bluuebunny/crossref_metadata_2025_split huggingface dataset:
8‐BuS‐ATP derivatives as specific NTPDase1 inhibitors
Authors: Lecka Joanna , Gillerman Irina , Fausther Michel , Salem Mabrouka , Munkonda Mercedes N , Brosseau Jean‐Philippe , Cadot Christine , Martín‐Satué Mireia , d'Orléans‐Juste Pedro , Rousseau Éric , Poirier Donald , Künzli Beat , Fischer Bilha , Sévigny Jean 
Published: February 2013

Background and PurposeEctonucleotidases control extracellular nucleotide levels and consequently, their (patho)physiological responses. Among these enzymes, nucleoside triphosphate diphosphohydrolase‐1 (NTPDase1), −2, −3 and −8 are the major ectonucleotidases responsible for nucleotide hydrolysis at the cell surface under physiological conditions, and NTPDase1 is predominantly located at the surface of vascular endothelial cells and leukocytes. Efficacious inhibitors of NTPDase1 are required to modulate responses induced by nucleotides in a number of pathological situations such as thrombosis, inflammation and cancer.Experimental ApproachHere, we present the synthesis and enzymatic characterization of five 8‐BuS‐adenine nucleotide derivatives as potent and selective inhibitors of NTPDase1.Key ResultsThe compounds 8‐BuS‐AMP, 8‐BuS‐ADP and 8‐BuS‐ATP inhibit recombinant human and mouse NTPDase1 by mixed type inhibition, predominantly competitive with Ki values <1 μM. In contrast to 8‐BuS‐ATP which could be hydrolyzed by other NTPDases, the other BuS derivatives were resistant to hydrolysis by either NTPDase1, −2, −3 or −8. 8‐BuS‐AMP and 8‐BuS‐ADP were the most potent and selective inhibitors of NTPDase1 expressed in human umbilical vein endothelial cells as well as in situ in human and mouse tissues. As expected, as a result of their inhibition of recombinant human NTPDase1, 8‐BuS‐AMP and 8‐BuS‐ADP impaired the ability of this enzyme to block platelet aggregation. Importantly, neither of these two inhibitors triggered platelet aggregation nor prevented ADP‐induced platelet aggregation, in support of their inactivity towards P2Y1 and P2Y12 receptors.Conclusions and ImplicationsThe 8‐BuS‐AMP and 8‐BuS‐ADP have therefore potential to serve as drugs for the treatment of pathologies regulated by NTPDase1.
Therapeutic potential of histamine H4 receptor agonists in triple‐negative human breast cancer experimental model
Authors: Martinel Lamas Diego J , Croci Maximo , Carabajal Eliana , Crescenti Ernesto J V , Sambuco Lorena , Massari Noelia A , Bergoc Rosa M , Rivera Elena S , Medina Vanina A 
Published: February 2013

Background and PurposeThe presence of the histamine H4 receptor (H4R) was previously reported in benign and malignant lesions and cell lines derived from the human mammary gland. The aim of this work was to evaluate the effects of H4R ligands on the survival, tumour growth rate and metastatic capacity of breast cancer in an experimental model.Experimental ApproachXenograft tumours of the highly invasive human breast cancer cell line MDA‐MB‐231 were established in immune deficient nude mice. The following H4R agonists were employed: histamine (5 mg kg−1), clozapine (1 mg kg−1) and the experimental compound JNJ28610244 (10 mg kg−1).ResultsData indicate that developed tumours were highly undifferentiated, expressed H4R and exhibited high levels of histamine content and proliferation marker (PCNA) while displaying low apoptosis. Mice of the untreated group displayed a median survival of 60 days and a tumour doubling time of 7.4 ± 0.6 days. A significant decrease in tumour growth evidenced by an augment of the tumour doubling time was observed in the H4R agonist groups (13.1 ± 1.2, P < 0.01 in histamine group; 15.1 ± 1.1, P < 0.001 in clozapine group; 10.8 ± 0.7, P < 0.01 in JNJ28610244 group). This effect was associated with a decrease in the PCNA expression levels, and also reduced intratumoural vessels in histamine and clozapine treated mice. Histamine significantly increased median survival (78 days; Log rank Mantel‐Cox Test, P = 0.0025; Gehan‐Breslow‐Wilcoxon Test, P = 0.0158) and tumoural apoptosis.Conclusions and ImplicationsHistamine through the H4R exhibits a crucial role in tumour progression. Therefore, H4R ligands offer a novel therapeutic potential as adjuvants for breast cancer treatment.Linked ArticlesThis article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/
10.1111/bph.2013.170.issue‐1
Rational Discovery of Dengue Type 2 Non‐Competitive Inhibitors
Authors: Heh Choon H. , Othman Rozana , Buckle Michael J. C. , Sharifuddin Yusrizam , Yusof Rohana , Rahman Noorsaadah A. 
Published: February 2013

