bluuebunny/crossref_metadata_2025_split huggingface dataset:
C‐reactive protein promotes atherosclerosis by increasing LDL transcytosis across endothelial cells
Authors: Bian Fang , Yang Xiaoyan , Zhou Fan , Wu Pin‐Hui , Xing Shasha , Xu Gao , Li Wenjing , Chi Jiangyang , Ouyang Changhan , Zhang Yonghui , Xiong Bin , Li Yongsheng , Zheng Tao , Wu Dan , Chen Xiaoqian , Jin Si 
Published: February 2014

Background and PurposeThe retention of plasma low‐density lipoprotein (LDL) particles in subendothelial space following transcytosis across the endothelium is the initial step of atherosclerosis. Whether or not C‐reactive protein (CRP) can directly affect the transcytosis of LDL is not clear. Here we have examined the effect of CRP on transcytosis of LDL across endothelial cells and have explored the underlying mechanisms.Experimental ApproachEffects of CRP on transcytosis of FITC‐labelled LDL were examined with human umbilical vein endothelial cells and venous rings in vitro and, in vivo, ApoE‐/‐ mice. Laser scanning confocal microscopy, immunohistochemistry and Oil Red O staining were used to assay LDL.Key ResultsCRP increased transcytosis of LDL. An NADPH oxidase inhibitor, diphenylene iodonium, and the reducing agent, dithiothreitol partly or completely blocked CRP‐stimulated increase of LDL transcytosis. The PKC inhibitor, bisindolylmaleimide I and the Src kinase inhibitor, PP2, blocked the trafficking of the molecules responsible for transcytosis. Confocal imaging analysis revealed that CRP stimulated LDL uptake by endothelial cells and vessel walls. In ApoE‐/‐ mice, CRP significantly promoted early changes of atherosclerosis, which were blocked by inhibitors of transcytosis.Conclusions and ImplicationsCRP promoted atherosclerosis by directly increasing the transcytosis of LDL across endothelial cells and increasing LDL retention in vascular walls. These actions of CRP were associated with generation of reactive oxygen species, activation of PKC and Src, and translocation of caveolar or soluble forms of the N‐ethylmaleimide‐sensitive factor attachment protein.
GABAB receptors in the bladder and bowel: therapeutic potential for positive allosteric modulators?: Commentary on Kalinichev et al., Br J Pharmacol 171: 995–1006
Authors: Hyland Niall P , Golubeva Anna V 
Published: February 2014

Linked ArticleThis article is a Commentary on Kalinichev M, Palea S, Haddouk H, Royer‐Urios I, Guilloteau V, Lluel P, Schneider M, Saporito M and Poli S (2014). ADX71441, a novel, potent and selective positive allosteric modulator of the GABAB receptor, shows efficacy in rodent models of overactive bladder. Br J Pharmacol 171: 995–1006. doi: 10.1111/bph.12517
Different mechanisms of homologous and heterologous μ‐opioid receptor phosphorylation
Authors: Mann Anika , Illing Susann , Miess Elke , Schulz Stefan 
Published: February 2014

The efficiency of μ‐opioid receptor signalling is tightly regulated and ultimately limited by the coordinated phosphorylation of intracellular serine and threonine residues. Here, we review and discuss recent progress in the generation and application of phosphosite‐specific μ‐opioid receptor antibodies, which have proved to be excellent tools for monitoring the spatial and temporal dynamics of receptor phosphorylation and dephosphorylation. Agonist‐induced phosphorylation of μ‐opioid receptors occurs at a conserved 10 residue sequence 370TREHPSTANT379 in the receptor's carboxyl‐terminal cytoplasmic tail. Diverse opioids induce receptor phosphorylation at S375, present in the middle of this sequence, but only high‐efficacy opioids have the ability to drive higher order phosphorylation on flanking residues (T370, T376 and T379). S375 is the initiating residue in a hierarchical phosphorylation cascade. In contrast, agonist‐independent heterologous μ‐opioid receptor phosphorylation occurs primarily at T370. The combination of phosphosite‐specific antibodies and siRNA knockdown screening also facilitated the identification of relevant kinases and phosphatases. In fact, morphine induces a selective S375 phosphorylation that is predominantly catalysed by GPCR kinase 5 (GRK5), whereas multisite phosphorylation induced by high‐efficacy opioids specifically requires GRK2/3. By contrast, T370 phosphorylation stimulated by phorbol esters or heterologous activation of Gq‐coupled receptors is mediated by PKCα. Rapid μ‐opioid receptor dephosphorylation occurs at or near the plasma membrane and is catalysed by protein phosphatase 1γ (PP1γ). These findings suggest that there are distinct phosphorylation motifs for homologous and heterologous regulation of μ‐opioid receptor phosphorylation. However, it remains to be seen to what extent different μ‐opioid receptor phosphorylation patterns contribute to the development of tolerance and dependence in vivo.Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Involvement of substance P in the development of cisplatin‐induced acute and delayed pica in rats
Authors: Yamamoto Kouichi , Asano Keiko , Tasaka Ayana , Ogura Yuko , Kim Seikou , Ito Yui , Yamatodani Atsushi 
Published: February 2014

