bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human secreted proteins SLURP‐1 and SLURP‐2 control the growth of epithelial cancer cells via interactions with nicotinic acetylcholine receptors
Authors: Lyukmanova E N , Bychkov M L , Sharonov G V , Efremenko A V , Shulepko M A , Kulbatskii D S , Shenkarev Z O , Feofanov A V , Dolgikh D A , Kirpichnikov M P 
Published: March 2018

Background and PurposeNicotinic acetylcholine receptors (nAChRs) are a promising target for development of new anticancer therapies. Here we have investigated the effects of the endogenous human proteins SLURP‐1 and SLURP‐2, antagonists of nAChRs, on human epithelial cancer cells.Experimental ApproachGrowth of epithelial cancer cells (A431, SKBR3, MCF‐7, A549, HT‐29) exposed to SLURP‐1, SLURP‐2, mecamylamine, atropine, timolol and gefitinib was measured by the WST‐1 test. Expression levels of SLURP‐1, α7‐nAChR and EGF receptors and their distribution in cancer cells were studied by confocal microscopy and flow cytometry. Secretion of endogenous SLURP‐1 by A431 cells under treatment with recombinant SLURP‐1 was analysed by Western‐blotting.Key ResultsSLURP‐1 and SLURP‐2 significantly inhibited growth of A431, SKBR3, MCF‐7 and HT‐29 cells at concentrations above 1 nM, to 40–70% of the control, in 24 h. Proliferation of A549 cells was inhibited only by SLURP‐1. The anti‐proliferative activity of SLURPs on A431 cells was associated with nAChRs, but not with β‐adrenoceptors or EGF receptors. Action of gefitinib and SLURPs was additive and resulted almost complete inhibition of A431 cell proliferation during 24 h. Exposure of A431 cells to recombinant SLURP‐1 down‐regulated α7‐nAChR expression and induced secretion of endogenous SLURP‐1 from intracellular depots, increasing its concentration in the extracellular media.Conclusions and ImplicationsSLURPs inhibit growth of epithelial cancer cells in vitro and merit further investigation as potential agents for anticancer therapy.Linked ArticlesThis article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc
Function and underlying mechanisms of seasonal colour moulting in mammals and birds: what keeps them changing in a warming world?
Authors: Zimova Marketa , Hackländer Klaus , Good Jeffrey M. , Melo‐Ferreira José , Alves Paulo Célio , Mills L. Scott 
Published: March 2018

ABSTRACTAnimals that occupy temperate and polar regions have specialized traits that help them survive in harsh, highly seasonal environments. One particularly important adaptation is seasonal coat colour (SCC) moulting. Over 20 species of birds and mammals distributed across the northern hemisphere undergo complete, biannual colour change from brown in the summer to completely white in the winter. But as climate change decreases duration of snow cover, seasonally winter white species (including the snowshoe hare Lepus americanus, Arctic fox Vulpes lagopus and willow ptarmigan Lagopus lagopus) become highly contrasted against dark snowless backgrounds. The negative consequences of camouflage mismatch and adaptive potential is of high interest for conservation. Here we provide the first comprehensive review across birds and mammals of the adaptive value and mechanisms underpinning SCC moulting. We found that across species, the main function of SCC moults is seasonal camouflage against snow, and photoperiod is the main driver of the moult phenology. Next, although many underlying mechanisms remain unclear, mammalian species share similarities in some aspects of hair growth, neuroendocrine control, and the effects of intrinsic and extrinsic factors on moult phenology. The underlying basis of SCC moults in birds is less understood and differs from mammals in several aspects. Lastly, our synthesis suggests that due to limited plasticity in SCC moulting, evolutionary adaptation will be necessary to mediate future camouflage mismatch and a detailed understanding of the SCC moulting will be needed to manage populations effectively under climate change.
Searching for strategy: Value for Money (VFM) audit choice in the new public management era
Authors: Adi Sana , Dutil Patrice 
Published: March 2018

