bluuebunny/crossref_metadata_2025_split huggingface dataset:
DHMEQ, a novel nuclear factor‐κB inhibitor, induces selective depletion of alloreactive or phytohaemagglutinin‐stimulated peripheral blood mononuclear cells, decreases production of T helper type 1 cytokines, and blocks maturation of dendritic cells
Authors: Nishioka Chie , Ikezoe Takayuki , Jing Yang , Umezawa Kazuo , Yokoyama Akihito 
Published: May 2008

SummaryDehydroxymethylepoxyquinomicin (DHMEQ), a novel nuclear factor κB (NF‐κB) inhibitor, has been shown to be active against variety types of solid tumours as well as haematological malignant cells. This study explored the anti‐inflammatory effects of DHMEQ in vitro. DHMEQ inhibited the proliferation of phytohaemagglutinin (PHA)‐stimulated or alloreactive peripheral blood mononuclear cells (PBMC) in mixed lymphocyte cultures as measured using a 3‐(4,5‐dimethylithiazol‐2‐yl)‐2,5‐diphenyl tetrazolium (MTT) assay. In contrast, DHMEQ did not affect the viability of resting PBMC. In addition, real‐time polymerase chain reaction showed that DHMEQ decreased PHA‐stimulated expression of T helper type 1 (Th1) cytokines, including interleukin‐2, interferon‐γ, and tumour necrosis factor α, in PBMC as well as Jurkat T‐lymphoblastic leukaemia cells, and also decreased levels of p65 isoforms of NF‐κB in the nucleus. Furthermore, we found that DHMEQ inhibited the endocytic capacity of dendritic cells (DCs) and down‐regulated the expression of cell surface antigen CD40, suggesting that DHMEQ blocked the maturation as well as the function of DCs. Taken together, the results suggest that DHMEQ may be useful for treatment of inflammatory diseases, including graft‐versus‐host disease after allogenic haematopoietic stem cell transplantation.
Functional characterization of the Arabidopsis ubiquitin‐specific protease gene family reveals specific role and redundancy of individual members in development
Authors: Liu Yanfen , Wang Feng , Zhang Huiyong , He Hang , Ma Ligeng , Deng Xing Wang 
Published: May 2008

SummaryUbiquitin‐specific proteases (UBPs) are a highly conserved family of proteins in eukaryotes, and play critical roles in protein de‐ubiquitination. Here we report a systematic genetic and expression profiling analysis of the UBP gene family in the Arabidopsis thaliana genome. Mutation analysis of 25 of the 27 member genes representing 13 of the 14 sub‐families of the UBP gene family revealed that single‐gene mutants of three genes in two sub‐families exhibit visible phenotypes. Two of these three genes belonging to the UBP15 sub‐family were selected for further characterization. The ubp15 mutants display narrower, serrated and flat rosette leaves, partially due to a defect in cell proliferation, as well as other phenotypes such as early flowering, weak apical dominance and reduced fertility, while the line over‐expressing UBP15 shows opposite phenotypes. We demonstrated that UPB15 has UBP activity in vitro, and that this biochemical activity is essential for its in vivo function. A genetic interaction analysis among members of this sub‐family revealed that UBP15 and UBP16, but not UBP17, have functional redundancy. Our data thus suggest that distinct UBPs, even within a closely related sub‐family, can function in different developmental pathways. Although there are clearly functional redundancies among related sub‐family members, those redundancies cannot be inferred simply based on the amino acid identity of the family members.
Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond
Authors: Pertwee Roger G. 
Published: May 2008

ABSTRACTA major finding—that (–)‐trans‐Δ9‐tetrahydrocannabinol (Δ9‐THC) is largely responsible for the psychotropic effects of cannabis—prompted research in the 1970s and 1980s that led to the discovery that this plant cannabinoid acts through at least two types of cannabinoid receptor, CB1and CB2, and that Δ9‐THC and other compounds that target either or both of these receptors as agonists or antagonists have important therapeutic applications. It also led to the discovery that mammalian tissues can themselves synthesize and release agonists for cannabinoid receptors, the first of these to be discovered being arachidonoylethanolamide (anandamide) and 2‐arachidonoylglycerol. These ‘endocannabinoids’ are released onto their receptors in a manner that appears to maintain homeostasis within the central nervous system and sometimes either to oppose or to mediate or exacerbate the unwanted effects of certain disorders. This review provides an overview of the pharmacology of cannabinoid receptors and their ligands. It also describes actual and potential clinical uses both for cannabinoid receptor agonists and antagonists and for compounds that affect the activation of cannabinoid receptors less directly, for example by inhibiting the enzymatic hydrolysis of endocannabinoids following their release.
The role of CB1 receptors in psychostimulant addiction
Authors: Wiskerke Joost , Pattij Tommy , Schoffelmeer Anton N.M. , De Vries Taco J. 
Published: May 2008

