bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non‐adrenergic inhibitory nerves in the gut
Authors: BURNSTOCK G. , CAMPBELL G. , SATCHELL D. , SMYTHE ANNE
Published: September 2011

. Stimulation of the vagal non‐adrenergic inhibitory innervation caused the release of adenosine and inosine into vascular perfusates from the stomachs of guinea‐pigs and toads.

. Stimulation of portions of Auerbach's plexus isolated from turkey gizzard caused the release of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP).

. ATP, added to solutions perfused through the toad stomach vasculature, was broken down to adenosine, inosine and adenine.

. Of a series of purine and pyrimidine derivatives tested for inhibitory activity on the guinea‐pig isolated taenia coli, ATP and ADP were the most potent.

. ATP caused inhibition of twelve other gut preparations previously shown to contain non‐adrenergic inhibitory nerves. The inhibitory action of ATP was not prevented by tetrodotoxin.

. Quinidine antagonized relaxations of the guinea‐pig taenia coli caused by catecholamines or adrenergic nerve stimulation. Higher concentrations of quinidine antagonized relaxations caused by ATP or non‐adrenergic inhibitory nerve stimulation.

. When tachyphylaxis to ATP had been produced in the rabbit ileum, there was a consistent depression of the responses to non‐adrenergic inhibitory nerve stimulation but not of responses to adrenergic nerve stimulation.

. It is suggested that ATP or a related nucleotide is the transmitter substance released by the non‐adrenergic inhibitory innervation of the gut.
Prostaglandins and the mechanism of analgesia produced by aspirin‐like drugs
Authors: FERREIRA S. H. , MONCADA S. , VANE J. R.
Published: September 2011

. Resting splenic venous outflow from anaesthetized dogs contains prostaglandin‐like material: the concentration increases after intra‐arterial injections of bradykinin into the spleen, and is abolished by treatment with indomethacin.

. Intra‐arterial injections of bradykinin into the spleen of lightly anaesthetized dogs elicit a dose‐dependent reflex increase in the blood pressure, which is reduced but not abolished by treatment with indomethacin.

. Addition of prostaglandin E1 or E2 either by injections or by infusions restores the reflex increase in the blood pressure due to bradykinin injections after indomethacin treatment.

. The sensitizing action of endogenously released prostaglandins at or near the afferent nerve endings is discussed.

. The analgesic activity of aspirin‐like drugs is explained in terms of the removal of the sensitizing activity of prostaglandins.
THE DISTRIBUTION OF METHIONINE‐ENKEPHALIN AND LEUCINE‐ENKEPHALIN IN THE BRAIN AND PERIPHERAL TISSUES
Authors: HUGHES J. , KOSTERLITZ H.W. , SMITH T.W.
Published: September 2011

A method is described for the rapid extraction of opioid peptides from the brain and other tissues. The method is based on acid extraction of tissues followed by adsorption of the extract onto Amberlite XAD‐2 resin. Elution with methanol separates the enkephalins and α‐endorphin from β‐endorphin.

Over 90% of the opioid peptide activity isolated from brain and gut of several species by our method was due to methionine‐ and leucine‐enkephalin. In contrast, the major opioid peptide activity recovered from the pituitary was due to peptides of much greater mol. wt. than the enkephalins.

An opioid peptide with properties unlike those of the known endorphins or enkephalins was present in brain extracts. This peptide, termed ∈‐endorphin, has an apparent mol. wt. of 700 to 1200; it constituted between 5 to 10% of the total opioid activity in our extracts.

A differential assay of methionine‐ and leucine‐enkephalin was made either by destroying methionine‐enkephalin activity with cyanogen bromide or by separating the peptides by thin layer chromatography.

The ratio of methionine‐enkephalin to leucine‐enkephalin varied greatly in different brain regions. The highest proportions of leucine‐enkephalin were found in the cerebral cortex and hippocampus.

Formaldehyde perfusion and fixation of the brain in vivo had no significant effect on the brain content of enkephalin, indicating that proteolytic breakdown is not a major problem in the extraction of these peptides.

It is suggested that the enkephalins may have a neurotransmitter role in both brain and peripheral tissues and that methionine‐ and leucine‐enkephalin may subserve separate neuronal functions.
PROSTACYCLIN (PGI2) INHIBITS THE FORMATION OF PLATELET THROMBI IN ARTERIOLES AND VENULES OF THE HAMSTER CHEEK POUCH
Authors: HIGGS E.A. , HIGGS G.A. , MONCADA S. , VANE J.R.
Published: September 2011

Isolated rings of hamster aorta produced an unstable substance which inhibited platelet aggregation in vitro and had the same characteristics as prostacyclin.

Prostacyclin inhibited adenosine diphosphate (ADP)‐induced aggregation of hamster platelets in vitro.

The effects of prostacyclin on ADP‐induced platelet thrombi in the microcirculation of the hamster cheek pouch were studied with a television microscope.

Prostacyclin caused a dose‐dependent increase in the time of iontophoretic application of ADP which was required to induce platelet thrombi formation and embolization in venules (30 to 40 μm diameter).

Prostacyclin caused a dose‐dependent reduction in the total time during which ADP‐induced thrombi were observed following local electrical damage to arterioles (40 to 80 μm diameter).

Thrombus formation in venules and arterioles was abolished by 500 ng/ml prostacyclin in the Krebs solution superfusing the hamster cheek pouch.

