bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agonist‐induced desensitisation of β3‐adrenoceptors: Where, when, and how?
Authors: Okeke Katerina , Angers Stephane , Bouvier Michel , Michel Martin C. 
Published: February 2019

β3‐Adrenoceptor agonists have proven useful in the treatment of overactive bladder syndrome, but it is not known whether their efficacy during chronic administration may be limited by receptor‐induced desensitisation. Whereas the β2‐adrenoceptor has phosphorylation sites that are important for desensitisation, the β3‐adrenoceptor lacks these; therefore, it had been assumed that β3‐adrenoceptors are largely resistant to agonist‐induced desensitisation. While all direct comparative studies demonstrate that β3‐adrenoceptors are less susceptible to desensitisation than β2‐adrenoceptors, desensitisation of β3‐adrenoceptors has been observed in many models and treatment settings. Chimeric β2‐ and β3‐adrenoceptors have demonstrated that the C‐terminal tail of the receptor plays an important role in the relative resistance to desensitisation but is not the only relevant factor. While the evidence from some models, such as transfected CHO cells, is inconsistent, it appears that desensitisation is observed more often after long‐term (hours to days) than short‐term (minutes to hours) agonist exposure. When it occurs, desensitisation of β3‐adrenoceptors can involve multiple levels including down‐regulation of its mRNA and the receptor protein and alterations in post‐receptor signalling events. The relative contributions of these mechanistic factors apparently depend on the cell type under investigation. Which if any of these factors is applicable to the human urinary bladder remains to be determined.Linked ArticlesThis article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc
The MC4 receptor agonist RO27‐3225 inhibits NLRP1‐dependent neuronal pyroptosis via the ASK1/JNK/p38 MAPK pathway in a mouse model of intracerebral haemorrhage
Authors: Chen Shengpan , Zuo Yuchun , Huang Lei , Sherchan Prativa , Zhang Jian , Yu Zhengtao , Peng Jianhua , Zhang Junyi , Zhao Lianhua , Doycheva Desislava , Liu Fei , Zhang John H. , Xia Ying , Tang Jiping 
Published: February 2019

Background and PurposeInflammasome‐mediated pyroptosis is an important neuronal cell death mechanism. Previous studies reported that activation of melanocortin MC4 receptor exerted neuroprotection in several neurological diseases. Here, we have investigated the role of MC4 receptor activation with RO27‐3225 in suppressing neuronal pyroptosis after experimental intracerebral haemorrhage (ICH) and the underlying mechanism.Experimental ApproachOne hundred and sixty‐nine male CD1 mice were used. ICH was induced by injection of bacterial collagenase into the right‐side basal ganglia. RO27‐3225, a selective agonist of MC4 receptor, was injected intraperitoneally at 1 hr after ICH. To elucidate the underlying mechanism, we used the specific MC4 receptor antagonist HS024 and NQDI‐1, a specific inhibitor of the apoptosis signalling‐regulating kinase 1 (ASK1). Neurological tests, Western blot, Fluoro‐Jade C, TUNEL, and immunofluorescence staining were conducted.Key ResultsExpression of MC4 receptor and the NOD‐like receptor family, pyrin domain containing 1 (NLRP1) inflammasome in brain were increased after ICH. RO27‐3225 treatment decreased neuronal pyroptosis and neurobehavioural deficits at 24 and 72 hr after ICH. RO27‐3225 reduced the expression of p‐ASK1, p‐JNK, p‐p38 MAPK, NLRP1 inflammasome, cleaved caspase‐1, and IL‐1β after ICH. HS024 pretreatment prevented the effects of RO27‐3225. Similar to RO27‐3225, NQDI‐1 alone improved neurological functions and down‐regulated ASK1/JNK/p38MAPK expression after ICH.Conclusions and ImplicationsRO27‐3225 suppressed NLRP1‐dependent neuronal pyroptosis and improved neurological function, possibly mediated by activation of MC4 receptor and inhibition of ASK1/JNK/p38 MAPK signalling pathways, after experimental ICH in mice. The MC4 receptor may be a promising therapeutic target for the management of ICH.
Pollen analogues are transported across greater distances in bee‐pollinated than in hummingbird‐pollinated species of Justicia (Acanthaceae)
Authors: Schmidt‐Lebuhn Alexander N. , Müller Matthias , Pozo Inofuentes Paola , Encinas Viso Francisco , Kessler Michael 
Published: February 2019