AbstractValue for Money (VFM) audits are now critical aspects of accountability in Westminster systems, based on the assumption that ministries are systematically examined. This study explores the VFM inquiries of the Auditor General of Ontario (AGO) between 1997 and 2014 as a case study to uncover trends of consistency of approach under the flourishing “new public management” philosophy of cutting costs and raising efficiencies. It asks three broad questions: does the frequency and intensity of VFM audits correlate with the financial importance of the ministries? Do political controversies affect the choice of what will be subject to a VFM audit? Finally, do Auditors General make a personal difference in what ministries will be audited through a VFM framework? The findings demonstrate a pattern of over‐auditing of some ministries while important ministries are consistently under‐audited.
Clinical outcomes after Descemet’s stripping endothelial keratoplasty using donor corneas from children younger than 3 years
Authors: Peng Rong‐mei , Guo Yu‐xin , Qiu Yuan , Hong Jing , Xiao Ge‐ge , Qu Hong‐qiang 
Published: March 2018

AbstractImportanceThere is limited literature on paediatric donors in endothelial keratoplasty.BackgroundThis study investigated the efficacy of and appropriate paediatric donor age for Descemet’s stripping endothelial keratoplasty (DSEK).DesignRetrospective and observational case series.ParticipantsThirty‐eight consecutive patients underwent DSEK with paediatric donor corneas.MethodsThe age of the donors ranged from 32 weeks gestation (premature neonate) to 3 years old. All donor consents were obtained from the parents. The causes of donor death included traffic accident, congenital heart disease and neonatal respiratory distress syndrome.Main Outcome MeasuresThe outcome measures included best‐corrected visual acuity, endothelial cell loss and complications.ResultsBest‐corrected visual acuity at last follow‐up was >20/40 in 28 of 38 eyes (73.7%). The mean preoperative endothelial cell density of donor corneas was 4682 ± 520 cells/mm2. The mean endothelial cell density of grafts was 3977 ± 556 cells/mm2 at 18 months postoperatively. Three lenticules from premature neonate donors exhibited severe contraction postoperatively. The edge of six lenticules from donors <1‐year‐old exhibited contraction in the early postoperative period and gradually flattened spontaneously. Graft detachment occurred in one patient.Conclusions and RelevanceDSEK with paediatric donor corneas can achieve good clinical outcomes. The corneal lenticules from 1‐ to 3‐year‐ old donors are suitable for DSEK while those from donors <1‐year‐old are less suitable due to the possibility of severe postoperative graft contraction.
Fak‐Mapk, Hippo and Wnt signalling pathway expression and regulation in distraction osteogenesis
Authors: Song Jian , Ye Bin , Liu Hanghang , Bi Ruiye , Zhang Nian , Hu Jing , Luo En 
Published: March 2018

AbstractObjectivesTo investigate the mechanism of mechanical stimulation in bone formation and regeneration during distraction osteogenesis.Materials and methodsIn this study, microarray technology was used to investigate the time course of bone‐related molecular changes in distraction osteogenesis in rats. Real‐timePCRand Western‐blot analyses were used to confirm the expression of genes identified in microarrays. Meanwhile, we used a lentivirus vector to inhibit Fak expression, in order to identify the osteogenic effect of Fak and Fak‐Mapk pathway during distraction osteogenesis.ResultsSeveral components of the Wnt and Hippo pathways were found to be up‐ or down‐regulated during distraction osteogenesis by microarray. Meanwhile, it was found that Fak, Src, Raf‐1, Erk1, Jnk and p38‐Mapk were up‐regulated during gradual distraction, compared with consolidation. To further determine whether Fak‐Mapk pathway played an important role in distraction osteogenesis, Fak was disrupted with a lentivirus vector. The expressions levels of p‐Fak, p‐Erk1/2, p‐JNKand p‐p38Mapk were decreased. Meanwhile, a poor early and late osteogenesis effect was found in the shRNA‐Fak group.ConclusionIt was inferred that the mechanical stimulus induces increased expression of Fak and activates Fak‐Mapk pathway, by activation of Erk, Jnk and p38‐Mapk pathway, and that Fak at least, in part, plays an important role in maintaining osteogenic effect by activating Fak‐Mapk pathway during distraction osteogenesis.
Antibiotic resistance evolution of Pseudomonas aeruginosa in cystic fibrosis patients (2010‐2013)
Authors: Lucca Francesca , Guarnieri Margherita , Ros Mirco , Muffato Giovanna , Rigoli Roberto , Da Dalt Liviana 
Published: March 2018