ABSTRACTRecent studies have implicated the endocannabinoid (eCB) system in the neuronal mechanisms underlying substance dependence. Here, we review results of studies using cannabinoid receptor subtype 1 (CB1) knockout mice as well as CB1 antagonists to elucidate the role of this neurotransmitter system in psychostimulant addiction. The overall picture is that CB1 receptors appear not to be involved in psychostimulant reward, nor in the development of dependence to such substances. In contrast, the eCB system appears to play a role in the persistence of psychostimulant addiction. In particular, CB1 receptors have been found to play a cardinal role in mediating reinstatement of previously extinguished drug‐seeking behavior upon re‐exposure to the drug or drug‐associated cues. The anatomical loci as well as the neuronal mechanisms of the relapse‐preventing effects of CB1 antagonists are still poorly understood, although interactions of the eCB system with afferent glutamatergic and possibly dopaminergic projections to the nucleus accumbens are most likely involved. In addition, CB1 receptors seem to modulate drug‐related memories, in line with the hypothesized role of the eCB system in memory‐related plasticity. Together, these findings suggest that modulators of the eCB system represent a promising novel type of therapy to treat drug addiction.
Blocking cannabinoid CB1receptors for the treatment of nicotine dependence: insights from pre‐clinical and clinical studies
Authors: Foll Bernard Le , Forget Benoit , Aubin Henri‐Jean , Goldberg Steven R. 
Published: May 2008

ABSTRACTTobacco use is one of the leading preventable causes of death in developed countries. Since existing medications are only partially effective in treating tobacco smokers, there is a great need for improved medications for smoking cessation. It has been recently proposed that cannabinoid CB1receptor antagonists represent a new class of therapeutic agents for drug dependence, and notably, nicotine dependence. Here, we will review current evidence supporting the use of this class of drugs for smoking cessation treatment. Pre‐clinical studies indicate that nicotine exposure produces changes in endocannabinoid content in the brain. In experimental animals, N‐piperidinyl‐5‐(4‐chlorophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methylpyrazole‐3‐carboxamide (rimonabant, SR141716) andN‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide (AM251), two cannabinoid CB1receptor antagonists, block nicotine self‐administration behavior, an effect that may be related to the blockade of the dopamine‐releasing effects of nicotine in the brain. Rimonabant also seems efficacious in decreasing the influence of nicotine‐associated stimuli over behavior, suggesting that it may act on two distinct neuronal pathways, those implicated in drug‐taking behavior and those involved in relapse phenomena. The utility of rimonabant has been evaluated in several clinical trials. It seems that rimonabant is an efficacious treatment for smoking cessation, although its efficacy does not exceed that of nicotine‐replacement therapy and its use may be limited by emotional side effects (nausea, anxiety and depression, mostly). Rimonabant also appears to decrease relapse rates in smokers. These findings indicate significant, but limited, utility of rimonabant for smoking cessation.
Temporal and Contextual Patterns of Killer Whale (Orcinus orca) Call Type Production
Authors: Foote Andrew D. , Osborne Richard W. , Rus Hoelzel A. 
Published: May 2008

