bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of variance components for carcass traits in Japanese Black cattle using 50K SNP genotype data
Authors: Watanabe Toshio , Matsuda Hirokazu , Arakawa Aisaku , Yamada Takahisa , Iwaisaki Hiroaki , Nishimura Shota , Sugimoto Yoshikazu 
Published: May 2013

AbstractGenomic selection using high‐density single nucleotide polymorphism (SNP) genotype data may accelerate genetic improvements in livestock animals. In this study, we attempted to estimate the variance components of six carcass traits in fattened Japanese Black steers using SNP genotype data. Six hundred and seventy‐three steers were genotyped using an Illumina Bovine SNP50 BeadChip and phenotyped for cold carcass weight, ribeye area, rib thickness, subcutaneous fat thickness, estimated yield percent and marbling score. Additive polygenic variance and the variance attributable to a set of SNPs that had statistically significant effects on the trait were estimated via Gibbs sampling with two models: (i) a model with the chosen SNPs and the additive polygenic effects; and (ii) a model with the polygenic effects alone. The proportion of the estimated variance attributable to the SNPs became higher as the number of SNP effects that fit increased. High correlations between breeding values estimated with the model containing the polygenic effect alone and those estimated by chosen SNPs were obtained. No fraction of the total genetic variance was explained by SNPs associated with the trait at P ≥ 0.1. Our results suggest that for the carcass traits of Japanese Black cattle, a maximum of half of the total additive genetic variance may be explained by SNPs between 100 several tens to several 100s.
A survey of fermentation products and bacterial communities in corn silage produced in a bunker silo in China
Authors: Wang Chao , Han Hongyan , Gu Xueying , Yu Zhu , Nishino Naoki 
Published: May 2013

AbstractTo evaluate the current practice of corn silage management in China, samples of bunker‐made silage were collected from 14 farms within a 500‐km radius of Beijing for the analysis of fermentation products and bacterial communities. Mean values for dry matter (DM) content were as low as 250 g/kg in both corn stover (St) and whole crop corn (Wc) silages, and pH values averaged 4.48 and 3.73, respectively. Only three of the 14 silages exhibited a lactic‐to‐acetic acid ratio > 1.0, indicating that the presence of acetic acid was predominant in fermentation. Although 1,2‐propanediol content was marginal in most cases (< 5.0 g/kg dry matter (DM)), two Wc silages had 1,2‐propanediol levels > 25 g/kg DM. In contrast, 3 St silages had large amounts (> 10 g/kg DM) of butyric acid, and two of the three butyrate silages also had high concentrations of 1‐propanol. Denaturing gradient gel electrophoresis analysis demonstrated that the bacterial community appeared similar in 10 out of the 14 silage samples. Bands indicating Lactobacillus buchneri, L. acetotolerans and Acetobacter pasteurianus were found in both the St and Wc silages, accounting for the high acetic acid content found across silage samples.
Intravenous Lipid Emulsion Entraps Amitriptyline into Plasma and Can Lower its Brain Concentration – An Experimental Intoxication Study in Pigs
Authors: Heinonen Juho A. , Litonius Erik , Backman Janne T. , Neuvonen Pertti J. , Rosenberg Per H. 
Published: May 2013

AbstractIntravenous lipid emulsion has been suggested as treatment for severe intoxications caused by lipophilic drugs, including tricyclic antidepressants. We investigated the effect of lipid infusion on plasma and tissue concentrations of amitriptyline and haemodynamic recovery, when lipid was given after amitriptyline distribution into well‐perfused organs. Twenty anaesthetized pigs received amitriptyline intravenously 10 mg/kg for 15 min. Thirty minutes later, in random fashion, 20% Intralipid® (Lipid group) or Ringer's acetate (Control group) was infused 1.5 ml/kg for 1 min. followed by 0.25 ml/kg/min. for 29 min. Arterial and venous plasma amitriptyline concentrations and haemodynamics were followed till 75 min. after amitriptyline infusion. Then, frontal brain and heart apex samples were taken for amitriptyline measurements. Arterial plasma total amitriptyline concentrations were higher in the Lipid than in the Control group (p < 0.03) from 20 min. on after the start of the treatment infusions. Lipid emulsion reduced brain amitriptyline concentration by 25% (p = 0.038) and amitriptyline concentration ratios brain/arterial plasma (p = 0.016) and heart/arterial plasma (p = 0.011). There were no differences in ECG parameters and no severe cardiac arrhythmias occurred. Two pigs developed severe hypotension during the lipid infusion and were given adrenaline. In conclusion, lipid infusion, given not earlier than after an initial amitriptyline tissue distribution, was able to entrap amitriptyline back into plasma from brain and possibly from other highly perfused, lipid‐rich tissues. In spite of the entrapment, there was no difference in haemodynamics between the groups.
Histamine H3 receptors, the complex interaction with dopamine and its implications for addiction
Authors: Ellenbroek B A 
Published: May 2013