Prostacyclin was approximately twenty times more potent than prostaglandin E1 in preventing thrombus formation in the microcirculation.
Relevance of the inner mitochondrial membrane enzyme F1F0‐ATPase as an autoantigen in autoimmune liver disorders
Authors: Preuß Beate , Berg Christoph , Dengjel Jörn , Stevanovic Stefan , Klein Reinhild
Published: September 2011

Background and Aims

Recently, a non‐M2‐related mitochondrial 60 kDa protein found to be recognized by antimitochondrial antibody (AMA) negative sera from patients with primary biliary cirrhosis (PBC) has been shown to contain parts of the five F1‐ATPase subunits α, β, γ, δ and ε. In this study, we examined whether this enzyme is, indeed, a target antigen in PBC.

Methods

Analysed were 60 AMA‐positive/anti‐M2‐negative and 103 anti‐M2‐positive PBC patients, 46 patients with autoimmune hepatitis (AIH), 35 patients with primary sclerosing cholangitis (PSC), 110 patients with viral hepatitis, 40 patients with inflammatory bowel diseases (IBD), 33 patients with connective tissue diseases (systemic lupus erythematosus, mixed connective tissue disease, Sjögren disease, systemic sclerosis) and 25 blood donors. The F1‐ATPase‐subunits α‐δ were recombinantly expressed in Escherichia coli, purified and applied to ELISA and Western blotting.

Results

In all, 40 of the 60 AMA‐positive/anti‐M2‐negative (67%) and 44 (43%) of the 103 anti‐M2‐positive PBC‐sera reacted with at least one of the F1‐subunits α‐δ. The β‐ and γ‐subunits were preferentially recognized. However, also up to 57% of patients with AIH and 34% of patients with PSC had anti‐β‐ or γ‐antibodies, while patients with viral hepatitis had these antibodies in up to 13%. Patients with IBD had anti‐β and anti‐γ‐antibodies in up to 20 and 5% respectively. None of the patients with connective tissue diseases had antibodies to the β‐ and only 6% to the γ‐subunit. Sera from healthy blood donors were negative.

Conclusions

Antibodies to the β‐ and γ‐subunits of F1‐ATPase are further AMAs in PBC but occur also in other autoimmune liver disorders; they may be, therefore, indicators for a general autoimmune process of the liver.
Use of aDacron Shape‐Memory Intravascular Coil to Achieve Slow, Progressive Occlusion of the Jugular Vein in Dogs
Authors: Nanfelt Michelle R. , Marolf Angela J. , Powers Barbara E. , Monnet Eric
Published: September 2011

Objective

To investigate the ability of shape memory Dacron polymer vascular coils to induce the complete, gradual occlusion of the canine jugular vein.

Study Design

Observational pilot study.

Animals

Nine purpose‐bred dogs.

Methods

Eighteen coils were deployed in nine dogs using fluoroscopic‐guided percutaneous transvenous coil implantation. Individual coil formulations varied around a Dacron polymer base. Jugular vein diameter, percent vessel occlusion, and thrombus echogenicity were monitored at weekly intervals using ultrasonography. Affected jugular veins were harvested at 6 weeks post‐implantation and histopathological analysis was performed to assess adventitial fibrosis, intimal layer thickening, and inflammation.

Results

Ten coils migrated from the jugular veins to the pulmonary vasculature within 0–2 weeks following implantation. Three jugular veins achieved at least 90% occlusion at six weeks. Histopathology of these jugular veins revealed marked perivascular thickening and fibrovascular proliferation, increased infiltration of macrophages, neutrophils and lymphocytes, and abundant fibroplasia.

Conclusions

Complete, gradual occlusion of a jugular vein was achieved in three dogs. Significant vessel wall reaction and inflammation can induce gradual vessel occlusion when a Dacron coil remains implanted within the jugular vein. Dacron polymer coils could be a feasible treatment option for the gradual occlusion of congenital portosystemic shunts in dogs using minimally invasive, percutaneous transvenous implantation.
Reimplantation of cultivated human bone cells from the posterior maxilla for sinus floor augmentation. Histological results from a randomized controlled clinical trial
Authors: Hermund Niels Ulrich , Stavropoulos Andreas , Donatsky Ole , Nielsen Henrik , Clausen Christian , Reibel Jesper , Pakkenberg Bente , Holmstrup Palle
Published: September 2011

Objectives

The aim of the present randomized clinical study was to evaluate histologically whether the addition of cultivated, autogenous bone cells to a composite graft of deproteinized bovine bone mineral (DBBM) and autogenous bone (AB) for sinus floor augmentation (SFA) enhance bone formation compared with what achieved after SFA with DBBM + AB alone.

Material and methods

Twenty patients with remaining posterior maxillary alveolar crest height of less than 3 mm received SFA after randomization either with an DBBM and AB composite in a 1 : 1 ratio or with DBBM + AB supplemented with autogenous bone cells, which were cultivated from a bone biopsy harvested earlier from the tuberosity area. Four months after SFA, two cylindrical biopsies were taken from the augmented sinuses concomitantly with the implant site preparation by means of a trephine bur. An additional biopsy was taken from the tuberosity area. Bone density at the augmented sinus and the tuberosity area and the height of augmentation were estimated on non‐decalcified histological sections prepared from the biopsies. A relative bone density index (RBD) was also calculated by dividing bone density at the augmented sinus with bone density at the tuberosity area.

