO cells, expressing a C‐terminal green fluorescent protein‐tagged human CCR5 receptor (CCR5‐GFP), were quantified using a confocal imaging plate reader.Key results:MIP‐1α [CCL3], MIP‐1β [CCL4] and RANTES [CCL5] were all able to stimulate potently the internalization of CCR5‐GFP. This effect was inhibited by the non‐peptide antagonist TAK 779. The CCR5 peptide antagonist met‐RANTES antagonized MIP‐1α‐mediated increases in intracellular free calcium but was also able to stimulate a substantial internalization of the human CCR5‐GFP receptor. However, CHO cells exhibited an aminopeptidase activity that was able to metabolize sufficient met‐RANTES into an agonist metabolite capable of stimulating calcium mobilization via CCR5 receptors in naïve cells.Conclusions and implications:These data suggest that there is an endogenous aminopeptidase activity on the surface of CHO cells, that produces a slow internalization of the receptor following a time‐dependent conversion of receptor‐bound met‐RANTES from a CCR5 receptor antagonist into a CCR5 agonist molecule.British Journal of Pharmacology(2008)153, 1513–1527; doi:10.1038/sj.bjp.0707691; published online 28 January 2008
Factorizations of invertible operators and 𝐾-theory of 𝐶*-algebras
Authors: Zhang Shuang 
Published: January 2008

Let

A

\mathcal {A}

be a unital

C

∗

{\text {C}}^{\ast }

-algebra. We describe K-skeleton factorizations of all invertible operators on a Hilbert

C

∗

{\text {C}}^{\ast }

-module

H

A

\mathcal {H}_\mathcal {A}

, in particular on

H

=

l
2

\mathcal {H}={l^2}

, with the Fredholm index as an invariant. We then outline the isomorphisms

K
0

(

A

)
≅

π

2
k

(

[
p

]
0

)
≅

π

2
k

(

G
L

r
p

(

A

)
)

{K_0}(\mathcal {A}) \cong {\pi _{2k}}({[p]_0}) \cong {\pi _{2k}}({GL}_r^p(\mathcal {A}))

and

K

1

(

A

)
≅

π

2
k
+
1

(

[
p

]
0

)
≅

π

2
k
+
1

(

G
L

r
p

(

A

)
)

{{K}_{1}}(\mathcal {A})\cong {{\pi }_{2k+1}}({[p]_0})\cong {{\pi }_{2k+1}}({GL}_r^p(\mathcal {A}))

for

k
≥
0

k \geq 0

, where

[
p

]
0

{[p]_0}

denotes the class of all compact perturbations of a projection p in the infinite Grassmann space

G
r

∞

(

A

)

{Gr}^{\infty }(\mathcal {A})

and

G
L

r
p

(

A

)

{GL}_r^p(\mathcal {A})

stands for the group of all those invertible operators on

H

A

{\mathcal {H}_\mathcal {A}}

essentially commuting with p.
Chemical shift assignment of the transmembrane helices of DsbB, a 20‐kDa integral membrane enzyme, by 3D magic‐angle spinning NMR spectroscopy
Authors: Li Ying , Berthold Deborah A. , Gennis Robert B. , Rienstra Chad M. 
Published: January 2008

AbstractThe Escherichia coli inner membrane enzyme DsbB catalyzes disulfide bond formation in periplasmic proteins, by transferring electrons to ubiquinone from DsbA, which in turn directly oxidizes cysteines in substrate proteins. We have previously shown that DsbB can be prepared in a state that gives highly resolved magic‐angle spinning (MAS) NMR spectra. Here we report sequential 13C and 15N chemical shift assignments for the majority of the residues in the transmembrane helices, achieved by three‐dimensional (3D) correlation experiments on a uniformly 13C, 15N‐labeled sample at 750‐MHz 1H frequency. We also present a four‐dimensional (4D) correlation spectrum, which confirms assignments in some highly congested regions of the 3D spectra. Overall, our results show the potential to assign larger membrane proteins using 3D and 4D correlation experiments and form the basis of further structural and dynamical studies of DsbB by MAS NMR.
Involvement of DPP‐IV catalytic residues in enzyme–saxagliptin complex formation
Authors: Metzler William J. , Yanchunas Joseph , Weigelt Carolyn , Kish Kevin , Klei Herbert E. , Xie Dianlin , Zhang Yaqun , Corbett Martin , Tamura James K. , He Bin , Hamann Lawrence G. , Kirby Mark S. , Marcinkeviciene Jovita 
Published: January 2008