Histamine H3 receptors are best known as presynaptic receptors inhibiting the release of histamine, as well as other neurotransmitters including acetylcholine and dopamine. However, in the dorsal and ventral striatum, the vast majority of H3 receptors are actually located postsynaptically on medium sized spiny output neurons. These cells also contain large numbers of dopamine (D1 and D2) receptors and it has been shown that H3 receptors form heterodimers with both D1 and D2 receptors. Thus, the anatomical localization of H3 receptors suggests a complex interaction that could both enhance and inhibit dopaminergic neurotransmission. Dopamine, especially within the striatal complex, plays a crucial role in the development of addiction, both in the initial reinforcing effects of drugs of abuse, as well as in maintenance, relapse and reinstatement of drug taking behaviour. It is, therefore, conceivable that H3 receptors can moderate the development and maintenance of drug addiction. In the present review, we appraise the current literature on the involvement of H3 receptors in drug addiction and try to explain these data within a theoretical framework, as well as provide suggestions for further research.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
O‐GlcNAcylation and p50/p105 binding of c‐Rel are dynamically regulated by LPS and glucosamine in BV2 microglia cells
Authors: Hwang So‐Young , Hwang Ji‐Sun , Kim Song‐Yi , Han Inn‐Oc 
Published: May 2013

Background and PurposePreviously, we demonstrated that glucosamine (GlcN) exerts a suppressive effect on LPS‐induced inducible NOS (iNOS) through the inhibition of NF‐κB activation in BV2 mouse microglial cells. The purpose of the present study was to examine the mechanisms by which GlcN inhibits NF‐κB activation.Experimental ApproachBV2 cells were stimulated with LPS with or without GlcN. NF‐κB/c‐Rel activities were studied by EMSA, nuclear translocation, reporter assay or chromatin immunoprecipitation. Wheat germ agglutinin precipitation or galactosyltransferase assay were used to measure O‐linked N‐acetylglucosamine (O‐GlcNAc) modification (O‐GlcNAcylation) of c‐Rel. Protein‐protein interactions were examined by co‐immunoprecipitation.Key ResultsLPS stimulated the activation of c‐Rel, increased the O‐GlcNAcylation of c‐Rel and enhanced the binding of c‐Rel to the NF‐κB site in the iNOS promoter; GlcN attenuated these effects of LPS. O‐GlcNAcylation of both nuclear and cytosolic forms of c‐Rel was increased by LPS and reduced by GlcN. LPS increased the interaction of c‐Rel with O‐GlcNAc transferase (OGT) and p50/p105, and GlcN suppressed these interactions. Knockdown of OGT reduced the c‐Rel O‐GlcNAcylation and c‐Rel–p50 interaction in response to LPS, but did not affect either the binding of c‐Rel to the iNOS promoter or the transcriptional activity of c‐Rel.Conclusions and ImplicationsIn BV2 microglial cells, the anti‐inflammatory effect of GlcN is mediated by prevention of the prolonged activation of transcription factors, c‐Rel and NF‐κB. Further clarification of the mechanism by which GlcN exerts this effect will facilitate the development of pharmacological strategies for preventing excessive NO formation when targeting inflammatory diseases of the periphery or CNS.
Activation of NF‐κB after chronic ethanol intake and haemorrhagic shock/resuscitation in mice
Authors: Maraslioglu M , Weber R , Korff S , Blattner C , Nauck C , Henrich D , Jobin C , Marzi I , Lehnert M 
Published: May 2013