AbstractIntroductionPseudomonas aeruginosa is the predominant pathogen responsible of chronic colonization of the airways in cystic fibrosis (CF) patients. There are few European data about antibiotic susceptibility evolution of P aeruginosa in CF patients.ObjectivesThe aim of this study is to evaluate the evolution of antibiotic resistance in the period 2010‐2013 in CF patients chronically colonized by P aeruginosa and to highlight the characteristics of this evolution in patients younger than 20 years.MethodsClinical and microbiological data were extracted from two electronic databases and analyzed. Antibiotic resistance was defined according to European Committee of Antimicrobial Susceptibility Testing for levofloxacin, ciprofloxacin, meropenem, amikacin and ceftazidime. The between‐group comparison was drawn with the Chi‐square test for proportions, with the T‐test for unpaired samples for normally distributed data and with Mann‐Whitney test for non‐normally distributed data. Significancy was defined by P < .05.ResultsFifty‐seven CF patients, including thirteen subjects aged less than 20 years, were enrolled. P.. aeruginosa antibiotic sensitivity decreased significantly for fluoroquinolones, mainly in patients aged <20 years, while it increased for amikacin and colistin. The analysis of minimum inhibitory concentration confirmed these trends. In pediatric patients treated with more than three antibiotic cycles per year, greater resistance was found, except for amikacin and colistin.ConclusionAn evolution in P aeruginosa antibiotic resistances is observed in the 4‐year period studied. Responsible and informed use of antibiotics is mandatory in CF.
Cardio‐hepatic risk assessment by CMR imaging in liver transplant candidates
Authors: Reddy Sahadev T. , Thai Ngoc L. , Oliva Jose , Tom Kusum B. , Dishart Michael K. , Doyle Mark , Yamrozik June A. , Williams Ronald B. , Shah Moneal , Wani Adil , Singh Anil , Maheswary Rishi , Biederman Robert W.W. 
Published: March 2018

AbstractBackgroundThe preoperative workup of orthotopic liver transplantation (OLT) patients is practically complex given the need for multiple imaging modalities. We recently demonstrated in our proof‐of‐concept study the value of a one‐stop‐shop approach using cardiovascular MRI (CMR) to address this complex problem. However, this approach requires further validation in a larger cohort, as detection of hepatocellular carcinoma (HCC) as well as cardiovascular risk assessment is critically important in these patients. We hypothesized that coronary risk assessment and HCC detectability is acceptable using the one‐stop‐shop CMR approach.MethodsIn this observational study, patients underwent CMRI evaluation including cardiac function, stress CMR, thoracoabdominal MRA, and abdominal MRI on a standard MRI scanner in one examination.ResultsOver 8 years, 252 OLT candidates underwent evaluation in the cardiac MRI suit. The completion rates for each segment of the CMR examination were 99% for function, 95% completed stress CMR, 93% completed LGE for viability, 85% for liver MRI, and 87% for MRA. A negative CMR stress examination had 100% CAD event‐free survival at 12 months. A total of 63 (29%) patients proceeded to OLT. Explant pathology confirmed detection/exclusion of HCC.ConclusionsThis study further defines the population suitable for the one‐stop‐shop CMR concept for preop evaluation of OLT candidates providing a road map for integrated testing in this complex patient population for evaluation of cardiac risk and detection of HCC lesions.
Early development of letter specialization in left fusiform is associated with better word reading and smaller fusiform face area
Authors: Centanni Tracy M , Norton Elizabeth S , Park Anne , Beach Sara D , Halverson Kelly , Ozernov‐Palchik Ola , Gaab Nadine , Gabrieli John DE 
Published: March 2018

AbstractA functional region of left fusiform gyrus termed “the visual word form area” (VWFA) develops during reading acquisition to respond more strongly to printed words than to other visual stimuli. Here, we examined responses to letters among 5‐ and 6‐year‐old early kindergarten children (N = 48) with little or no school‐based reading instruction who varied in their reading ability. We used functional magnetic resonance imaging (fMRI) to measure responses to individual letters, false fonts, and faces in left and right fusiform gyri. We then evaluated whether signal change and size (spatial extent) of letter‐sensitive cortex (greater activation for letters versus faces) and letter‐specific cortex (greater activation for letters versus false fonts) in these regions related to (a) standardized measures of word‐reading ability and (b) signal change and size of face‐sensitive cortex (fusiform face area or FFA; greater activation for faces versus letters). Greater letter specificity, but not letter sensitivity, in left fusiform gyrus correlated positively with word reading scores. Across children, in the left fusiform gyrus, greater size of letter‐sensitive cortex correlated with lesser size of FFA. These findings are the first to suggest that in beginning readers, development of letter responsivity in left fusiform cortex is associated with both better reading ability and also a reduction of the size of left FFA that may result in right‐hemisphere dominance for face perception.
Single unit activity of periaqueductal gray and deep mesencephalic nucleus neurons involved in sleep stage switching in the mouse
Authors: Sakai K. 
Published: March 2018