Various works have been carried out in developing therapeutics against dengue. However, to date, no effective vaccine or anti‐dengue agent has yet been discovered. The development of protease inhibitors is considered as a promising option, but most previous works have involved competitive inhibition. In this study, we focused on rational discovery of potential anti‐dengue agents based on non‐competitive inhibition of DEN‐2 NS2B/NS3 protease. A homology model of the DEN‐2 NS2B/NS3 protease (using West Nile Virus NS2B/NS3 protease complex, 2FP7, as the template) was used as the target, and pinostrobin, a flavanone, was used as the standard ligand. Virtual screening was performed involving a total of 13 341 small compounds, with the backbone structures of chalcone, flavanone, and flavone, available in the ZINC database. Ranking of the resulting compounds yielded compounds with higher binding affinities compared with the standard ligand. Inhibition assay of the selected top‐ranking compounds against DEN‐2 NS2B/NS3 proteolytic activity resulted in significantly better inhibition compared with the standard and correlated well with in silico results. In conclusion, via this rational discovery technique, better inhibitors were identified. This method can be used in further work to discover lead compounds for anti‐dengue agents.
Incidence rate and clinical features of hyperthyroidism in a long‐term iodine sufficient area of Sweden (Gothenburg) 2003–2005
Authors: Nyström Helena Filipsson , Jansson Svante , Berg Gertrud 
Published: February 2013

SummaryObjectivesTo study hyperthyroidism in long‐term iodine sufficiency (IS), as iodine supply affects its occurrence.DesignProspective descriptive study.PatientsIn 2003–2005, all referred cases of subclinical (SH) and overt hyperthyroidism (OH) were registered at diagnosis from a population (n = 631 239) in Gothenburg, Sweden.MeasurementsInformation on age, gender, smoking, thyroid associated ophthalmopathy (TAO), thyroid hormones and TSH receptor antibodies (TRab) was collected. Incidences were calculated. SH and OH cases with Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA) were compared. In GD, TRab+ and TRab− cases and patients with (TAO+) and without TAO (TAO−) were compared.ResultsThe total incidence (n/100 000/year) of hyperthyroidism was 27·6; OH 23·8; SH 3·8; GD 21·4; TMNG 4·3; and STA 1·8. SH was more common among TMNG (40·2%) and STA (45·7%) than in GD (5·9%). SH‐GD patients were older, more often smokers and had lower TRab levels than OH‐GD patients. FreeT4 and T3 levels in GD were higher than in TMNG and STA. FreeT4, T3 and TRab decreased with age in patients with GD, P < 0·0001. TRab‐ patients had lower T3 than TRab+ patients, P < 0·001. TRab was positively correlated to FreeT4, P < 0·0001. TAO occured in 20% of patients with GD. TAO+ patients were younger than TAO‐ patients. Smokers did not have more TAO.ConclusionThe total incidence of hyperthyroidism was low. GD dominated with an age‐related decline of thyroid hormones and TRab levels. The spectrum of hyperthyroidism in this long‐term IS area may represent the future situation for countries with shorter history of IS.
Conometric retention for complete fixed prosthesis supported by four implants: 2‐years prospective study
Authors: Bressan Eriberto , Lops Diego 
Published: February 2013

