bluuebunny/crossref_metadata_2025_split huggingface dataset:
The availability of prescription‐only analgesics purchased from the internet in the UK
Authors: Raine Connie , Webb David J. , Maxwell Simon R. J. 
Published: November 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Increasing numbers of people are accessing medicines from the internet.• This online market is poorly regulated and represents a potential threat to the health of patients and members of the public. WHAT THIS STUDY ADDS • Prescription‐only analgesics, including controlled opioids, are readily available to the UK public through internet pharmacies that are easily identified by popular search engines.• The majority of websites do not require the customer to possess a valid prescription for the drug.• Less than half provide an online health screen to assess suitability for supply.• The majority have no registered geographical location.• Analgesic medicines are usually purchased at prices significantly above British National Formulary prices and are often supplied in large quantities.• These findings are of particular relevance to pain‐management specialists who are trying to improve the rational use of analgesic drugs.AIMS To explore the availability to the UK population of prescription‐only analgesics from the internet.METHODS Websites were identified by using several keywords in the most popular internet search engines. From 2000 websites, details of 96 were entered into a database.RESULTS Forty‐six (48%) websites sold prescription analgesics, including seven opioids, two non‐opioids and 18 nonsteroidal anti‐inflammatory drugs. Thirty‐five (76%) of these did not require the customer to possess a valid prescription.CONCLUSION Prescription‐only analgesics, including controlled opioids, are readily available from internet websites, often without a valid prescription.
Synergistic effects of cyclic strain and Th1-like cytokines on tenascin-C production by rheumatic aortic valve interstitial cells
Authors: Jiang L , Wei X F , Yi D H , Xu P , Liu H , Chang Q , Yang S M , Li Z F , Gao H B , Hao G J 
Published: November 2008

Summary
Tenascin-C (TN-C) is a key component of extracellular matrix (ECM) and its expression process is poorly understood during rheumatic heart valvular disease (RHVD). In this study, we found that interferon (IFN)-γ, tumour necrosis factor (TNF)-α and TN-C concentrations in patients with RHVD were significantly higher than in normal controls. More IFN-γ receptors and TNF receptors were found being expressed on rheumatic aortic valves interstitial cells than on non-rheumatic ones and their expression was patients' sera dependent. Antibodies neutralizing IFN-γ or TNF-α could attenuate patients' sera-induced TN-C transcription by isolated rheumatic aortic valves interstitial cells. By application with different protein kinase inhibitors, we found that combined with cyclic strain, TNF-α and IFN-γ induced TN-C transcription through the RhoA/ROCK signalling pathway. At the same time, p38 mitogen-activated protein kinase was involved in TNF-α and IFN-γ induced TN-C transcription. TNF-α also increased TN-C mRNA level by additional PKC and ERK 1/2 activation. Our finding revealed a new insight into ECM remodelling during RHVD pathogenesis and new mechanisms involved in the clinical anti-IFN-γ and anti-TNF-α therapy.
The hinge region fragment of immunoglobulin G improves immunogenicity of recombinant gonadotrophin‐releasing hormone conjugated to the T‐helper epitope in designing peptide vaccines
Authors: Xu Jinshu , Wu Jie , Wang Xuejun , Zhang Yin , Li Wenjia , Zhu Zheng , Zhu Dongya , Hu Zhuoyi , Roque Rouel S. , Liu Jingjing 
Published: November 2008

SummaryIn our previous study, the hinge fragment (225–232/225′–232′) of human immunoglobulin G1 (IgG1) was used as a space peptide linker for synthesizing the GnRH3–hinge–MVP chimeric peptide, whereby three repeated gonadotrophin‐releasing hormone (GnRH) units and a T‐cell epitope from measles virus fusion protein (MVP) were amide‐bond‐linked at the N and C terminus, respectively, to the hinge peptide for producing anti‐GnRH antibody responses. To investigate whether or not the hinge region fragment can improve the immunogenicity of GnRH, we further synthesized and purified GnRH3–hinge–MVP, GnRH3–hinge and GnRH3–MVP using recombinant DNA technology. Under high pH conditions, GnRH3–hinge–MVP was capable of forming double‐chain structures. Immunization of male mice with the immunogens of GnRH3–hinge–MVP resulted in the generation of high‐titre antibodies specific for GnRH. The synthetic GnRH3–hinge and GnRH3–MVP induced a lower titre of anti‐GnRH antibody than GnRH3–hinge–MVP. This was followed by a decrease in serum testosterone levels, which resulted in a low level of expression of the relaxin‐like factor gene in the testis. Our data suggest that peptide and T‐cell epitopes oriented at the N‐terminus or C‐terminus of hinge peptides simplify the antigenic peptide conjugates and may be considered as potential synthetic immunogens.
Identification of the proteome composition occurring during the course of embryonic development of bees (Apis mellifera)
Authors: Li J. , Zhang L. , Feng M. , Zhang Z. , Pan Y. 
Published: November 2008

