bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Effects of Feature-based Attention Depend on Surprise
Authors: Smout Cooper A. , Garrido Marta I. , Mattingley Jason B. 
Published: September 2019

AbstractRecent studies have shown that prediction and attention can interact under various circumstances, suggesting that the two processes are based on interdependent neural mechanisms. In the visual modality, attention can be deployed to the location of a task-relevant stimulus (‘spatial attention’) or to a specific feature of the stimulus, such as colour or shape, irrespective of its location (‘feature-based attention’). Here we asked whether predictive processes are influenced by feature-based attention outside the current spatial focus of attention. Across two experiments, we recorded neural activity with electroencephalography (EEG) as human observers performed a feature-based attention task at fixation and ignored a stream of peripheral stimuli with predictable or surprising features. Central targets were defined by a single feature (colour or orientation) and differed in salience across the two experiments. Task-irrelevant peripheral patterns usually comprised one particular conjunction of features (standards), but occasionally deviated in one or both features (deviants). Consistent with previous studies, we found reliable effects of feature-based attention and prediction on neural responses to task-irrelevant patterns in both experiments. Crucially, we observed an interaction between prediction and feature-based attention in both experiments: the neural effect of feature-based attention was larger for surprising patterns than it was for predicted patterns. These findings suggest that global effects of feature-based attention depend on surprise, and are consistent with the idea that attention optimises the precision of predictions by modulating the gain of prediction errors.Significance StatementTwo principal mechanisms facilitate the efficient processing of sensory information: prediction uses prior information to guide the interpretation of sensory events, whereas attention biases the processing of these events according to their behavioural relevance. A recent theory proposes to reconcile attention and prediction under a unifying framework, casting attention as a ‘precision optimisation’ mechanism that enhances the gain of prediction errors. Crucially, this theory suggests that attention and prediction interact to modulate neural responses, but this hypothesis remains to be tested with respect to feature-based attention mechanisms outside the spatial focus of attention. Here we show that global effects of feature-based attention are enhanced when stimuli possess surprising features, suggesting that feature-based attention and prediction are interdependent neural mechanisms.
Re-definition of claudin-low as a breast cancer phenotype
Authors: Fougner Christian , Bergholtz Helga , Norum Jens Henrik , Sørlie Therese 
Published: September 2019

The claudin-low breast cancer subtype is defined by gene expression characteristics and encompasses a remarkably diverse range of breast tumors. Here, we investigate genomic, transcriptomic, and clinical features of claudin-low breast tumors. We show that claudin-low is not simply a subtype analogous to the intrinsic subtypes (basal-like, HER2-enriched, luminal A, luminal B and normal-like) as previously portrayed, but is a complex additional phenotype which may permeate breast tumors of various intrinsic subtypes. Claudin-low tumors were distinguished by low genomic instability, mutational burden and proliferation levels, and high levels of immune and stromal cell infiltration. In other aspects, claudin-low tumors reflected characteristics of their intrinsic subtype. Finally, we have developed an alternative method for identifying claudin-low tumors and thereby uncovered potential weaknesses in the established claudin-low classifier. In sum, these findings elucidate the heterogeneity in claudin-low breast tumors, and substantiate a re-definition of claudin-low as a cancer phenotype.Contact informationC.F. christian.fougner@rr-research.noH.B. helga.bergholtz@rr-research.noJ.H.N. jens.henrik.norum@rr-research.noT.S. therese.sorlie@rr-research.no
Chemical variations in Quercus pollen as a tool for taxonomic identification: implications for long-term ecological and biogeographical research
Authors: Muthreich Florian , Zimmermann Boris , Birks H. John B. , Vila-Viçosa Carlos M. , Seddon Alistair W.R 
Published: September 2019