AbstractObjectiveThe aim of this study was to verify the reliability of a conometric system for a fixed retention of complete prostheses (CPs) on four implants followed for 2 years.Material and methodsTwenty‐five patients received four implants and only one CPs for a total of 100 implants followed. Each prosthesis was supported by four implants. An immediate loading surgical protocol was used. The CPs were provided to be fixed to conometric abutments without prostheses removal by the patients, to test this retention for a fixed instead of a removable rehabilitation. Clinical and radiographical parameters were assessed at the yearly follow‐up visit. A follow‐up of 2 years was observed for each patient. Moreover, biological and technical complications were recorded. Changes overtime of clinical and radiographic parameters were analyzed as well as the satisfaction degree for each patient.ResultsNo patient was classified as “dropout.” The following results were observed after 2 years of follow‐up: all the implants supporting the 25 CPs completed the follow‐up examination. No implant, reconstruction, and abutment failure were recorded; therefore, the prosthetic survival was 100% for all the abutments and restorations. No significant differences in biological indexes were observed when compared with the baseline. No significant change of the mean marginal bone level (MBL) was found between the baseline and the last follow‐up. No loss of retention was recorded for the CPs. No technical complications referred to abutments and frameworks were observed: a prosthetic survival rate of 100% can be recorded. Mucositis was recorded for two implants and successfully treated with interceptive supportive therapy.No significant differences (P < 0.05) were found between plaque index and MBi parameters at baseline and after 2 years of function. Similar results were recorded for the mean probing pocket depth Index at baseline (1.2 mm with SD of 0.3 mm) and after 2 years of function (1.2 mm with SD of 0.2 mm).ConclusionsThe present implant‐supported conometric retention system can be used to give a fixed retention to a CPs supported by four implants immediately loaded. Furthermore, costs reduction and simplified treatment procedures were provided by such a clinical approach.
Marginal bone loss around implants placed in maxillary native bone or grafted sinuses: a retrospective cohort study
Authors: Galindo‐Moreno P. , Fernández‐Jiménez A. , Avila‐Ortiz G. , Silvestre F.J. , Hernández‐Cortés P. , Wang H.L. 
Published: February 2013

AbstractObjectivesTo assess differences in marginal bone loss around implants placed in maxillary pristine bone and implants placed following maxillary sinus augmentation over a period of 3 years after functional loading.Material and methodsTwo cohorts of subjects (Group 1: Subjects who received sinus augmentation with simultaneous implant placement; Group 2: Subjects who underwent conventional implant placement in posterior maxillary pristine bone) were included in this retrospective study. Radiographic marginal bone loss was measured around one implant per patient on digitized panoramic radiographs that were obtained at the time of prosthesis delivery (baseline) and 12, 24, and 36 months later. The influence of age, gender, smoking habits, history of periodontal disease, and type of prosthetic connection (internal or external) on marginal bone loss was analyzed in function of the type of osseous support (previously grafted or pristine).ResultsA total of 105 subjects were included in this study. Cumulative radiographic marginal bone loss ranged from 0 mm to 3.9 mm after 36 months of functional loading. There were statistically significant differences in marginal bone loss between implants placed in grafted and pristine bone at the 12‐month assessment, but not in the subsequent progression rate. External prosthetic connection, smoking, and history of periodontitis negatively influenced peri‐implant bone maintenance, regardless of the type of osseous substrate.ConclusionsImplants placed in sites that received maxillary sinus augmentation exhibited more marginal bone loss than implants placed in pristine bone, although marginal bone loss mainly occurred during the first 12 months after functional loading. Implants with external implant connection were strongly associated with increased marginal bone loss overtime.
The LRRK2 R1628P Variant Plays a Protective Role in Han Chinese Population with Alzheimer's Disease
Authors: Li Hong‐Lei , Lu Shen‐Ji , Sun Yi‐Min , Guo Qi‐Hao , Sadovnick Adele Dessa , Wu Zhi‐Ying 
Published: February 2013

SummaryAimsAlzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent neurodegenerative disorders that may share some overlapping etiologies. Mutations within leucine‐rich repeat kinase 2 (LRRK2) have been reported to be responsible for PD, and the location of LRRK2 is within a linkage peak for sporadic AD (SAD). The aim of this study was to investigate two Asian‐specific LRRK2 variants, R1628P and G2385R, with the association of Han Chinese SAD.MethodsGenotyping of R1628P and G2385R was performed by PCR‐restriction fragment length polymorphism (RFLP) analysis in 390 patients with SAD and 545 unrelated age‐ and sex‐matched healthy controls.ResultsThe frequency of the C allele within R1628P was more than three times higher in control group (1.7%) than in patients with SAD (0.5%) (OR 0.264; 95% CI, 0.088–0.792, P = 0.018). After stratification by the presence of one or two apolipoprotein E ε4 alleles, the protective effect becomes stronger (ε44: OR 0.028; 95% CI, 0.003–0.303, P = 0.003; ε4: OR 0.104; 95% CI, 0.013–0.818, P = 0.031). However, no difference was found in G2385R variant.ConclusionOur study suggested that R1628P variant within LRRK2 plays a protective role in Han Chinese population with SAD and such effect has an interaction with the APOE genotype.
From “Special K” to “Special M”: The Evolution of the Recreational Use of Ketamine and Methoxetamine
Authors: Corazza Ornella , Assi Sulaf , Schifano Fabrizio 
Published: February 2013

