bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cannabinoid self‐administration in rats: sex differences and the influence of ovarian function
Authors: Fattore L , Spano M S , Altea S , Angius F , Fadda P , Fratta W 
Published: September 2007

Background and purpose:We recently demonstrated the existence of strain differences in self‐administration of the cannabinoid CB1 receptor agonist WIN55,212‐2 (WIN) by Long Evans (LE) and Lister Hooded (LH) but not Sprague‐Dawley (SD) male rats. This follow‐up study is aimed at verifying whether sex and ovarian hormones might also be critical factors in the initiation, retention and extinction of WIN self‐administration.Experimental approach:LE, LH and SD male and female rats, the latter either intact or bilaterally ovariectomized (OVX), were trained to self‐administer WIN (12.5 μg kg−1 per infusion) under a FR1 reinforcement schedule, using lever‐pressing.Key results:Data showed that contrary to the findings in SD rats, LE and LH rats developed robust cannabinoid intake, with rates of responding for WIN being constantly higher in intact females than in males (+45 and +42% for LE and LH strains, respectively). In comparison with intact females, OVX females of both strains acquired self‐administration at lower rates, displaying slower acquisition, lower drug intake (−42 and −52% for LE and LH, respectively) and longer extinction.Conclusions and implications:These findings provide the first evidence of significant sex differences in cannabinoid self‐administration, females acquiring stable WIN intake at higher rates and more rapidly than males. Moreover, when compared to intact females, a lower percentage of LE and LH OVX rats acquired and maintained stable drug intake, suggesting that ovarian hormones might represent a critical factor in modulating the reinforcing effect of cannabinoids.British Journal of Pharmacology (2007) 152, 795–804; doi:10.1038/sj.bjp.0707465; published online 24 September 2007
CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies
Authors: Arévalo‐Martín Á , García‐Ovejero D , Gómez O , Rubio‐Araiz A , Navarro‐Galve B , Guaza C , Molina‐Holgado E , Molina‐Holgado F 
Published: September 2007

Amongst the various demyelinating diseases that affect the central nervous system, those induced by an inflammatory response stand out because of their epidemiological relevance. The best known inflammatory‐induced demyelinating disease is multiple sclerosis, but the immune response is a common pathogenic mechanism in many other less common pathologies (e.g., acute disseminated encephalomyelitis and acute necrotizing haemorrhagic encephalomyelitis). In all such cases, modulation of the immune response seems to be a logical therapeutic approach. Cannabinoids are well known immunomodulatory molecules that act through CB1 and CB2 receptors. While activation of CB1 receptors has a psychotropic effect, activation of CB2 receptors alone does not. Therefore, to bypass the ethical problems that could result from the treatment of inflammation with psychotropic molecules, considerable effort is being made to study the potential therapeutic value of activating CB2 receptors. In this review we examine the current knowledge and understanding of the utility of cannabinoids as therapeutic molecules for inflammatory‐mediated demyelinating pathologies. Moreover, we discuss how CB2 receptor activation is related to the modulation of immunopathogenic states.British Journal of Pharmacology (2008) 153, 216–225; doi:10.1038/sj.bjp.0707466; published online 24 September 2007
Vascular pharmacology of a novel cannabinoid‐like compound, 3‐(5‐dimethylcarbamoyl‐pent‐1‐enyl)‐N‐(2‐hydroxy‐1‐methyl‐ethyl)benzamide (VSN16) in the rat
Authors: Hoi P M , Visintin C , Okuyama M , Gardiner S M , Kaup S S , Bennett T , Baker D , Selwood D L , Hiley C R 
Published: September 2007