Results

All patients but one could receive two implants after SFA; in one patient, only one implant could be placed. All implants were osseointegrated and could be loaded. Median bone density in the sinus was 30% and 25% in the cell seeded and no‐cells added DBBM + AB groups, respectively. Bone augmentation height averaged 6.0 and 5.4 mm and RBD averaged 0.48 and 0.73 in the cell seeded and no‐cells added DBBM + AB groups, respectively. None of the differences between groups was statistically significant.

Conclusions

Cultivated autogenous bone cell seeded to a DBBM + AB composite did not significantly improve bone formation (density and height) after SFA, compared with what was achieved with DBBM + AB alone. Both approaches resulted into enough bone to support implant placement and osseointegration.
Dimensions of buccal bone and mucosa at immediately placed implants after 7 years: a clinical and cone beam computed tomography study
Authors: Benic Goran I. , Mokti Muizzaddin , Chen Chun‐Jung , Weber Hans‐Peter , Hämmerle Christoph H. F. , Gallucci German O.
Published: September 2011

Objective

The objective of this study was to evaluate the dimensions of buccal bone and soft tissue at immediately placed implants over a 7‐year period.

Material and methods

Twenty‐four patients, that participated in a clinical prospective study and received implants immediately placed into extraction socket, were enrolled for this study. Residual bone defects were grafted with xenogenic bone substitute and covered by means of collagen membrane. Baseline examination included measurements of full‐mouth plaque and bleeding scores, width of keratinized mucosa, and dimensions of residual bone defects at the buccal aspect. Seven years after implant placement, full‐mouth plaque score, full‐mouth bleeding score, width of keratinized mucosa, and probing pocket depth were assessed and cone beam computed tomography images acquired. Dimensions of buccal bone and soft tissue were evaluated on the cross‐sectional cone beam computed tomography reconstructions. Differences between two time‐points were tested using the two‐sided t‐test. Correlation analysis was used to investigate the influence of baseline bone defect dimensions on the bone dimensions measured at the 7‐year follow‐up.

Results and conclusions

Fourteen patients attended the follow‐up examination. In five implants almost no buccal bone was detected, whereas in the remaining nine implants the buccal bone was found covering the rough implant surface. No correlation was found between initial bone defects and bone dimensions at the follow‐up examination. The sites without radiographically detectable buccal bone at the 7‐year control presented with 1 mm more apical mucosal level in comparison to implants with intact buccal bone.
Are marginal bone levels and implant stability/mobility affected by single‐stage platform switched dental implants? A comparative clinical study
Authors: Dursun Erhan , Tulunoglu Ibrahim , Canpınar Pınar , Uysal Serdar , Akalın Ferda Alev , Tözüm Tolga F.
Published: September 2011

Objectives

The aim of this study was to evaluate short‐term bone level and stability/mobility measurement alterations at platform switched (PS) and standard platform (SP) implants placed in mandibular premolar/molar regions using a single‐stage protocol.

Materials and methods

Sixteen PS and 16 SP implants restorated with fixed prosthesis were included. Standard implant dimensions were used for both implant systems. After 3 months of osseointegration, implants were connected to abutments and final restorations were performed. Marginal bone loss was measured by standardized periapical radiographs. Implant stability/mobility was determined by resonance frequency analysis (RFA) and mobility measuring (MM) device values. Peri‐implant parameters were evaluated with clinical periodontal indices and all parameters were assessed at baseline, 1, 3, and 6 months after the surgery.

Results

After 6 months, all implants showed uneventful healing. Radiographic evaluation showed a mean bone loss of 0.72 mm for PS and 0.56 mm for SP implants, and there were no significant differences between implant types. At 6 months, mean implant stability quotient (ISQ) values were 73.38 and 77 for PS and SP implants, respectively. Mean MM values were −4.75 for PS and −6.38 for SP implants. Mean MM values were lower for SP implants compared to PS implants at all time points. No significant differences were detected between implant types according to clinical peri‐implant parameters.

Conclusions

The micro‐gap at crestal level which immediately exposed to the oral cavity in non‐submerged two part implants seems to have adverse influence on the marginal bone level.
Bacterial leakage along the implant–abutment interface: culture and DNA Checkerboard hybridization analyses
Authors: do Nascimento Cássio , Miani Paola Kirsten , Pedrazzi Vinícius , Muller Kátia , de Albuquerque Junior Rubens Ferreira
Published: September 2011

Objective

Bacterial species have been found harboring the internal surface of dental implants as consequence of their failed connections. The aim of the present study was to compare the detection frequency of bacterial leakage from human saliva through the implant–abutment interface, under non‐loading conditions, using either DNA Checkerboard or culture method.

Materials and methods

Thirty dental implants with hexagonal platforms were connected to pre‐machined abutments according to the manufacturers’ specifications. The assemblies were individually incubated in human saliva under anaerobic conditions for 7 days at 37°C. Afterward, contents from the inner parts of the implants were collected and evaluated with either DNA Checkerboard (s = 15) or culture (n = 15). Subsequently, identification and quantitation of bacterial species from saliva and implants were carried out for the group evaluated with the DNA Checkerboard method.

Results

Both DNA Checkerboard and culture showed positive signals of bacterial leakage in 6 of the 15 evaluated samples. Capnocytophaga gingivalis and Streptococcus mutans were the most frequently detected species harboring the internal surface of the implants followed by Veillonella parvula.