SummaryThis article reviews the recreational use of ketamine (“Special K”; KET) and explores the recent diffusion of its new derivative methoxetamine (“Special M”; MXE). The literature search on the nonclinical/recreational use of KET and MXE was carried out in a range of medical databases. Considering the limitations of peer‐reviewed information, data were integrated with a qualitative assessment of a range of websites, drug fora, and other online resources including e‐newsgroups, chat rooms, mailing lists, e‐newsletters, and bulletin boards. The recreational use of KET has started since its discovery in 1962. This was due to its rapid onset, short duration of action, and peculiar psychotropic effects (“K‐hole”). The latter effect ranges from confusion to dissociation and depersonalization (near‐death experience). However, KET abuse is often associated with physical and psychological side effects, of which the worst is urological/bladder toxicity. Recently, MXE has emerged as a legal and “bladder‐friendly” KET alternative. MXE presents with the same dissociative effect of KET, but with slower onset and longer duration of action. However, MXE seems to be associated with worse side effects than KET, ranging from mood disturbances/suicidal attempts to acute cerebellar toxicity. After 50 years of its discovery, KET has led to the emergence of MXE. However, this latter derivative does not appear to be a safer alternative to KET itself.
A Zn isotope perspective on the rise of continents
Authors: Pons M.‐L. , Fujii T. , Rosing M. , Quitté G. , Télouk P. , Albarède F. 
Published: February 2013

AbstractZinc isotope abundances are fairly constant in igneous rocks and shales and are left unfractionated by hydrothermal processes at pH < 5.5. For that reason, Zn isotopes in sediments can be used to trace the changing chemistry of the hydrosphere. Here, we report Zn isotope compositions in Fe oxides from banded iron formations (BIFs) and iron formations of different ages. Zinc from early Archean samples is isotopically indistinguishable from the igneous average (δ66Zn ~0.3‰). At 2.9–2.7 Ga, δ66Zn becomes isotopically light (δ66Zn < 0‰) and then bounces back to values >1‰ during the ~2.35 Ga Great Oxygenation Event. By 1.8 Ga, BIF δ66Zn has settled to the modern value of FeMn nodules and encrustations (~0.9‰). The Zn cycle is largely controlled by two different mechanisms: Zn makes strong complexes with phosphates, and phosphates in turn are strongly adsorbed by Fe hydroxides. We therefore review the evidence that the surface geochemical cycles of Zn and P are closely related. The Zn isotope record echoes Sr isotope evidence, suggesting that erosion starts with the very large continental masses appearing at ~2.7 Ga. The lack of Zn fractionation in pre‐2.9 Ga BIFs is argued to reflect the paucity of permanent subaerial continental exposure and consequently the insignificant phosphate input to the oceans and the small output of biochemical sediments. We link the early decline of δ66Zn between 3.0 and 2.7 Ga with the low solubility of phosphate in alkaline groundwater. The development of photosynthetic activity at the surface of the newly exposed continents increased the oxygen level in the atmosphere, which in turn triggered acid drainage and stepped up P dissolution and liberation of heavy Zn into the runoff. Zinc isotopes provide a new perspective on the rise of continents, the volume of carbonates on continents, changing weathering conditions, and compositions of the ocean through time.
Variation of first‐order root traits across climatic gradients and evolutionary trends in geological time
Authors: Chen Weile , Zeng Hui , Eissenstat David M. , Guo Dali 
Published: February 2013