Background and purpose:A putative novel cannabinoid receptor mediates vasorelaxation to anandamide and abnormal‐cannabidiol and is blocked by O‐1918 and by high concentrations of rimonabant. This study investigates VSN16, a novel water‐soluble agonist, as a vasorelaxant potentially acting at non‐CB1, non‐CB2cannabinoid receptors in the vasculature.Experimental approach:VSN16 and some analogues were synthesized and assayed for vasodilator activity in the rat third generation mesenteric artery using wire myography. Also carried out with VSN16 were haemodynamic studies in conscious rats and binding studies to CB1receptors of rat cerebellum.Key results:VSN16 relaxed mesenteric arteries in an endothelium‐dependent manner. The vasorelaxation was antagonized by high concentrations of the classical cannabinoid antagonists, rimonabant and AM 251, as well as by O‐1918, an antagonist at the abnormal‐cannabidiol receptor but not at CB1or CB2receptors. It did not affect [3H]CP55,940 binding to CB1receptors in rat cerebellum. The vasorelaxation was notpertussistoxin‐sensitive but was reduced by inhibition of nitric oxide synthesis, Ca2+‐sensitive K+channels (KCa) and TRPV1receptors. In conscious rats VSN16 transiently increased blood pressure and caused a longer‐lasting increase in mesenteric vascular conductance. Structure‐activity studies on vasorelaxation showed a stringent interaction with the target receptor.Conclusions and implications:VSN16 is an agonist at a novel cannabinoid receptor of the vasculature. It acts on the endothelium to release nitric oxide and activate KCaand TRPV1. As it is water‐soluble it might be useful in bringing about peripheral cannabinoid‐like effects without accompanying central or severe cardiovascular responses.British Journal of Pharmacology(2007)152, 751–764; doi:10.1038/sj.bjp.0707470; published online 24 September 2007
Comparative potencies of 3,4‐methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [3H]noradrenaline and [3H]5‐HT transport in mammalian cell lines
Authors: Montgomery T , Buon C , Eibauer S , Guiry P J , Keenan A K , McBean G J 
Published: September 2007

Background and purpose:Illegal ‘ecstasy’ tablets frequently contain 3,4‐methylenedioxymethamphetamine (MDMA)‐like compounds of unknown pharmacological activity. Since monoamine transporters are one of the primary targets of MDMA action in the brain, a number of MDMA analogues have been tested for their ability to inhibit [3H]noradrenaline uptake into rat PC12 cells expressing the noradrenaline transporter (NET) and [3H]5‐HT uptake into HEK293 cells stably transfected with the 5‐HT transporter (SERT).Experimental approach:Concentration–response curves for the following compounds at both NET and SERT were determined under saturating substrate conditions: 4‐hydroxy‐3‐methoxyamphetamine (HMA), 4‐hydroxy‐3‐methoxymethamphetamine (HMMA), 3,4‐methylenedioxy‐N‐hydroxyamphetamine (MDOH), 2,5‐dimethoxy‐4‐bromophenylethylamine (2CB), 3,4‐dimethoxymethamphetamine (DMMA), 3,4‐methylenedioxyphenyl‐2‐butanamine (BDB), 3,4‐methylenedioxyphenyl‐N‐methyl‐2‐butanamine (MBDB) and 2,3‐methylenedioxymethamphetamine (2,3‐MDMA).Key results:2,3‐MDMA was significantly less potent than MDMA at SERT, but equipotent with MDMA at NET. 2CB and BDB were both significantly less potent than MDMA at NET, but equipotent with MDMA at SERT. MBDB, DMMA, MDOH and the MDMA metabolites HMA and HMMA, were all significantly less potent than MDMA at both NET and SERT.Conclusions and implications:This study provides an important insight into the structural requirements of MDMA analogue affinity at both NET and SERT. It is anticipated that these results will facilitate understanding of the likely pharmacological actions of structural analogues of MDMA.British Journal of Pharmacology (2007) 152, 1121–1130; doi:10.1038/sj.bjp.0707473; published online 24 September 2007
Small‐world networks and management science research: a review
Authors: Uzzi Brian , Amaral Luis AN , Reed‐Tsochas Felix 
Published: September 2007

AbstractThis paper reviews the literature on small‐world networks in social science and management. This relatively new area of research represents an unusual level of cross‐disciplinary research within social science and between social science and the physical sciences. We review the findings of this emerging area with an eye to describing the underlying theory of small worlds, the technical apparatus, promising facts, and unsettled issues for future research.
The value and costs of modularity: a problem‐solving perspective
Authors: Brusoni Stefano , Marengo Luigi , Prencipe Andrea , Valente Marco 
Published: September 2007

AbstractThis paper discusses the issue of modularity from a problem‐solving perspective. Modularity is in fact a decomposition heuristic, through which a complex problem is decomposed into independent or quasi‐independent sub‐problems. By means of a model of problem decomposition, this paper studies the trade‐offs of modularity: on the one hand finer modules increase the speed of search, but on the other hand they usually determine lock‐in into sub‐optimal solutions. How to balance effectively this trade‐off depends upon the problem environment and in particular on its complexity and volatility: we show that in stationary and complex environments there exists an evolutionary advantage to over‐modularization, while in highly volatile environments, contrary to usual wisdom, modular search is inefficient in the long run. The empirical relevance of our findings is discussed especially with reference to the literature on systems integration.
Science of complex systems for tackling challenges of the 21st century: a brief overview
Authors: Dum Ralph 
Published: September 2007