Conclusion

Occurrence of bacterial leakage along the implant–abutment interface is comparably detected with both DNA Checkerboard hybridization and conventional culture methods.
“Tired with all these, for restful death I cry”. Autoeroticism and Decadence in Shakespeare’s Sonnets 62–75
Authors: Brooks Jason
Published: September 2011

Scholars have noted, but scarcely, the autoerotic thematic at work in Shakespeare’s Sonnets. Curiously, most attention to masturbation and other manifestations of autoeroticism have come from the Procreation Sonnets. Rarely have scholars pushed the sodomitic envelope beyond homoeroticism or Shakespeare’s affection for the Dark Lady. Critics have, of course, used the three major sonnet sequences (viz. the Procreation, Young Man, and Dark Lady sequences) to forward discussion of sexuality, but they also frequently look at individual sonnets out of their sequence context to explore their theses. This essay identifies a heretofore unseen mini‐sequence in the Sonnets, and, through a close analysis of this mini‐sequence, begins to fill the autoerotic lacuna. Following Duncan‐Jones’s defense of the stability of the sequence in the poems, the present essay contends that sonnets 62–75 constitute an economy of autoeroticism situated in the fin de siècle motif of decadence and decay.
There’s More to It Already. Typography and Literature Studies: A Critique of Nina Nørgaard’s ‘The semiotics of typography in literary texts’ (2009)
Authors: Kurz Stephan
Published: September 2011

Recently, typography has increasingly become a field explored by scholars of various disciplines, not all of them philologists. Although co‐operation and mutual exchange are on the rise in the field, there are still deficits in this area. The aim of this article is a review primarily of the German‐speaking academic discussion since 2000, but also of the long‐existing field of ‘bibliography’. It is in the form of a critique of an article published in Orbis Litterarum in 2009 (vol. 64, no. 2), and takes the opportunity to complement the original paper in discussing the relation between typography and literature in three subject areas: historicity of print technology and typographical convention, differences between analogue and digital print production, and the scope of the term ‘typography’. The main methodological argument put forward is a claim for context‐oriented approaches taking into account historical depth and technology, but also the latter’s application by workers in the printing trade and authors from the literary field alike. Despite its relatively small scope as a reaction to a single article, the paper is written to spark further discussion.
HIV‐1 Vpu Antagonizes BST‐2 by Interfering Mainly with the Trafficking of Newly Synthesized BST‐2 to the Cell Surface
Authors: Dubé Mathieu , Paquay Catherine , Roy Bibhuti Bhusan , Bego Mariana G. , Mercier Johanne , Cohen Éric A.
Published: September 2011

Bone marrow stromal cell antigen‐2 (BST‐2) inhibits human immunodeficiency virus type 1 (HIV‐1) release by cross‐linking nascent virions on infected cell surface. HIV‐1 Vpu is thought to antagonize BST‐2 by downregulating its surface levels via a mechanism that involves intracellular sequestration and lysosomal degradation. Here, we investigated the functional importance of cell‐surface BST‐2 downregulation and the BST‐2 pools targeted by Vpu using an inducible proviral expression system. Vpu established a surface BST‐2 equilibrium at ∼60% of its initial levels within 6 h, a condition that coincided with detection of viral release. Analysis of BST‐2 post‐endocytic trafficking revealed that the protein is engaged in a late endosomal pathway independent of Vpu. While Vpu moderately enhanced cell‐surface BST‐2 clearance, it strongly affected the protein resupply to the plasma membrane via newly synthesized proteins. Noticeably, Vpu affected clearance of surface BST‐2 more substantially in Jurkat T cells than in HeLa cells, suggesting a cell‐dependent impact of Vpu on the pool of surface BST‐2. Collectively, our data reveal that Vpu imposes a new BST‐2 equilibrium, incompatible with efficient restriction of HIV‐1 release, by combining an acceleration of surface BST‐2 natural clearance, whose degree might be cell‐type dependent, to a severe impairment of the protein resupply to the plasma membrane.
Sowing of low and high diversity seed mixtures in ecological restoration of surface mined‐land
Authors: Kirmer Anita , Baasch Annett , Tischew Sabine
Published: September 2011

Questions

What are the differences in speed and pathway of vegetation development on nutrient‐poor, unvegetated slopes sown with low‐diversity seed mixtures of cultivars and high‐diversity seed mixtures of regional species? And how is the susceptibility of the different sowing treatments to immigration events via seed rain? We compared differences in using a low‐diversity seed mixture in comparison with a high‐diversity seed mixture, both sown on nutrient‐deficient raw soil. We assessed differences of speed and pathway of vegetation development of different variants as well as their susceptibility to immigration events via seed rain.

Location

CentralGerman Lignite Mining District.

Methods

In December 2004, the trial was established in complete block design with four variants: sowing of a low‐diversity seed mixture with three grass cultivars and sowing of a high‐diversity seed mixture with 40 herbs and 11 grasses of local provenance, both with and without an additional mulch layer. Vegetation surveys were made between 2005 and 2010. Using generalized linear models (GLM), we tested for treatment effects on species diversity, above‐ground biomass, total coverage of vegetation as well as number and coverage of target grassland species. In addition, we estimatedBray‐Curtis distances between treatments using non‐metric‐multidimensional scaling.

Results

Sowing of a high‐diversity seed mixture clearly accelerated the vegetation development and led to a significantly higher biomass production in the 1st year. On both variants, the additional mulch layer facilitated the establishment of sown species and led to a higher coverage of the herb layer in the 1st year. After 6 yr, the influence of the mulch layer decreased for the benefit of the seed mixture. Despite species exchange between sites, sites sown with different seed mixtures were still dominated by different sets of species in the final year of our study. Whereas high‐diversity mixtures sped up vegetation development in the direction of highly diverse semi‐natural grasslands, low‐diversity mixtures considerably delayed the successional progress.