AbstractFish‐eating killer whales Orcinus orca in the northeastern Pacific live in highly stable matrifocal social groups called pods. Each pod produces a repertoire of seven or more stereotyped call types. We compared the relative production of call types of free‐ranging killer whale pods over time and between social contexts. The relative production of call types by each pod during directional travel was distinct over a 27‐yr period; however, both temporal stability and pod distinctiveness were strongly influenced by a subset of dominant call types within the repertoire of each pod. Some call types within the repertoires contain biphonation (two overlapping independently modulated tones) and have a higher estimated active space than call types containing just one tone. In multi‐pod aggregations the relative production of the dominant call types of each pod decreased and the relative production of a subset of call types that are rarely recorded from single‐pod groupings increased. The majority of these contained biphonation. The data suggest a distinction between a subset of dominant call types that may function to identify the pod and a subset of less common call types including several call types containing biphonation that are more commonly produced during inter‐pod affiliations.
Multiplicative random regression model for heterogeneous variance adjustment in genetic evaluation for milk yield in Simmental
Authors: Lidauer M.H. , Emmerling R. , Mäntysaari E.A. 
Published: May 2008

SummaryA multiplicative random regression (M‐RRM) test‐day (TD) model was used to analyse daily milk yields from all available parities of German and Austrian Simmental dairy cattle. The method to account for heterogeneous variance (HV) was based on the multiplicative mixed model approach of Meuwissen. The variance model for the heterogeneity parameters included a fixed region × year × month × parity effect and a random herd × test‐month effect with a within‐herd first‐order autocorrelation between test‐months. Acceleration of variance model solutions after each multiplicative model cycle enabled fast convergence of adjustment factors and reduced total computing time significantly. Maximum Likelihood estimation of within‐strata residual variances was enhanced by inclusion of approximated information on loss in degrees of freedom due to estimation of location parameters. This improved heterogeneity estimates for very small herds. The multiplicative model was compared with a model that assumed homogeneous variance. Re‐estimated genetic variances, based on Mendelian sampling deviations, were homogeneous for the M‐RRM TD model but heterogeneous for the homogeneous random regression TD model. Accounting for HV had large effect on cow ranking but moderate effect on bull ranking.
Genetic diversity in Egyptian and Italian goat breeds measured with microsatellite polymorphism
Authors: Agha S.H. , Pilla F. , Galal S. , Shaat I. , D’Andrea M. , Reale S. , Abdelsalam A.Z.A. , Li M.H. 
Published: May 2008

SummarySeven microsatellite markers were used to study genetic diversity of three Egyptian (Egyptian Baladi, Barki and Zaraibi) and two Italian (Maltese and Montefalcone) goat breeds. The microsatellites showed a high polymorphic information content (PIC) of more than 0.5 in most of the locus–breed combinations and indicated that the loci were useful in assessing within‐ and between‐breed variability of domestic goat (Capra hircus). The expected heterozygosity of the breeds varied from 0.670 to 0.792. In the geographically wider distributed Egyptian Baladi breed there were indications for deviations from random breeding. Analysis of genetic distances and population structure grouped the three Egyptian goat breeds together, and separated them from the two Italian breeds. The studied Mediterranean breeds sampled from African and European populations seem to have differentiated from each other with only little genetic exchange between the geographically isolated populations.
Trends in genetic variance components during 30 years of hybrid maize breeding at the University of Hohenheim
Authors: Fischer S. , Möhring J. , Schön C. C. , Piepho H.‐P. , Klein D. , Schipprack W. , Utz H. F. , Melchinger A. E. , Reif J. C. 
Published: May 2008

AbstractThe ratio of variance due to specific vs. general combining ability (GCA) (σ2SCA:σ2GCA) is of central importance for predicting hybrid performance from GCA effects. The objectives of our study were to (1) analyse the changes in estimates of σ2GCA, σ2SCA and their ratio during 30 years of hybrid maize breeding and (2) compare the observed trends in genetic variances with those expected under a simple genetic model. We analysed multilocation yield trials based on the North Carolina Design II conducted in the maize breeding programme of the University of Hohenheim from 1975 to 2004 for grain yield (GY) and dry matter content (DMC). GY showed a significant (P < 0.05) annual increase of 0.17 Mg/ha, but no linear trend was found for DMC. Since the beginning of hybrid breeding at the University of Hohenheim, the sum of estimates of σ2GCA of the flint and dent heterotic groups were higher than the estimates of their σ2SCA. This predominance did not change with ongoing inter‐population improvement. Consequently, superior hybrids can be identified and selected mainly based on their prediction from GCA effects.
A model calculation approach towards the optimization of a standard scheme of seed‐parent line development in hybrid rye breeding
Authors: Tomerius A.‐M. , Miedaner T. , Geiger H. H. 
Published: May 2008

