bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indicator value of oribatid mites in determining past permafrost dynamics in northern European sub‐Arctic peatlands
Authors: Markkula Inkeri , Oksanen Pirita , Kuhry Peter 
Published: March 2018

Permafrost dynamics play an important role in the surface hydrology and carbon balance of northern peatlands. Plant macrofossil analysis with radiocarbon dating has been widely used in detecting past permafrost dynamics in peatlands; however, there is a lack of permafrost‐specific plant indicator species, which makes it challenging to determine the exact timing of historical permafrost aggradation. We investigated the indicator value of oribatid mites in determining past permafrost dynamics in sub‐Arctic peatlands. Analyses of subfossil oribatid mite assemblages of Holocene peat profiles from two mires, one in northern Finland and one in northeastern European Russia, were carried out and interpreted using modern calibration data from the same study areas. The results were compared with previously published reconstructions of permafrost history based on plant macrofossil analyses from the same locations. The results suggest that the oribatid mites Carabodes labyrinthicus, Chamobates borealis and Neoribates aurantiacus are promising indicator species to detect past permafrost occurrence in peatlands. In addition, N. aurantiacus is clearly associated with the presence of lichens, which is particularly useful because lichen remains are rarely preserved in peat deposits. Results are in accordance with earlier studies showing that oribatid mites are useful indicators of past environmental change.
The non‐biphenyl‐tetrazole angiotensin AT1 receptor antagonist eprosartan is a unique and robust inverse agonist of the active state of the AT1 receptor
Authors: Takezako Takanobu , Unal Hamiyet , Karnik Sadashiva S , Node Koichi 
Published: March 2018

Background and PurposeConditions such as hypertension and renal allograft rejection are accompanied by chronic, agonist‐independent, signalling by angiotensin II AT1 receptors. The current treatment paradigm for these diseases entails the preferred use of inverse agonist AT1 receptor blockers (ARBs). However, variability in the inverse agonist activities of common biphenyl‐tetrazole ARBs for the active state of AT1 receptors often leads to treatment failure. Therefore, characterization of robust inverse agonist ARBs for the active state of AT1 receptors is necessary.Experimental ApproachTo identify the robust inverse agonist for active state of AT1 receptors and its molecular mechanism, we performed site‐directed mutagenesis, competition binding assay, inositol phosphate production assay and molecular modelling for both ground‐state wild‐type AT1 receptors and active‐state N111G mutant AT1 receptors.Key ResultsAlthough candesartan and telmisartan exhibited weaker inverse agonist activity for N111G‐ compared with WT‐AT1 receptors, only eprosartan exhibited robust inverse agonist activity for both N111G‐ and WT‐ AT1 receptors. Specific ligand–receptor contacts for candesartan and telmisartan are altered in the active‐state N111G‐ AT1 receptors compared with the ground‐state WT‐AT1 receptors, suggesting an explanation of their attenuated inverse agonist activity for the active state of AT1 receptors. In contrast, interactions between eprosartan and N111G‐AT1 receptors were not significantly altered, and the inverse agonist activity of eprosartan was robust.Conclusions and ImplicationsEprosartan may be a better therapeutic option than other ARBs. Comparative studies investigating eprosartan and other ARBs for the treatment of diseases caused by chronic, agonist‐independent, AT1 receptor activation are warranted.
Boosting phagocytosis and anti‐inflammatory phenotype in microglia mediates neuroprotection by PPARγ agonist MDG548 in Parkinson's disease models
Authors: Lecca Daniela , Janda Elzbieta , Mulas Giovanna , Diana Andrea , Martino Concetta , Angius Fabrizio , Spolitu Stefano , Casu Maria Antonietta , Simbula Gabriella , Boi Laura , Batetta Barbara , Spiga Saturnino , Carta Anna R 
Published: March 2018

