bluuebunny/crossref_metadata_2025_split huggingface dataset:
C3a receptor antagonist therapy is protective with or without thrombolysis in murine thromboembolic stroke
Authors: Ahmad Saif , Pandya Chirayu , Kindelin Adam , Bhatia Kanchan , Chaudhary Rafay , Dwivedi Alok Kumar , Eschbacher Jennifer M. , Liu Qiang , Waters Michael F. , Hoda Md Nasrul , Ducruet Andrew F. 
Published: January 2020

Background and PurposeIntravenous thrombolysis (IVT) after stroke enhances C3a generation, which may abrogate the benefits of reperfusion. The C3aR antagonist SB290157 is neuroprotective following transient but not permanent middle cerebral artery occlusion (MCAo). SB290157 remains untested in thromboembolic (TE) models, which better approximate human stroke and also facilitate testing in combination with IVT. We hypothesized SB290157 would confer neuroprotection in TE stroke with and without “late” IVT.Experimental ApproachWe used two different models of TE stroke to examine the efficacy of SB290157 alone and in combination with late IVT. We evaluated the benefit of SB290157 in attenuating post‐ischaemic behavioural deficits, infarction, brain oedema and haemorrhage.Key ResultsPlasma C3a was elevated 6 hr after TE stroke alongside increased cerebrovascular C3aR expression, which was sustained to 4 weeks. Increased C3aR expression also was visualized in human ischaemic brain. In a photothrombotic (PT) stroke model, which exhibits rapid spontaneous reperfusion, SB290157 given at 1 hr post‐PT significantly improved neurofunction and reduced infarction at 48 hr. In an embolic (eMCAo) model, SB290157 administered at 2 hr improved histological and functional outcomes. Conversely, late IVT administered 4.5 hr post‐eMCAo was ineffective likely due to increased haemorrhage and brain oedema. However, SB290157 administered prior to late IVT ameliorated haemorrhage and oedema and improved outcomes.Conclusions and ImplicationsWe conclude that SB290157 is safe and effective with and without late IVT following TE stroke. Therefore, C3a receptor antagonist therapy represents a promising candidate for clinical translation in stroke, particularly as an adjuvant to IVT.
Bone sarcomas in the immunotherapy era
Authors: Heymann Marie‐Françoise , Schiavone Kristina , Heymann Dominique 
Published: January 2020

Bone sarcomas are primary bone tumours found mainly in children and adolescents, as osteosarcoma and Ewing's sarcoma, and in adults in their 40s as chondrosarcoma. The last four decades the development of therapeutic approaches was based on drug combinations have shown no real improvement in overall survival. Recently oncoimmunology has allowed a better understand of the crucial role played by the immune system in the oncologic process. This led to clinical trials with the aim of reprogramming the immune system to facilitate cancer cell recognition. Immune infiltrates of bone sarcomas have been characterized and their molecular profiling identified as immune therapeutic targets. Unfortunately, the clinical responses in trials remain anecdotal but highlight the necessity to improve the characterization of tumour micro‐environment to unlock the immunotherapeutic response, especially in their paediatric forms. Bone sarcomas have entered the immunotherapy era and here we overview the recent developments in immunotherapies in these sarcomas.LINKED ARTICLESThis article is part of a themed issue on The molecular pharmacology of bone and cancer‐related bone diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.9/issuetoc
Anthrax toxin receptor 1/tumor endothelial marker 8 promotes gastric cancer progression through activation of the PI3K/AKT/mTOR signaling pathway
Authors: Cai Chen , Dang Wei , Liu Shilei , Huang Ling , Li Yang , Li Guoqiang , Yan Siyuan , Jiang Chengkai , Song Xiaoling , Hu Yunping , Gu Jun 
Published: January 2020