Background and PurposeAlthough substance P (SP) and neurokinin NK1 receptors have been reported to be involved in cisplatin‐induced acute and delayed emesis, their precise roles remain unclear. Pica, the consumption of non‐nutrient materials such as kaolin in rats, can be used as a model of nausea in humans. We investigated the time‐dependent changes in cisplatin‐induced pica and the involvement of SP and NK1 receptors in this behaviour.Experimental ApproachRats were administered cisplatin with or without a daily injection of a 5‐HT3 receptor antagonist (granisetron) or an NK1 receptor antagonist (aprepitant), and kaolin intake was then monitored for 5 days. The effects of granisetron on the cisplatin‐induced expression of preprotachykinin‐A (PPT‐A) mRNA, which encodes mainly for SP, and on SP release in the medulla, measured by in vivo brain microdialysis, were also investigated.Key ResultsCisplatin induced pica within 8 h of its administration that continued for 5 days. Granisetron inhibited the acute phase (day 1), but not the delayed phase (days 2–5), of pica, whereas aprepitant abolished both phases. Within 24 h of the injection of cisplatin, PPT‐A mRNA expression and SP release in the medulla were significantly increased; these findings lasted during the observation period and were inhibited by granisetron for up to 24 h.Conclusions and ImplicationsThe profiles of cisplatin‐induced pica in rats are similar to clinical findings for cisplatin‐induced emesis in humans, and we showed that SP production in the medulla and activation of NK1 receptors are involved in this cisplatin‐induced pica.
Resource allocation to reproduction in animals
Authors: Kooijman Sebastiaan A. L. M. , Lika Konstadia 
Published: February 2014

ABSTRACTThe standard Dynamic Energy Budget (DEB) model assumes that a fraction κ of mobilised reserve is allocated to somatic maintenance plus growth, while the rest is allocated to maturity maintenance plus maturation (in embryos and juveniles) or reproduction (in adults). All DEB parameters have been estimated for 276 animal species from most large phyla and all chordate classes. The goodness of fit is generally excellent. We compared the estimated values of κ with those that would maximise reproduction in fully grown adults with abundant food. Only 13% of these species show a reproduction rate close to the maximum possible (assuming that κ can be controlled), another 4% have κ lower than the optimal value, and 83% have κ higher than the optimal value. Strong empirical support hence exists for the conclusion that reproduction is generally not maximised. We also compared the parameters of the wild chicken with those of races selected for meat and egg production and found that the latter indeed maximise reproduction in terms of κ, while surface‐specific assimilation was not affected by selection. We suggest that small values of κ relate to the down‐regulation of maximum body size, and large values to the down‐regulation of reproduction. We briefly discuss the ecological context for these findings.
Japanese phase I study ofGC33, a humanized antibody against glypican‐3 for advanced hepatocellular carcinoma
Authors: Ikeda Masafumi , Ohkawa Shinichi , Okusaka Takuji , Mitsunaga Shuichi , Kobayashi Satoshi , Morizane Chigusa , Suzuki Ikue , Yamamoto Shunsuke , Furuse Junji 
Published: February 2014