Conclusions

In grassland restoration in surface‐mined land, high‐diversity mixtures performed similar or even better than low‐diversity mixtures of grass cultivars with respect to ecosystem services such as biomass production and ground cover (erosion control). An additional mulch layer considerably accelerated the vegetation development in the 1st years on both sowing variants. In contrast to sowing of low‐diversity seed mixtures of grass cultivars, the use of high‐diversity seed mixtures of local provenance contributes to the enhancement of local biodiversity. Although target grassland species were able to migrate into the low‐diversity sites, this process is slow and only possible when appropriate seed sources are nearby.
Extracellular TG2: emerging functions and regulation
Authors: Belkin Alexey M.
Published: September 2011

Tissue transglutaminase (TG2) is a ubiquitously expressed member of the transglutaminase family of Ca2+‐dependent crosslinking enzymes. Unlike other family members, TG2 is a multifunctional protein, which has several other well documented enzymatic and non‐enzymatic functions. A significant body of evidence accumulated over the last decade reveals multiple and complex activities of this protein on the cell surface and in the extracellular matrix (ECM), including its role in the regulation of cell–ECM interactions and outside‐in signaling by several types of transmembrane receptors. Moreover, recent findings indicate a dynamic regulation of the levels and functions of extracellular TG2 by several complementary mechanisms. This review summarizes and assesses recent research into the emerging functions and regulation of extracellular TG2.
Gender, but not CYP7A1 or SLCO1B1 Polymorphism, Affects the Fasting Plasma Concentrations of Bile Acids in Human Beings
Authors: Xiang Xiaoqiang , Backman Janne T. , Neuvonen Pertti J. , Niemi Mikko
Published: September 2011

Abstract:  Cholesterol 7α‐hydroxylase (CYP7A1) is the rate‐limiting enzyme of bile acid production in human beings, and organic anion‐transporting polypeptide 1B1 (OATP1B1) may influence bile acid hepatic uptake and cholesterol and bile acid synthesis rate. Our purpose was to investigate the effects of gender and CYP7A1 and SLCO1B1 polymorphisms on the fasting plasma concentrations of bile acids, bile acid synthesis marker and total cholesterol in a Finnish population. Fasting plasma concentrations of 16 endogenous bile acids, their synthesis marker (7α‐hydroxy‐4‐cholesten‐3‐one) and total cholesterol were measured in 243 samples from 143 healthy volunteers. The volunteers were genotyped for 6 haplotype‐tagging single‐nucleotide polymorphisms (SNPs) of CYP7A1 and two functionally relevant SNPs in SLCO1B1. The mean plasma concentrations of chenodeoxycholic acid, glycochenodeoxycholic acid, ursodeoxycholic acid and glycoursodeoxycholic acid were 61–111% higher in men than in women (P ≤ 0.001). Accordingly, the mean concentration of total bile acids was 51% higher in men than in women (P = 0.001). The CYP7A1 rs8192879 and rs1023652 SNPs were associated with deoxycholic acid and hyodeoxycholic acid concentrations, respectively, but the associations were not significant after correction for multiple testing. None of the six CYP7A1 SNPs was associated with the plasma concentrations of cholesterol or 7α‐hydroxy‐4‐cholesten‐3‐one. SLCO1B1 genotype was associated with total plasma cholesterol concentration only, but the association was not significant after correction for multiple testing. In general, the gender contributes substantially more to variation in fasting plasma bile acid concentrations than CYP7A1 or SLCO1B1 polymorphism do. Common genetic variability in CYP7A1 is unlikely to play a significant role in cholesterol metabolism and bile acid homeostasis under normal physiological conditions.
Physiological Remodelling of the Maternal Uterine Circulation during Pregnancy
Authors: Mandala Maurizio , Osol George
Published: September 2011

Abstract:  Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodelling of the entire maternal uterine vasculature. The main focus of this MiniReview is to provide information on upstream (pre‐placental) maternal uterine vascular remodelling that facilitates gestational increases in uterine blood flow. Consideration of the three‐dimensional pattern of remodelling (circumferential enlargement versus axial elongation), changes in vessel biomechanical properties, and underlying mechanisms [shear stress, nitric oxide, vascular endothelial growth factor (VEGF)/placental growth factor (PlGF), the renin–angiotensin system] and pathways (local versus systemic; venoarterial exchange) are provided using the rat as the principal animal model, although findings from other species are incorporated wherever possible to provide a comparative perspective. The process of maternal gestational uterine vascular remodelling involves a number of cellular processes and mechanisms, including trophoblast invasion, hyperplasia and hypertrophy, and changes in extracellular matrix composition. In addition, changes in cellular function, e.g. the secretory and contractile properties of smooth muscle and an up‐regulation of endothelial vasodilatory influences may contribute to uteroplacental blood flow increases through changes in tone as well as in structure. Future studies aimed at better understanding the inter‐relationship between changes in vessel structure (remodelling) and function (reactivity) would likely generate new mechanistic insights into the fascinating process of maternal gestational uterine vascular adaptation and provide a more physiological perspective of the underlying cellular processes involved in its regulation.
Transient relativistic ejections and stationary core in XTE J1752−223
Authors: Yang J. , Paragi Z. , Corbel S. , Gurvits L. I. , Campbell R. M. , Brocksopp C.
Published: September 2011