AbstractThe article provides a brief overview of the emerging ‘Science of Complex Systems’ and of some of the programmes sponsored by the European Commission and the DG for Information Society and Media. I explain what are the drivers for this emerging research area, what are its new concepts and what is its potential impact on science, society and business. The research landscape in Europe is described by focussing on programmes in the European Commission.
Use of insulin glargine during pregnancy
Authors: PÖYHÖNEN‐ALHO MARITTA , RÖNNEMAA TAPANI , SALTEVO JUHA , EKBLAD ULLA , KAAJA RISTO J. 
Published: September 2007

AbstractBackground. Good metabolic control maintained throughout pregnancy reduces maternal and fetal complications in diabetic women. The long‐acting insulin analogue glargine has 24‐h persistence and a peakless action profile, and could contribute to more stable daily plasma glucose levels and improved glycemic control. We evaluated the metabolic control associated with insulin glargine during pregnancy in comparison with conventional basal insulin therapy. Methods. Retrospective case‐control analysis of glycemic control and pregnancy complications in 100 type 1 diabetic pregnancies with intermediate‐acting NPH insulin or insulin glargine prior to conception and throughout pregnancy. Results. Overall, glycemic control was not different between the groups, though the decrease in HbA1c from the first to the third trimester was greater with insulin glargine (0.8 versus 0.3%, p = 0.04). The rate of hypoglycemia was comparable. Conclusions. Our findings suggest that, as regards metabolic control, insulin glargine in women with type 1 diabetes is comparable with NPH insulin as basal insulin therapy. No adverse effects were associated with glargine use at the time of conception and during pregnancy.
MRI urethrovesical junction mobility is associated with global pelvic floor laxity in female stress incontinence
Authors: ANSQUER YAN , FERNANDEZ PEDRO , AIMOT SABINE , BENNIS MALIKA , SALOMON LAURENCE , CARBONNE BRUNO 
Published: September 2007

AbstractObjective. To assess in a population of stress incontinent patients without genital prolapse whether urethrovesical junction mobility is associated with global pelvic floor laxity. Methods. Dynamic MRI of 40 patients referred prior to surgery for urinary stress incontinence were reviewed retrospectively. The orientation of the urethrovesical junction was evaluated at rest and at straining in reference to the pubococcygeal line, and defined as the bladder neck pubococcygeal angle. The urethrovesical junction mobility was calculated as the difference between the bladder neck pubococcygeal angles at rest and at straining. Urethrovesical junction mobility and bladder neck pubococcygeal angles at rest and at straining were tested for correlations with the resting and straining position of different pelvic organs, urogenital hiatus size, levator plate angle, and anterior rectal bulging when straining. Results. Urethrovesical junction mobility was correlated with the position of the bladder neck (p<0.0001), bladder base (p<0.0001) and uterine cervix (p<0.0001) at straining, as well as the hiatus length (p = 0.0012) and width (p = 0.0002), and levator plate angle (p<0.0001). The bladder neck pubococcygeal angle at rest was correlated with the resting position of the bladder neck (p<0.0001), bladder base (p<0.0001), uterine cervix (p = 0.02), and the hiatus length (p = 0.0004) and width (p = 0.045) at rest, whereas the bladder neck pubococcygeal angle at straining was correlated with the straining position of the bladder neck (p<0.0001), bladder base (p<0.0001), uterine cervix (p<0.0001), and hiatus length (p = 0.0005) and width (p = 0.0004), and levator plate angle (p<0.0001) at straining. Conclusion. In a population of stress incontinent patients, the urethrovesical junction mobility was correlated with global pelvic floor laxity.
Use of recombinant activated factor VII for massive postpartum hemorrhage
Authors: HOSSAIN NAZLI , SHAMSI TAHIR , HAIDER SAEEDA , SOOMRO NARGIS , KHAN NUSRAT H. , UMER MEMON GHUFFRANA , FARZANA TASNEEM , ANSARI SAQIB , TRICHE ELIZABETH W. , KUCZYNSKI EDWARD , LOCKWOOD CHARLES J. , PAIDAS MICHAEL J. 
Published: September 2007