AbstractTo investigate the proteome during embryonic development of honeybees, Apis mellifera, proteins were identified by two‐dimensional gel electrophoresis, mass spectrometry and protein engine identification tools that were applied to MASCOT and Xproteo search engines. 312, 320, 315 proteins were detected in 24, 48 and 72 h embryos. Thirty‐eight highly abundant proteins were identified at the three time points by MS fingerprinting. All 21 proteins could be identified as products of annotated genes of the honeybee. Identified proteins included six proteins related to the metabolism of carbohydrates and energy production, six proteins belonging to the heat shock protein family, three cytoskeletal proteins, four proteins related to the antioxidant system of the embryo and two proteins related to growth regulation of the embryo. Quantitative proteomics was applied to analyze differences in amounts of these proteins during the three above mentioned developmental stages. Our data present an initial molecular picture of honeybee embryos, and will hopefully pave the way for future research on this animal.
Habitat structure mediates predation risk for sedentary prey: experimental tests of alternative hypotheses
Authors: Chalfoun Anna D. , Martin Thomas E. 
Published: November 2008

Summary

Predation is an important and ubiquitous selective force that can shape habitat preferences of prey species, but tests of alternative mechanistic hypotheses of habitat influences on predation risk are lacking.
We studied predation risk at nest sites of a passerine bird and tested two hypotheses based on theories of predator foraging behaviour. The total‐foliage hypothesis predicts that predation will decline in areas of greater overall vegetation density by impeding cues for detection by predators. The potential‐prey‐site hypothesis predicts that predation decreases where predators must search more unoccupied potential nest sites.
Both observational data and results from a habitat manipulation provided clear support for the potential‐prey‐site hypothesis and rejection of the total‐foliage hypothesis. Birds chose nest patches containing both greater total foliage and potential nest site density (which were correlated in their abundance) than at random sites, yet only potential nest site density significantly influenced nest predation risk.
Our results therefore provided a clear and rare example of adaptive nest site selection that would have been missed had structural complexity or total vegetation density been considered alone.
Our results also demonstrated that interactions between predator foraging success and habitat structure can be more complex than simple impedance or occlusion by vegetation.
Effect of current reproduction on apparent survival, breeding dispersal, and future reproduction in barn swallows assessed by multistate capture–recapture models
Authors: Schaub Michael , Von Hirschheydt Johann 
Published: November 2008

SummaryTheoretical models predict a negative effect of current reproduction on breeding dispersal, survival and future reproduction, and many studies confirm these predictions. Yet, results of most previous studies may be difficult to interpret because the fate of the affected individuals cannot always be observed. Detection is almost always imperfect and some individuals emigrate from the study area, resulting in biased estimates of both survival and dispersal.Most studies bypass these problems with strong assumptions. We use a multistate capture–recapture model that does not require these assumptions. States are defined based on classes of reproductive success and on observed dispersal events within the study area. By accounting for imperfect detection within the study area, the model allows estimation of the effect of reproductive success on apparent survival, dispersal probabilities within the study area and the annual transition probabilities among classes of reproductive success. Based on an assumption about the estimate of real survival, the model allows the estimation of total dispersal that is not specific to a fixed study area.We applied this model to capture–recapture data of 2262 adult barn swallows (Hirundo rustica) sampled from 1997–2004 in eight local populations in Switzerland.We found that dispersal within the study area decreased with increasing reproductive success in both sexes, that reproductive success was not affected by preceding dispersal and that apparent survival of females but not of males increased with increasing reproductive success. Apparent survival of females with high reproductive success was identical to apparent survival of males suggesting that this estimate of apparent survival (0·48) was close to true survival. Total breeding dispersal was generally higher in females and it increased with decreasing reproductive success in both sexes. Current reproductive success depended on reproductive success in the preceding year suggesting that individual differences were of importance.Our study highlights that reproductive success was an important factor affecting breeding dispersal and population turnover. While unsuccessful males mainly remained in the local populations, many unsuccessful females left them. Population turnover of adult swallows was mainly due to unsuccessful females.
The long‐term ecology of the lost forests of La Laguna, Tenerife (Canary Islands)
Authors: De Nascimento Lea , Willis Katherine J. , Fernández‐Palacios José María , Criado Constantino , Whittaker Robert J. 
Published: November 2008

