bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional pharmacology of H1 histamine receptors expressed in mouse preoptic/anterior hypothalamic neurons
Authors: Tabarean I V 
Published: August 2013

Background and PurposeHistamine H1 receptors are highly expressed in hypothalamic neurons and mediate histaminergic modulation of several brain‐controlled physiological functions, such as sleep, feeding and thermoregulation. In spite of the fact that the mouse is used as an experimental model for studying histaminergic signalling, the pharmacological characteristics of mouse H1 receptors have not been studied. In particular, selective and potent H1 receptor agonists have not been identified.Experimental ApproachCa2+ imaging using fura‐2 fluorescence signals and whole‐cell patch‐clamp recordings were carried out in mouse preoptic/anterior hypothalamic neurons in culture.Key ResultsThe H1 receptor antagonists mepyramine and trans‐triprolidine potently antagonized the activation by histamine of these receptors with IC50 values of 0.02 and 0.2 μM respectively. All H1 receptor agonists studied had relatively low potency at the H1 receptors expressed by these neurons. Methylhistaprodifen and 2‐(3‐trifluoromethylphenyl)histamine had full‐agonist activity with potencies similar to that of histamine. In contrast, 2‐pyridylethylamine and betahistine showed only partial agonist activity and lower potency than histamine. The histamine receptor agonist, 6‐[2‐(4‐imidazolyl)ethylamino]‐N‐(4‐trifluoromethylphenyl)heptanecarboxamide (HTMT) had no agonist activity at the H1 receptors H1 receptors expressed by mouse preoptic/anterior hypothalamic neurons but displayed antagonist activity.Conclusions and ImplicationsMethylhistaprodifen and 2‐(3‐trifluoromethylphenyl)histamine were identified as full agonists of mouse H1 receptors. These results also indicated that histamine H1 receptors in mice exhibited a pharmacological profile in terms of agonism, significantly different from those of H1 receptors expressed in other species.
A single channel mutation alters agonist efficacy at 5‐HT3A and 5‐HT3AB receptors
Authors: Thompson A J , Lummis S C R 
Published: August 2013

Background and Purpose5‐HT3 receptors are composed of 5‐HT3A subunits (homomeric receptors), or combinations of 5‐HT3A and other 5‐HT3 receptor subunits (heteromeric receptors, the best studied of which are 5‐HT3AB receptors). Here we explore the effects of partial agonists at 5‐HT3A and 5‐HT3AB receptors, and the importance of a channel‐lining residue in determining the efficacy of activation.Experimental ApproachWild type and mutant 5‐HT3A and 5‐HT3AB receptors were expressed in Xenopus oocytes and examined using two‐electrode voltage‐clamp, or expressed in HEK293 cells and examined using [3H]granisetron binding.Key ResultsDopamine, quipazine and VUF10166 were partial agonists at wild type 5‐HT3A and 5‐HT3AB receptors, with quipazine and VUF10166 causing a long‐lived (>20 min) inhibition of subsequent agonist responses. At 5‐HT3A receptors, mCPBG was a partial agonist, but was a superagonist at 5‐HT3AB receptors, as it produced a response 2.6× greater than that of 5‐HT. A T6'S substitution in the 5‐HT3A subunit decreased EC50 and increased Rmax of dopamine and quipazine at both homomeric and heteromeric receptors. The greatest changes were seen with VUF10166 at 5‐HT3AT6'SB receptors, where it became a full agonist (EC50 = 7 nM) with an EC50 58‐fold less than 5‐HT (EC50 = 0.4 μM) and no longer caused inhibition of subsequent agonist responses.Conclusions and ImplicationsThese results indicate that a mutation in the pore lining domain in both 5‐HT3A and 5‐HT3AB receptors alters the relative efficacy of a series of agonists, changing some (e.g. quipazine) from apparent antagonists to potent and efficacious agonists.
SERCA2a stimulation by istaroxime: a novel mechanism of action with translational implications
Authors: Huang Christopher L H 
Published: August 2013