GC33 is a humanizedmAb against human glypican‐3 (GPC3). In the first‐in‐human study carried out in the USA, GC33 was well tolerated and showed preliminary antitumor activity in patients with advanced hepatocellular carcinoma. This study aimed to assess the safety, tolerability, and pharmacokinetic characteristics of GC33 in Japanese patients with advanced hepatocellular carcinoma. The study design was a conventional 3 + 3 dose‐escalation design to determine the maximum tolerated dose of GC33 given i.v. at 5, 10, or 20 mg/kg weekly. Immunohistochemistry was carried out on tumor biopsies to evaluate GPC3 expression. Thirteen patients were enrolled across the three dose levels, and no patients observed any dose‐limiting toxicity up to the highest planned dose of 20 mg/kg. The most common adverse events were decreased lymphocyte count, decreased natural killer cell count, increased C‐reactive protein, and pyrexia. Grade 3 adverse events (increased blood pressure, decreased lymphocyte count, and decreased platelet count) were observed in two or more patients. The AUCinfshowed a dose‐proportional increase from the 5 mg/kg dose group to the 20 mg/kg dose group. The trough concentrations of GC33 appeared to reach a steady state after the fourth to the sixth dose. Seven of the 13 patients showed stable disease, the other six showed progressive disease. Furthermore, three patients showed long‐term stable disease of more than 5 months. In conclusion, GC33 given at up to 20 mg/kg weekly was well tolerated in Japanese patients with advanced hepatocellular carcinoma.
The PedPAD study: boys predominate in the hypogammaglobulinaemia registry of the ESID online database
Authors: Schatorjé E J H , Gathmann B , van Hout R W N M , de Vries E , Alsina L , Baumann U , Belohradsky BH , Bienemann K , Boardman B , Borte M , Bredius RG , Brodszki N , Caracseghi F , Ciznar P , de Vries E , Driessen GJ , Dückers G , Duppenthaler A , Farmaki E , Galal N , Gennery A , Gonzalez-Granado LI , Hlavackova E , Hoernes M , Kilic SS , Krüger R , Kuijpers TW , Kütükcüler N , Llobet P , Marques L , van Montfrans JM , Papadopoulou-Alataki E , Paschenko O , Pasic S , Pietrogrande MC , Pignata C , Reda SM , Reisli I , Roesler J , Santos JL , Schölvinck EH , Schulze Ilka , Seidel MG , Shcherbina A , Sundin M , Szaflarska A , Velbri S , Warnatz K , Warris A 
Published: February 2014

Summary
Hypogammaglobulinaemias are the most common primary immunodeficiency diseases. This group of diseases is very heterogeneous, and little is known about these diseases in children. In the Pediatric Predominantly Antibody Deficiencies (PedPAD) study, we analysed data from the European Society for Immunodeficiencies (ESID) online database to gain more insight into the characteristics of children with hypogammaglobulinaemia; 46 centres in 18 different countries agreed to participate. Data from 2076 of the 3191 children who were registered at the time of data extraction with a diagnosis of hypogammaglobulinaemia (this excludes agammaglobulinaemia and defects in class-switch recombination) were available for analysis. The data set showed several limitations. Because of country-related differences in diagnostic criteria used for the classification of different types of primary hypogammaglobulinaemia, further analysis of the data was performed in the combined data set. The most striking observation is the strong majority of male patients in the group of children with primary hypogammaglobulinaemia (n = 1292, 63%). This male predominance was observed in each of the 18 countries involved. The boys were younger at diagnosis (mean age males 5·3 years; mean age females 5·8 years). Moreover, one or more complications were more frequently reported in boys (12%) compared to girls (5%). The male predominance suggests that patients with an undetected or unknown X-linked genetic cause are included in this group of children registered as primary hypogammaglobulinaemia.
State‐of‐the‐Art in Compressed GPU‐Based Direct Volume Rendering
Authors: Balsa Rodríguez M. , Gobbetti E. , Iglesias Guitián J.A. , Makhinya M. , Marton F. , Pajarola R. , Suter S.K. 
Published: February 2014

AbstractGreat advancements in commodity graphics hardware have favoured graphics processing unit (GPU)‐based volume rendering as the main adopted solution for interactive exploration of rectilinear scalar volumes on commodity platforms. Nevertheless, long data transfer times and GPU memory size limitations are often the main limiting factors, especially for massive, time‐varying or multi‐volume visualization, as well as for networked visualization on the emerging mobile devices. To address this issue, a variety of level‐of‐detail (LOD) data representations and compression techniques have been introduced. In order to improve capabilities and performance over the entire storage, distribution and rendering pipeline, the encoding/decoding process is typically highly asymmetric, and systems should ideally compress at data production time and decompress on demand at rendering time. Compression and LOD pre‐computation does not have to adhere to real‐time constraints and can be performed off‐line for high‐quality results. In contrast, adaptive real‐time rendering from compressed representations requires fast, transient and spatially independent decompression. In this report, we review the existing compressed GPU volume rendering approaches, covering sampling grid layouts, compact representation models, compression techniques, GPU rendering architectures and fast decoding techniques.
Inexpensive Reconstruction and Rendering of Realistic Roadside Landscapes
Authors: Andújar C. , Chica A. , Vico M. A. , Moya S. , Brunet P. 
Published: February 2014