vi.AbstractAimFossil pollen is an important tool for understanding biogeographic patterns in the past, but the taxonomic resolution of the fossil-pollen record may be limited to genus or even family level. Chemical analysis of pollen grains has the potential to increase the taxonomic resolution of pollen, but present-day chemical variability is poorly understood. This study aims to investigate whether a phylogenetic signal is present in the chemical variations of Quercus L. pollen and to assess the prospects of chemical techniques for identification in biogeographic research.LocationPortugalTaxonSix taxa (five species, one subspecies) of Quercus L., Q. faginea, Q. robur, Q. robur ssp. estremadurensis, Q. coccifera, Q. rotundifolia and Q. suber belonging to three sections: Cerris, Ilex, and Quercus (Denk, Grimm, Manos, Deng, & Hipp, 2017)MethodsWe collected pollen samples from 297 individual Quercus trees across a 4° (∼450 km) latitudinal gradient and determined chemical differences using Fourier-transform infrared spectroscopy (FTIR). We used canonical powered partial least-squares regression (CPPLS) and discriminant analysis to describe within- and between-species chemical variability.ResultsWe find clear differences in the FTIR spectra from Quercus pollen at the section level (Cerris: ∼98%; Ilex: ∼100%; Quercus: ∼97%). Successful discrimination is based on spectral signals related to lipids and sporopollenins. However, discrimination of species within individual Quercus sections is more difficult: overall, species recall is ∼76% and species misidentifications within sections lie between 18% and 31% of the test-set.Main ConclusionsOur results demonstrate that subgenus level differentiation of Quercus pollen is possible using FTIR methods, with successful classification at the section level. This indicates that operator-independent FTIR approaches can surpass traditional morphological techniques using the light microscope. Our results have implications both for providing new insights into past colonisation pathways of Quercus, and likewise for forecasting future responses to climate change. However, before FTIR techniques can be applied more broadly across palaeoecology and biogeography, our results also highlight a number of research challenges that still need to be addressed, including developing sporopollenin-specific taxonomic discriminators and determining a more complete understanding of the effects of environmental variation on pollen-chemical signatures in Quercus.
Neuro-Current Response Functions: A Unified Approach to MEG Source Analysis under the Continuous Stimuli Paradigm
Authors: Das Proloy , Brodbeck Christian , Simon Jonathan Z. , Babadi Behtash 
Published: September 2019

AbstractCharacterizing the neural dynamics underlying sensory processing is one of the central areas of investigation in systems and cognitive neuroscience. Neuroimaging techniques such as magnetoencephalography (MEG) and Electroencephalography (EEG) have provided significant insights into the neural processing of continuous stimuli, such as speech, thanks to their high temporal resolution. Existing work in the context of auditory processing suggests that certain features of speech, such as the acoustic envelope, can be used as reliable linear predictors of the neural response manifested in M/EEG. The corresponding linear filters are referred to as temporal response functions (TRFs). While the functional roles of specific components of the TRF are well-studied and linked to behavioral attributes such as attention, the cortical origins of the underlying neural processes are not as well understood. In this work, we address this issue by estimating a linear filter representation of cortical sources directly from neuroimaging data in the context of continuous speech processing. To this end, we introduce Neuro-Current Response Functions (NCRFs), a set of linear filters, spatially distributed throughout the cortex, that predict the cortical currents giving rise to the observed ongoing MEG (or EEG) data in response to continuous speech. NCRF estimation is cast within a Bayesian framework, which allows unification of the TRF and source estimation problems, and also facilitates the incorporation of prior information on the structural properties of the NCRFs. To generalize this analysis to M/EEG recordings which lack individual structural magnetic resonance (MR) scans, NCRFs are extended to free-orientation dipoles and a novel regularizing scheme is put forward to lessen reliance on fine-tuned coordinate co-registration. We present a fast estimation algorithm, which we refer to as the Champ-Lasso algorithm, by leveraging recent advances in optimization, and demonstrate its utility through application to simulated and experimentally recorded MEG data under auditory experiments. Our simulation studies reveal significant improvements over existing methods that typically operate in a two-stage fashion, in terms of spatial resolution, response function reconstruction, and recovering dipole orientations. The analysis of experimentally-recorded MEG data without MR scans corroborates existing findings, but also delineates the distinct cortical distribution of the underlying neural processes at high spatiotemporal resolution. In summary, we provide a principled modeling and estimation paradigm for MEG source analysis tailored to extracting the cortical origin of electrophysiological responses to continuous stimuli.
Genetic Basis ofDe NovoAppearance of Carotenoid Ornamentation in Bare-Parts of Canaries
Authors: Anna Gazda Małgorzata , Toomey Matthew B. , Araújo Pedro M. , Lopes Ricardo J. , Afonso Sandra , Myers Connie A. , Serres Kyla , Kiser Philip D. , Hill Geoffrey E. , Corbo Joseph C. , Carneiro Miguel 
Published: September 2019

ABSTRACTUnlike wild and domestic canaries (Serinus canaria), or any of the three dozen species of finches in genusSerinus, the domestic urucum breed of canaries exhibits bright red bills and legs. This novel bare-part coloration offers a unique opportunity to understand how leg and bill coloration evolve in birds. To identify the causative locus, we resequenced the genome of urucum canaries and performed a range of analyses to search for genotype-to-phenotype associations across the genome. We identified a nonsynonymous mutation in the geneBCO2(beta-carotene oxygenase 2, also known asBCDO2), an enzyme involved in the cleavage and breakdown of full-length carotenoids into short apocarotenoids. Protein structural models andin vitrofunctional assays indicate that the urucum mutation abrogates the carotenoid cleavage activity of BCO2. Consistent with the predicted loss of carotenoid cleavage activity, urucum canaries had increased levels of full-length carotenoid pigments in bill tissue and a significant reduction in levels of carotenoid cleavage products (apocarotenoids) in retinal tissue compared to other breeds of canaries. We hypothesize that carotenoid-based bare-part coloration might be readily gained, modified, or lost through simple switches in the enzymatic activity or regulation ofBCO2and this gene may be an important mediator in the evolution of bare-part coloration among bird species.
Null models for community dynamics: Beware of the cyclic shift algorithm
Authors: Kalyuzhny Michael 
Published: September 2019