Background and PurposeChronic ethanol abuse and haemorrhagic shock are major causes of global mortality and, separately, induce profound hepato‐ and immune‐toxic effects via activation of NF‐κB. Here, we assessed the effects of chronic ethanol intake upon the pathophysiological derangements after haemorrhagic shock with subsequent resuscitation (H/R), with particular attention to the contribution of NF‐κB.Experimental ApproachTransgenic NF‐κBEGFP mice, expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF‐κB cis‐elements were fed a Lieber‐DeCarli diet containing ethanol (EtOH‐diet) or an isocaloric control diet for 4 weeks and were then pairwise subjected to H/R. Liver tissues and peripheral blood were sampled at 2 or 24 h after H/R. Cytokines in blood and tissue and leukocyte activation (as CD11b expression) were measured, along with EGFP as a marker of NF‐κB activation.Key ResultsThe EtOH‐diet increased mortality at 24 h after H/R and elevated liver injury, associated with an up‐regulation of NF‐κB‐dependent genes and IL‐6 release; it also increased production of NF‐κB‐driven intercellular adhesion molecule 1 (ICAM‐1) and EGFP in liver tissue. At 2h after the H/R procedure in ethanol‐fed mice we observed the highest proportion of NF‐κB activated non‐parenchymal cells and an NF‐κB‐dependent increase in polymorphonuclear leukocyte CD11b expression.Conclusions and ImplicationsThe EtOH‐diet exacerbated liver injury after H/R, accompanying an overwhelming hepatic and systemic immune response. Our findings contribute to evidence implicating NF‐κB as a key player in the orchestration of the immune response in haemorrhagic shock patients with a history of chronic ethanol abuse.
Enhanced endothelin receptor type B‐mediated vasodilation and underlying [Ca2+]i in mesenteric microvessels of pregnant rats
Authors: Mazzuca Marc Q , Dang Yiping , Khalil Raouf A 
Published: May 2013

Background and PurposeNormal pregnancy is associated with decreased vascular resistance and increased release of vasodilators. Endothelin‐1 (ET‐1) causes vasoconstriction via endothelin receptor type A (ETAR), but could activate ETBR in the endothelium and release vasodilator substances. However, the roles of ETBR in the regulation of vascular function during pregnancy and the vascular mediators involved are unclear.Experimental ApproachPressurized mesenteric microvessels from pregnant and virgin Sprague–Dawley rats were loaded with fura‐2/AM for simultaneous measurement of diameter and [Ca2+]i.Key ResultsHigh KCl (51 mM) and phenylephrine (PHE) caused increases in vasoconstriction and [Ca2+]i that were similar in pregnant and virgin rats. ET‐1 caused vasoconstriction that was less in pregnant than virgin rats, with small increases in [Ca2+]i. Pretreatment with the ETBR antagonist BQ‐788 caused greater enhancement of ET‐1‐induced vasoconstriction in pregnant rats. ACh caused endothelium‐dependent relaxation and decreased [Ca2+]i, and was more potent in pregnant than in virgin rats. ET‐1 + ETAR antagonist BQ‐123, and the ETBR agonists sarafotoxin 6c (S6c) and IRL‐1620 caused greater vasodilation in pregnant than in virgin rats with no changes in [Ca2+]i, suggesting up‐regulated ETBR‐mediated relaxation pathways. ACh‐, S6c‐ and IRL‐1620‐induced relaxation was reduced by the NO synthase inhibitor Nω‐nitro‐l‐arginine methyl ester, and abolished by tetraethylammonium or endothelium removal. Western blots revealed greater amount of ETBR in intact microvessels of pregnant than virgin rats, but reduced levels in endothelium‐denuded microvessels, supporting a role of endothelial ETBR.Conclusions and ImplicationsThe enhanced ETBR‐mediated microvascular relaxation may contribute to the decreased vasoconstriction and vascular resistance during pregnancy.
Quercetin and allopurinol reduce liver thioredoxin‐interacting protein to alleviate inflammation and lipid accumulation in diabetic rats
Authors: Wang Wei , Wang Chuang , Ding Xiao‐Qin , Pan Ying , Gu Ting‐Ting , Wang Ming‐Xing , Liu Yang‐Liu , Wang Fu‐Meng , Wang Shui‐Juan , Kong Ling‐Dong 
Published: May 2013