AbstractSeveral hummingbird‐pollinated plant lineages have been demonstrated to show increased rates of diversification compared to related insect‐pollinated lineages. It has been argued that this pattern is produced by a higher degree of specialization on part of both hummingbirds and plants. We here test an alternative hypothesis: The often highly territorial hummingbirds may on average carry pollen over shorter distances than other pollinators and drive diversification by reducing gene flow distances. We present experimental data from pollen analogue tracking showing shorter dispersal distances in hummingbird‐pollinated than in bee‐pollinated species among ten Neotropical species of Justicia (Acanthaceae).Abstract in Spanish is available with online material.
QSAR of clinically important EGFR mutant L858R/T790M pyridinylimidazole inhibitors
Authors: Fatima Shehnaz , Pal Divyani , Agarwal Subhash Mohan 
Published: February 2019

AbstractEGFR is a well‐established therapeutic target of clinical relevance in cancer. However, acquisition of secondary mutation (T790M) makes first‐generation inhibitors ineffective. Therefore, to circumvent the problem of resistance, new T790M/L858R (TMLR) double mutant inhibitors are required. In this study, fragment‐based QSAR models (GQSAR) were generated for pyridinylimidazole derivatives having biological activity against TMLR mutants. The GQSAR model developed using partial least squares regression via stepwise forward–backward variable selection technique showed best results as judged using statistical parameters (r2, q2, and pred_r2). Additionally, applicability domain of the model was verified using Williams plot, which indicated that the predicted data are reliable. The GQSAR provided site‐specific clues wherein modifications related to decreasing lipophilic character and rotatable bonds and increasing SaaCHE‐index are required for improving inhibitory activity. Overall, the study indicated that the presence of acrylamide at R5 is essential for covalent bond formation with Cys797 and occurrence of aromatic residue at R2 is required for occupying hydrophobic region next to Met790 gatekeeper residue. Based on this information, new derivatives were designed that show better inhibitory activity than the experimentally reported most active molecules. Thus, the model developed can be used to design new pyridinylimidazole derivatives with improved TMLR bioactivity.
Immunosuppressive and monoclonal antibody treatment for myasthenia gravis: A network meta‐analysis
Authors: Wang Liang , Huan Xiao , Xi Jian‐Ying , Wu Hui , Zhou Lei , Lu Jia‐Hong , Zhang Tian‐Song , Zhao Chong‐Bo 
Published: February 2019

SummaryBackgroundWe intended to compare and rank all the immunotherapies including immunosuppressant agents or monoclonal antibodies for myasthenia gravis (MG).MethodsA network meta‐analysis was performed to synthesize the direct evidence and indirect evidence. Quantitative MG score (QMGS) was defined as the primary outcome. The secondary outcomes included the glucocorticoid reduction and hazard ratios (HR) from the counts of adverse events (AEs).ResultsWe identified 14 studies including 808 MG patients. For the primary outcome, cyclosporine A (CsA) was hierarchically the best with statistical significances of −1.18 (−1.81, −0.59) vs placebo (PLA), −0.98 (−1.72, −0.23) vs mycophenolate mofetil, and −0.77 (−1.57, −0.032) vs tacrolimus (TAC). When the intervention periods were controlled, both eculizumab (ECZ) of −1.50 (−2.81, −0.18) and CsA of −1.23 (−1.81, −0.64) vs PLA reached a statistical significance. Belimumab and ECZ ranked the most tolerable therapies while CsA of 2.41 (0.58, 10.01) ranked the last vs PLA.ConclusionThese findings demonstrated that ECZ represented the most effective and tolerable therapeutic alternative to be recommended for refractory MG. TAC may be a beneficial therapy to treat MG extensively while the efficacy of CsA and cyclophosphamide may be limited by their multiple or severe AEs.
Enhancement of conservation knowledge through increased access to botanical information
Authors: Canteiro Cátia , Barcelos Laísa , Filardi Fabiana , Forzza Rafaela , Green Laura , Lanna João , Leitman Paula , Milliken William , Pires Morim Marli , Patmore Kristina , Phillips Sarah , Walker Barnaby , Weech Marie‐Hélène , Nic Lughadha Eimear 
Published: February 2019