AbstractAimTemporal patterns of community dynamics are drawing increasing interest due to their potential to shed light on assembly processes and anthropogenic effects. However, interpreting such patterns considerably benefits from comparing observed dynamics to the reference of a null model. For that aim, the cyclic shift permutations algorithm, which generates randomized null communities based on empirically observed time series, has recently been proposed. The use of this algorithm, which shifts each species time series randomly in time, has been justified by the claim that it preserves the temporal autocorrelation of single species. Hence it has been used to test the significance of various community patterns, in particular excessive compositional changes, biodiversity trends and community stability.InnovationHere we critically study the properties of the cyclic shift algorithm for the first time. We show that, unlike previously suggested, this algorithm does not preserve temporal autocorrelation due to the need to “wrap” the time series and assign the last observations to the first years. Moreover, this algorithm scrambles the initial state of the community, making any dynamics that results from deviations from equilibrium seem excessive. We exemplify that these two issues lead to a highly elevated type I error rate in tests for excessive compositional changes and richness trends.ConclusionsCaution is needed when using the cyclic shift permutation algorithm and interpreting results obtained using it. Interpretation is further complicated because the algorithm removes all correlations between species. We suggest guidelines for using this method and discuss several possible alternative approaches. More research is needed on the best practices for using null models for temporal patterns.
Differences in the chitinolytic activity of mammalian chitinases on soluble and crystalline substrates
Authors: Barad Benjamin A. , Liu Lin , Diaz Roberto Efrain , Basilio Ralp , Van Dyken Steven J. , Locksley Richard M. , Fraser James S. 
Published: September 2019

AbstractChitin is an abundant polysaccharide used by a large range of organisms for structural rigidity and water repulsion. As such, the insoluble crystalline structure of chitin poses significant challenges for enzymatic degradation. Vertebrates do not produce chitin, but do express chitin degrading enzymes. Acidic mammalian chitinase, the primary enzyme involved in the degradation of environmental chitin in mammalian lungs, is a processive glycosyl hydrolase that may be able to make multiple hydrolysis events for each binding event. Mutations to acidic mammalian chitinase have been associated with asthma, and genetic deletion of the enzyme in mice results in significantly increased morbidity and mortality with age. We initially set out to reverse this phenotype by engineering hyperactive acidic mammalian chitinase variants. Using a directed evolution screening approach using commercial fluorogenic substrates, we identified mutations with consistent increases in activity. To determine whether the activity increases observed with oligomeric substrates were consistent with more biologically relevant chitin substrates, we developed new assays to quantify chitinase activity with colloidal crystalline chitin, and identified a high throughput fluorogenic assay that gives sufficient signal to noise advantages to quantify changes to activity due to the addition or removal of a chitin binding domain to the enzyme. We show that the activity increasing mutations derived from our directed evolution screen were lost when crystalline substrates were used. In contrast, naturally occurring gain-of-function mutations gave similar results with oligomeric and crystalline substrates. We also show that the activity differences between acidic mammalian chitinase and chitotriosidase are reduced in the context of crystalline substrate, suggesting that previously reported activity differences with oligomeric substrates may have been largely driven by differential substrate specificity for the oligomers. These results highlight the need for assays against more physiological substrates when engineering complex metabolic enzymes, and provide a new approach that may be broadly applicable to engineering glycosyl hydrolases.
Integrated evolutionary and structural analysis reveals xenobiotics and pathogens as the major drivers of mammalian adaptation
Authors: Slodkowicz Greg , Goldman Nick 
Published: September 2019

AbstractUnderstanding the molecular basis of adaptation to the environment is a central question in evolutionary biology, yet linking detected signatures of positive selection to molecular mechanisms remains challenging. Here we demonstrate that combining sequence-based phylogenetic methods with structural information assists in making such mechanistic interpretations on a genomic scale. Our integrative analysis shows that positively selected sites tend to co-localise on protein structures and that positively selected clusters are found in functionally important regions of proteins, indicating that positive selection can contravene the well-known principle of evolutionary conservation of functionally important regions. This unexpected finding, along with our discovery that positive selection acts on structural clusters, opens new strategies for the development of better models of protein evolution. Remarkably, proteins where we detect the strongest evidence of clustering belong to just two functional groups: components of immune response and metabolic enzymes. This gives a coherent picture of immune response and xenobiotic metabolism as the drivers of adaptive evolution of mammals.
Early pathological signs in youngdysf−/−mice are improved by halofuginone
Authors: Barzilai-Tutsch Hila , Genin Olga , Pines Mark , Halevy Orna 
Published: September 2019

