bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAR study on inhibitors of GIIA secreted phospholipase A2 using machine learning methods
Authors: Zhang Shengde , Li Yang , Qin Zijian , Tu Guipin , Chen Guang , Yan Aixia 
Published: December 2018

AbstractGIIA secreted phospholipase A2 (GIIA sPLA2) is a potent target for drug discovery. To distinguish the activity level of the inhibitors of GIIA sPLA2, we built 24 classification models by three machine learning algorithms including support vector machine (SVM), decision tree (DT), and random forest (RF) based on 452 compounds. The molecules were represented by CORINA descriptors, MACCS fingerprints, and ECFP4 fingerprints, respectively. The dataset was split into a training set containing 312 compounds and a test set containing 140 compounds by Kohonen's self‐organizing map (SOM) strategy and a random strategy. A recursive feature elimination (RFE) method and an information gain (IG) method were used in the selection of molecular descriptors. Three favorable performing models were obtained. They were built by SVM algorithm with CORINA descriptors (Models 1A and 2A) and ECFP4 fingerprints (Model 10A). In the prediction of test set of Model 10A, the accuracy reached 90.71%, and the Matthews correlation coefficient (MCC) values reached 0.82. In addition, the 452 inhibitors were clustered into eight subsets by K‐Means algorithm for analyzing their structural features. It was found that highly active inhibitors mainly contained indole scaffold or indolizine scaffold and four side chains.
Peptide and protein mimetics by retro and retroinverso analogs
Authors: Rai Jagdish 
Published: December 2018

AbstractRetroinverso analog of a natural polypeptide can sometimes mimic the structure and function of the natural peptide. The additional advantage of using retroinverso analog is that it is resistant to proteolysis. The retroinverso analogs have peptide sequence in reverse direction with respect to natural peptide and also have chirality of amino acid inverted from L to D. The D amino acids cannot be recognized by common proteases of the body; therefore, these peptides will not be degraded easily and have a longer‐lasting effect as vaccine and inhibitor drugs. There have been many contested propositions about the geometric relationship between a peptide and its retro, inverso, or retroinverso analog. A retroinverso analog sometimes fails to adopt the structure that can mimic the function of the natural peptide. In such cases, partial retroinverso analog and other modifications can help in achieving the desired structure and function. Here, we review the theory, major experimental attempts, prediction methods, and alternative strategies related to retroinverso peptidomimetics.
Immunotherapies based on PD-1/PD-L1 pathway inhibitors in ovarian cancer treatment
Authors: Pawłowska A , Suszczyk D , Okła K , Barczyński B , Kotarski J , Wertel I 
Published: December 2018

Summary
Immunotherapies based on anti-programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway inhibitors may turn out effective in ovarian cancer (OC) treatment. They can be used in combination with standard therapy and are especially promising in recurrent and platinum-resistant OC. There is growing evidence that the mechanism of the PD-1/PD-L1 pathway can be specific for a particular histological cancer type. Interestingly, the data have shown that the PD-1/PD-L1 pathway blockade may be effective, especially in the endometrioid type of OC. It is important to identify the cause of anti-tumor immune response suppression and exclude its other mechanisms in OC patients. It is also necessary to conduct subsequent studies to confirm in which OC cases the treatment is effective and how to select patients and combine drugs to improve patient survival.
Sparse, Inconsistent and Unreliable: Tax Records and the World Inequality Report 2018
Authors: Galbraith James K. 
Published: December 2018