AbstractAim  We report the first analysis of the long‐term ecology of Tenerife, in order to establish a pre‐colonization base‐line and to assess the effect of human activity and the role of climatic variation on vegetation during the Late Holocene.Location  A former lake bed in the city of La Laguna (Tenerife, Canary Islands, Spain).Methods  A sedimentary sequence of over 2 m was obtained from the former lake bed. Fossil pollen and microfossil charcoal concentrations were analysed. Radiocarbon dating of the sequence indicates that it spans approximately the last 4700 years. The pollen diagram was zoned using optimal splitting within psimpoll 4.25.Results  Three pollen zones were differentiated: (1) in Zone L1 (c. 4700–2900 cal. yr bp) a mixed forest was dominated by Quercus, Carpinus, Myrica and Pinus; (2) in Zone L2 (c. 2900–2000 cal. yr bp) the laurel forest taxa increased, while Pinus, Juniperus and Phoenix declined; and (3) Zone L3 (c. 2000–400 cal. yr bp) was characterized by the decline of Carpinus and Quercus and the abundance of laurel forest taxa (e.g. Myrica). Neither Carpinus nor Quercus was hitherto considered to be native to the Canary Islands. Their decline started c. 2000 years ago, coinciding with microfossil charcoal evidence of increased burning and with archaeological evidence for the first human settlement on Tenerife.Main conclusions  Between c. 4700 and 2000 cal. yr bp, the composition of the forest in the valley of La Laguna was very different from what it is at present. In particular, Quercus and Carpinus appear to have been significant components, alongside components of the present‐day laurel forest, and the native pine (Pinus canariensis) forest and thermophilous woodland were also more prevalent in the region (but probably not within the lake basin itself) until 3000 cal. yr bp. The subsequent decline of Quercus and Carpinus led to the establishment of the present laurel forest in the region and a shift to more open vegetation types. These changes indicate that the aboriginal inhabitants of the islands, the Guanches, had a far more profound impact on the vegetation of Tenerife than hitherto realized.
A new methodology for reconstructing climate and vegetation from modern pollen assemblages: an example from British Columbia
Authors: Goring Simon , Pellatt Marlow G. , Lacourse Terri , Walker Ian R. , Mathewes Rolf W. 
Published: November 2008

AbstractAim We used modern pollen assemblages to develop a method for climate reconstruction that reduces the spatial autocorrelation of residuals and accounts for the strong topographic and climatic variation that occurs in British Columbia, Canada.Location British Columbia, Canada, including sites both on the mainland and on adjacent islands (Queen Charlotte Islands and Vancouver Island).Methods New pollen assemblages from surface‐sediment samples collected in British Columbia were combined with other published and unpublished samples (n = 284). Multivariate rank‐distances between sample sites and a randomized set of sites within the province were calculated for climate parameters to determine whether gaps in the current network of present‐day pollen sample sites exist. Lacustrine surface‐sediment pollen assemblages (n = 145) were ordinated using non‐metric multidimensional scaling (NMDS), and a generalized additive model (GAM) was used to reconstruct modern mean warmest month temperature (MWMT) and mean annual precipitation (MAP) from the NMDS ordination. The results were compared with standard climate reconstruction techniques, including the modern analogue technique, partial least squares, weighted averaging, weighted averaging–partial least squares and factor analysis.Results Reconstructions of MWMT and MAP using NMDS and GAM were comparable to those of existing models. When reconstructing MWMT, the NMDS/GAM method had a lower root‐mean‐squared error of prediction (RMSEP), lower spatial autocorrelation and higher correlation with observed temperature values than the other methods tested. When reconstructing MAP, the partial least squares method performed better than the NMDS/GAM method for RMSEP and correlation with observed values; however, the NMDS/GAM method had a lower spatial autocorrelation of residuals.Main conclusions NMDS reveals strong relationships among modern pollen assemblages, vegetation and climate parameters. Climate models using NMDS and GAM are comparable to other palaeoecological reconstruction models, but provide lower spatial autocorrelation of residuals for both parameters tested. An inverse distance‐weighted surface of multivariate rank‐climate distances generated from the network of pollen sample sites indicates that greater sampling intensity in north‐western and central‐interior British Columbia is required in order to obtain an accurate representation of climatic and vegetation diversity in the province.
The role of dispersal ability, climate and spatial separation in shaping biogeographical patterns of phylogenetically distant plant groups in seasonally dry Andean forests of Bolivia
Authors: Linares‐Palomino Reynaldo , Kessler Michael 
Published: November 2008