AbstractHerbarium specimens are increasingly recognized as an important resource for conservation science and virtual herbaria are making specimens freely available to a wider range of users than ever before. Few virtual herbaria are designed with conservation use as a primary driver. Exceptionally, Brazil's Reflora Virtual Herbarium (RVH) was created to increase knowledge and conservation of the Brazilian flora. The RVH is closely integrated with the Flora of Brazil 2020 platform on which Brazil's new national Flora is under construction. Both resources are accessible via the Reflora home page and thousands of users move seamlessly between these Reflora resources. To understand how the Reflora resources are currently used and their impact on conservation science, we conducted a literature review and an online survey. We searched for publications of studies in which Reflora resources were used and publications resulting from Brazilian researchers who were part of Reflora's research and mobility program. The survey contained multiple choice questions and questions that required a written response. We targeted Reflora webpage visitors with the survey to capture a wider range of Reflora users than the literature review. Reflora resources were used for a variety of conservation‐relevant purposes. Half the 806 scientific publications in which Reflora was cited and 81% of the 1069 survey respondents accessing Reflora resources mentioned conservation‐relevant research outputs. Most conservation‐relevant uses of the Reflora resources in scientific publications were research rather than implementation focused. The survey of Reflora users showed conservation uses and impacts of virtual herbaria were more numerous and diverse than the uses captured in the literature review. Virtual herbaria are vital resources for conservation science, but they must document use and impacts more comprehensively to ensure sustainability.
The significance of batch and patch test method in establishing contact allergy to fragrance mix I—EDEN Fragrance Study Group
Authors: Bruze Magnus , Mowitz Martin , Ofenloch Robert , Coenraads Pieter‐Jan , Diepgen Thomas L. , Elsner Peter , Gonçalo Margarida , Naldi Luigi , Svensson Åke 
Published: February 2019

BackgroundA fragrance mix consisting of eight separate fragrance ingredients (fragrance mix I [FM I]) is present in most baseline patch test series. Patch testing with the TRUE Test technique is considered to detect less contact allergy to FM I than testing with the Finn Chamber technique.ObjectiveTo investigate the possible significance of batch and patch test method in establishing contact allergy to FM I.MethodsThree thousand one hundred and nineteen individuals representing a sample of the general population were patch tested with two batches of FM I with two patch test techniques at six dermatology clinics in five European countries. The TRUE Test technique and the Finn Chamber technique with pet. preparations were used. McNemar's test was used for statistical calculations.ResultsThe contact allergy prevalences varied between 0.7% and 2.6%. The patch tests with the mixes containing Evernia prunastri (oak moss) with a high content of chloratranol/atranol resulted in substantially more positive reactions than the corresponding tests with the mixes containing oak moss with a low content of chloratranol/atranol. The Finn Chamber technique detected significantly more contact allergic reactions than the TRUE Test technique (P < 0.001).ConclusionThe Finn Chamber technique detects more contact allergy to FM I than the TRUE Test technique.
Significant polyp and early colorectal cancer – SPECC
Authors: Taylor C. , Mackay L. , Dawson C. , Richards N. 
Published: February 2019

AbstractAimsThe colorectal Clinical Nurse Specialist (CNS) makes an important contribution to the care of individuals diagnosed with a significant polyp and early colorectal cancer (SPECC).MethodsThis paper offers an expert opinion on the role of the CNS in SPECC, informed by relevant literature.ResultsA CNS can support the patient through the diagnostic and treatment pathway acting as the patient's advocate as a core member of the multidisciplinary team. They will offer support and information to help patients understand their diagnosis, make choices about their available treatment options and help them to feel prepared for any treatment undertaken.ConclusionBy providing care that is respectful of, and responsive to, individual patient preferences, needs and values, the CNS can play an important role in promoting patient‐centred care.
Intrapleural immunotherapy: An update on emerging treatment strategies for pleural malignancy
Authors: Murthy Vivek , Katzman Daniel , Sterman Daniel H. 
Published: February 2019