ABSTRACTThis article reviews the World Inequality Report 2018, a large collaborative data project based on the work of Thomas Piketty and the late Anthony Atkinson, which critiques the entire literature of inequality measurement from survey data and purports to provide superior, unprecedented and reliable coverage of income and wealth inequalities over the entire world, based primarily on tax records. The article examines three major issues: the coverage provided by tax data in the world economy, the consistency of tax data with other sources of information on income inequality, and the peculiarities of tax‐based measurement of inequality in the United States. Then a comparison is made with measures drawn from other forms of administrative data — specifically payroll records — which are generally more consistent with records of inequality measured in household surveys than are tax records. Following this, the article discusses the analysis of wealth and wealth inequality before offering a few closing remarks about policy.
Bilingual toddlers’ comprehension of mixed sentences is asymmetrical across their two languages
Authors: Potter Christine E. , Fourakis Eva , Morin‐Lessard Elizabeth , Byers‐Heinlein Krista , Lew‐Williams Casey 
Published: December 2018

AbstractIn bilingual language environments, infants and toddlers listen to two separate languages during the same key years that monolingual children listen to just one and bilinguals rarely learn each of their two languages at the same rate. Learning to understand language requires them to cope with challenges not found in monolingual input, notably the use of two languages within the same utterance (e.g., Do you like the perro? or ¿Te gusta el doggy?). For bilinguals of all ages, switching between two languages can reduce the efficiency in real‐time language processing. But language switching is a dynamic phenomenon in bilingual environments, presenting the young learner with many junctures where comprehension can be derailed or even supported. In this study, we tested 20 Spanish–English bilingual toddlers (18‐ to 30‐months) who varied substantially in language dominance. Toddlers’ eye movements were monitored as they looked at familiar objects and listened to single‐language and mixed‐language sentences in both of their languages. We found asymmetrical switch costs when toddlers were tested in their dominant versus non‐dominant language, and critically, they benefited from hearing nouns produced in their dominant language, independent of switching. While bilingualism does present unique challenges, our results suggest a united picture of early monolingual and bilingual learning. Just like monolinguals, experience shapes bilingual toddlers’ word knowledge, and with more robust representations, toddlers are better able to recognize words in diverse sentences.
Interspecific and intraspecific variation in diet preference in five Atlantic forest dung beetle species
Authors: Raine Elizabeth H. , Mikich Sandra B. , Lewis Owen T. , Slade Eleanor M. 
Published: December 2018

1. Dung beetles are commonly assumed to be generalist feeders, but there has been limited work in identifying whether there is interspecific variation in feeding preference. Equally, there has been no work exploring whether generalist feeding behaviour in a species is a result of within‐species specialisation.2. This study identified the individual and species‐level feeding preferences of five dung beetle species towards human, jaguar and pig dung using a choice experiment.3. It was found that species varied in their preference for the dung types, but there was no evidence that within a species, individual beetles varied in their dung choice. These findings were similar to results from field experiments that are more typically used to assess feeding preferences in dung beetles.4. The results suggest that individual specialism in feeding may not be common in dung beetles. However, there is variation in feeding preferences among species, which is often overlooked and can have implications for the ecosystem functions they provide. It is suggested that choice arenas can be used to assess feeding preferences in dung beetle species that are not abundant enough to reliably estimate dietary choice from field studies.
Evaluation of the effectiveness of the presentation of virtual histology slides by students during classes. Are there any differences in approach between dentistry and general medicine students?
Authors: Tauber Zdenek , Cizkova Katerina , Lichnovska Radka , Lacey Helena , Erdosova Bela , Zizka Radovan , Kamarad Vojtech 
Published: December 2018