Sarcoplasmic reticular (SR) Ca2+‐ATPase (SERCA2a) is central to cardiac electrophysiological and mechanical function. It ensures full diastolic relaxation minimizing delayed after‐potentials that would otherwise compromise membrane electrophysiological stability, and optimizes SR Ca2+ refilling and systolic contraction. Previous studies demonstrated that the small molecule agent istaroxime stimulates SERCA2a‐ATPase activity, restoring its function in failing hearts, and enhancing indices of mechanical, and SR Ca2+ release and re‐uptake, activity. Ferrandi et al (2013) now elegantly demonstrate its ability to dissociate the phospholamdan (PB) bound to cardiac SERCA2a, thereby removing the inhibitory effect of PB on SERCA2a. This effect was independent of the cAMP/PKA system and modified a specific SERCA2a reaction step. They used SERCA‐enriched SR preparations from a rigorously validated and realistic physiological, canine model of cardiac failure with established Na+‐K+‐ATPase sensitivity to cardiac glycosides and SR Ca2+ handling features. These findings potentially translate into a novel management of the major and increasingly important public health challenge of chronic cardiac failure.Linked ArticleThis article is a commentary on Ferrandi et al., pp. 1849–1861 of volume 169 issue 8. To view this paper visit http://dx.doi.org/10.1111/bph.12278.
Effect of Mas‐related gene (Mrg) receptors on hyperalgesia in rats with CFA‐induced inflammation via direct and indirect mechanisms
Authors: Jiang Jianping , Wang Dongmei , Zhou Xiaolong , Huo Yuping , Chen Tingjun , Hu Fenjuan , Quirion Rémi , Hong Yanguo 
Published: August 2013

Background and PurposeMas oncogene‐related gene (Mrg) receptors are exclusively distributed in small‐sized neurons in trigeminal and dorsal root ganglia (DRG). We investigated the effects of MrgC receptor activation on inflammatory hyperalgesia and its mechanisms.Experimental ApproachA selective MrgC receptor agonist, bovine adrenal medulla peptide 8‐22 (BAM8‐22) or melanocyte‐stimulating hormone (MSH) or the μ‐opioid receptor (MOR) antagonist CTAP was administered intrathecally (i.t.) in rats injected with complete Freund's adjuvant (CFA) in one hindpaw. Thermal and mechanical nociceptive responses were assessed. Neurochemicals were measured by immunocytochemistry, Western blot, ELISA and RT‐PCR.Key ResultsCFA injection increased mRNA for MrgC receptors in lumbar DRG. BAM8‐22 or MSH, given i.t., generated instant short and delayed long‐lasting attenuations of CFA‐induced thermal hyperalgesia, but not mechanical allodynia. These effects were associated with decreased up‐regulation of neuronal NOS (nNOS), CGRP and c‐Fos expression in the spinal dorsal horn and/or DRG. However, i.t. administration of CTAP blocked the induction by BAM8‐22 of delayed anti‐hyperalgesia and inhibition of nNOS and CGRP expression in DRG. BAM8‐22 also increased mRNA for MORs and pro‐opiomelanocortin, along with β‐endorphin content in the lumbar spinal cord and/or DRG. MrgC receptors and nNOS were co‐localized in DRG neurons.Conclusions and ImplicationsActivation of MrgC receptors suppressed up‐regulation of pronociceptive mediators and consequently inhibited inflammatory pain, because of the activation of up‐regulated MrgC receptors and subsequent endogenous activity at MORs. The uniquely distributed MrgC receptors could be a novel target for relieving inflammatory pain.
A single‐center analysis of abdominal imaging in the evaluation of kidney transplant recipients
Authors: Winship Brenton , Ramakrishnan Swetha , Evans Jonathan , Lurie Christina , Martin Diego , Pearson Thomas , Turgeon Nicole 
Published: August 2013

AbstractMany transplantation programs utilize noninvasive abdominal and pelvic imaging in the pre‐operative evaluation of recipient candidates. Practice patterns vary, and consensus guidelines addressing the risks and benefits of computed tomography (CT) and magnetic resonance imaging (MRI) in the pre‐transplant evaluation process do not currently exist. In this single‐center study, we examined the frequency, clinical significance, and associated costs of CT and MRI findings during the pre‐transplant evaluation of renal transplant recipients. A retrospective chart review of 3041 adult patients who underwent a CT/CTA or MRI/MRA of the abdomen and pelvis for pre‐transplant evaluation between 2005 and 2010 was performed. Pre‐transplant imaging with MRI offered a more sensitive evaluation in comparison with CT, with the notable exception of abnormalities in which calcium was detected. Patients imaged with CT had a significantly greater proportion of subsequent clinical actions arising from imaging findings. The total financial cost of MRI was greater than that of CT. No cases of nephrogenic systemic fibrosis (NSF) in patients who received MultiHance gadolinium contrast were reported. In conclusion, the risks, benefits, and costs of CT/CTA and MRI/MRA must be carefully considered to optimize the pre‐operative evaluation of renal transplant recipients.
Inter‐specific competition and competition‐free space in the tephritid parasitoids Utetes anastrephae and Doryctobracon areolatus (Hymenoptera: Braconidae: Opiinae)
Authors: ALUJA MARTIN , OVRUSKI SERGIO M. , SIVINSKI JOHN , CÓRDOVA‐GARCÍA GUADALUPE , SCHLISERMAN PABLO , NUÑEZ‐CAMPERO SEGUNDO R. , ORDANO MARIANO 
Published: August 2013