Background and PurposeMicroglial phenotype and phagocytic activity are deregulated in Parkinson's disease (PD). PPARγ agonists are neuroprotective in experimental PD, but their role in regulating microglial phenotype and phagocytosis has been poorly investigated. We addressed it by using the PPARγ agonist MDG548.Experimental ApproachMurine microglial cell line MMGT12 was stimulated with LPS and/or MDG548, and their effect on phagocytosis of fluorescent microspheres or necrotic neurons was investigated by flow cytometry. Cytokines and markers of microglia phenotype, such as mannose receptor C type 1; MRC1), Ym1 and CD68 were measured by elisa and fluorescent immunohistochemistry. Levels of Beclin‐1, which plays a role in microglial phagocytosis, were measured by Western blotting. In the in vivo MPTP–probenecid (MPTPp) model of PD in mice, MDG548 was tested on motor impairment, nigral neurodegeneration, microglial activation and phenotype.Key ResultsIn LPS‐stimulated microglia, MDG548 increased phagocytosis of both latex beads and necrotic cells, up‐regulated the expression of MRC1, CD68 and to a lesser extent IL‐10, while blocking the LPS‐induced increase of TNF‐α and iNOS. MDG548 also induced Beclin‐1. Chronic MPTPp treatment in mice down‐regulated MRC1 and TGF‐β and up‐regulated TNF‐α and IL‐1β immunoreactivity in activated CD11b‐positive microglia, causing the death of nigral dopaminergic neurons. MDG548 arrested MPTPp‐induced cell death, enhanced MRC1 and restored cytokine levels.Conclusions and ImplicationsThis study adds a novel mechanism for PPARγ‐mediated neuroprotection in PD and suggests that increasing phagocytic activity and anti‐inflammatory markers may represent an effective disease‐modifying approach.
Subtle changes in elevation shift bat‐assemblage structure in Central Amazonia
Authors: Capaverde Ubirajara Dutra , Pereira Lucas Gabriel do Amaral , Tavares Valéria da Cunha , Magnusson William E. , Baccaro Fabricio Beggiato , Bobrowiec Paulo Estefano D. 
Published: March 2018

AbstractThe distribution patterns of animal species at local scales have been explained by direct influences of vegetation structure, topography, food distribution, and availability. However, these variables can also interact and operate indirectly on the distribution of species. Here, we examined the direct and indirect effects of food availability (fruits and insects), vegetation clutter, and elevation in structuring phyllostomid bat assemblages in a continuous terra firme forest in Central Amazonia. Bats were captured in 49 plots over 25‐km² of continuous forest. We captured 1138 bats belonging to 52 species with 7056 net*hours of effort. Terrain elevation was the strongest predictor of species and guild compositions, and of bat abundance. However, changes in elevation were associated with changes in vegetation clutter, and availability of fruits and insects consumed by bats, which are likely to have had direct effects on bat assemblages. Frugivorous bat composition was more influenced by availability of food‐providing plants, while gleaning‐animalivore composition was more influenced by the structural complexity of the vegetation. Although probably not causal, terrain elevation may be a reliable predictor of bat‐assemblage structure at local scales in other regions. In situations where it is not possible to collect local variables, terrain elevation can substitute other variables, such as vegetation structure, and availability of fruits and insects.
Tim-3 exacerbates kidney ischaemia/reperfusion injury through the TLR-4/NF-κB signalling pathway and an NLR-C4 inflammasome activation
Authors: Guo Y , Zhang J , Lai X , Chen M , Guo Y 
Published: March 2018

Summary
T cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3), a member of the immunoglobulin superfamily, has been shown to play a crucial role in host adaptive immunity and tolerance. However, its role in kidney ischaemia–reperfusion injury (IRI) remains unknown. In this study, we investigated the role and mechanism of Tim-3 signalling after kidney IRI. In an established murine model of kidney IRI, we found that Tim-3 expression is enhanced on monocytes/macrophages. Anti-Tim-3 antibody RMT3-23 ameliorates biochemical and histological kidney injury, reduces apoptosis and decreases macrophage infiltration and cytokine production in ischaemic kidneys. Cell culture experiments also demonstrated that the role of Tim-3 in IRI-induced macrophage activation leads to the secretion of proinflammatory cytokines and chemokines. In addition, Toll-like receptor (TLR)-4 and Nod-like receptor (NLR) family CARD domain-containing protein 4 (NLR-C4) expression were enhanced after kidney IRI and decreased significantly by RMT3-23. Tim-3 not only promotes TLR-mediated nuclear factor kappa B (NF-κB) activation and cytokine and chemokine release, but also participates in NLR-C4 inflammasome activation. Taken together, our data confirm that Tim-3 signalling enhances injury after kidney IRI and demonstrated that Tim-3 is involved in regulating TLR-4/NF-κB signalling and NLR-C4 inflammasome activation, which provide evidence that Tim-3 signalling is critical for kidney IRI and may provide a new means to ameliorate kidney tissue immune responses in the clinics.
XPC gene mutations in families with xeroderma pigmentosum from Pakistan; prevalent founder effect
Authors: Ijaz Ambreen , Basit Sulman , Gul Ajab , Batool Lilas , Hussain Abrar , Afzal Sibtain , Ramzan Khushnooda , Ahmad Jamil , Wali Abdul 
Published: March 2018