AbstractThe importance of hybrid rye (Secale cereale L.) breeding has steadily increased over the last decades. This paper presents results of model calculations aiming to optimize the number of candidates, testers to assess combining ability and test locations at each selection stage of a standard scheme of seed‐parent line development. Two variants of the scheme differing in the number of stages and the cycle length are investigated. Optimization criterion is the expected selection gain per year under the restriction of a fixed budget. Prediction of selection gain rests on quantitative–genetic and economic parameters estimated from breeders’ data. Optimization covers different genetical and economical situations. Results show that the optimum number of testers to assess combining ability depends on the relative amount of dominance variance. The efficiency of a breeding scheme strongly increases with decreasing cycle length. A larger budget should mainly be used to increase the number of candidates at all selection stages. Recommendations for practical breeding schemes are given. We conclude that model calculations are a valuable tool for the optimization of breeding schemes.
Inheritance of very high linoleic acid content and its relationship with nuclear male sterility in safflower
Authors: Hamdan Y. A. S. , Pérez‐Vich B. , Fernández‐Martínez J. M. , Velasco L. 
Published: May 2008

AbstractSafflower (Carthamus tinctorius L.) possesses the highest amount of linoleic acid among the 10 major vegetable oil crops of the world. Very high linoleic acid content is controlled by recessive alleles at a single locus Li. However, deviated segregations from the expected monogenic inheritance have been observed in crosses involving nuclear male‐sterile (NMS) lines. The present research was undertaken to study the inheritance of very high linoleic acid content in safflower and its relationship with nuclear male sterility. F1, F2, F3, BC1F1 and BC1F2 seed generations were evaluated in a cross between CR‐142 (a line with very high linoleic acid content, 88%) and CL1 (an NMS line with wild‐type linoleic acid content, 74%). The genetics of linoleic acid content in male‐sterile plants was determined by testcrossing with CR‐142. The results confirmed monogenic inheritance. The analysis of the F3 and BC1F2 to CL1 seed generations demonstrated a repulsion‐phase linkage between Li and Ms loci, the latter conferring the NMS trait. The recombination rate between Li and Ms was estimated to be 0.09.
Biphasic insulin aspart 30 in the treatment of elderly patients with type 2 diabetes: a subgroup analysis of the PRESENT Korea NovoMix®study
Authors: Jang H. C. , Lee S. R. , Vaz J. A. 
Published: May 2008

Aims:  To evaluate the efficacy, safety and treatment satisfaction with biphasic insulin aspart 30 (BIAsp30) in elderly patients with type 2 diabetes.Methods:  The Physicians’ Routine Evaluation of Safety and Efficacy of NovoMix®30 Therapy Korea study was a 6‐month, prospective, observational study. No study‐specific interventions were involved except the collection of data. All patients with type 2 diabetes not adequately controlled on their previous therapy, and who were prescribed BIAsp30 as monotherapy, or in combination with oral hypoglycaemic agents, were eligible for the study. This subgroup analysis was based on the outcomes in patients ≥65 years (n = 1720).Results:  BIAsp30 treatment was associated with significant mean reductions in haemoglobin A1c, fasting plasma glucose and post‐prandial plasma glucose levels of 1.2 ± 1.6%, 2.3 ± 3.5 mmol/l and 4.8 ± 5.3 mmol/l at 6 months (p < 0.0001 for all), from baseline levels of 9.1 ± 1.7%, 10.7 ± 3.4 mmol/l and 16.7 ± 5.0 mmol/l, respectively. The rate of hypoglycaemia declined from 3.02 to 1.31 episodes per patient year, between baseline and study end. The proportion of patients reporting adverse drug reactions was low (0.3 and 0.1% at 3 and 6 months, respectively). Body weight gain was mild at <0.1 kg at 3 months, and 0.3 kg at 6 months. As compared to the previous treatment, >80% of patients were rated as being either ‘very satisfied’ or ‘satisfied’ with BIAsp30 treatment.Conclusions:  In this subanalysis of Korean elderly patients with type 2 diabetes inadequately controlled on their previous therapies, treatment with BIAsp30 offered improvements in glycaemic control and was well tolerated. Body weight gain was minimal with BIAsp30, and treatment satisfaction among these patients appeared to be high.
Systematic review of the effects of aromatase inhibitors on pain associated with endometriosis
Authors: Patwardhan S , Nawathe A , Yates D , Harrison GR , Khan KS 
Published: May 2008

