bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term reduction of brain‐derived neurotrophic factor levels and signaling impairment following prenatal treatment with the cannabinoid receptor 1 receptor agonist (R)‐(+)‐[2,3‐dihydro‐5‐methyl‐3‐(4‐morpholinyl‐methyl) pyrrolo[1,2,3‐de]‐1,4‐benzoxazin‐6‐yl]‐1‐ naphthalenylmethanone
Authors: Maj Paola Francesca , Collu Maria , Fadda Paola , Cattaneo Annamaria , Racagni Giorgio , Riva Marco Andrea 
Published: June 2007

AbstractIt is well accepted that adverse life events occurring early in development may alter the correct program of brain maturation leading to enhanced vulnerability to neuropsychiatric disorders. It has recently been demonstrated that prenatal exposure to the cannabinoid receptor 1 agonist (R)‐(+)‐[2,3‐dihydro‐5‐methyl‐3‐(4‐morpholinyl‐methyl)pyrrolo[1,2,3‐de]‐1,4‐benzoxazin‐6‐yl]‐1‐naphthalenylmethanone (WIN 55,212‐2) produces memory deficit in adulthood, an effect associated with a reduced functionality of the glutamatergic system. The aim of our study was to identify molecular changes produced by prenatal exposure to WIN 55,212‐2 that might contribute to late disruption in synaptic plasticity and cognition. For this purpose, WIN 55,212‐2 was injected in pregnant wistar rats from gestation day 5 to 20 and a detailed analysis of the levels of the neurotrophin brain‐derived neurotrophic factor (BDNF) as well as of the signaling molecules extracellular signal‐regulated kinase (ERK)1/2 and α‐calcium/calmodulin‐dependent protein kinase II (α‐CaMKII) was carried out in adult offspring. We found that exposure to WIN 55,212‐2 significantly reduced BDNF levels in hippocampus and frontal cortex. This effect was associated with decreased activation of pathways linked to neurotrophin and glutamate receptor signaling. In particular, prenatal cannabinoid treatment reduced the phosphorylated levels of ERK1/2 in selected subcellular compartments of hippocampus, frontal and prefrontal cortex, whereas no changes were observed in the total levels of these proteins. Furthermore, a robust reduction of total and phospho‐α‐CaMKII was found in the hippocampus of rats prenatally exposed to WIN 55,212‐2. In summary, the present data suggest that deficits of BDNF levels and signaling through ERK1/2 and α‐CaMKII might contribute to cognitive and neuroplastic defects associated with prenatal exposure to cannabinoids.
Cloning and early expression pattern of two melatonin biosynthesis enzymes in the turbot (Scophthalmus maximus)
Authors: Vuilleumier Robin , Boeuf Gilles , Fuentes Michael , Gehring Walter J. , Falcón Jack 
Published: June 2007

AbstractMelatonin biosynthesis from serotonin involves the sequential activation of the arylalkylamine N‐acetyltransferase (AANAT) and hydroxyindole‐O‐methyltransferase (HIOMT). Photoperiod synchronizes a daily rhythm in pineal and retinal melatonin secretion through controlling AANAT activity. Teleost fish possess two Aanat, one expressed in the retina (AANAT1) and the other expressed in the pineal gland (AANAT2). We report here the full‐length cloning of Aanat1, Aanat2, SmHiomt and Otx5 (orthodenticle homeobox homolog 5) in the turbot (Scophthalmus maximus, Sm), a flatfish belonging to an evolutionary recent group of Teleost. The temporal expression pattern of the genes investigated is consistent with the idea that OTX5 is needed for photoreceptor specification, and that the pineal gland differentiates before the retina. SmAanat2 expression remained pineal specific during the period of time investigated, whereas SmOtx5 and SmHiomt expressions were seen in both the retina and pineal gland. Our results do not support the existence of a second SmHiomt, as is the case for SmAanat. Neither SmAanat2 nor SmHiomt mRNAs displayed cyclic accumulation in the pineal organ of embryos and larvae maintained under a light–dark cycle from fertilization onward. This is in marked contrast with the situation observed with zebrafish Aanat2, indicating that the molecular mechanisms controlling the development of the pineal melatonin system have been modified during the evolution of Teleost.
Incorporating dispersal distance into the disperser effectiveness framework: frugivorous birds provide complementary dispersal to plants in a patchy environment
Authors: Spiegel Orr , Nathan Ran 
Published: June 2007