AbstractThe inhibition of DPP‐IV by saxagliptin has been proposed to occur through formation of a covalent but reversible complex. To evaluate further the mechanism of inhibition, we determined the X‐ray crystal structure of the DPP‐IV:saxagliptin complex. This structure reveals covalent attachment between S630 and the inhibitor nitrile carbon (C–O distance <1.3 Å). To investigate whether this serine addition is assisted by the catalytic His‐Asp dyad, we generated two mutants of DPP‐IV, S630A and H740Q, and assayed them for ability to bind inhibitor. DPP‐IVH740Q bound saxagliptin with an ∼1000‐fold reduction in affinity relative to DPP‐IVWT, while DPP‐IVS630A showed no evidence for binding inhibitor. An analog of saxagliptin lacking the nitrile group showed unchanged binding properties to the both mutant proteins, highlighting the essential role S630 and H740 play in covalent bond formation between S630 and saxagliptin. Further supporting mechanism‐based inhibition by saxagliptin, NMR spectra of enzyme–saxagliptin complexes revealed the presence of three downfield resonances with low fractionation factors characteristic of short and strong hydrogen bonds (SSHB). Comparison of the NMR spectra of various wild‐type and mutant DPP‐IV:ligand complexes enabled assignment of a resonance at ∼14 ppm to H740. Two additional DPP‐IV mutants, Y547F and Y547Q, generated to probe potential stabilization of the enzyme–inhibitor complex by this residue, did not show any differences in inhibitor binding either by ITC or NMR. Together with the previously published enzymatic data, the structural and binding data presented here strongly support a histidine‐assisted covalent bond formation between S630 hydroxyl oxygen and the nitrile group of saxagliptin.
Interpretation of authigenicvs.allogenic green peloids of ferric clay in the Proterozoic Penganga Group, southern India
Authors: Bandopadhyay P. C. 
Published: January 2008

AbstractFerric illite in the Neoproterozoic Penganga Group, southern India, occurs in a lenticular unit of reworked arkoses conformably enclosed in carbonate mudstones, deposited in a shelf-margin carbonate slope setting influenced by deep marine sediment gravity flows. The structures and textures of the arkoses suggest emplacement by fine-grained debris flows and deposition in channels incised into the carbonate slope.Ferric illite is sparse in the arkoses and has small concentrations and grainsizes within the same size fraction of the associated detritus, uniform chemical composition and an association with reworked facies. It consists predominantly of granular grains that are mostly sorted spherical, ovoid, capsule-shaped and vermicular peloids; many broken and micaceous. These attributes provide a comprehensive framework for suggesting an allogenic origin for the ferric illite previously interpreted as authigenic. The methodology adopted here is a useful approach in the interpretation of in situ vs. reworked origins of glauconitic minerals.
Illite ‘crystallinity’, maturation of organic matter and microstructural development associated with lowest-grade metamorphism of Neoproterozoic sediments in the Teplá-Barrandian unit, Czech Republic
Authors: Suchý V. , Sýkorová I. , Melka K. , Filip J. , Machovič V. 
Published: January 2008

AbstractMetamorphic grade, palaeothermal history and the influence of tectonic strain on clay minerals and organic matter transformation were studied in the eastern part of the Teplá-Barrandian unit in the Czech Republic. The metamorphic grade of pelitic sediments ranges from the lower anchizone (IC ~0.30–0.36Δº2θ) to the lowermost epizone (IC ~0.24–0.26Δº2θ). Increase in metamorphic grade is paralleled by the development of anastomosing cleavage and lenticular quartz grains in the anchizone which give way to slaty cleavage and dynamically recrystallized ribbon quartz grains in the lower epizone. White mica in highly strained rocks generally has greater IC values whereas chlorite displays reduced values in deformed and cleaved samples. The organic matter dispersed in the sediments represents a complex assemblage of highly matured particles of uncertain origin, pyrobitumen and ‘transitional matter’. The reflectance of organic fragments generally varies from 3.1% to 7.7% ofRmaxwhich suggests anthracite to meta-anthracite rank progrades to semigraphite in higher-grade samples, although the overall link betweenRmaxand IC values is weak, if present at all. Newly formed shear-induced graphite appears abruptly near the anchizone-epizone boundary and correlates with the onset of plastic deformation and dynamic recrystallization of quartz grains in the host sediments.Maximum metamorphic temperatures within the Neoproterozoic sequence in the range of 250–350ºC were attained during the Cadomian (Pan-African) orogeny at 540–550 Ma. Apatite fission-track analysis reveals a subsequent decrease in rock temperature over the period 340–350 Ma that persisted throughout the late Palaeozoic. The most recent episode of accelerated cooling occurred between 20 and 40 Ma, corresponding with the regional uplift of the Bohemian Massif due to the Alpine orogeny.
Characterization of a Mg-rich and low-charge saponite from the Neogene lacustrine basin of Eskisşehir, Turkey
Authors: Yeniyol M. 
Published: January 2008