The Galactic X-ray transient XTE J1752−223 was shown to have properties of black hole binary candidates. As reported in our previous paper, we identified transient and decelerating ejecta in multi-epoch Very Long Baseline Interferometry (VLBI) observations with the European VLBI Network (EVN) and the NRAO Very Long Baseline Array (VLBA). Here we present new EVN and VLBA data in which a new transient ejection event and later a stationary component are identified. The latter is interpreted as a reappearance of the radio core/compact jet during the transition from soft to hard X-ray state. This component appears to be highly variable in brightness although effects of tropospheric instabilities might play a role too. We also re-analyse the earlier VLBI data and find that the transient ejecta closer to the core position has significantly higher proper motion, further strengthening the case for strongly decelerating ejecta on the scale of several hundred milliarcsecond, never observed in X-ray binaries before. Although the distance of the source is not well constrained, it is clear that these ejectas are at least mildly relativistic at the early stages. Moreover, we show the large scale environment of the transient from the Westerbork synthesis array data recorded in parallel during the EVN run.
Interpreting clinical trial results for moderate‐to‐severe rheumatoid arthritis: Practical applications for rheumatology healthcare providers
Authors: Furfaro Nicole , Mease Philip J.
Published: September 2011

Purpose: To provide a general overview of clinical trials and more specifically define measurements common to rheumatoid arthritis clinical trials for the purpose of providing a foundation for rheumatology healthcare providers to translate clinical trial findings into their clinical practice and enhance their patient education discussions.

Data sources: English‐language publications cited in the MEDLINE database were used to develop the content of this review article.

Conclusions: The role of rheumatology healthcare providers has evolved to include numerous vital functions, such as expanding communication between specialists and primary care providers, patient education and counseling, assistance with coping strategies, monitoring response to therapy, and administration of therapy. Education regarding clinical trial design, rationale, and discussion of endpoints has not been strongly emphasized for rheumatology healthcare providers who are increasingly introduced to novel agents and need to assimilate findings from clinical trials into daily practice.

Implications for practice: Familiarity with the basics of clinical trial design and efficacy endpoints of new rheumatoid arthritis therapeutics, translation and application of that knowledge into daily practice, and the ability to explain this information with patients will further enhance the ability of the rheumatology healthcare provider to optimize care for their patients with rheumatoid arthritis.
Negation, Denial, and Rejection
Authors: Ripley David
Published: September 2011

At least since Frege (1960) and Geach (1965), there has been some consensus about the relation between negation, the speech act of denial, and the attitude of rejection: a denial, the consensus has had it, is the assertion of a negation, and a rejection is a belief in a negation. Recently, though, there have been notable deviations from this orthodox view. Rejectivists have maintained that negation is to be explained in terms of denial or rejection, rather than vice versa. Some other theorists have maintained that negation is a separate phenomenon from denial, and that neither is to be explained in terms of the other. In this paper, I present and consider these heterodox theories of the relation between negation, denial, and rejection
Aesthetics of Opera
Authors: Thom Paul
Published: September 2011

An inclusive sense of ‘opera’ is distinguished from the Western high‐art sense. The problem of aesthetic unity in opera is discussed in relation to (i) hybrid art forms (Kivy’s idea of antithetical arts, Levinson’s account of hybridity, and Ridley’s critique of it); (ii) specific operatic styles (Hegel on Handel and Rossini, Kerman, Kivy and Davies on Mozart, Goehr and Magee on Wagner); (iii) individual operatic productions and performances (Tanner on Kupfer, Williams on Sellars). The article includes links to video clips from operatic performances.
Introduction to the Philosophy of Statistical Mechanics: Can Probability Explain the Arrow of Time in the Second Law of Thermodynamics?
Authors: Shenker Orly , Hemmo Meir
Published: September 2011

The arrow of time is a familiar phenomenon we all know from our experience: we remember the past but not the future and control the future but not the past. However, it takes an effort to keep records of the past, and to affect the future. For example, it would take an immense effort to unmix coffee and milk, although we easily mix them. Such time directed phenomena are subsumed under the Second Law of Thermodynamics. This law characterizes our experience of the arrow of time in terms of an increase of a theoretical magnitude called entropy. Statistical mechanics tries to explain the Second Law as an effect of the behavior of the microscopic particles that make up the universe. Since our senses are too coarse to see this microstructure, statistical mechanics describes our experience in terms of probability, or in terms of the partial information we have about the particles. In this paper we explain the workings of statistical mechanics; how it accounts for probability as an objective feature of the world based on the underlying dynamics; how it accounts for our memories of the past; how the statistical mechanical probability underwrites the Second Law; and how, at the same time, it leads to a violation of the Second Law by the so‐called Maxwell’s Demon.
Comment on ‘Birdstrikes and barcoding: can DNA methods help make the airways safer?’
Authors: FEDERHEN SCOTT
Published: September 2011

GenBank is the database of record for public sequence data. Results reported in the scientific literature that are based on sequence data cannot be evaluated if the underlying data is not in the public record.
The increased prevalence of myopia in Finland
Authors: Pärssinen Olavi
Published: September 2011

Purpose:  To study change in the prevalence of myopia in Finland during the 20th century.

Methods:  A review of the literature on the prevalence of myopia in Finland.

Results:  During the 20th century, the prevalence of myopia among 7‐ to 8‐year‐old schoolchildren did not increase in Finland and varied between 0.5% and 1.9%. Among 14‐ to 15‐year‐old school children, myopia doubled to about 21%. Among adults born during the first three decades of the 20th century, the prevalence of myopia was <10%, whereas among those born during the second half of the 20th century, the prevalence rose to 21–30%. The change in mean refraction was towards myopia.