AbstractFleshy‐fruited plants are usually dispersed by an array of frugivores, differing in the effectiveness of the dispersal service they provide to the plant. Body size differences among frugivores are hypothesized to affect seed dispersal distances and consequently their effectiveness as dispersers. We tested this hypothesis by comparing the effectiveness of two passerine birds, grackles (Onychognathus tristramii) and bulbuls (Pycnonotus xanthopygos), dispersing the desert shrub Ochradenus baccatus. Laboratory experiments, quantifying gut retention time and the effect on germination, were combined with field observations quantifying bird movements and fruit consumption rates. An empirically parameterized mechanistic model showed that the two dispersers switch roles as a function of spatial‐scale: while most seeds within the local habitat were dispersed by bulbuls, the larger grackles were exclusively responsible for between‐patches, long‐distance dispersal. We suggest that distance‐related differences are common and important to plant fitness, and thus should explicitly be considered in studies of disperser effectiveness.
The multicopper oxidase (CueO) and cell aggregation in Escherichia coli
Authors: Tree Jai J. , Ulett Glenn C. , Hobman Jon L. , Constantinidou Chrystala , Brown Nigel L. , Kershaw Christopher , Schembri Mark A. , Jennings Michael P. , McEwan Alastair G. 
Published: June 2007

Summary cueO encodes a periplasmic multicopper oxidase, which is known to be involved in copper homeostasis and protection against oxidative stress in Escherichia coli K12. Transcriptional profiling showed that expression of genes associated with motility was lowered in a cueO mutant while expression of genes associated with autoaggregation was elevated. Increased aggregation was correlated with increased expression of cell surface proteins antigen 43 and curli. Changes in gene expression caused by the deletion of cueO were essentially independent of SoxR and OxyR, the global regulators of oxidative stress response.
Bilateral synchronous sporadic renal cell carcinoma: surgical management, oncological and functional outcomes
Authors: Pahernik Sascha , Cudovic Dragan , Roos Frederik , Melchior Sebastian W. , Thüroff Joachim W. 
Published: June 2007

OBJECTIVETo analyse the functional and oncological outcomes of surgical treatment of bilateral synchronous sporadic renal cell carcinoma (RCC).PATIENTS AND METHODSBetween 1969 and 2006, 57 patients with bilateral synchronous sporadic RCC were identified from our kidney database. The mean (range) follow‐up was 4.8 (0.1–23.8) years; 28 patients (49%) had radical nephrectomy (RN) and contralateral nephron‐sparing surgery (NSS), and 22 (39%) had bilateral NSS. The oncological outcome and long‐term renal function were analysed.RESULTSAfter excluding four patients (7%) with bilateral benign renal tumours, six (11%) with metastatic bilateral RCC and three (5%) who had bilateral RN, the cancer‐specific outcome was analysed. For 44 patients with bilateral RCC who had surgery with intent to cure and avoid dialysis, 13 (30%) had stage pT1a, 10 (23%) pT1b, nine (17%) pT2 and 12 (27%) pT3 disease. At 5 and 10 years, the cancer‐specific survival rates were 86% and 75%, and the local recurrence‐free survival rates were 87% and 80%. The median serum creatinine level at the latest follow‐up was 1.18 mg/dL in patients after bilateral NSS and 1.40 mg/dL after unilateral NSS and contralateral RN (P < 0.05).CONCLUSIONSThese long‐term data support the concept that NSS, whenever possible bilateral, is the treatment of choice for bilateral synchronous sporadic RCC. NSS provides adequate local tumour control and cancer‐specific survival. Preservation of renal function is more efficient with bilateral NSS than with unilateral NSS and contralateral RN.
Research and development (R&D) beyond manufacturing: the strange case of services R&D
Authors: Miles Ian 
Published: June 2007