AbstractA total of 668 single units were recorded in the mouse periaqueductal gray (PAG) and adjacent deep mesencephalic nucleus (DpMe) to determine their role in the switching of sleep–wake states, that is, wakefulness (W), slow‐wave sleep (SWS) and paradoxical (or rapid eye movement) sleep (PS) in general, and, in particular, to determine whether PS‐on and PS‐off neurons involved in PS state switching are present in these structures and to identify neuronal substrates for the SWS‐PS switching mediated by DpMe neurons. Both structures were found to contain similar percentages of W/PS‐active neurons, which discharge at a higher rate during W and PS than during SWS, while W‐active neurons, which discharge maximally during W, were found mainly in the PAG. Both also contained similar percentages of SWS/PS‐active neurons, which discharge at higher rates during SWS and PS than during W, and PS‐active neurons, which discharge maximally during PS, while SWS‐active neurons, which discharge maximally during SWS, were found almost exclusively in the PAG. Both structures contained virtually no PS‐on or PS‐off neurons, which, respectively, discharge or cease firing selectively and tonically just prior to, and during, PS. Unlike the PAG, the DpMe contained many SWS/PS‐on neurons, which discharge selectively at high rates during SWS and PS, but show a decrease in discharge rate at the transition from SWS to PS. Analysis of discharge profiles and trends in spike activity at the state transitions strongly suggests that PAG and DpMe neurons play an important role in the W‐SWS, SWS‐PS and/or PS‐W switches.
“Now We Live for the Money”: Shifting Markers of Status, Stress, and Immune Function in the Peruvian Amazon
Authors: Tallman Paula 
Published: March 2018

AbstractThis article examines the relationship between cultural changes, socioeconomic status (SES), and psychobiological health outcomes among the Awajún, an indigenous group living in the Peruvian Amazon. Specifically, it documents how historically important markers of status for the Awajún, such as spiritual visions and war‐time success, were replaced by Western markers of status including occupation, income, education and Spanish‐language use. These changes are linked to the broader political‐economic and social agendas of Peruvian government officials and American missionaries who sought religious conversion and economic gain in the deepest reaches of the Amazon. The resulting socioeconomic hierarchies have implications for the health and well‐being of Awajún men and women in the present. Independent of other relevant factors such as age and community, men with lower SES tended to have higher Epstein‐Barr Virus (EBV) antibodies, indicating suppressed immune function, and both men and women with lower SES tended to have higher reported psychological stress levels. This critical biocultural analysis suggests that existing socioeconomic hierarchies in Awajún communities are the result of active colonial, evangelical, and capitalist efforts and shows that local histories and social spheres “get under the skin” to influence the mind and body. [lifestyle change, socioeconomic status (SES), psychological stress, Epstein‐Barr Virus (EBV) antibodies, Amazon, Awajún]
The Ethic of Spirituality and the Non‐Angry Subject
Authors: Simchai Dalit , Shoshana Avihu 
Published: March 2018

AbstractThis article is based on ethnographic studies of several spiritual groups in Israel. It offers a critical analysis of the discursive practices employed with regard to the link between spirituality and anger. We found that the emotion of anger occupies a singular status in New Age culture. By marking it as an uncontrollable and explosive emotion, anger is constructed as a key emotion that reflects and signifies the subject's proximity to the ideal spiritual personality. Our findings furthermore reveal two main emotion pedagogies employed to construct anger and to cope with it. In the discussion section, we address the affinity between the spiritual ethic and the nonangry subject, and the alliance between the spiritual, the therapeutic and the neo‐liberal discourses that sustains this affinity. This discursive alliance stands in the way of the adoption of critical cultural orientations toward the emotion of anger. [spirituality, emotions, anger, subjectivity, discursive alliance, emotion pedagogies]
Short‐ and long‐term evolution in our arms race with cancer: Why the war on cancer is winnable
Authors: Rosenheim Jay A. 
Published: March 2018