Background and PurposeThioredoxin‐interacting protein (TXNIP), a regulator of cellular oxidative stress, has been associated with activation of NOD‐like receptor 3 (NLRP3) inflammasome, inflammation and lipid metabolism, suggesting it has a role in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD) in diabetes. In this study we investigated whether TXNIP is involved in type 1 diabetes‐associated NAFLD and whether antioxidants, quercetin and allopurinol, alleviate NAFLD by targeting TXNIP.Experimental ApproachDiabetes was induced in male Sprague‐Dawley rats by a single i.p. injection of 55 mg·kg−1 streptozotocin. Quercetin and allopurinol were given p.o. to diabetic rats for 7 weeks. Hepatic function, oxidative stress, inflammation and lipid levels were determined. Rat BRL‐3A and human HepG2 cells were exposed to high glucose (30 mM) in the presence and absence of antioxidants, TXNIP siRNA transfection or caspase‐1 inhibitor, Ac‐YVAD‐CMK.Key ResultsQuercetin and allopurinol significantly inhibited the TXNIP overexpression, activation of NLRP3 inflammasome, down‐regulation of PPARα and up‐regulation of sterol regulatory element binding protein‐1c (SREBP‐1c), SREBP‐2, fatty acid synthase and liver X receptor α, as well as elevation of ROS and IL‐1β in diabetic rat liver. These effects were confirmed in hepatocytes in vitro and it was further shown that TXNIP down‐regulation contributed to the suppression of NLRP3 inflammasome activation, inflammation and changes in PPARα and SREBPs.Conclusions and ImplicationsInhibition of hepatic TXNIP by quercetin and allopurinol contributes to the reduction in liver inflammation and lipid accumulation under hyperglycaemic conditions. The targeting of hepatic TXNIP by quercetin and allopurinol may have therapeutic implications for prevention of type 1 diabetes‐associated NAFLD.
Mechanistic analysis of the function of agonists and allosteric modulators: reconciling two‐state and operational models
Authors: Roche David , Gil Debora , Giraldo Jesús 
Published: May 2013

Two‐state and operational models of both agonism and allosterism are compared to identify and characterize common pharmacological parameters. To account for the receptor‐dependent basal response, constitutive receptor activity is considered in the operational models. By arranging two‐state models as the fraction of active receptors and operational models as the fractional response relative to the maximum effect of the system, a one‐by‐one correspondence between parameters is found. The comparative analysis allows a better understanding of complex allosteric interactions. In particular, the inclusion of constitutive receptor activity in the operational model of allosterism allows the characterization of modulators able to lower the basal response of the system; that is, allosteric modulators with negative intrinsic efficacy. Theoretical simulations and overall goodness of fit of the models to simulated data suggest that it is feasible to apply the models to experimental data and constitute one step forward in receptor theory formalism.Linked ArticlesAnother recent review on allosteric modulation can be found at:Kenakin, T (2013). New concepts in pharmacological efficacy at 7TM receptors: IUPHAR Review 2. British Journal of Pharmacology 168: 554–575. doi: 10.1111/j.1476‐5381.2012.02223.xAnd in this issue of BJP there is an article on a new allosteric modulator:Newman AS, Batis N, Grafton G, Caputo F, Brady CA, Lambert J, Peters JA, Gordon J, Brain KL, Powell AD and Barnes NM (2013). 5‐Chloroindole: a potent allosteric modulator of the 5‐HT3 receptor. British Journal of Pharmacology 169: 1228–1238. doi: 10.1111/bph.12213
Functional interaction between pre‐synaptic α6β2‐containing nicotinic and adenosine A2A receptors in the control of dopamine release in the rat striatum
Authors: Garção P , Szabó E C , Wopereis S , Castro A A , Tomé Â R , Prediger R D , Cunha R A , Agostinho P , Köfalvi A 
Published: May 2013