The share of business research and development (R&D) expenditure stemming from the services sector of the economy has been growing rapidly in many (though not all) OECD countries, according to official statistics. The same data sources also indicate, however, that services contribute less to R&D than would be expected given their large shares of employment and output in national economies. In part, incomplete sampling of services in R&D surveys may lead to some underestimation of their R&D activity, but this is unlikely to account for their apparently poor performance. This paper draws on an analysis of existing statistical sources, and on interviews and workshops with service firms' managers. It finds difficulties associated with the ways in which R&D has been operationalised in survey questions. Examination of survey questionnaires suggests that the formulation of these questions, focusing on technological R&D and ruling out much social scientific R&D, disproportionately reduces the reporting of R&D by service firms. But beyond this, the R&D concept itself has some problematic features where it comes to documenting innovation in service firms. This was investigated through a programme of interviews and workshops with service firms, where a lack of familiarity with the R&D concept and R&D management practices was found to be commonplace. R&D performance and innovation activities vary across services of different sorts, even though most service subsectors appear to be low R&D investors. It is thus important to examine services' innovation patterns and processes, to establish what types of R&D‐like activity are underway in these subsectors. While some modification in R&D measurement would be desirable to capture services' activities, effort to understand the non‐R&D elements of services innovation is also important – for management and for policy (given that governments are seeking to create R&D incentives and targets for services and other sectors).There are grounds for expecting (a) services' share of business R&D to continue to grow; (b) this share to continue to be well below what would be expected from the prevalence of services in economic activity, and (c) for many services' innovation to continue to rely heavily on sources that are not directly associated with R&D.
FLYING WHERE YOU DON'T WANT TO GO: AN EMPIRICAL ANALYSIS OF HUBS IN THE GLOBAL AIRLINE NETWORK
Authors: DERUDDER BEN , DEVRIENDT LOMME , WITLOX FRANK 
Published: June 2007

ABSTRACTThis paper aims to contribute to the literature on the rise of so‐called ‘network cities’ through an empirical analysis of hubs in the global airline network. Standard airline databases do not feature the actual routes flown by passengers, and therefore, a new and previously untapped database is introduced. The employed data are transnational and feature origin/destination statistics with additional information on intermediate stops (if any), which allows a thorough assessment of hub structures in the global airline network. The first part of the empirical analysis presents a threefold hub assessment, i.e. (i) an overview of the major hubs in absolute terms, (ii) a similar overview of hubs in relative terms, and (iii) a measure that focuses on the number of cities that make intense use of a hub. The second part of the empirical analysis focuses on some aspects of the spatiality of hub‐and‐spoke organisation. This is achieved through an examination of the proportion of ‘regional’ hub passengers and some notable case studies.
Anti‐Individualism, Content Preservation, and Discursive Justification
Authors: Goldberg Sanford C. 
Published: June 2007

AbstractMost explorations of the epistemic implications of Semantic Anti‐Individualism (SAI) focus on issues of self‐knowledge (first‐person authority) and/or external‐world skepticism. Less explored has been SAI's implications for the epistemology of reasoning. In this paper I argue that SAI has some nontrivial implications on this score. I bring these out by reflecting on a problem first raised by Boghossian (1992). Whereas Boghossian's main interest was in establishing the incompatibility of SAI and “the a priority of logical abilities” (Boghossian 1992: 22), I argue that Boghossian's argument is better interpreted as pointing to SAI's implications for the nature of discursive justification.
A Role for Mathematics in the Physical Sciences
Authors: Pincock Christopher 
Published: June 2007

AbstractConflicting accounts of the role of mathematics in our physical theories can be traced to two principles. Mathematics appears to be both (1) theoretically indispensable, as we have no acceptable non‐mathematical versions of our theories, and (2) metaphysically dispensable, as mathematical entities, if they existed, would lack a relevant causal role in the physical world. I offer a new account of a role for mathematics in the physical sciences that emphasizes the epistemic benefits of having mathematics around when we do science. This account successfully reconciles theoretical indispensability and metaphysical dispensability and has important consequences for both advocates and critics of indispensability arguments for platonism about mathematics.
Pharmacokinetic evaluation of the effects of ribavirin on zidovudine triphosphate formation: ACTG 5092s Study Team
Authors: Aweeka FT , Kang M , Yu J‐Y , Lizak P , Alston B , Chung RT ,   the AIDS Clinical Trials Group 5092s Study Team
Published: June 2007