ABSTRACTXeroderma pigmentosum (XP) is a rare autosomal recessive skin disorder characterized by hyperpigmentation, premature skin aging, ocular and cutaneous photosensitivity, and increased risk of skin carcinoma. We investigated seven consanguineous XP families with nine patients from Pakistan. All the Patients exhibited typical clinical symptoms of XP since first year of life. Whole genome SNP genotyping identified a 14 Mb autozygous region segregating with the disease phenotype on chromosome 3p25.1. DNA sequencing of XPC gene revealed a founder homozygous splice site mutation (c.2251‐1G>C) in patients from six families (A–F) and a homozygous nonsense mutation (c.1399C>T; p.Gln467*) in patients of family G. This is the first report of XPC mutations, underlying XP phenotype, in Pakistani population.
Patients with perianal Crohn's fistulas experience delays in accessing anti‐TNF therapy due to slow recognition, diagnosis and integration of specialist services: lessons learned from three referral centres
Authors: Lee M. J. , Freer C. , Adegbola S. , Elkady S. , Parkes M. , Hart A. , Fearnhead N. S. , Lobo A. J. , Brown S. R. 
Published: March 2018

AbstractAimCrohn's anal fistula should be managed by a multidisciplinary team. There is no clearly defined ‘patient pathway’ from presentation to treatment. The aim of this study was to describe the patient route from presentation with symptomatic Crohn's anal fistula to starting anti‐tumour necrosis factor (anti‐TNF) therapy.MethodCase note review was undertaken at three hospitals with established inflammatory bowel disease services. Patients with Crohn's anal fistula presenting between 2010 and 2015 were identified through clinical coding and local databases. Baseline demographics were captured. Patient records were interrogated to identify route of access, and clinical contacts during the patient pathway.ResultsSeventy‐nine patients were included in the study, of whom 54 (68%) had an established diagnosis of Crohn's disease (CD). Median time from presentation to anti‐TNF therapy was 204 days (174 vs 365 days for existing and new diagnosis of CD, respectively; P = 0.019). The mean number of surgical outpatient attendances, operations and MRI scans per patient was 1.03, 1.71 and 1.03, respectively. Patients attended a mean of 1.49 medical clinics. Seton insertion was the most common procedure, accounting for 48.6% of all operations. Where care episodes (‘clinical events per 30 days’) were infrequent this correlated with prolongation of the pathway (r = −0.87; P < 0.01).ConclusionThis study highlights two key challenges in the treatment pathway: (i) delays in diagnosis of underlying CD in patients with anal fistula and (ii) the pathway to anti‐TNF therapy is long, suggesting issues with service design and delivery. These should be addressed to improve patient experience and outcome.
Undifferentiated‐type component mixed with differentiated‐type early gastric cancer is a significant risk factor for endoscopic non‐curative resection
Authors: Horiuchi Yusuke , Fujisaki Junko , Yamamoto Noriko , Ishizuka Naoki , Omae Masami , Ishiyama Akiyoshi , Yoshio Toshiyuki , Hirasawa Toshiaki , Yamamoto Yorimasa , Nagahama Masatsugu , Takahashi Hiroshi , Tsuchida Tomohiro 
Published: March 2018