AbstractObjectivesMalignant pleural mesothelioma and malignant pleural effusions are a major therapeutic challenge, and are associated with impairment in quality of life and increased mortality. Advances in systemic therapies of malignant pleural mesothelioma have demonstrated limited clinical benefit and there is ongoing interest in intrapleural immunotherapies which have been demonstrated to be well tolerated overall with variable clinical responses. We have reviewed the literature to provide a comprehensive summary of novel intrapleural immunotherapeutic paradigms, including oncolytic virus therapy, gene‐mediated cytotoxic immunotherapy, direct cytokine‐mediated immunotherapies, innate immunomodulators and adoptive transfer of intrapleural chimeric antigen receptor T‐cell therapy.Data sourcesA review of PubMed for original manuscripts and conference reports published between 1998 and 2018 pertaining to intrapleural immunotherapy, as well as examination of reference lists from reviewed manuscripts.Study selectionHuman clinical trials on intrapleural immunotherapies in subjects with malignant pleural mesothelioma or malignant pleural effusion were included in this review, including some relevant preclinical studies and anticipated ongoing trials reported on Clinicaltrials.gov.ResultsTwenty‐six clinical trials were identified, in addition to three trials currently in progress.ConclusionIntrapleural immunotherapies for pleural malignancy have demonstrated promise with regard to generating durable tumor‐specific immune responses with possible clinical benefits which merit further investigation as part of multimodal chemotherapeutic and immunotherapeutic regimens.
Dracula orchids exploit guilds of fungus visiting flies: new perspectives on a mushroom mimic
Authors: Policha Tobias , Grimaldi David A. , Manobanda Rocío , Troya Adrian , Ludden Ashley , Dentinger Bryn T. M. , Roy Bitty A. 
Published: February 2019

1. Dracula orchids mimic mushrooms in appearance and scent, and are pollinated by mushroom flies. This study examined the guilds of insect visitors to Dracula species and to co‐occurring mushrooms in an Ecuadorean cloud forest. Significant visitor overlap was documented (mostly in the genera Zygothrica and Hirtodrosophila; Drosophilidae). To test the brood‐site mimicry hypothesis, behavioural observations were also performed and rearing success was examined.2. Many fly species that visit Dracula are also found on mushrooms. Furthermore, the presence of pollinia enabled us to document the fact that particular individuals visiting mushrooms also visit Dracula. Roughly two‐thirds of the visitors to these unusual flowers are fungal‐associated, and the rest appear to be Dracula specialists.3. A variety of behaviours common on both host groups were observed, including courtship semaphoring, feeding, sheltering, defending territory, and mating. Given this suite of shared reproductive behaviour, it was hypothesised that flies may also oviposit in both substrates. Flies were reared from mushrooms, Dracula spp., and other flowers (controls) to determine which substrate led to the highest fitness for the flies. Very few flies emerged from the Dracula flowers and there was no species overlap between the emergent insects and the known pollinators.4. Despite the fact that there is evidence for brood‐site mimicry, the Dracula situation is complex. All the flies could derive many of the same fitness benefits from the flowers as they do from mushrooms (shelter, food, mating), but they are clearly not gaining the same fitness benefit, in terms of progeny, on flowers compared with mushrooms.
A caterpillar (Callopistria floridensis G. (Lepidoptera: Noctuidae)) accumulates arsenic from an arsenic‐hyperaccumulating fern (Pteris vittata L.).
Authors: Jaffe Benjamin D. , Guédot Christelle , Ketterer Michael , Kok‐Yokomi Moh Leng , Leibee Gary L. 
Published: February 2019