AbstractAimPlant roots are crucial for water and nutrient absorption, but large‐scale patterns and underlying mechanisms of root trait variation and evolution are poorly understood. Here we quantify the degree of variation in functional traits for the first‐order roots across large geographical scales and examine the potential mechanisms underlying these patterns.LocationChina.MethodsWe collected first‐order roots (stream‐based ordering system) and leaf samples of 65 tree species in six forests from subtropical to temperate zones and determined the key morphological, architectural and chemical traits.ResultsWe found wider variation in root morphology in the subtropical zone, where species with very thick and very thin first‐order roots coexisted, in contrast with narrower variation among species in the temperate zone. Inconsistent with the predictions of trait economics spectrum, root nitrogen concentration was uncorrelated with root morphology. Furthermore, average root diameter at the plant family level decreased markedly with their divergence time in both piecewise and phylogenetic independent contrast regression analyses.Main conclusionsHigher variation in root morphology in the subtropical zone appears to result from the coexistence of tree species with thick and thin roots, probably because of a more favourable water supply. Patterns of root evolution towards thinner roots were driven by both phylogeny and possible adaptation of newly diverged species to drier habitats from mid to late Cretaceous. Our findings reveal contrasting selection pressures at the root and leaf level in different climatic zones during plant evolution, and suggest that a single vector of variation linking morphology to resource acquisition or life span (‘trait economics’) remains elusive in roots.
Where lynx prevail, foxes will fail – limitation of a mesopredator in Eurasia
Authors: Pasanen‐Mortensen Marianne , Pyykönen Markku , Elmhagen Bodil 
Published: February 2013

AbstractAimClimate change and loss of apex predators can affect ecosystem structure and function through modified limitation processes. We investigated, on a continental scale, whether mesopredator abundance is limited from the top down by large predators, as predicted by the mesopredator release hypothesis, or by bottom‐up factors. The mesopredator in focus is the red fox Vulpes vulpes, a key predator in many ecosystems due to its strong effects on prey abundance.LocationEurope and northern Asia.MethodsData on red fox density were compiled from published papers and reports. For each site, we collated presence–absence data on large carnivores (Lynx lynx, Canis lupus, Canis aureus) and remote sensing data for factors potentially related to bottom‐up limitation (winter severity, summer temperature, human density, primary productivity, tree cover). The data were analysed through structural equation modelling.ResultsThe presence of lynx had a direct negative effect on red foxes, suppressing fox abundance. Also winter severity had a negative effect on red fox abundance, and in Eurasia as a whole this effect was partially mediated through lynx. Within the lynx distribution range, winter severity was the only bottom‐up factor significantly affecting red fox abundance. Outside the lynx distribution range, primary productivity, summer temperature and human density had a positive effect on red fox abundance.Main conclusionsOur results show that apex predators can limit mesopredator abundance on a continental scale, thus supporting the mesopredator release hypothesis. Winter severity also affected red fox abundance, partially due to an interaction between lynx and winter conditions. On the continental scale a complex network of processes operates with varying effects depending on mediation processes. Our results imply that apex predators can have an important effect on ecosystem structure by limiting mesopredator abundance, and we suggest that apex predators may dampen increases in mesopredator abundance driven by global warming.
Genetic similarity analysis within Pyropia yezoensis blades developed from both conchospores and blade archeospores using AFLP1
Authors: He Linwen , Zhu Jianyi , Lu Qinqin , Niu Jianfeng , Zhang Baoyu , Lin Apeng , Wang Guangce 
Published: February 2013

Pyropia yezoensis (Ueda) M. S. Hwang et H. G. Choi (previously called Porphyra yezoensis) is an economically important alga. The blades generated from conchospores are genetic chimeras, which are not suitable for genetic similarity analysis. In this study, two types of blades from a single filament of P. yezoensis sporophyte filament were obtained. One type, ConB, consisted of 40 blades that had germinated from conchospores. The other type, ArcB, consisted of 88 blades that had germinated from archeospores released from ConB. Both of them were analyzed by amplified fragment length polymorphism. The low genetic similarity levels for both conchospore‐germinated and archeospore‐germinated blades demonstrated that the conchcelis we used was cross‐fertilized. Furthermore, a higher polymorphic loci ratio (98.6%) was detected in ArcB than in ConB (80.7%), and the average genetic similarity of ArcB (average 0.61) was lower than that of ConB (average 0.71). These differences indicated that genetic analysis using ArcB gives more accurate results.