Background and PurposePre‐synaptic nicotinic ACh receptors (nAChRs) and adenosine A2A receptors (A2ARs) are involved in the control of dopamine release and are putative therapeutic targets in Parkinson's disease and addiction. Since A2ARs have been reported to interact with nAChRs, here we aimed at mapping the possible functional interaction between A2ARs and nAChRs in rat striatal dopaminergic terminals.Experimental ApproachWe pharmacologically characterized the release of dopamine and defined the localization of nAChR subunits in rat striatal nerve terminals in vitro and carried out locomotor behavioural sensitization in rats in vivo.Key ResultsIn striatal nerve terminals, the selective A2AR agonist CGS21680 inhibited, while the A2AR antagonist ZM241385 potentiated the nicotine‐stimulated [3H]dopamine ([3H]DA) release. Upon blockade of the α6 subunit‐containing nAChRs, the remaining nicotine‐stimulated [3H]DA release was no longer modulated by A2AR ligands. In the locomotor sensitization experiments, nicotine enhanced the locomotor activity on day 7 of repeated nicotine injection, an effect that no longer persisted after 1 week of drug withdrawal. Notably, ZM241385‐injected rats developed locomotor sensitization to nicotine already on day 2, which remained persistent upon nicotine withdrawal.Conclusions and ImplicationsThese results provide the first evidence for a functional interaction between nicotinic and adenosine A2AR in striatal dopaminergic terminals, with likely therapeutic consequences for smoking, Parkinson's disease and other dopaminergic disorders.
Profiling of histamine H4 receptor agonists in native human monocytes
Authors: Gschwandtner M , Koether B , Werfel T , Stark H , Gutzmer R 
Published: May 2013

Background and PurposeSince the identification of the histamine H4 receptor, several ligands activating this receptor have been described and more compounds are in development. These ligands are well characterized in pharmacological assays, including radioligand competition binding studies, GTPγS and GTPase assays. In most cases, these experiments are performed in transfected cell lines, expressing unnaturally high levels of target receptors and G‐protein signalling components. In this study we investigated the specific properties of H4 receptor ligands in native cells.Experimental ApproachHistamine and five different H4 receptor agonists – 4‐methylhistamine, UR‐PI376, clobenpropit, VUF8430 and ST‐1006 – were characterized in freshly isolated human monocytes. The ligands (10 nM–10 μM) were tested as inhibitors of IL‐12p70 secretion from human monocytes and the effects of the H2 receptor antagonist ranitidine and the H4 receptor antagonist JNJ7777120 on their action was investigated.Key ResultsHistamine and all the tested agonists reduced IL‐12p70 secretion into monocyte supernatants by 40–70%. The potencies varied with pEC50 values ranging from 5.7 to 6.9, depending on the agonist used. All potencies were lower than those determined in the original investigations of the compounds. Pretreatment of monocytes with H2 or H4 receptor antagonists showed that some H4 receptor ligands also had low activity at the H2 receptor.Conclusions and ImplicationsOur study demonstrates discrepancies between the potencies obtained from assays in transfected cell lines and assays in native human cells, indicating the importance of evaluating H4 receptor ligands in native cells.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
Death receptors as targets in cancer
Authors: Micheau O , Shirley S , Dufour F 
Published: May 2013

Anti‐tumour therapies based on the use pro‐apoptotic receptor agonists, including TNF‐related apoptosis‐inducing ligand (TRAIL) or monoclonal antibodies targeting TRAIL‐R1 or TRAIL‐R2, have been disappointing so far, despite clear evidence of clinical activity and lack of adverse events for the vast majority of these compounds, whether combined or not with conventional or targeted anti‐cancer therapies. This brief review aims at discussing the possible reasons for the lack of apparent success of these therapeutic approaches and at providing hints in order to rationally design optimal protocols based on our current understanding of TRAIL signalling regulation or resistance for future clinical trials.Linked ArticlesThis article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue‐8
Reading Angles in Maps
Authors: Izard Véronique , O'Donnell Evan , Spelke Elizabeth S. 
Published: May 2013

Preschool children can navigate by simple geometric maps of the environment, but the nature of the geometric relations they use in map reading remains unclear. Here, children were tested specifically on their sensitivity to angle. Forty‐eight children (age 47:15–53:30 months) were presented with fragments of geometric maps, in which angle sections appeared without any relevant length or distance information. Children were able to read these map fragments and compare two‐dimensional to three‐dimensional angles. However, this ability appeared both variable and fragile among the youngest children of the sample. These findings suggest that 4‐year‐old children begin to form an abstract concept of angle that applies both to two‐dimsional and three‐dimensional displays and that serves to interpret novel spatial symbols.