AbstractIntroductionVirtual microscopy, used as a method to teach histology, has many undeniable advantages. However, the usefulness of this method is somewhat limited by the difficulties students face in finding their way through huge amounts of digital data, compounded by decreased interaction between students and teachers. We describe the results of a recent pilot project which combined the modern teaching methods of active learning, where students themselves present histological slides and make use of the virtual microscopy system.MethodsStudents’ responses to a structured questionnaire and examination results were evaluated.ResultsWe found that a combination of both electronic materials and textbooks was commonly used by students to prepare for practical teaching sessions, with electronic resources being used regularly by the majority of students. No statistically relevant differences were found between the approaches of dentistry vs general medicine students. Cooperation between students’ groups during the preparation for individual presentations was seen to be beneficial by a majority of dentistry students; they reported that the introduction of student‐led presentations improved their quality of preparation for practical lessons, as well as increasing their participation and activity level in the lessons themselves. These different approaches and motivations between students of dentistry and general medicine are reflected in the test results where dentistry students are more successful.ConclusionWe confirm that there are differences in motivation, approaches and examination results between both groups of students, which should be taken into account and which could lead to differentiation of future curricula for both study courses.
Sexual selection, environmental robustness, and evolutionary demography of maladapted populations: A test using experimental evolution in seed beetles
Authors: Martinossi‐Allibert Ivain , Thilliez Emma , Arnqvist Göran , Berger David 
Published: December 2018

AbstractWhether sexual selection impedes or aids adaptation has become an outstanding question in times of rapid environmental change and parallels the debate about how the evolution of individual traits impacts on population dynamics. The net effect of sexual selection on population viability results from a balance between genetic benefits of “good‐genes” effects and costs of sexual conflict. Depending on how these facets of sexual selection are affected under environmental change, extinction of maladapted populations could be either avoided or accelerated. Here, we evolved seed beetles under three alternative mating regimes to disentangle the contributions of sexual selection, fecundity selection, and male–female coevolution to individual reproductive success and population fitness. We compared these contributions between the ancestral environment and two stressful environments (elevated temperature and a host plant shift). We found evidence that sexual selection on males had positive genetic effects on female fitness components across environments, supporting good‐genes sexual selection. Interestingly, however, when males evolved under sexual selection with fecundity selection removed, they became more robust to both temperature and host plant stress compared to their conspecific females and males from the other evolution regimes that applied fecundity selection. We quantified the population‐level consequences of this sex‐specific adaptation and found evidence that the cost of sociosexual interactions in terms of reduced offspring production was higher in the regime applying only sexual selection to males. Moreover, the cost tended to be more pronounced at the elevated temperature to which males from the regime were more robust compared to their conspecific females. These results illustrate the tension between individual‐level adaptation and population‐level viability in sexually reproducing species and suggest that the relative efficacies of sexual selection and fecundity selection can cause inherent sex differences in environmental robustness that may impact demography of maladapted populations.
The use of biologic agents in the management of uveitis
Authors: Trivedi Amruta , Katelaris Constance 
Published: December 2018

AbstractThe uveitides are a heterogenous group of ocular inflammatory disorders that account for the third highest cause of blindness worldwide, responsible for 5–10% of visual impairment globally. Up to 35% of patients with uveitis can suffer significant vision loss. To prevent irreversible structural damage and blindness, it is important that the diagnosis and commencement of appropriate therapy occurs promptly. Management includes topical and systemic corticosteroid therapy and conventional immunomodulatory agents, including methotrexate, azathioprine, mycophenolate mofetil and cyclosporin. Significant progress has been made in the past decade in our understanding of the immunopathological pathways that drive intraocular inflammation, allowing the development of targeted therapy with biologic agents. These include TNF‐α inhibitors, such as infliximab, adalimumab and etanercept; interleukin blockers, such as tocilizumab and daclizumab; and other targeted therapies, such as rituximab and abatacept. The efficacy of these agents has been studied in cases of severe uveitis that are refractory to conventional immunomodulatory agents and provide exciting results that have revolutionised uveitis management. Though the biologic era has provided a large armamentarium to treat uveitis, ongoing challenges and cases of recalcitrant uveitis remain, posing a challenge to internal medicine physicians. This comprehensive review aims to construct an updated summary on the existing evidence pertaining to the use of biologic agents in the treatment of uveitis. Methods include a systematic search for studies between 2000 and 2018 using PubMed, EMBASE, Ovid MEDLINE and Cochrane libraries.
Variation in compositional and structural components of community assemblage and its determinants
Authors: Yao Jie , Zhang Chunyu , De Cáceres Miquel , Legendre Pierre , Zhao Xiuhai 
Published: December 2018