AbstractAnthrax toxin receptor 1 (ANTXR1), a type I transmembrane protein, is one of the receptors that facilitates the entrance of anthrax toxin into cells. Previous studies have confirmed the pivotal role of ANTXR1 in progression and tumorigenesis of diverse cancer types. However, the biological function of ANTXR1 in gastric cancer (GC) is still unknown. The present study aimed to investigate the role of ANTXR1 in GC and illuminate the potential molecular mechanisms. Bioinformatics analysis found that ANTXR1 expression was significantly upregulated in GC tissue and its overexpression was associated with poor prognosis of GC patients. Moreover, we confirmed the upregulation of ANTXR1 in GC cell lines and GC tissue by quantitative PCR, western blot analysis, and immunohistochemical analysis. Additionally, high protein expression level of ANTXR1 was positively associated with several clinicopathological parameters in GC patients. In our study, a series of in vitro and in vivo assays were undertaken through strategies of loss/gain‐of‐function and rescue assays. Consequently, our results indicated that ANTXR1 induced proliferation, cell cycle progression, invasion and migration, and tumorigenicity and induced suppressed apoptosis in GC. Mechanistic investigation indicated that ANTXR1 exerted its promoting effects on GC through activation of the PI3K/AKT/mTOR signaling pathway. In conclusion, our findings suggested that ANTXR1 plays a crucial role in the development and progression of GC and could serve as a novel prognostic biomarker and potential therapeutic target for GC.
Replisome genes regulation by antitumor miR‐101‐5p in clear cell renal cell carcinoma
Authors: Yamada Yasutaka , Nohata Nijiro , Uchida Akifumi , Kato Mayuko , Arai Takayuki , Moriya Shogo , Mizuno Keiko , Kojima Satoko , Yamazaki Kazuto , Naya Yukio , Ichikawa Tomohiko , Seki Naohiko 
Published: January 2020

AbstractAnalysis of microRNA (miRNA) regulatory networks is useful for exploring novel biomarkers and therapeutic targets in cancer cells. The Cancer Genome Atlas dataset shows that low expression of both strands of pre‐miR‐101 (miR‐101‐5p and miR‐101‐3p) significantly predicted poor prognosis in clear cell renal cell carcinoma (ccRCC). The functional significance of miR‐101‐5p in cancer cells is poorly understood. Here, we focused on miR‐101‐5p to investigate the antitumor function and its regulatory networks in ccRCC cells. Ectopic expression of mature miRNAs or siRNAs was investigated in cancer cell lines to characterize cell function, ie, proliferation, apoptosis, migration, and invasion. Genome‐wide gene expression and in silico database analyses were undertaken to predict miRNA regulatory networks. Expression of miR‐101‐5p caused cell cycle arrest and apoptosis in ccRCC cells. Downstream neighbor of son (DONSON) was directly regulated by miR‐101‐5p, and its aberrant expression was significantly associated with shorter survival in propensity score‐matched analysis (P = .0001). Knockdown of DONSON attenuated ccRCC cell aggressiveness. Several replisome genes controlled by DONSON and their expression were closely associated with ccRCC pathogenesis. The antitumor miR‐101‐5p/DONSON axis and its modulated replisome genes might be a novel diagnostic and therapeutic target for ccRCC.
Improved fuzzy weighted‐iterative association rule based ontology postprocessing in data mining for query recommendation applications
Authors: Sumathi G. , Akilandeswari J. 
Published: January 2020

AbstractThe usage of association rules is playing a vital role in the field of knowledge data discovery. Numerous rules have to be processed and plot based on the ranges on the schema. The step in this process depends on the user's queries. Previously, several projects have been proposed to reduce work and improve filtration processes. However, they have some limitations in preprocessing time and filtration rate. In this article, an improved fuzzy weighted‐iterative concept is introduced to overcome the limitation based on the user request and visualization of discovering rules. The initial step includes the mix of client learning with posthandling to use the semantics. The above advance was trailed by surrounding rule schemas to fulfill and anticipate unpredictable guidelines dependent on client desires. Preparing the above developments can be imagined by the use of yet another clever method of study. Standards on guidelines are recognized by the average learning professionals.
Factors that influence participation of Puerto Rican coffee farmers in conservation programs
Authors: Gladkikh Tatiana M. , Collazo Jaime A. , Torres‐Abreu Alejandro , Reyes Angelica M. , Molina Marysol 
Published: January 2020