Objective  To assess the effects of aromatase inhibitors in women symptomatic of pain with endometriosis.Design  A systematic review of published literature.Material and methods  We conducted a comprehensive literature search to identify all the published observational and randomised studies evaluating the efficacy of aromatase inhibitors on pain associated with endometriosis. A combination of keywords was used to identify the maximum number of relevant citations in MEDLINE, EMBASE, CINAHL and the Cochrane Database.Outcome  Pain relief, lesion size and quality of life.Results  There were eight studies (137 women) evaluating outcomes of aromatase inhibitors. In case series/reports (seven studies, 40 women), aromatase inhibitors combined with progestogens or oral contraceptive pill or gonadotrophin‐releasing hormone (GnRH) analogues reduced mean pain scores and lesion size and improved quality of life. An RCT (97 women) demonstrated that aromatase inhibitors in combination with GnRH analogues significantly improved pain (P < 0.0001) compared with GnRH analogues alone together with significant improvement in multidimensional patient scores (P < 0.0001). There was no significant reduction in spine or hip‐bone densities.Conclusion  Aromatase inhibitors appear to have a promising effect on pain associated with endometriosis, but the strength of this inference is limited due to a dearth of the evidence available.
Efficacy and Tolerability of Almotriptan in Adolescents: A Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Linder Steven L. , Mathew Ninan T. , Cady Roger K. , Finlayson Gary , Ishkanian Gary , Lewis Donald W. 
Published: May 2008

Objectives.— To assess the efficacy and safety of almotriptan 6.25 mg, 12.5 mg, and 25 mg vs placebo for acute migraine treatment in adolescents.Patients and Methods.— In this double‐blind, placebo‐controlled, parallel‐group, multicenter trial, 866 patients aged 12 to 17 years with a >1 year history of migraine (per International Headache Society criteria) were randomized to treat one migraine headache with almotriptan 6.25 mg, 12.5 mg, 25 mg, or placebo. The primary efficacy endpoint was headache pain relief 2 hours after dosing, adjusted for baseline severity, with absence of nausea, photophobia, and phonophobia 2 hours after dosing as coprimary endpoints.Results.— The 2‐hour pain‐relief rate was significantly higher with almotriptan 25 mg compared with placebo (66.7% vs 55.3%; P = .022). The incidence of nausea, photophobia, and phonophobia at 2 hours (adjusted for baseline pain intensity) for the almotriptan 25 mg and placebo groups was not significantly different. The 2‐hour pain‐relief rates (unadjusted) were significantly higher with almotriptan 6.25 mg (71.8%), 12.5 mg (72.9%), and 25 mg (66.7%) than with placebo (55.3%; P = .001, P < .001, and P = .028, respectively). Rates for sustained pain relief also were significantly greater with almotriptan 6.25 mg (67.2%), 12.5 mg (66.9%), and 25 mg (64.5%) than with placebo group (52.4%), P < .01 for the 6.25‐ and 12.5‐mg doses and P < .05 for the 25‐mg dose. Age group subanalysis demonstrated significantly greater 2‐hour pain‐relief rates with all 3 doses of almotriptan compared with placebo for patients aged 15 to 17 years, a significantly lower incidence of photophobia and phonophobia at 2 hours with almotriptan 12.5 mg compared with placebo for patients aged 15 to 17 years, and a significantly lower incidence of photophobia with almotriptan 12.5 mg compared with placebo for those aged 12 to 14 years. Almotriptan treatment was well tolerated, with the most common adverse events (>2%) of nausea, dizziness, and somnolence.Conclusions.— Oral almotriptan was efficacious for relieving migraine headache pain in adolescents, with the 12.5‐mg dose associated with the most favorable efficacy profile with respect to relieving headache pain and associated symptoms of migraine (photophobia and phonophobia). Almotriptan treatment was well tolerated in this adolescent population.