AbstractHuman society is engaged in an arms race against cancer, which pits one evolutionary process—human cultural evolution as we develop novel cancer therapies—against another evolutionary process—the ability of oncogenic selection operating among cancer cells to select for lineages that are resistant to our therapies. Cancer cells have a powerful ability to evolve resistance over the short term, leading to patient relapse following an initial period of apparent treatment efficacy. However, we are the beneficiaries of a fundamental asymmetry in our arms race against cancer: Whereas our cultural evolution is a long‐term and continuous process, resistance evolution in cancer cells operates only over the short term and is discontinuous — all resistance adaptations are lost each time a cancer patient dies. Thus, our cultural adaptations are permanent, whereas cancer's genetic adaptations are ephemeral. Consequently, over the long term, there is good reason to expect that we will emerge as the winners in our war against cancer.
Multiple pharmacological approaches on Fibigia eriocarpa extracts by in vitro and computational assays
Authors: Zengin Gokhan , Lobine Devina , Mollica Adriano , Locatelli Marcello , Carradori Simone , Mahomoodally Mohamad Fawzi 
Published: March 2018

AbstractThe ethyl acetate, methanolic, and water extracts of Fibigia eriocarpa were assessed for a panoply of bioactivities. Total phenolic and flavonoid content were quantified as well as individual phenolic compounds by HPLC‐DAD. The in vitro antioxidant and enzyme (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α‐amylase, and α‐glucosidase) inhibitory potential of the extracts were evaluated. In silico molecular docking was used to investigate possible interaction between dominant compounds and selected enzymes. Vanillin (303 μg/g extract), apigenin (270 μg/g extract), and kaempferol (180 μg/g extract) were the main compounds in the ethyl acetate extract, while the methanolic extract was characterized by the presence of vanillin, rutin, and apigenin (616, 616 and 252 μg/g extract, respectively). (+)‐catechin (1422 μg/g extract) was the main compound in the water extracts. The ethyl acetate extract was found to be a superior source of antioxidant compounds and enzyme inhibitors against above‐mentioned enzymes. Docking studies revealed that p‐hydroxybenzoic and (+)‐catechin have the best scores for tyrosinase, while kaempferol and apigenin showed the best binding pose for α‐glucosidase, AChE, and BChE. Results amassed herein are the first report on the phytochemical and biological attributes of F. eriocarpa, which tend to validate the pharmacological uses of this plant as an alternative medicine.
Population collapse dynamics in Acropora downingi, an Arabian/Persian Gulf ecosystem‐engineering coral, linked to rising temperature
Authors: Riegl Bernhard , Johnston Matthew , Purkis Sam , Howells Emily , Burt John , Steiner Sascha C. C. , Sheppard Charles R. C. , Bauman Andrew 
Published: March 2018

AbstractAs in the tropical Atlantic, Acropora populations in the southern Persian/Arabian Gulf plummeted within two decades after having been ecosystem engineers on most wave‐exposed reefs since the Pleistocene. Since 1996/1998 live coral cover in the Gulf declined by over 90% in many areas, primarily due to bleaching and diseases caused by rising temperatures. In the formerly dominant table‐coral species A. downingi, population dynamics corresponding to disturbance regimes was quantified in three transition matrices (lower disturbance pre‐1996; moderate disturbance from 1998 to 2010 and 2013 to 2017, disturbed in 1996/1998, 2010/11/12, 2017). Increased disturbance frequency and severity caused progressive reduction in coral size, cover, and population fecundity. Small size‐classes were bolstered more by partial colony mortality than sexual recruitment. Some large corals had a size refuge and resisted die‐back but were also lost with increasing disturbance. Matrix and biophysical larval flow models suggested one metapopulation. Southern, Arabian, populations could be connected to northern, Iranian, populations but this connectivity was lost under assumptions of pelagic larval duration at rising temperatures shortened to a third. Then, the metapopulation disintegrated into isolated populations. Connectivity required to avoid extinctions increased exponentially with disturbance frequency and correlation of disturbances across the metapopulation. Populations became unsustainable at eight disturbances in 15 years, when even highest theoretical recruitment no longer compensated mortality. This lethal disturbance frequency was 3‐fold that of the moderately disturbed monitoring period and 4‐fold of the preceding low‐disturbance period—suggesting ongoing shortening of the disturbance‐free period. Observed population collapse and environmental changes in the Gulf suggest that A. downingi is heading toward at least functional extinction mainly due to increasingly frequent temperature‐induced mortality events, clearly linked to climate change.