AbstractQuestionsWhat are the ecological processes that determine the spatial distribution of species and species diversity? Partitioning beta diversity can provide fundamental insights into the processes that determine the spatial variation of species assemblages. However, studying beta diversity is conventionally based only on species composition data, ignoring the structural component of communities.Study siteTemperate mixed broadleaf–conifer forest in Jiaohe, Jilin Province, northeastern China.MethodsWe characterized the variation of community assemblages in terms of species composition, size structure, or considering both components. We then employed environmental and spatial variables as explanatory factors to partition the variation in both compositional and structural components of community assemblage and assess the relative contributions of the niche and neutral processes to community assembly.ResultsThe values of overall beta diversity (BD statistics) and the relative contribution of individual sampling units to beta diversity (LCBD indices) depended on whether the species composition, size structure, or both together had been taken into account. The value of compositional–structural beta diversity was the largest, followed by traditional compositional beta diversity; the smallest was the structural beta diversity. The sites with high contributions to beta diversity (LCBD values) varied among structural and compositional components. The explanatory power of the environmental variables and the spatial variables also varied widely with different components of a community. The combination of environmental and spatial variables explained the highest proportion of variation (43.8%) in the compositional component and explained the lowest proportion of variation (25.4%) in the structural component of community assemblage.ConclusionBoth deterministic and stochastic processes are acting to determine community assemblages in terms of species composition and structure in our temperate forest site. Our study highlights the importance of considering the structural component of forest communities, in addition to compositional data, when studying beta diversity.
Daphnia galeata and D. dentifera are geographically and ecologically separated whereas their hybrids occur in intermediate habitats: A survey of 44 Chinese lakes
Authors: Ma Xiaolin , Hu Wei , Smilauer Petr , Yin Mingbo , Wolinska Justyna 
Published: December 2018

AbstractThe idea that hybridization promotes range expansion has received recent attention, but support from field studies is limited. We hypothesized that in the cladoceran waterflea genus Daphnia, parental species are geographically and ecologically separated, whereas hybrids occupy intermediate or occasionally extreme environments, potentially facilitating range expansion of parental species. We assessed the distribution of Daphnia dentifera, Daphnia galeata and their interspecific hybrids across 44 lakes in China (using mitochondrial and microsatellite markers), and related it to geographical and environmental lake descriptors. Parental species were geographically separated: D. dentifera occurred in western and central China, and D. galeata in eastern and central China, whereas hybrids were found in the western and central parts of the country. However, after controlling for geographical differences, the effect of environment on species distribution was strong and significant. Specifically, D. dentifera was present in high‐altitude oligotrophic lakes, D. galeata in low‐altitude eutrophic lakes and hybrids at intermediate to high altitudes, mainly in mesotrophic lakes. Microsatellite data indicated that hybrids were locally produced rather than having migrated from elsewhere; they probably resulted from encounters between expanding D. galeata and resident D. dentifera. The present study provides evidence that hybrids can survive in habitats that are otherwise suitable for only one of their parental species, emphasizing the importance of hybridization in expansion of species gene pools.
Plumage microbiota covaries with the major histocompatibility complex in blue petrels
Authors: Leclaire Sarah , Strandh Maria , Dell’Ariccia Gaia , Gabirot Marianne , Westerdahl Helena , Bonadonna Francesco 
Published: December 2018