AbstractSustainable, conservation‐oriented agricultural practices like shade coffee and agroforestry can enhance conservation objectives in tropical landscapes. Adoption of these practices, however, is influenced by numerous factors. We conducted a survey of 89 coffee farmers in Puerto Rico to understand their farming practices, experience with existing incentives, and willingness to participate in conservation programs. Quantitative analysis showed that current farming practices, farm size, and annual income from farming were associated with willingness to participate in conservation programs. Qualitative results suggested that financial considerations, conflicting state and federal incentives, lack of information about conservation programs, distrust in government, and land use restrictions might hinder participation. Some farmers perceived that sun farming—a practice incompatible with sustainable conservation—was required to be eligible for state agricultural incentives. The way some farmers practiced shade farming differed from the way suggested for conservation purposes, particularly in the type of shade trees and their cover density. Farmers highlighted the need for financial incentives to encourage adoption of shade farming. They also expressed concerns that participation in conservation programs could limit their land management autonomy. We suggest that availability of financial incentives, reconciliation of institutional barriers, increased outreach, and involvement of farmers in design of conservation programs can increase adoption and retention of conservation practices.
The role of historical sources in the restoration of Long Swamp, Discovery Bay, Victoria
Authors: Bachmann Mark R. 
Published: January 2020

Inspired by the success of restoration efforts in the adjacent Piccaninnie Ponds Karst Wetlands Ramsar site, the local community was anxious for progress to address observed changes to the hydrology of Long Swamp, near Nelson, Victoria. Uncertainty about the original character and condition of the wetland system required deep exploration of a vast range of historical reference material. This is a story of how disparate sources of historical information can complement modern scientific methods, help resolve contentious issues and contribute to refining reference ecosystem models to improve restoration outcomes.Long Swamp from Oxbow Lake (A) to Lake Momboeng (B), showing the Glenelg River Mouth (1) and ocean outlet locations at White Sands (2) and Nobles Rocks (3). The hypothesised original main direction of surface flows was from east to west (from B to A). N = north.image
Courtship display speed varies daily and with body size in the Ruffed Grouse (Bonasa umbellus)
Authors: Déaux Eloïse C. , O'Neil Nicholas P. , Jensen Ashley M. , Charrier Isabelle , Iwaniuk Andrew N. 
Published: January 2020

AbstractCourtship displays are typically comprised of the same behavioral pattern, or patterns, repeated several times by males. Both the quantity and quality of the displays produced by a given male bird are not, however, constant. The number and/or quality of displays can decrease over time, indicating fatigue, or males can increase the number and/or quality as they display more, indicating a warm‐up period. Although there is evidence for fatigue or warm‐up periods for many types of courtship displays, data on motor components of avian courtship are scant, despite how commonly they are used. Here, we test whether drumming, a non‐vocal motor display, in male ruffed grouse (Bonasa umbellus) changes in relation to the number of displays executed. Using a large number of recordings, our linear mixed models yielded a significant effect of cumulative number of drumming displays on the number of wingbeats per second, referred to as pulse rate. Across males, pulse rate is slowest when males begin drumming each day and increases until approximately 50 drumming displays have been produced. The rate of increase is also modulated by the nighttime low temperature such that cooler conditions are associated with lower pulse rates and a slower increase in pulse rate relative to the cumulative number of displays. Further, the maximum pulse rate recorded and average pulse rate after 50 displays is inversely correlated with body mass such that larger males are slower than smaller males. We suggest that the daily changes in pulse rate likely reflect a warm‐up period based upon the effects of cumulative drumming count and temperature on pulse rate. Whether these dynamic changes in the production of a motor display are informative to female grouse is unknown. However, we propose that daily changes in how motor displays are performed may be a common feature of avian courtship that has gone relatively unnoticed, despite the potential for motor performance to be a trait that is important for female mate choice.
Resolving fine‐scale population structure and fishery exploitation using sequenced microsatellites in a northern fish
Authors: Layton Kara K. S. , Dempson Brian , Snelgrove Paul V. R. , Duffy Steven J. , Messmer Amber M. , Paterson Ian G. , Jeffery Nicholas W. , Kess Tony , Horne John B. , Salisbury Sarah J. , Ruzzante Daniel E. , Bentzen Paul , Côté David , Nugent Cameron M. , Ferguson Moira M. , Leong Jong S. , Koop Ben F. , Bradbury Ian R. 
Published: January 2020