Utetes anastrephae (Viereck) and Doryctobracon areolatus (Szépligeti) are common, native, Neotropical braconid parasitoids of tephritid fruit flies that are sympatric and often found attacking the same host.
The coexistence of the two species may be due in part to the longer ovipositor of D. areolatus that permits it to attack larvae in larger fruit than can U. anastrephae. This increases its potential host range and provides ‘competitor‐free space’.
The capacity of U. anastrephae to persist in smaller fruit, exploitable by D. areolatus, suggested that it was a superior competitor in multiparasitised hosts. As predicted U. anastrephae had a competitive advantage over D. areolatus and this advantage occurred regardless of the order in which the two parasitoids attacked. Although we could not identify the precise mechanisms used for elimination of competitors, a possible cause is suggested by the formidable mandibles of the first‐instar U. anastrephae.
However, D. areolatus survival increased significantly if eggs had been deposited 24 h prior to exposure to U. anastrephae. Older D. areolatus larvae might be more competitive after a period of development.
Utetes anastrephae females were less likely to oviposit into hosts previously attacked by D. areolatus than vice versa. This was a second case of the relatively rare phenomenon of inter‐specific discrimination of a previously exploited host within the opiine braconid parasitoids of frugivorous tephritids.
Network mechanisms of responsiveness to continuous theta‐burst stimulation
Authors: Rizk Sviatlana , Ptak Radek , Nyffeler Thomas , Schnider Armin , Guggisberg Adrian G. 
Published: August 2013

AbstractContinuous theta‐burst stimulation (cTBS) can modify behavior, but effects are inconsistent and their mechanisms insufficiently understood. As coherence in resting‐state networks influences human behavior, we hypothesized that cTBS may act via modulation of neural oscillation coherence. This study used electroencephalography (EEG) to investigate whether behavioral effects of cTBS on visuospatial attention are associated with coherence changes in the attention network. In healthy human subjects, cTBS of the right posterior parietal cortex (PPC) and the right frontal eye field was compared with sham stimulation. Effects on visuospatial attention were quantified with a visual exploration task, and network effects were assessed from surface EEG with inverse solutions and source coherence analyses. Before stimulation, left visual exploration was linearly correlated with alpha‐band coherence between the right temporo‐parietal cortex and the rest of the brain. Posterior parietal cortex stimulation induced neglect‐like visual exploration behavior in the majority, but not all, subjects. It reduced alpha‐band coherence between the stimulation site and the rest of the brain but also enhanced it between the contralateral left parietal cortex and the rest of the brain. The contralateral increase correlated with the induced reduction in left visual attention. The behavioral response of individual participants to cTBS could be predicted by coherence in the right temporo‐parietal junction before stimulation. Behavioral effects of cTBS therefore depend on network states before stimulation and are linearly associated with changes in network interactions. In particular, cTBS modulates an interhemispheric competition in alpha‐band coherence. EEG network imaging might help to optimize therapeutic cTBS in the future.
Deviations between observed and RothC‐simulated Δ14C values despite improved IOM initialization
Authors: Shirato Y. , Jomura M. , Wagai R. , Kondo M. , Tanabe K. , Uchida M. 
Published: August 2013