AbstractIn this paper, we present an inexpensive approach to create highly detailed reconstructions of the landscape surrounding a road. Our method is based on a space‐efficient semi‐procedural representation of the terrain and vegetation supporting high‐quality real‐time rendering not only for aerial views but also at road level. We can integrate photographs along selected road stretches. We merge the point clouds extracted from these photographs with a low‐resolution digital terrain model through a novel algorithm which is robust against noise and missing data. We pre‐compute plausible locations for trees through an algorithm which takes into account perceptual cues. At runtime we render the reconstructed terrain along with plants generated procedurally according to pre‐computed parameters. Our rendering algorithm ensures visual consistency with aerial imagery and thus it can be integrated seamlessly with current virtual globes.
Fresh‐Socket Implants of Different Collar Length: Clinical Evaluation in the Aesthetic Zone
Authors: Crespi Roberto , Capparè Paolo , Polizzi Elisabetta , Gherlone Enrico 
Published: February 2014

AbstractBackgroundThe aim of this clinical study was to compare clinical evaluations of implants in the aesthetic zone with smooth collars of different length.Materials and MethodsSixty‐six patients requiring extractions of one, two, or three teeth in the aesthetic zone of the maxilla were enrolled in this study. Ninety‐four implants were positioned and were loaded immediately after tooth extraction. Forty‐seven implants with a short smooth collar of 0.5 mm (SCI) and 47 implants with a long smooth collar of 1.8 mm (LCI) were utilized in this study and were placed using a nonsubmerged approach. Clinical (gingival index, modified plaque index, modified bleeding index, probing depth, gingival recession) and intraoral digital radiographic parameters were measured at baseline and after 6, 12, 24, and 36 months of healing to evaluate crestal bone loss levels over time.ResultsAfter a follow‐up period of 36 months, a survival rate of 100% was reported. The SCI group showed a mean bone loss of 1.07 ± 0.38 mm at 12 months and 1.09 ± 0.38 mm at 36 months. The LCI group showed a mean bone loss of 0.46 ± 0.14 mm at 12 months and 0.53 ± 0.12 mm at 36 months. After the 36‐month follow‐up period, both groups showed stable bone levels over time. Statistically significant differences were found between groups (p < .05).No statistically significant differences were found between SCI and LCI groups with regard to clinical parameters over time.ConclusionsThis study revealed significant differences in radiographically observed marginal bone loss between the two types of implant with different smooth‐collar lengths, but no differences in gingival vestibular margin outcome were observed.
Evaluation of Zirconia‐Based All‐Ceramic Single Crowns and Fixed Dental Prosthesis on Zirconia Implants: 5‐Year Results of a Prospective Cohort Study
Authors: Spies Benedikt Christopher , Stampf Susanne , Kohal Ralf‐Joachim 
Published: February 2014

AbstractObjectiveThe objective of this 5‐year cohort investigation was to determine the survival and success rate of all‐ceramic reconstructions on zirconia oral implants.Material and MethodsNinety‐three patients received 122 one‐piece zirconia implants. One hundred seventeen implants were restored with 63 single crowns (SCs) and 27 three‐unit bridges (fixed dental prostheses, FDPs) fabricated using zirconia frameworks (Procera® Zirconia, Nobel Biocare®, Göteborg, Sweden) hand‐layered with a silicate ceramic (NobelRondo™ Zirconia, Nobel Biocare®). With any occurrence of chipping regarded as an event, Kaplan‐Meier success curves were plotted. Covariates (gender, location, manufacturing date) were estimated by the use of log‐rank tests.ResultsEighty‐nine patients received prosthetic reconstructions. Sixty‐three of them were seen at the 5‐year follow‐up, with a mean observation time of 58.2 months (47 patients with SCs, 16 patients with FDPs). Reasons for the decreasing number of patients at the follow‐up sessions included dropouts due to implant loss (n = 21), moving (n = 3), missed appointments (n = 1), and severe illness (n = 1). Over half of the SCs (57.2%) and 38% of the FDPs were successful after an observation time of 5 years (overall success rate of 51.7%). The performed log‐rank tests revealed no statistically significant differences for the success curves regarding the above‐mentioned covariates. Among the 63 restorations that completed the study, 11 of 47 SCs and one of 16 FDPs had to be replaced due to the severity of the observed chipping. This results in survival rates of 76.6% for the SCs and 93.8% for the FDPs. No framework fractures or decementations were observed in any group.ConclusionHand‐layering of zirconia‐based SCs and FDPs with NobelRondo™ Zirconia restoring one‐piece zirconia implants did not show acceptable survival and success rates. Meanwhile, the material has been recalled from the market. It is advised that new materials should undergo adequate preclinical evaluation before coming to the market.
Network Analysis of Translocated Takahe Populations to Identify Disease Surveillance Targets
Authors: GRANGE ZOË L. , VAN ANDEL MARY , FRENCH NIGEL P. , GARTRELL BRETT D. 
Published: February 2014