AbstractObjective. We hypothesised that patients with massive postpartum hemorrhage (PPH), defined as blood loss >1,500 ml, may benefit from the use of activated recombinant factor VII (rFVIIa). Design. Retrospective cohort study. Setting. Department of Obstetrics & Gynaecology, Dow University of Health Sciences. Population. Thirty‐four women with a diagnosis of massive PPH. Methods. All patients with PPH who were admitted to the Department of Obstetrics & Gynecology and Surgical Intensive Care Unit of Civil Hospital Karachi, Pakistan, were included in the study. From March 2005 to October 2006, 34 patients fulfilled the criteria of massive PPH, of which 18 received rFVIIa to control bleeding, and 16 patients did not. Availability and cost of rFVIIa were the factors in drug allocation. Main outcome measures. Maternal mortality, correction of coagulopathy, the amount of blood products transfused and preservation of fertility. Results. Patients receiving rFVIIa had lower maternal mortality (5/18, 28% versus 8/16, 50%, OR: 0.04 (0.002, 0.83)), and received a lower number of packed red cell transfusions (4.0±4.46 versus 9.61±6.7, p value 0.007), against the comparison group. Patients receiving rFVIIa had lower activated partial thromboplastin (median: 13.0; 25–75th percentile: −25.0, −8.0, signed rank p<0.0001), and lower prothrombin times (median: −8.8; 25–75th percentile: −24.2, −4.8), after administration of drug. There was no significant difference in the rate of hysterectomy between the 2 groups (11/18 (61%) versus 6/16 (38%)). No adverse event attributable to rFVIIa was observed in the study. Conclusion. Activated recombinant factor VII can be a life‐saving drug in patients with massive PPH.
CXCL12 and CCL20 Play a Significant Role in Mucosal T‐Lymphocyte Adherence to Intestinal Microvessels in Mice
Authors: OYAMA TOKUSHIGE , MIURA SOICHIRO , WATANABE CHIKAKO , HOKARI RYOTA , FUJIYAMA YOICHI , KOMOTO SHUNSUKE , TSUZUKI YOSHIKAZU , HOSOE NAOKI , NAGATA HIROSHI , HIBI TOSHIFUMI 
Published: September 2007

ABSTRACTObjective: Although it is known that the chemokines CXCL12 and CCL20 are expressed in the intestine, their contribution to lymphocyte homing has not been investigated in detail. The authors investigated whether the CXCL12‐CXCR4 and CCL20‐CCR6 systems are involved in T lymphocyte–endothelial interaction in microvessels of the small and large intestines.Methods: Labeled lamina proprial lymphocytes (LPLs) were administered to mice, and their adhesion to microvessels of normal and TNF‐α –induced inflamed intestinal mucosa was observed under an intravital microscope. Antibodies against CXCL12, CCL‐20, or CCL‐25 were administered prior to lymphocyte administration, and in some experiments CXCR4 or CCR6 on LPLs was desensitized with an excess amount of chemokine.Results: LPLs adhered to microvessels of the ileum and colon, and TNF‐α induced a significant accumulation at both sites. Blocking of the CXCL12‐CXCR4 system significantly inhibited the LPL adhesion in the ileum and colon under both normal and TNF‐α –treated conditions. However, blocking of the CCL20‐CCR6 system significantly attenuated LPL adhesion only under a TNF‐α –treated condition. There was an additive inhibitory effect on LPL adherence by CXCL12 and CCL20 blocking in TNF‐α –induced inflamed intestines. There was also an additive function of the CCL25‐CCR9 system in LPL accumulation in the small intestine.Conclusion: Several chemokine systems may play significant roles cooperatively in vivo in LPL adherence to microvessels of intestinal mucosa.
Understanding researchers: findings from a focus group
Authors: PITTS SiNae , STANLEY Adrian 
Published: September 2007

ABSTRACTIn November 2006, a focus group of researchers was assembled at a conference hosted by the Society of Scholarly Publishers in Washington, DC. The panel addressed a series of prepared questions regarding current research practices, perceptions, and preferences, particularly as they applied to scientific and medical publications, in corporate, academic, and medical environments. This article highlights issues and views the panel discussed, with the aim of narrowing the gap of understanding between researchers and publishers. This information will help publishers to develop content and delivery methods that are closely aligned with the needs of researchers.
Structure of the Murray Valley encephalitis virus RNA helicase at 1.9 Å resolution
Authors: Mancini Erika J. , Assenberg Rene , Verma Anil , Walter Thomas S. , Tuma Roman , Grimes Jonathan M. , Owens Raymond J. , Stuart David I. 
Published: September 2007