AbstractDysferlinopathies are a non-lethal group of late-onset muscular dystrophies. Here, we evaluated the fusion ability of primary myoblasts from youngdysf−/−mice and the muscle histopathology prior to, and during early stages of disease onset. The ability of primary myoblasts of 5-weekolddysf−/−mice to form large myotubes was delayed compared to their wild-type counterparts, as evaluated by scanning electron microscopy. However, their fusion activity, as reflected by the presence of actin filaments connecting several cells, was enhanced by the antifibrotic drug halofuginone. Early dystrophic signs were already apparent in 4-week-olddysf−/−mice; their collagen level was double that in wild-type mice and continued to rise until 5 months of age. Continuous treatment with halofuginone from 4 weeks to 5 months of age reduced muscle fibrosis in a phosphorylated-Smad3 inhibition-related manner. Halofuginone also enhanced myofiber hypertrophy, reduced the percentage of centrally nucleated myofibers, and increased muscle performance. Together, the data suggest an inhibitory effect of halofuginone on the muscle histopathology at very early stages of dysferlinopathy, and better generation of force and muscle performance. These results offer new opportunities for early pharmaceutical treatment in dysferlinopathies with favorable outcomes at later stages of life.
AfricanSalmonellaTyphimurium sequence type 313 lineage 2 evades MAIT cell recognition by overexpressing RibB
Authors: Preciado-Llanes Lorena , Aulicino Anna , Canals Rocío , Moynihan Patrick , Zhu Xiaojun , Jambo Ndaru , Nyirenda Tonney , Kadwala Innocent , Owen Siân V. , Veerapen Natacha , Besra Gurdyal S. , Gordon Melita A. , Hinton Jay C. D. , Napolitani Giorgio , Salio Mariolina , Simmons Alison 
Published: September 2019

SUMMARYMucosal-associated invariant T (MAIT) cells are a subset of innate T lymphocytes activated by bacteria that produce vitamin B2 metabolites. Mouse models of infection have demonstrated a role for MAIT cells in antimicrobial defence. However, proposed protective roles of MAIT cells in human infections remain unproven and clinical conditions associated with a selective absence of MAIT cells have not been identified. We report that typhoidal and non-typhoidalS. entericastrains generally activate MAIT cells. However, African invasive disease-associated multidrug-resistantS.Typhimurium sequence type 313 lineage 2 strains escape MAIT cell recognition through overexpression ofribB, a bacterial gene that encodes the 4-dihydroxy-2-butanone 4-phosphate synthase enzyme of the riboflavin biosynthetic pathway. This MAIT cell-specific phenotype did not extend to other innate lymphocytes. We propose thatribBoverexpression is an evolved trait that facilitates evasion from immune recognition by MAIT cells and contributes to the invasive pathogenesis ofS.Typhimurium sequence type 313 lineage 2in vivo.
A unified simulation model for understanding the diversity of cancer evolution
Authors: Niida Atsushi , Hasegawa Takanori , Innan Hideki , Shibata Tatsuhiro , Mimori Koshi , Miyano Satoru 
Published: September 2019

ABSTRACTBecause cancer evolution underlies the therapeutic difficulties of cancer, it is clinically important to understand the evolutionary dynamics of cancer. Thus far, a number of evolutionary processes have been proposed to be working in cancer evolution. However, there exists no simulation model that can describe the different evolutionary processes in a unified manner. In this study, we constructed a unified simulation model for describing the different evolutionary processes and performed sensitivity analysis on the model to determine the conditions in which cancer growth is driven by each of the different evolutionary processes. Our sensitivity analysis has successfully provided a series of novel insights into the evolutionary dynamics of cancer. For example, we found that, while a high neutral mutation rate shapes neutral intratumor heterogeneity (ITH) characterized by a fractal-like pattern, a stem cell hierarchy can also contribute to shaping neutral ITH by apparently increasing the mutation rate. Although It has been reported that the evolutionary principle shaping ITH shifts from selection to accumulation of neutral mutations during colorectal tumorigenesis, our simulation revealed the possibility that this evolutionary shift is triggered by drastic evolutionary events that occur in a a short time and confer a marked fitness increase on one or a few cells. This result helps us understand that each process works not separately but simultaneously and continuously as a series of phases of cancer evolution. Collectively, this study serves as a basis to understand in greater depth the diversity of cancer evolution.