AbstractThe saponite examined occurs as two 0.1 m thick layers in a Pliocene sequence consisting of dolomite and dolomitic marl. To characterize this material, mineralogical and structural analyses (XRD, SEM and FTIR), thermal analyses (DTA, TG) and chemical analyses (ICP-ES) were performed. From XRD patterns of randomly-oriented powder samples, the first basal reflection appears as an asymmetric and broad peak withd001values varying between 16.55 and 17.32 Å. In oriented and air-dried samples, this reflection occurs between 14.45 and 16.42 Å and is fairly symmetrical with FWHM of 2.7º2θ. Oriented and ethylene glycol-solvated samples produce a rational series of basal reflections, where 001 occurs at ~17.8 Å as an intense, narrow (1.1º2θ) and fairly symmetrical reflection. Upon solvation with glycerol, the 001 reflection shifts to ~18.7 Å.The chemical composition of this saponite is similar to stevensite. However, the structural formula of Na0.114Ca0.013K0.003(Mg2.957Al0.004Fe0.028Ti0.004)(Si3.826Al0.174)O10(OH)2indicates that vacancies in the octahedral sheet do not exist. The negative layer charge arises nearly entirely from the substitutions in the tetrahedral sheet, with the net layer charge of –0.148, smaller than for common smectites.Due to the XRD characteristics and particularly the layer-charge distribution, it was concluded that this mineral is a Mg-rich saponite with low layer charge. The saponite was formed by direct precipitation in an alkaline lake environment from Mg- and Si-rich solutions at high pH.
CCL3 and CXCL12 regulate trafficking of mouse bone marrow NK cell subsets
Authors: Bernardini Giovanni , Sciumè Giuseppe , Bosisio Daniela , Morrone Stefania , Sozzani Silvano , Santoni Angela 
Published: January 2008

Abstract
Herein we have analyzed chemokine involvement in the trafficking of developing and mature mouse natural killer (NK) cells in the bone marrow (BM). We observed drastic changes of CCR1, CXCR3, and CXCR4 expression and function during progression from precursor NK (pNK) cells to immature DX5− NK (iNK) and mature DX5+ NK (mNK) cells. pNK and mNK cells expressed the 3 receptors, while only CXCR4 was detected on iNK cells. Correspondingly, mNK cells migrated to CXCL12, CXCL10, and CCL3, and pNK and iNK cells to CXCL12, whereas pNK cells migrated to CCL3 and CXCL10 only after CXCL12 stimulation. Comparison of BM, peripheral blood, and spleen mNK cell populations revealed that CXCL12, CXCL10, and CCL3 preferentially affected BM mNK cell migration. Administration of the CXCR4 antagonist, AMD-3100, to C57BL/6 mice induced strong reduction of mNK and iNK cells in the BM and increased their number in blood and spleen. Conversely, CCL3 administration selectively mobilized mNK cells from the BM and this effect correlated with its ability to inhibit CXCL12-mediated mNK cell responses in vitro. Our results suggest that the combined action of chemokines selectively regulates localization of NK cell subsets in the BM and direct their maturation and migration to the periphery.
Development of a New Test Method for Air Intrusion Quantification of Roofing Assemblies
Authors: Molleti Suda , Baskaran Bas A. , Ko Steven Kee Ping 
Published: January 2008

Abstract
In North America, approximately one-fourth of low-slope buildings are roofed with a mechanically attached assembly (MAA) with a single-ply membrane. During wind suctions, the membrane can lift and billow. This creates localized suction under the membrane. If design provisions are not made to control the air intruison at the deck level, this suction pressure can draw the indoor conditioned air into the assembly. Two main factors influence the air intrusion: the air permeability of the components and shape or volume changes during the wind uplift. Available standard test procedures can quantify the former for roof materials. However, there is no widely accepted standard specification or test to address the air intrusion characteristics of roofing assemblies. Air leakage measurement techniques used for walls are also not applicable for roof assemblies due to the membrane shape and volume changes in the roof assembly. Research efforts are under way at the National Research Council of Canada to quantify the air intrusion rate of roof assemblies. This paper presents the details of the experimental setup, test procedure, and validation effort of this newly developed test method.
Antidepressant Drug Use and Risk of Venous Thromboembolism
Authors: Jick Susan S. , Li Lin 
Published: January 2008

Study Objective.: To evaluate the risk of idiopathic venous thromboembolism associated with antidepressant use and to further assess the risk by class of antidepressant and by individual antidepressant drug.Design.: Nested case‐control study.Data Source.: United Kingdom General Practice Research Database.Subjects.: Seven hundred eighty‐two case patients with a confirmed diagnosis of venous thromboembolism who were taking an antidepressant drug and 3085 matched control subjects.Measurements and Main Results.: We identified all people in the database aged 70 years or younger with venous thromboembolism who had filled at least one prescription for an antidepressant drug between 1990 and 2005; up to four control subjects were matched to each case patient by age, sex, practice attended, index date, and duration of computerized medical record. We compared the risks of current and recent use of antidepressant drugs with nonuse of an antidepressant before the index date (date of diagnosis of venous thromboembolism) by using conditional logistic regression. Current exposure to tricyclic antidepressants was associated with a small increased risk of idiopathic venous thromboembolism compared with nonuse (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1‐1.8), whereas we found no increased risk among users of selective serotonin reuptake inhibitors or other antidepressant drugs. When we evaluated individual drugs, we found that amitriptyline conferred an increased risk of thromboembolism (OR 1.7, 95% CI 1.2‐2.4) that increased with increasing dose (> 25 mg/day). No other individual antidepressant drug was associated with an increase in risk of venous thromboembolism.Conclusion. Current exposure to amitriptyline, particularly at high doses, was associated with an increased risk of idiopathic venous thromboembolism.Current exposure to amitriptyline, particularly at high doses, was associated with an increased risk of idiopathic venous thromboembolism.