Conclusions:  During the course of the 20th century, myopia among teenagers and adults in Finland significantly increased and the mean change in refraction was towards myopia. Increased education is proposed as the main reason behind these changes.
Characterization of solitary pulmonary nodules using double phase Tc‐99m methoxyisobutylisonitrile scan: Comparison of visual and quantitative analyses
Authors: Kim Seong‐Jang , Kim In Joo , Kim Yun‐Seong
Published: September 2011

Background:  We assessed the diagnostic usefulness of Tc‐99m methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) for the evaluation of solitary pulmonary nodule (SPN).

Methods:  Thirty‐five patients (17 malignant and 18 benign) were recruited. Double phase Tc‐99m MIBI SPECT was performed 10 min and then 2 h after an injection of 925 MBq of Tc‐99m MIBI. Visual interpretation grades of the Tc‐99m MIBI scan were used for the determination of SPN characteristics. Receiver–operator curve analyses were performed for the optimal cut‐off values of visual and quantitative indices for differentiation of benign and malignant SPN.

Results:  The optimal visual grades were grade 4 and 5. When 3+ was used as the cut‐off value for the detection of malignant SPN, the sensitivity and specificity of Tc‐99m SPECT were 47.1% and 88.9%, respectively. The area under curve (AUC) was 0.758. The optimal planar lesions to non‐lesion (L/N) ratios were 2.3 for the early image and 1.6 for the delayed image. The optimal SPECT L/N ratios were 3.1 for the early and 1.6 for the delayed image. The SPECT early L/N was superior to other quantitative indices and visual analysis.

Conclusion:  This study shows that Tc‐99m MIBI SPECT is a useful non‐invasive method for the evaluation of SPN.
The Endocast of MH1,
Australopithecus sediba
Authors: Carlson Kristian J. , Stout Dietrich , Jashashvili Tea , de Ruiter Darryl J. , Tafforeau Paul , Carlson Keely , Berger Lee R.
Published: September 2011

The brain endocast of
Australopithecus sediba
shows that despite retaining a small brain size, some reorganization of the frontal lobe had commenced, hinting at the later neural development seen in
Homo
.
Chromosome Organization by a Nucleoid-Associated Protein in Live Bacteria
Authors: Wang Wenqin , Li Gene-Wei , Chen Chongyi , Xie X. Sunney , Zhuang Xiaowei
Published: September 2011

Super-resolution imaging in live
Escherichia coli
reveals protein clusters that sequester DNA loci and organize the chromosome.
Mother Tongue and Y Chromosomes
Authors: Forster Peter , Renfrew Colin
Published: September 2011

A global picture is emerging of sex-specific transmission of language change in quite different regions and continents.
HCN2 Ion Channels Play a Central Role in Inflammatory and Neuropathic Pain
Authors: Emery Edward C. , Young Gareth T. , Berrocoso Esther M. , Chen Lubin , McNaughton Peter A.
Published: September 2011

Action potential firing, initiated by HCN2 ion channels, is the basic mechanism underlying neuropathic pain.
Light-Induced Structural and Functional Plasticity in
Drosophila
Larval Visual System
Authors: Yuan Quan , Xiang Yang , Yan Zhiqiang , Han Chun , Jan Lily Yeh , Jan Yuh Nung
Published: September 2011

Postsynaptic plasticity participates in the adaptation of a sensory circuit to the environment.
Boosting Health Services Research
Authors: Cook-Deegan Robert
Published: September 2011

We need a research program to improve the $2.7 trillion per year health system.
d(scientist)/dt
Wrestling with Nature
From Omens to Science

Peter Harrison, Ronald L. Numbers, and Michael H. Shank, Eds.

University of Chicago Press, Chicago, 2011. 426 pp. $95, 61.50. ISBN 9780226317816. Paper, $35, £22.50. ISBN 9780226317830.
Authors: Jones Matthew L.
Published: September 2011

To illuminate the roots and development of science in the Western tradition, the authors "examine how students of nature ... have understood and represented their work."
Computing as Science and Practice

Histories of Computing
by Michael Sean Mahoney; Thomas Haigh, Ed.

Harvard University Press, Cambridge, MA, 2011. 262 pp. $49.95, £36.95, €45. ISBN 9780674055681.
Authors: Ensmenger Nathan
Published: September 2011

In these essays and articles, Mahoney explores the history of computing and its place in technology studies.
Still Vulnerable in 2011
Authors: Branscomb Lewis M.
Published: September 2011

Terror attacks on innocent people have continued around the world since 11 September 2001, but not on the scale of the 2001 attack on the United States, which claimed more than 2500 lives. That disaster made us realize our vulnerabilities in many sectors. When a critical industry, such as transportation, communications, energy, or water services, is disrupted in a disaster, it may also cause collateral damage to other services. For example, the 2003 Northeast blackout cut off power to 55 million people. This not only cut off electricity to homes and offices—trains stopped, water purification failed, cell phones went uncharged, and factories shut down. Clearly, attention needs to be paid to improving the resilience of the most critical infrastructure industries.
Big Budget Squeeze Looms for Major New Facilities
Authors: Mervis Jeffrey
Published: September 2011

Recent actions by Congress raise serious questions about the National Science Foundation's ability to obtain funding in a timely and orderly manner for major new facilities.
Piqued Chinese Dean Throws Down the Gauntlet
Authors: Xin Hao
Published: September 2011