AbstractMurray Valley encephalitis virus (MVEV), a mosquito‐borne flavivirus endemic to Australia, is closely related to Japanese encephalitis virus and West Nile virus. Nonstructural protein 3 (NS3) is a multifunctional enzyme with serine protease and DEXH/D‐box helicase domains, whose activity is central to flavivirus replication and is therefore a possible target for anti‐flaviviral compounds. Cloning, purification, and crystal structure determination to 1.9 Å resolution of the NS3 helicase of MVEV and characterization of its enzymatic activity is reported. Comparison with the structures of helicases from related viruses supports a possible mechanism of ATP hydrolysis‐driven strand separation.
The Bacillus licheniformis BlaP β‐lactamase as a model protein scaffold to study the insertion of protein fragments
Authors: Vandevenne Marylène , Filee Patrice , Scarafone Natacha , Cloes Benoît , Gaspard Gilles , Yilmaz Nursel , Dumoulin Mireille , François Jean‐Marie , Frère Jean‐Marie , Galleni Moreno 
Published: September 2007

AbstractUsing genetic engineering technologies, the chitin‐binding domain (ChBD) of the human macrophage chitotriosidase has been inserted into the host protein BlaP, a class A β‐lactamase produced by Bacillus licheniformis. The product of this construction behaved as a soluble chimeric protein that conserves both the capacity to bind chitin and to hydrolyze β‐lactam moiety. Here we describe the biochemical and biophysical properties of this protein (BlaPChBD). This work contributes to a better understanding of the reciprocal structural and functional effects of the insertion on the host protein scaffold and the heterologous structured protein fragments. The use of BlaP as a protein carrier represents an efficient approach to the functional study of heterologous protein fragments.
Reduced Cβ statistical potentials can outperform all‐atom potentials in decoy identification
Authors: Fitzgerald James E. , Jha Abhishek K. , Colubri Andres , Sosnick Tobin R. , Freed Karl F. 
Published: September 2007

AbstractWe developed a series of statistical potentials to recognize the native protein from decoys, particularly when using only a reduced representation in which each side chain is treated as a single Cβ atom. Beginning with a highly successful all‐atom statistical potential, the Discrete Optimized Protein Energy function (DOPE), we considered the implications of including additional information in the all‐atom statistical potential and subsequently reducing to the Cβ representation. One of the potentials includes interaction energies conditional on backbone geometries. A second potential separates sequence local from sequence nonlocal interactions and introduces a novel reference state for the sequence local interactions. The resultant potentials perform better than the original DOPE statistical potential in decoy identification. Moreover, even upon passing to a reduced Cβ representation, these statistical potentials outscore the original (all‐atom) DOPE potential in identifying native states for sets of decoys. Interestingly, the backbone‐dependent statistical potential is shown to retain nearly all of the information content of the all‐atom representation in the Cβ representation. In addition, these new statistical potentials are combined with existing potentials to model hydrogen bonding, torsion energies, and solvation energies to produce even better performing potentials. The ability of the Cβ statistical potentials to accurately represent protein interactions bodes well for computational efficiency in protein folding calculations using reduced backbone representations, while the extensions to DOPE illustrate general principles for improving knowledge‐based potentials.
Solution structure and proposed domain–domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase
Authors: Alekseyev Viktor Y. , Liu Corey W. , Cane David E. , Puglisi Joseph D. , Khosla Chaitan 
Published: September 2007

AbstractPolyketides are a medicinally important class of natural products. The architecture of modular polyketide synthases (PKSs), composed of multiple covalently linked domains grouped into modules, provides an attractive framework for engineering novel polyketide‐producing assemblies. However, impaired domain–domain interactions can compromise the efficiency of engineered polyketide biosynthesis. To facilitate the study of these domain–domain interactions, we have used nuclear magnetic resonance (NMR) spectroscopy to determine the first solution structure of an acyl carrier protein (ACP) domain from a modular PKS, 6‐deoxyerythronolide B synthase (DEBS). The tertiary fold of this 10‐kD domain is a three‐helical bundle; an additional short helix in the second loop also contributes to the core helical packing. Superposition of residues 14–94 of the ensemble on the mean structure yields an average atomic RMSD of 0.64 ± 0.09 Å for the backbone atoms (1.21 ± 0.13 Å for all non‐hydrogen atoms). The three major helices superimpose with a backbone RMSD of 0.48 ± 0.10 Å (0.99 ± 0.11 Å for non‐hydrogen atoms). Based on this solution structure, homology models were constructed for five other DEBS ACP domains. Comparison of their steric and electrostatic surfaces at the putative interaction interface (centered on helix II) suggests a model for protein–protein recognition of ACP domains, consistent with the previously observed specificity. Site‐directed mutagenesis experiments indicate that two of the identified residues influence the specificity of ACP recognition.