SummaryThe 14C contents and the carbon (C) pool sizes for Rothamsted Carbon (RothC) model pools and soil fractions determined by physical separation and subsequent chemical oxidation were directly compared for an agricultural topsoil (Dystric Cambisol) from a long‐term experimental field in central Japan. The RothC model was run from 1975 to 2009 and the C concentration and Δ14C value of each pool and for the bulk soil were compared with the physical fractions that have been, according to literature, suggested as corresponding with model pools. When compared with the default estimate of the inert organic matter (IOM) pool size derived from an exponential dependency on total organic carbon (TOC), direct estimation of IOM pool size determined from the C remaining after chemical oxidation of the silt plus clay (< 63 µm) fraction improved the model performance for TOC changes over the 34‐year experimental period. The size of each model pool matched that of the physical fractions well, whereas the Δ14C values clearly differed between modelled pools and corresponding physical fractions. The physical fractions showed more negative Δ14C values with 50–190‰ (indicating slower turnover rates) compared with the active pools in RothC, whereas using the oxidation residue generated more positive Δ14C values with 700‰ (faster turnover) than the original RothC IOM pool. These results suggest that (i) the proposed physical fractionation scheme improves the model performance in simulating TOC changes at the temporal scale of decades under the current climate and (ii) long‐term predictions should be interpreted carefully because of the large discrepancy in 14C‐based turnover rate between the physical fractions and RothC model pools.
Psychogenic nonepileptic seizures in children: A review
Authors: Reilly Colin , Menlove Leanne , Fenton Virginia , Das Krishna B. 
Published: August 2013

SummaryOne of the considerations when a child presents with paroxysmal events is psychogenic nonepileptic seizures (PNES). PNES are discernible changes in behavior or consciousness that resemble epileptic seizures but are not accompanied by electrophysiologic changes. They are usually understood as the manifestation of a conversion disorder that reflects underlying psychological distress. There is a lack of population‐based data on the prevalence or incidence of PNES in pediatric populations. The prevalence of PNES in children would appear to be lower than that in the adult population, but the prevalence of PNES seems to increase with age, and nonepileptic paroxysmal events are more likely to be PNES in adolescence than earlier in childhood. In terms of manifestation, PNES in childhood have been described using various categorizations and terminology, making comparisons across studies difficult. There is some evidence that events are more likely to involve unresponsiveness in younger children and prominent motor symptoms in older children. The most common precipitating factors would appear to be school‐related difficulties and interpersonal conflict within the child's family. In terms of psychopathology, children with PNES are at high risk for symptoms of depression and anxiety. Accurate diagnosis of PNES in children is likely to involve taking a comprehensive description of the episodes, garnering the child's medical/developmental history, video‐electroencephalography (video‐EEG) to rule out epileptic seizures, and an evaluation of family functioning. The importance of effective and sensitive communication of the diagnosis of PNES has been emphasized and management approaches will typically involve multidisciplinary efforts to safely manage the events at home and at school. Interventions to reduce the effect of precipitating psychosocial stressors and the involvement of a mental health professional to treat comorbid psychopathology will also form part of an effective management plan. Outcome at follow‐up is reported to be largely positive, although studies have not been able to follow all children, and few studies have focused on predictors of a good outcome. Future controlled intervention studies using a range of outcome measures are needed to identify efficacious approaches and predictors of best outcome.
When local isn't best
Authors: Jones Thomas A. 
Published: August 2013

AbstractThis paper attempts to explain circumstances under which local may be or may not be best. Natural selection may lead to local adaptation (LA), or it may be constrained by gene flow, founder effects, small population size, genetic drift, and archetype. ‘Specialist’ species display greater LA than ‘generalist’ species. Local genotypes are to a certain extent transient, being a consequence of past historical genetic patterns. Two recent meta‐analyses found that while local performance exceeded the performance of a randomly chosen nonlocal population in 71% of comparisons, general adaptation across environments was as frequent as LA. Genotypes for restoration are most likely to be effective if they are adapted to current site conditions. As environmental change accelerates, both globally and locally, exceptions to ‘local is best’ may increase. For these reasons, ‘local is best’ may be better thought of as a testable hypothesis rather than as a general assumption. While either local or nonlocal plant material may be most effective for restoration practice depending on individual circumstances, local material will continue to be the first choice for restoration practitioners whenever this option is feasible and effective.
Isotopic biosignatures in carbonate‐rich, cyanobacteria‐dominated microbial mats of the Cariboo Plateau, B.C.
Authors: Brady A. L. , Druschel G. , Leoni L. , Lim D. S. S. , Slater G. F. 
Published: August 2013