AbstractThe resiliency of populations and species to environmental change is dependent on the maintenance of genetic diversity, and as such, quantifying diversity is central to combating ongoing widespread reductions in biodiversity. With the advent of next‐generation sequencing, several methods now exist for resolving fine‐scale population structure, but the comparative performance of these methods for genetic assignment has rarely been tested. Here, we evaluate the performance of sequenced microsatellites and a single nucleotide polymorphism (SNP) array to resolve fine‐scale population structure in a critically important salmonid in north eastern Canada, Arctic Charr (Salvelinus alpinus). We also assess the utility of sequenced microsatellites for fisheries applications by quantifying the spatial scales of movement and exploitation through genetic assignment of fishery samples to rivers of origin and comparing these results with a 29‐year tagging dataset. Self‐assignment and simulation‐based analyses of 111 genome‐wide microsatellite loci and 500 informative SNPs from 28 populations of Arctic Charr in north‐eastern Canada identified largely river‐specific genetic structure. Despite large differences (~4X) in the number of loci surveyed between panels, mean self‐assignment accuracy was similar with the microsatellite loci and the SNP panel (>90%). Subsequent analysis of 996 fishery‐collected samples using the microsatellite panel revealed that larger rivers contribute greater numbers of individuals to the fishery and that coastal fisheries largely exploit individuals originating from nearby rivers, corroborating results from traditional tagging experiments. Our results demonstrate the efficacy of sequence‐based microsatellite genotyping to advance understanding of fine‐scale population structure and harvest composition in northern and understudied species.
Energy landscape of domain motion in glutamate dehydrogenase deduced from cryo‐electron microscopy
Authors: Oide Mao , Kato Takayuki , Oroguchi Tomotaka , Nakasako Masayoshi 
Published: January 2020

Analysis of the conformational changes of protein is important to elucidate the mechanisms of protein motions correlating with their function. Here, we studied the spontaneous domain motion of unliganded glutamate dehydrogenase from Thermococcus profundus using cryo‐electron microscopy and proposed a novel method to construct free‐energy landscape of protein conformations. Each subunit of the homo‐hexameric enzyme comprises nucleotide‐binding domain (NAD domain) and hexamer‐forming core domain. A large active‐site cleft is situated between the two domains and varies from open to close according to the motion of a NAD domain. A three‐dimensional map reconstructed from all cryo‐electron microscopy images displayed disordered volumes of NAD domains, suggesting that NAD domains in the collected images adopted various conformations in domain motion. Focused classifications on NAD domain of subunits provided several maps of possible conformations in domain motion. To deduce what kinds of conformations appeared in EM images, we developed a novel analysis method that describe the EM maps as a linear combination of representative conformations appearing in a 200‐ns molecular dynamics simulation as reference. The analysis enabled us to estimate the appearance frequencies of the representative conformations, which illustrated a free‐energy landscape in domain motion. In the open/close domain motion, two free‐energy basins hindered the direct transformation from open to closed state. Structure models constructed for representative EM maps in classifications demonstrated the correlation between the energy landscape and conformations in domain motion. Based on the results, the domain motion in glutamate dehydrogenase and the analysis method to visualize conformational changes and free‐energy landscape were discussed.DatabaseThe EM maps of the four conformations were deposited to Electron Microscopy Data Bank (EMDB) as accession codes EMD‐9845 (open), EMD‐9846 (half‐open1), EMD‐9847 (half‐open2), and EMD‐9848 (closed), respectively. In addition, the structural models built for the four conformations were deposited to the Protein Data Bank (PDB) as accession codes 6JN9 (open), 6JNA (half‐open1), 6JNC (half‐open2), and 6JND (closed), respectively.
On the fatigue crack growth behaviour of selective laser melting fabricated Inconel 625: Effects of build orientation and stress ratio
Authors: Hu Xiaoan , Xue Zhiyuan , Ren TingTing , Jiang Yun , Dong ChengLi , Liu Fencheng 
Published: January 2020

AbstractThe building of Inconel 625 material was carried out using the selective laser melting method, and its fatigue crack growth property at ambient temperature was experimentally investigated. Compact‐tension specimens with different building orientations were utilized to determine the stress intensity factor threshold and fatigue crack growth rate curves at different stress ratios (R). The results indicated that the fatigue crack growth properties in the near threshold stress intensity factor and Paris regions were greatly affected by the loading factor, as well as the orientation of the alloy. The mechanism of fatigue crack growth at different stages was observed and discussed using scanning electron microscopy. Finally, based on the framework of the linear elastic fracture, a new and applicable effective driving force factor range was introduced to replace the traditional stress intensity factor range (ΔK) with good accuracy for all of the fatigue crack growth test data, considering both the stress ratio and orientation.
Molybdenum Mass Fractions and Stable Isotope Compositions of Sedimentary Carbonate and Silicate Reference Materials
Authors: Gaspers Natalie , Magna Tomáš , Ackerman Lukáš 
Published: January 2020