AbstractTo increase fitness, a wide range of vertebrates preferentially mate with partners that are dissimilar at the major histocompatibility complex (MHC) or that have high MHC diversity. Although MHC often can be assessed through olfactory cues, the mechanism by which MHC genes influence odour remains largely unclear. MHC class IIB molecules, which enable recognition and elimination of extracellular bacteria, have been suggested to influence odour indirectly by shaping odour‐producing microbiota, i.e. bacterial communities. However, there is little evidence of the predicted covariation between an animal's MHC genotype and its bacterial communities in scent‐producing body surfaces. Here, using high‐throughput sequencing, we tested the covariation between MHC class IIB genotypes and feather microbiota in the blue petrel (Halobaena caerulea), a seabird with highly developed olfaction that has been suggested to rely on oduor cues during an MHC‐based mate choice. First, we show that individuals with similar MHC class IIB profiles also have similar bacterial assemblages in their feathers. Then, we show that individuals with high MHC diversity have less diverse feather microbiota and also a reduced abundance of a bacterium of the genus Arsenophonus, a genus in which some species are symbionts of avian ectoparasites. Our results, showing that feather microbiota covary with MHC, are consistent with the hypothesis that individual MHC genotype may shape the semiochemical‐producing microbiota in birds.
The Cu chaperone CopZ is required for Cu homeostasis in Rhodobacter capsulatus and influences cytochrome cbb3 oxidase assembly
Authors: Utz Marcel , Andrei Andreea , Milanov Martin , Trasnea Petru‐Iulian , Marckmann Dorian , Daldal Fevzi , Koch Hans‐Georg 
Published: December 2018

SummaryCu homeostasis depends on a tightly regulated network of proteins that transport or sequester Cu, preventing the accumulation of this toxic metal while sustaining Cu supply for cuproproteins. In Rhodobacter capsulatus, Cu‐detoxification and Cu delivery for cytochrome c oxidase (cbb3‐Cox) assembly depend on two distinct Cu‐exporting P1B‐type ATPases. The low‐affinity CopA is suggested to export excess Cu and the high‐affinity CcoI feeds Cu into a periplasmic Cu relay system required for cbb3‐Cox biogenesis. In most organisms, CopA‐like ATPases receive Cu for export from small Cu chaperones like CopZ. However, whether these chaperones are also involved in Cu export via CcoI‐like ATPases is unknown. Here we identified a CopZ‐like chaperone in R. capsulatus, determined its cellular concentration and its Cu binding activity. Our data demonstrate that CopZ has a strong propensity to form redox‐sensitive dimers via two conserved cysteine residues. A ΔcopZ strain, like a ΔcopA strain, is Cu‐sensitive and accumulates intracellular Cu. In the absence of CopZ, cbb3‐Cox activity is reduced, suggesting that CopZ not only supplies Cu to P1B‐type ATPases for detoxification but also for cuproprotein assembly via CcoI. This finding was further supported by the identification of a ~150 kDa CcoI‐CopZ protein complex in native R. capsulatus membranes.
Contributions of crust proteins to spore surface properties in Bacillus subtilis
Authors: Shuster Bentley , Khemmani Mark , Abe Kimihiro , Huang Xiaoyu , Nakaya Yusei , Maryn Nina , Buttar Sally , Gonzalez Adriana N. , Driks Adam , Sato Tsutomu , Eichenberger Patrick 
Published: December 2018

SummarySurface properties, such as adhesion and hydrophobicity, constrain dispersal of bacterial spores in the environment. In Bacillus subtilis, these properties are influenced by the outermost layer of the spore, the crust. Previous work has shown that two clusters, cotVWXYZ and cgeAB, encode the protein components of the crust. Here, we characterize the respective roles of these genes in surface properties using Bacterial Adherence to Hydrocarbons assays, negative staining of polysaccharides by India ink and Transmission Electron Microscopy. We showed that inactivation of crust genes caused increases in spore relative hydrophobicity, disrupted the spore polysaccharide layer, and impaired crust structure and attachment to the rest of the coat. We also found that cotO, previously identified for its role in outer coat formation, is necessary for proper encasement of the spore by the crust. In parallel, we conducted fluorescence microscopy experiments to determine the full network of genetic dependencies for subcellular localization of crust proteins. We determined that CotZ is required for the localization of most crust proteins, while CgeA is at the bottom of the genetic interaction hierarchy.