AbstractSocial network analysis is being increasingly used in epidemiology and disease modeling in humans, domestic animals, and wildlife. We investigated this tool in describing a translocation network (area that allows movement of animals between geographically isolated locations) used for the conservation of an endangered flightless rail, the Takahe (Porphyrio hochstetteri). We collated records of Takahe translocations within New Zealand and used social network principles to describe the connectivity of the translocation network. That is, networks were constructed and analyzed using adjacency matrices with values based on the tie weights between nodes. Five annual network matrices were created using the Takahe data set, each incremental year included records of previous years. Weights of movements between connected locations were assigned by the number of Takahe moved. We calculated the number of nodes (itotal) and the number of ties (ttotal) between the nodes. To quantify the small‐world character of the networks, we compared the real networks to random graphs of the equivalent size, weighting, and node strength. Descriptive analysis of cumulative annual Takahe movement networks involved determination of node‐level characteristics, including centrality descriptors of relevance to disease modeling such as weighted measures of in degree (kiin), out degree (kiout), and betweenness (Bi). Key players were assigned according to the highest node measure of kiin, kiout, and Bi per network. Networks increased in size throughout the time frame considered. The network had some degree small‐world characteristics. Nodes with the highest cumulative tie weights connecting them were the captive breeding center, the Murchison Mountains and 2 offshore islands. The key player fluctuated between the captive breeding center and the Murchison Mountains. The cumulative networks identified the captive breeding center every year as the hub of the network until the final network in 2011. Likewise, the wild Murchison Mountains population was consistently the sink of the network. Other nodes, such as the offshore islands and the wildlife hospital, varied in importance over time. Common network descriptors and measures of centrality identified key locations for targeting disease surveillance. The visual representation of movements of animals in a population that this technique provides can aid decision makers when they evaluate translocation proposals or attempt to control a disease outbreak.Análisis de Redes de Poblaciones de Takahe Translocadas para Identificar Objetivos de Supervivencia a Enfermedades
Kidney donor risk index is a good prognostic tool for graft outcomes in deceased donor kidney transplantation with short, cold ischemic time
Authors: Han Miyeun , Jeong Jong Cheol , Koo Tai Yeon , Jeon Hee Jung , Kwon Hyuk Yong , Kim Yoon Jung , Ryu Hyun Jin , Ahn Curie , Yang Jaeseok 
Published: February 2014

AbstractBackgroundWe performed a retrospective cohort study to determine the prognostic value of standard criteria donor/expanded criteria donor (SCD/ECD) designation, with regard to one‐yr GFR and graft survival rate, in a region with short, cold ischemic time (CIT), and how this designation compares with the kidney donor risk index (KDRI) and zero‐time kidney biopsies.MethodsWe reviewed 362 cases of deceased donor kidney transplantation (DDKT). Donor kidneys were classified as SCD or ECD. They were also assessed by the KDRI. Zero‐time kidney biopsy was performed in 196 patients, and histologic score was assessed.ResultsMedian follow‐up duration was 46 months. Forty‐two cases (11.6%) used ECD kidneys. The mean CIT was only 4.9 ± 2.7 h. Graft survival rates were not significantly different between ECD and SCD groups. The KDRI showed the best correlation with one‐yr estimations of glomerular filtration rate (eGFR) (R2 = 0.230, p < 0.001), and higher KDRI was associated with a higher risk of graft failure (hazard ratio 2.63, 95% confidence interval 1.01–6.87). However, higher histologic score was not associated with a higher risk of graft failure.ConclusionKDRI has greater predictive value for short‐term outcomes in DDKT with short CIT than the SCD/ECD designation or pathology.