AbstractAim  To assess biogeographical patterns of Acanthaceae, Bromeliaceae, Cactaceae and Pteridophyta in Bolivian Andean seasonally dry forest islands and to explain current floristic differences between these islands by means of extrinsic (precipitation, elevation) and intrinsic (dispersal ability) factors.Location  Ten isolated and disjunct seasonally dry forest areas in the Bolivian Andes and the adjacent seasonal forest areas of the Chiquitanía and Chaco regions.Methods  We collated species data from recently updated and revised taxonomic treatments and herbarium collections for Acanthaceae, Bromeliaceae, Cactaceae and Pteridophyta, constructed floristic distance matrices to estimate beta diversity at the study sites and subjected them to Mantel correlation analyses. Multiple regressions on distance matrices allowed us to test the influence of geographical distance and environmental (elevation and precipitation) differences on floristic differentiation.Results  Acanthaceae and Bromeliaceae, and to a lesser extent Cactaceae, showed coincident biogeographical patterns and suggested the presence of two seasonally dry forest groups in Andean Bolivia: one including all small isolated northern dry valleys and another including all southern valleys with connections to the lowland seasonal forests of the Chiquitanía and the Chaco. Most of the variation in the floristic distance matrices in these plant groups, with seed dispersal typically restricted to short distances, was explained by spatial separation between habitat islands. In contrast, pteridophytes showed a different biogeographical pattern. Their floristic differences between sites were determined by the environmental variables. The anemochorous and spore‐based dispersal system of this plant group seems to be a highly effective mechanism allowing pteridophytes to easily reach even the isolated dry valleys in inter‐Andean Bolivia.Main conclusions  Current biogeographical patterns in dry Andean habitat islands can provide insights into the factors that control the processes of community assembly. We show that differences in community composition of phylogenetically distant plant groups in the understorey of seasonally dry forest islands can be explained by a combination of the habitat characteristics where the group is present (either precipitation, elevation or both) and, more interestingly, by group specific dispersal limitation (as inferred by geographical distance between island habitats).
Free fatty acid kinetics during long‐term treatment with pioglitazone added to sulfonylurea or metformin in Type 2 diabetes
Authors: Roden M. , Mariz S. , Brazzale A. R. , Pacini G. 
Published: November 2008