Background and AimPrevious studies of surgical specimens have found that the presence of mixed histological components in differentiated‐type early gastric cancer (EGC) is a risk factor for lymph node metastasis and indicates greater malignancy. As there have been no reports on its endoscopic treatment, we examined endoscopic curative resection in relation to differentiated‐type‐predominant mixed‐type (MT).MethodsThis was a single‐center, retrospective study. Subjects were 2585 differentiated‐type EGC in 2551 patients treated with endoscopic submucosal dissection (ESD) in our hospital between March 2005 and January 2016. These lesions comprised 2231 cases of curative resection and 354 cases of non‐curative resection. Histologically, 2339 lesions were pure differentiated‐type (PDT) and 246 lesions were MT. Rates of curative resection were compared, according to tumor size, between different histological types.ResultsWhen curative and non‐curative cases were compared using multivariate analysis among lesions measuring ≤20 mm for factors other than those determining curative resection, significant differences were obtained for tumor diameter, ulcer, and MT. Among lesions measuring 21–30 mm, ulcer and MT were associated with significant differences. Among lesions measuring >30 mm, upper region and MT were associated with significant differences. Curative resection rates, in relation to histological type among lesions measuring ≤20 mm, were 93.4% for PDT and 63.4% for MT, whereas corresponding rates were 85.1% and 60.0%, respectively, among lesions measuring 21–30 mm, and 55.3% and 30.2%, respectively, among lesions measuring >30 mm.ConclusionWe found that MT was a risk factor for non‐curative resection irrespective of lesion size.
Ruptured mitral valve aneurysm: A devastating complication of aortic valve endocarditis
Authors: Hajsadeghi Shokoufeh , Marzban Mehrab , Joghataie Pegah , Iranpour Aida 
Published: March 2018

Mitral valve aneurysm is a rare clinical entity that is mostly resulted from infective endocarditis, in particular, aortic valve endocarditis. Once mitral valve aneurysm ruptures and severe mitral regurgitation and hemodynamic instability develop, prompt surgery should be considered. Here we report a patient with ruptured mitral valve aneurysm associated with native aortic valve endocarditis that was improved after a successful mitral and aortic valve replacement surgery associated with antibiotic therapy for 6 weeks.
The predictive value of global longitudinal strain on clinical outcome in patients with ST‐segment elevation myocardial infarction and preserved systolic function
Authors: Bendary Ahmed , Tawfeek Wael , Mahros Mohammed , Salem Mohamed 
Published: March 2018

BackgroundLeft ventricular ejection fraction (LVEF) is fundamental for risk stratification after ST‐segment elevation myocardial infarction (STEMI). However, it lacks discrimination power within normal range. Novel echocardiographic deformation parameters may be of benefit for those with post‐MI preserved LVEF.ObjectivesWe hypothesized that semiautomated calculation of baseline global longitudinal strain (GLS) can identify high‐risk group among patients with LVEF ≥ 50% following STEMI.MethodsDuring the period from January to July 2017, 110 patients with successful reperfusion of STEMI and LVEF ≥ 50% were prospectively included. Within 48 hours, patients underwent a baseline GLS study with follow‐up study at 30 days. The endpoint was a composite of cardiovascular mortality, rehospitalization for heart failure, and urgent revascularization.ResultsMean GLS value changed from −16 ± 4% at baseline to −12 ± 4% at 30‐day follow‐up (P < .001). At 30 days, cardiovascular mortality was reported in 4.5%, 11.8% were rehospitalized due to heart failure, and 5.4% underwent urgent revascularization. ROC curve analysis showed that a cutoff baseline GLS value >−12.65% predicted 30‐day MACEs with a sensitivity and specificity of 77.8% and 83.7%, respectively (AUC 0.784, 95% CI 0.646–0.921, P < .001). An adjusted multivariate logistic regression analysis revealed that baseline GLS value >−12.65% to be the only significant independent predictor for occurrence of MACEs (OR 19.54, 95% CI 6.3–61.1, P < .001).ConclusionEarly GLS calculation predicts 30‐day outcome in patients with preserved LVEF following reperfusion of STEMI.
Within‐species patterns challenge our understanding of the leaf economics spectrum
Authors: Anderegg Leander D. L. , Berner Logan T. , Badgley Grayson , Sethi Meera L. , Law Beverly E. , HilleRisLambers Janneke 
Published: March 2018

AbstractThe utility of plant functional traits for predictive ecology relies on our ability to interpret trait variation across multiple taxonomic and ecological scales. Using extensive data sets of trait variation within species, across species and across communities, we analysed whether and at what scales leaf economics spectrum (LES) traits show predicted trait–trait covariation. We found that most variation in LES traits is often, but not universally, at high taxonomic levels (between families or genera in a family). However, we found that trait covariation shows distinct taxonomic scale dependence, with some trait correlations showing opposite signs within vs. across species. LES traits responded independently to environmental gradients within species, with few shared environmental responses across traits or across scales. We conclude that, at small taxonomic scales, plasticity may obscure or reverse the broad evolutionary linkages between leaf traits, meaning that variation in LES traits cannot always be interpreted as differences in resource use strategy.
The taphonomic fate of isorenieratene in Lower Jurassic shales—controlled by iron?
Authors: Reinhardt M. , Duda J.‐P. , Blumenberg M. , Ostertag‐Henning C. , Reitner J. , Heim C. , Thiel V. 
Published: March 2018