ObjectivesRibavirin (RBV) is used for the treatment of hepatitis C virus (HCV) infection in subjects with HIV‐1 infection who may require antiretroviral treatment (ART) with nucleoside reverse transcriptase inhibitors including zidovudine (ZDV). We sought to investigate the potential antagonism between RBV and ZDV by evaluating the impact of RBV on the formation of intracellular ZDV triphosphate (TP) in HIV‐infected patients receiving ZDV who were treated for HCV infection.MethodsSerial plasma and intracellular ZDV TP pharmacokinetics (PK) were determined in 14 subjects at entry (within 2 weeks prior to RBV administration) and at 8 weeks following initiation of RBV. Intracellular ZDV TP in peripheral blood mononuclear cells (PBMC) was quantified by a validated cartridge/liquid chromatography/tandem mass spectrometry method. PK exposure was estimated from the steady‐state area under the concentration vs time curve (AUC0–12 h) in plasma and PBMC.ResultsRibavirin did not have a statistically significant impact on ZDV TP AUC0–12 h, plasma ZDV AUC0–12 h or the ratio of ZDV TP AUC0–12 h to plasma ZDV AUC0–12 h, although there was a trend towards an increase post‐RBV ratio compared with pre‐RBV. There was extensive variability in the ZDV TP AUC0–12 h.ConclusionsRibavirin did not inhibit formation of ZDV TP in PBMC in 14 patients receiving ZDV as part of ART and RBV‐based HCV therapy for 8 weeks. These results are consistent with those of a previously published limited study in seven subjects. These PK findings should be weighed carefully against emerging clinical reports of significant anaemia associated with combination ZDV and high‐dose RBV therapy.
Use of complementary and alternative medicines among a multistate, multisite cohort of people living with HIV/AIDS
Authors: Josephs JS , Fleishman JA , Gaist P , Gebo KA ,   for the HIV Research Network
Published: June 2007

ObjectiveThe aim of the study was to assess the prevalence of and factors associated with use of complementary or alternative medicine (CAM) in a multistate, multisite cohort of HIV‐infected patients.MethodsDuring 2003, 951 adult patients from 14 sites participated in face‐to‐face interviews. Patients were asked if they received treatment from any alternative therapist or practitioner in the previous 6 months. Logistic regression was performed to examine associations between demographic and clinical variables and CAM use.ResultsThe majority of the participants were male (68%) and African American (52%) with a median age of 45 years (range 20–85 years). Sixteen per cent used any CAM in the 6 months prior to the interview. Factors associated with use of CAM were the HIV risk factor injecting drug use [adjusted odds ratio (AOR) 0.51] compared with men who have sex with men (MSM), former drug use (AOR=2.12) compared with never having used drugs, having a college education (AOR=2.43), and visiting a mental health provider (AOR=2.76).ConclusionsThis study demonstrated similar rates of CAM use in the current highly active antiretroviral therapy (HAART) era compared with the pre‐HAART era. Factors associated with CAM – such as education, use of mental health services, and MSM risk factor – suggest that CAM use may be associated with heightened awareness regarding the availability of such therapies. Given the potential detrimental interactions of certain types of CAM and HAART, all HIV‐infected patients should be screened for use of CAM.
Bone morphogenetic protein rescues the lack of secondary cartilage in Runx2‐deficient mice
Authors: Fukuoka Hiroki , Shibata Shunichi , Suda Naoto , Yamashita Yasuo , Komori Toshihisa 
Published: June 2007

AbstractSecondary cartilages including mandibular condylar cartilage have unique characteristics. They originate from alkaline phosphatase (ALP)‐positive progenitor cells of the periosteum, and exhibit characteristic modes of differentiation. They also have a unique extracellular matrix, and coexpress type I, II and X collagens. We have previously shown that there is a total absence of secondary cartilages in Runx2‐deficient (Runx2–/–) mice. To clarify whether Runx2 is essential for chondrocytic differentiation of secondary cartilages, we performed an organ culture system using mandibular explants derived from Runx2–/– mice at embryonic day 18.0. Since mRNA for bone morphogenetic protein 2 (BMP2) was strongly expressed in osteoblasts of condylar anlagen in wild‐type mice, and was down‐regulated in those of Runx2–/– mice, we chose to investigate BMP2 effects on secondary cartilage formation. Condensed mesenchymal cells of mandibular condylar anlagen in precultured explants were ALP‐positive and expressed type I collagen and Sox9. After culture with recombinant human (rh) BMP2, chondrocytic cells showing ALP activity and expressing Sox5, Sox9, and type I and II collagens, appeared from mesenchymal condensation. This expression profile was comparable with the reported pattern of chondrocytes in mouse secondary cartilages. However, chondrocyte hypertrophy was not observed in the explants. These findings indicate that BMP2 partially rescued chondrocyte differentiation but not chondrocyte hypertrophy in secondary cartilage formation in Runx2–/– mice. Runx2 is required for chondrocyte hypertrophy in secondary cartilage formation, and it is likely that BMP2, which is abundantly secreted by osteoblasts in condylar anlagen, contributes to the early process of secondary cartilage formation.
Alpha‐synuclein pathology in the olfactory pathways of dementia patients
Authors: Hubbard Paul S. , Esiri Margaret M. , Reading Margaret , McShane Rupert , Nagy Zsuzsanna 
Published: June 2007