AbstractPhotosynthetic activity in carbonate‐rich benthic microbial mats located in saline, alkaline lakes on the Cariboo Plateau, B.C. resulted in pCO2 below equilibrium and δ13CDIC values up to +6.0‰ above predicted carbon dioxide (CO2) equilibrium values, representing a biosignature of photosynthesis. Mat‐associated δ13Ccarb values ranged from ~4 to 8‰ within any individual lake, with observations of both enrichments (up to 3.8‰) and depletions (up to 11.6‰) relative to the concurrent dissolved inorganic carbon (DIC). Seasonal and annual variations in δ13C values reflected the balance between photosynthetic 13C‐enrichment and heterotrophic inputs of 13C‐depleted DIC. Mat microelectrode profiles identified oxic zones where δ13Ccarb was within 0.2‰ of surface DIC overlying anoxic zones associated with sulphate reduction where δ13Ccarb was depleted by up to 5‰ relative to surface DIC reflecting inputs of 13C‐depleted DIC. δ13C values of sulphate reducing bacteria biomarker phospholipid fatty acids (PLFA) were depleted relative to the bulk organic matter by ~4‰, consistent with heterotrophic synthesis, while the majority of PLFA had larger offsets consistent with autotrophy. Mean δ13Corg values ranged from −18.7 ± 0.1 to −25.3 ± 1.0‰ with mean Δ13Cinorg‐org values ranging from 21.1 to 24.2‰, consistent with non‐CO2‐limited photosynthesis, suggesting that Precambrian δ13Corg values of ~−26‰ do not necessitate higher atmospheric CO2 concentrations. Rather, it is likely that the high DIC and carbonate content of these systems provide a non‐limiting carbon source allowing for expression of large photosynthetic offsets, in contrast to the smaller offsets observed in saline, organic‐rich and hot spring microbial mats.
Potential role of catalase in mice with lipopolysaccharide/D‐galactosamine‐induced fulminant liver injury
Authors: Jia Mengying , Jing Yuping , Ai Qing , Jiang Rong , Wan Jingyuan , Lin Ling , Zhou Dan , Che Qian , Li Longjiang , Tang Li , Shen Yi , Zhang Li 
Published: August 2013

AimLipopolysaccharide (LPS)‐induced liver injury in D‐galactosamine (D‐Gal)‐sensitized mice is a well‐established animal model widely used in exploring the pathogenesis of fulminant hepatitis. Increasing evidence has indicated that reactive oxygen species (ROS)‐induced oxidative injury may be involved in LPS/D‐Gal‐induced hepatitis. Catalase (CAT) is a major antioxidant enzyme while aminotriazole (ATZ) is commonly used as a CAT inhibitor. In the present study, the effects of ATZ on LPS/D‐Gal‐induced liver injury were investigated.MethodsFuliminant liver injury was induced by intraperitoneal injection of LPS combined with D‐Gal, ATZ was administrated 0.5 h prior to LPS/D‐Gal challenge. The degree of liver injury, the level of hepatic oxidative stress, the grade of hepatic apoptosis and the survival of experimental animals were determined.ResultsOur experimental data showed that treatment with ATZ significantly enhanced LPS/D‐Gal‐induced elevation of serum aspartate transaminase (AST) and alanine transaminase (ALT), exacerbated the hepatic histopathological abnormality and decreased the survival rate of experimental animals. ATZ inhibited the activity of CAT, increased the content of H2O2 and the levels of malondialdehyde (MDA) in liver tissues. In addition, treatment with ATZ also enhanced LPS/D‐Gal‐induced hepatic apoptosis as evidenced by increased caspases activities in liver tissues and increased number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells in liver sections.ConclusionThese findings suggested that CAT might be involved in the progression of LPS/D‐Gal‐induced fulminant liver injury.
Conversion to Islam: A Case Study for the Use of Legal Sources
Authors: Simonsohn Uriel 
Published: August 2013

AbstractThe past few decades have witnessed increasing calls in modern scholarship for revisions of the portrayal of early Islamic rule history. Such calls not only challenge older historiographic paradigms but also encourage historians to seek answers in sources hitherto neglected. Accordingly, in recent years there has been a dramatic proliferation of studies offering new historical conceptions, many of which are indebted to new kinds of source material, including coinage, official documents, inscriptions, and material artifacts, alongside more conventional forms of data like historiographic treatises, biographical dictionaries, apologetic literature, theological essays, and scriptural texts. Assembled together, new and older historical materials were now being processed, synthesized, and analyzed through the lenses of fresh paradigms and often in collaboration with other disciplines, especially the social sciences and comparative literature.The present contribution offers further support of this latter approach by highlighting the utility of legal sources for discussing the process of conversion to Islam in the early Islamic period. Following a brief historical survey, the discussion turns to address one of the central, yet highly elusive, episodes in early Islamic history – the process of conversion to Islam. The goal of this sample analysis of legal sources is twofold – to provide new historiographic insights, but also, from a methodological perspective, to underscore the remarkable utility of these sources for historians.