A double‐spike method in combination with MC‐ICP‐MS was applied to obtain molybdenum (Mo) mass fractions and stable isotope compositions in a suite of sedimentary silicate (marine, lake, stream, estuarine, organic‐rich sediment, shales, slate, chert) and carbonate reference materials (coral, dolomite, limestones, carbonatites), and a manganese nodule reference material, poorly characterised for stable Mo isotope compositions. The Mo contents vary between 0.076 and 364 μg g−1, with low‐Mo mass fractions (< 0.29 μg g−1) found almost exclusively in carbonates. Intermediate Mo contents (0.73–2.70 μg g−1) are reported for silicate sediments, with the exception of chert JCh‐1 (0.24 μg g−1), organic‐rich shale SGR‐1b (36.6 μg g−1) and manganese nodule NOD‐A‐1 (364 μg g−1). The Mo isotope compositions (reported as δ98Mo relative to NIST SRM 3134) range from −1.77 to 1.03‰, with the intermediate precision varying between ± 0.01 and ± 0.12‰ (2s) for most materials. Low‐temperature carbonates show δ98Mo values ranging from 0.21 to 1.03‰ whereas δ98Mo values of −1.77 and −0.17‰ were obtained for carbonatites CMP‐1 and COQ‐1, respectively. Silicate materials have δ98Mo values varying from −1.56 to 0.73‰. The range of δ98Mo values in reference materials may thus reflect the increasingly important relevance of Mo isotope investigations in the fields of palaeoceanography, weathering, sedimentation and provenance, as well as the magmatic realm.
The membrane binding and deformation property of vaccinia virus K1 ankyrin repeat domain protein
Authors: Kitamata Manabu , Hotta Mitsukuni , Hamada‐Nakahara Sayaka , Suetsugu Shiro 
Published: January 2020

AbstractMembrane lipids are essential participants in cellular events, but only a small number of lipid‐interacting proteins have been characterized. Taking advantage of the small genome (~270 genes) of the vaccinia virus, we screened for soluble lipid‐binding proteins and found 27 proteins to be soluble after expression in Escherichia coli. Among them, 4 proteins were found to strongly bind to the total bovine brain lipid extract (Folch I fraction) that contained large amounts of phosphatidylserine in vitro. Out of the 4 proteins, 3 were unique proteins to viruses. Another protein, K1, solely contained an ankyrin repeat domain (ARD). ARD is conserved in large numbers of proteins in bacteria, archaea, eukaryotes and viruses, suggesting the possibilities of the membrane binding of ARDs in varieties of proteins. Furthermore, K1 deformed the lipid membrane dependently on the charged lipids. The tubulation and membrane binding was enhanced with increased negative membrane charge from phosphatidylinositol 4,5‐bisphosphate (PI(4,5)P2). The basic amino acid residues in the ARD were essential for membrane deformation, suggesting electrostatic interactions between K1 and the membrane for membrane deformation.
Loa loa filariasis in a tropical savanna area: report of one case in Ouagadougou
Authors: Ouédraogo Nomtondo A. , Korsaga‐Somé Nina , Traoré Fagnima , Kaboret Nadia , Zida Adama , Tapsoba Gilbert P. , Ouédraogo Muriel S. , Ouédraogo Moussa , Bougma Roland , Drabo François , Bougouma Clarisse , Barro‐Traoré Fatou , Niamba Pascal , Traoré Adama 
Published: January 2020

AbstractLoa loa filariasis is usually found in the forest areas of Central and West Africa. We report a case that was diagnosed in Ouagadougou (Burkina Faso), a savanna area. The patient lived in Gabon but was visiting his family in Ouagadougou. He complained of fatigue, fever, itchy legs with scratch marks, and intermittent edema of the legs. A blood smear was first examined for malaria parasites, but Loa loa microfilariae were observed. Laboratory tests showed hypereosinophilia (30%). Transient angioedema (Calabar edema) was observed. Loa loa filariasis was diagnosed based on these findings. There were no other laboratory test abnormalities, and ophthalmological examination was normal. The patient received a single dose of ivermectin at 200 µg/kg. After 1 month, the patient's course was favorable and a control blood smear was negative.