AbstractLewy‐type pathology is a characteristic of a number of neurodegenerative disorders, including Parkinson's disease and dementia with Lewy bodies. Thus far, the definitive diagnosis of these dementias can only be confirmed at post‐mortem. However, it is known that the loss of smell (anosmia) is an early symptom in patients who develop dementia, and the use of the smell test has been proposed as an early diagnostic procedure. The aim of this study was to understand further the extent of Lewy pathology in the olfactory system of patients with neurodegenerative disorders. Post‐mortem tissue from 250 subjects was obtained from the OPTIMA brain bank. Five areas of the olfactory pathway were examined by immunolabelling for alpha‐synuclein – a major component of Lewy pathology: the olfactory tract/bulb (n = 79), the anterior olfactory nucleus in the lateral olfactory gyrus (n = 193), the region of olfactory projection to the orbito‐frontal cortex (n = 225), the hippocampus (n = 236) and the amygdala (n = 201). Results show that Lewy pathology affects different parts of the olfactory pathways differentially, suggesting a specific pattern of development of pathology. Clinical Parkinson's disease is most likely to be identified if the orbito‐frontal cortex is affected, while the diagnosis is less likely if the pathology is restricted to the olfactory bulb or tract. These results suggest that pathology in the olfactory bulb and tract occurs prior to clinical signs of Parkinson's disease. Furthermore, the results presented here provide further evidence supporting the possible value of a smell test to aid the clinical diagnosis of neurodegenerative diseases.
Computational mouse atlases and their application to automatic assessment of craniofacial dysmorphology caused by the Crouzon mutation Fgfr2C342Y
Authors: Ólafsdóttir Hildur , Darvann Tron A. , Hermann Nuno V. , Oubel Estanislao , Ersbøll Bjarne K. , Frangi Alejandro F. , Larsen Per , Perlyn Chad A. , Morriss‐Kay Gillian M. , Kreiborg Sven 
Published: June 2007

AbstractCrouzon syndrome is characterized by premature fusion of sutures and synchondroses. Recently, the first mouse model of the syndrome was generated, having the mutation Cys342Tyr in Fgfr2c, equivalent to the most common human Crouzon/Pfeiffer syndrome mutation. In this study, a set of micro‐computed tomography (CT) scannings of the skulls of wild‐type mice and Crouzon mice were analysed with respect to the dysmorphology caused by Crouzon syndrome. A computational craniofacial atlas was built automatically from the set of wild‐type mouse micro‐CT volumes using (1) affine and (2) non‐rigid image registration. Subsequently, the atlas was deformed to match each subject from the two groups of mice. The accuracy of these registrations was measured by a comparison of manually placed landmarks from two different observers and automatically assessed landmarks. Both of the automatic approaches were within the interobserver accuracy for normal specimens, and the non‐rigid approach was within the interobserver accuracy for the Crouzon specimens. Four linear measurements, skull length, height and width and interorbital distance, were carried out automatically using the two different approaches. Both automatic approaches assessed the skull length, width and height accurately for both groups of mice. The non‐rigid approach measured the interorbital distance accurately for both groups while the affine approach failed to assess this parameter for both groups. Using the full capability of the non‐rigid approach, local displacements obtained when registering the non‐rigid wild‐type atlas to a non‐rigid Crouzon mouse atlas were determined on the surface of the wild‐type atlas. This revealed a 0.6‐mm bending in the nasal region and a 0.8‐mm shortening of the zygoma, which are similar to characteristics previously reported in humans. The most striking finding of this analysis was an angulation of approximately 0.6 mm of the cranial base, which has not been reported in humans. Comparing the two different methodologies, it is concluded that the non‐rigid approach is the best way to assess linear skull parameters automatically. Furthermore, the non‐rigid approach is essential when it comes to analysing local, non‐linear shape differences.