Abstract.Background.  Free fatty acids (FFAs) are linked to impaired insulin action, but their role in mediating long‐term insulin sensitization during diabetes treatment is unclear.Objectives.  To examine the effect of pioglitazone addition to existing therapy on FFA dynamics and insulin action.Design.  Two 2‐year, randomized, parallel‐group, double‐blind, double‐dummy, clinical trials.Setting.  One hundred and seventy‐one centres in Europe, Australia and Canada.Subjects.  Male and female patients with Type 2 diabetes inadequately managed with metformin or sulfonylurea.Interventions.  Patients were randomized to pioglitazone (15–45 mg day−1; n = 319) or metformin (850–2550 mg day−1; n = 320) as add‐on therapy to gliclazide or pioglitazone (n = 317) versus gliclazide (80–320 mg day−1; n = 313) as add‐on therapy to metformin.Outcome measure.  Plasma FFA profiles during oral glucose tolerance tests in selected centres before and during treatment (n = 588).Results.  At Week 104, pioglitazone treatment decreased fasting FFAs by 0.08 mmol L−1 when added to sulfonylurea and by 0.11 mmol L−1 when added to metformin versus the respective sulfonylurea + metformin groups (0.03 mmol L−1, P = 0.05 and 0.04 mmol L−1, P < 0.05), and this was accompanied by significant improvements in fasting adipose tissue insulin sensitivity. Changes in postchallenge FFAs were similar between groups and not related to changes in liver transaminases, insulin action and secretion. However, the sensitivity of FFA to insulin was affected by treatment (P < 0.001) and visit (P < 0.05). Insulin sensitivity of FFA rose when pioglitazone was added to sulfonylurea (P < 0.05), but decreased for gliclazide + metformin (P < 0.05).Conclusion.  Long‐term improvements in adipose tissue insulin sensitivity and reduction in fasting FFAs with pioglitazone may help to reduce lipotoxicity in Type 2 diabetes.
Characterization of the dTDP‐d‐fucofuranose biosynthetic pathway in Escherichia coli O52
Authors: Wang Quan , Ding Peng , Perepelov Andrei V. , Xu Yanli , Wang Ying , Knirel Yuriy A. , Wang Lei , Feng Lu 
Published: November 2008

Summary d‐fucofuranose (d‐Fucf) is a component of Escherichia coli O52 O antigen. This uncommon sugar is also the sugar moiety of the anticancer drug – gilvocarcin V produced by many streptomycetes. In E. coli O52, rmlA, rmlB, fcf1 and fcf2 were proposed in a previous study by our group to encode the enzymes of the dTDP‐d‐Fucf (the nucleotide‐activated form of d‐Fucf) biosynthetic pathway. In this study, Fcf1 and Fcf2 from E. coli O52 were expressed, purified and assayed for their respective activities. Novel product peaks from enzyme‐substrate reactions were detected by capillary electrophoresis and the structures of the product compounds were elucidated by electro‐spray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. Fcf1 was confirmed to be a dTDP‐6‐deoxy‐d‐xylo‐hex‐4‐ulopyranose reductase for the conversion of dTDP‐6‐deoxy‐d‐xylo‐hex‐4‐ulopyranose to dTDP‐d‐fucopyranose (dTDP‐d‐Fucp), and Fcf2 a dTDP‐d‐Fucp mutase for the conversion of dTDP‐d‐Fucp to dTDP‐d‐Fucf. The Km of Fcf1 for dTDP‐6‐deoxy‐d‐xylo‐hex‐4‐ulopyranose was determined to be 0.38 mM, and of Fcf2 for dTDP‐d‐Fucp to be 3.43 mM. The functional role of fcf1 and fcf2 in the biosynthesis of E. coli O52 O antigen were confirmed by mutation and complementation tests. This is the first time that the biosynthetic pathway of dTDP‐d‐Fucf has been fully characterized.
Regulation of glutamate metabolism by protein kinases in mycobacteria
Authors: O'Hare Helen M. , Durán Rosario , Cerveñansky Carlos , Bellinzoni Marco , Wehenkel Anne Marie , Pritsch Otto , Obal Gonzalo , Baumgartner Jens , Vialaret Jérome , Johnsson Kai , Alzari Pedro M. 
Published: November 2008

SummaryProtein kinase G of Mycobacterium tuberculosis has been implicated in virulence and in regulation of glutamate metabolism. Here we show that this kinase undergoes a pattern of autophosphorylation that is distinct from that of other M. tuberculosis protein kinases characterized to date and we identify GarA as a substrate for phosphorylation by PknG. Autophosphorylation of PknG has little effect on kinase activity but promotes binding to GarA, an interaction that is also detected in living mycobacteria. PknG phosphorylates GarA at threonine 21, adjacent to the residue phosphorylated by PknB (T22), and these two phosphorylation events are mutually exclusive. Like the homologue OdhI from Corynebacterium glutamicum, the unphosphorylated form of GarA is shown to inhibit α‐ketoglutarate decarboxylase in the TCA cycle. Additionally GarA is found to bind and modulate the activity of a large NAD+‐specific glutamate dehydrogenase with an unusually low affinity for glutamate. Previous reports of a defect in glutamate metabolism caused by pknG deletion may thus be explained by the effect of unphosphorylated GarA on these two enzyme activities, which may also contribute to the attenuation of virulence.