AbstractFossil derivatives of isorenieratene, an accessory pigment in brown‐colored green sulfur bacteria, are often used as tracers for photic zone anoxia through Earth's history, but their diagenetic behavior is still incompletely understood. Here, we assess the preservation of isorenieratene derivatives in organic‐rich shales (1.5–8.4 wt.% TOC) from two Lower Jurassic anoxic systems (Bächental oil shale, Tyrol, Austria; Posidonia Shale, Baden‐Württemberg, Germany). Bitumens and kerogens were investigated using catalytic hydropyrolysis (HyPy), closed‐system hydrous pyrolysis (in gold capsules), gas chromatography–mass spectrometry (GC–MS) and gas chromatography combustion isotope ratio‐mass spectrometry (GC‐C‐IRMS). Petrography and biomarkers indicate a syngenetic relationship between bitumens and kerogens. All bitumens contain abundant isorenieratane, diverse complex aromatized isorenieratene derivatives, and a pseudohomologous series of 2,3,6‐trimethyl aryl isoprenoids. In contrast, HyPy and mild closed‐system hydrous pyrolysis of the kerogens yielded only minor amounts of these compounds. Given the overall low maturity of the organic matter (below oil window), it appears that isorenieratene and its abundant derivatives from the bitumen had not been incorporated into the kerogens. Accordingly, sulfur cross‐linking, the key mechanism for sequestration of functionalized lipids into kerogens in anoxic systems, was not effective in the Jurassic environments studied. We explain this by (i) early cyclization/aromatization and (ii) hydrogenation reactions that have prevented effective sulfurization. In addition, (iii) sulfide was locally removed via anoxygenic photosynthesis and efficiently trapped by the reaction with sedimentary iron, as further indicated by elevated iron contents (4.0–8.7 wt.%) and the presence of abundant pyrite aggregates in the rock matrix. Although the combined processes have hampered the kerogen incorporation of isorenieratene and its derivatives, they may have promoted the long‐term preservation of these biomarkers in the bitumen fraction via early defunctionalization. This particular taphonomy of aromatic carotenoids has to be considered in studies of anoxic iron‐rich environments (e.g., the Proterozoic ocean).
Time lag and negative responses of forest greenness and tree growth to warming over circumboreal forests
Authors: Tei Shunsuke , Sugimoto Atsuko 
Published: March 2018

AbstractThe terrestrial forest ecosystems in the northern high latitude region have been experiencing significant warming rates over several decades. These forests are considered crucial to the climate system and global carbon cycle and are particularly vulnerable to climate change. To obtain an improved estimate of the response of vegetation activity, e.g., forest greenness and tree growth, to climate change, we investigated spatiotemporal variations in two independent data sets containing the dendroecological information for this region over the past 30 years. These indices are the normalized difference vegetation index (NDVI3g) and the tree‐ring width index (RWI), both of which showed significant spatial variability in past trends and responses to climate changes. These trends and responses to climate change differed significantly in the ecosystems of the circumarctic (latitude higher than 67°N) and the circumboreal forests (latitude higher and lower than 50°N and 67°N, respectively), but the way in which they differed was relatively similar in the NDVI3g and the RWI. In the circumarctic ecosystem, the climate variables of the current summer were the main climatic drivers for the positive response to the increase in temperatures showed by both the NDVI3g and the RWI indices. On the other hand, in the circumboreal forest ecosystem, the climate variables of the previous year (from summer to winter) were also important climatic drivers for both the NDVI3g and the RWI. Importantly, both indices showed that the temperatures in the previous year negatively affected the ecosystem. Although such negative responses to warming did not necessarily lead to a past negative linear trend in the NDVI3g and the RWI over the past 30 years, future climate warming could potentially cause severe reduction in forest greenness and tree growth in the circumboreal forest ecosystem.