Peking University dean of life sciences Rao Yi has been in the spotlight for his outspoken criticism of China's research culture. Rao responded to critics in a recent interview with
Science
.
Warning of H5N1 Resurgence Surprises Community
Authors: Normile Dennis
Published: September 2011

Last week, the U.N. Food and Agriculture Organization warned of "a major resurgence of the H5N1 highly pathogenic avian influenza," but other international health organizations quickly played down the significance.
Little Foot, Big Mystery
Authors: Balter Michael
Published: September 2011

After nearly 15 years of excavation, the most complete hominin skeleton ever discovered, dubbed "Little Foot," is expected to be out of the cave in which it was discovered within the next 2 months.
Enhanced Effect of DNA Immunization plus
In Vivo
Electroporation with a Combination of Hepatitis B Virus Core-PreS1 and S-PreS1 Plasmids
Authors: Chen Hong , Wen Bo , Deng Yao , Wang Wen , Yin Xiao , Guan Jie , Ruan Li , Tan Wenjie
Published: September 2011

To develop a novel, effective HBV therapeutic vaccine, we constructed two HBV DNA immunogens that contained PreS1, HBSS1, and HBCS1. Several delivery methods, such as intramuscular (i.m.) injection, intramuscular injection plus electroporation (i.m.-EP), and intradermal injection plus electroporation (i.d.-EP) were used in a murine model to analyze and compare the immune responses that were induced by the DNA immunogens. We found that i.d.-EP accelerated specific antibody seroconversion and produced high antibody (anti-PreS1, anti-S, and anti-C antibody) titers after HBSS1 and HBCS1 immunization. Combining the HBSS1 and HBCS1 DNA immunogens with i.d.-EP produced the strongest multiantigen (PreS1, S, and C)-specific cellular immune response and the highest specific PreS1 antibody levels. The results indicated that DNA immunization using HBSS1 and HBCS1 might be an ideal candidate, with its ability to elicit robust B and T cell immune responses against multiantigen when combined with optimized delivery technology. The present study provides a basis for the design and rational application of a novel HBV DNA vaccine.
Anti-Gamma Interferon Antibodies Enhance the Immunogenicity of Recombinant Adenovirus Vectors
Authors: Jackson Shawn S. , Schmitz Jörn E. , Letvin Norman L.
Published: September 2011

Vaccination for eliciting antigen-specific memory CD8+T cells may be facilitated by manipulating the pleiotropic effects of gamma interferon (IFN-γ). We assessed strategies for modulating the contribution of IFN-γ during the development of antigen-specific cytotoxic T lymphocyte (CTL) populations. We first showed that recombinant IFN-γ suppressed antigen expressionin vitrofrom a recombinant adenovirus (rAd) vector in a dose-dependent manner and that addition of an anti-IFN-γ antibody (Ab) eliminated this suppression. Consistent with thesein vitrofindings, we found that HIV-1 envelope (Env)-specific CTL responses were higher in IFN-γ-knockout (GKO) mice than in wild-type mice following immunization with rAd. Since these observations suggested that IFN-γ might suppress rAd-induced CTL development, we assessed the ability of anti-IFN-γ Ab administration to augment rAd-elicited CTLin vivo. In fact, blockage of IFN-γ activity by monoclonal Ab administration was associated with elevated levels of interleukin 7 receptor alpha chain-positive (IL-7Rα+) Env-specific CTL populations postboost. These observations illustrate the utility of an anti-IFN-γ Ab for potentiating rAd immunizations to effect quantitative and qualitative changes in the effector and memory CTL populations.
Concomitant Administration of Mycobacterium bovis BCG with the Meningococcal C Conjugate Vaccine to Neonatal Mice Enhances Antibody Response and Protective Efficacy
Authors: Brynjolfsson Siggeir F. , Bjarnarson Stefania P. , Mori Elena , Del Giudice Giuseppe , Jonsdottir Ingileif
Published: September 2011

Mycobacterium bovisBCG is administered to human neonates in many countries worldwide. The objective of the study was to assess if BCG could act as an adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby induce protective immunity against encapsulated bacteria in early infancy when susceptibility is high. We assessed whether BCG could enhance immune responses to a meningococcal C (MenC) conjugate vaccine, MenC-CRM197, in mice primed as neonates, broaden the antibody response from a dominant IgG1 toward a mixed IgG1 and IgG2a/IgG2b response, and increase protective efficacy, as measured by serum bactericidal activity (SBA). Two-week-old mice were primed subcutaneously (s.c.) with MenC-CRM197. BCG was administered concomitantly, a day or a week before MenC-CRM197. An adjuvant effect of BCG was observed only when it was given concomitantly with MenC-CRM197,with increased IgG response (P= 0.002) and SBA (8-fold) after a second immunization with MenC-CRM197without BCG, indicating increased T-cell help. In neonatal mice (1 week old) primed s.c. with MenC-CRM197together with BCG, MenC-polysaccharide (PS)-specific IgG was enhanced compared to MenC-CRM197alone (P= 0.0015). Sixteen days after the second immunization with MenC-CRM197, increased IgG (P< 0.05), IgG1 (P< 0.05), IgG2a (P= 0.06), and IgG2b (P< 0.05) were observed, and only mice primed with MenC-CRM197plus BCG showed affinity maturation and detectable SBA (SBA > 128). Thus, vaccination with a meningococcal conjugate vaccine (and possibly with other conjugates) may benefit from concomitant administration of BCG in the neonatal period to accelerate and enhance production of protective antibodies, compared to the current infant administration of conjugate which follows BCG vaccination at birth.