1. The consumption of arsenic is toxic to most biota. However, a noctuid caterpillar was recently reported feeding on a plant known to hyperaccumulate arsenic.2. The aim of this study was to investigate the effects of arsenic‐rich Pteris vittata L. consumption by Callopistria floridensis G., and measure differences in arsenic concentrations at various stages of development (larval and adult), and associated with exuviae and frass.3. Callopistria floridensis accumulated extraordinary concentrations of arsenic. The relative accumulation of arsenic was highest in exuviae and larvae. Larvae invariably preferred P. vittata grown on low arsenic soil to P. vittata grown on higher soil arsenic concentrations, and appeared able to selectively forage on lower arsenic concentrations within each treatment.4. These findings show that C. floridensis is tolerant of arsenic, and successfully develops to adulthood containing elevated concentrations of arsenic. Callopistria floridensis represents the only known terrestrial animal capable of accumulating arsenic, and may have developed novel physiological and behavioural adaptations to regulate the negative effects of arsenic.
Reputational risk and environmental performance auditing: A study in the Australian commonwealth public sector
Authors: Rika Nacanieli , Jacobs Kerry 
Published: February 2019

AbstractThis paper examines how reputational risk to government is generated through framing and overflows evident in environmental performance auditing. It analyses two high‐profile performance audits conducted by the Australian National Audit Office. It is motivated by a gap in the literature on performance auditing and environmental auditing, which both acknowledge that audits may give rise to reputational risk but have not analysed the process through which this occurs. Using ideas of framing (Goffman, 1974) and overflow (Callon, 1983), this paper extends the work of Power (2007) by explaining how different accounts can be constructed from the same underlying events through the application of different frames. Alternative framings generate reputational risk by highlighting contentious issues that may otherwise have been ignored or received minimal consideration. In particular, representatives of the opposition and media can use political and public interest frames to construct performance accounts which differ from and challenge the improvement frame emphasised by performance auditors and favoured by government. This paper shows that auditors’ roles are more complex than often assumed and that auditors relate to different audiences through different frames.
Public sector audit in contemporary society: A short review and introduction
Authors: Johnsen Åge 
Published: February 2019

AbstractThis article gives a short review of recent research on public sector audit, and then introduces six articles in a special issue on public sector audit in contemporary society. Many countries have developed their audit institutions and expanded the audit activities in particular since the 1980s. New public management and the theory of the ‘audit society’ explain much of this development well, also in some international organizations, but some countries have also experienced a contraction in the audit activities in the public sector. Moreover, literature on public sector audit outside the Anglo‐American and North European contexts, and especially from Africa, Asia and Latin‐America, is limited. There are big variations in how audit institutions are organized, in what they produce, in their relations to stakeholders and media, and in their impacts on organizations and society. Overall, auditors are little active in the fight against corruption, and the Napoleonic court system for organizing supreme audit institutions seems to be little effective. The audit institutions in the Anglo‐American and Nordic accountability regimes seem to be relatively effective, but the recent research show that auditors' independence and relevance are persistent challenging issues in public sector audit.
The Family Resilience Inventory: A Culturally Grounded Measure of Current and Family‐of‐Origin Protective Processes in Native American Families
Authors: Burnette Catherine E. , Boel‐Studt Shamra , Renner Lynette M. , Figley Charles R. , Theall Katherine P. , Miller Scarnato Jennifer , Billiot Shanondora 
Published: February 2019

The purpose of this article is to introduce the Family Resilience Inventory (FRI) and present findings on initial efforts to validate this measure. The FRI is designed to assess family resilience in one's current family and in one's family of origin, enabling the assessment of family protective factors across these generations. The development of the FRI was the result of many years of ethnographic research with Southeastern Native American tribes; yet, we believe that this scale is applicable to families of various backgrounds. Items for the FRI were derived directly from thematic analysis of qualitative data with 436 participants, resulting in two 20‐item scales. Due to missing data, eight cases were removed from the 127 participants across two tribes, resulting in an analytic sample size of 119. Conceptually, the FRI is comprised of two factors or scales measuring distinct dimensions of family resilience (i.e., resilience in one's current family and resilience in one's family of origin). The results of the confirmatory factor analysis supported the hypothesized two‐factor structure (X2(644) = 814.14, p = .03, X2/df = 1.10, RMSEA = .03, CFI = .97, TLI = .96). Both the subscales and the total FRI scale (α = .92) demonstrated excellent reliability. The results also provided preliminary evidence of convergent and discriminant validity. This measure fills a gap in the absence of community‐based, culturally grounded, and empirical measures of family resilience. The examination of family resilience, which may occur across generations, is an exciting new contribution of the FRI.