bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fingerprints of high-dimensional coexistence in complex ecosystems
Authors: Barbier Matthieu , de Mazancourt Claire , Loreau Michel , Bunin Guy 
Published: May 2019

AbstractThe coexistence of many competing species is a long-standing puzzle in ecology. Classic niche theory explains coexistence by trade-offs between a few essential species traits. Here we study an unexplored frontier of this theory: we assume that coexistence is intrinsically high-dimensional, arising from many traits and trade-offs at once. Species interactions then appear almost random, but their disorder hides a diffuse statistical structure: competitors that become successful start by subtly favoring each other, and partitioning their impacts on other species. We validate our quantitative predictions using data from grassland biodiversity experiments. We conclude that a high biodiversity can be attained through a pattern of collective organization that cannot be understood at the species level, but exhibits the fingerprint of high-dimensional interactions.
Polygenic risk score of alcohol consumption predicts alcohol-related morbidity and all-cause mortality
Authors: Kiiskinen Tuomo , Mars Nina J. , Palviainen Teemu , Koskela Jukka , Ripatti Pietari , Rämö Joel T. , Ruotsalainen Sanni ,   FinnGen, GSCAN Consortium, Palotie Aarno , Madden Pamela A.F. , Rose Richard J. , Kaprio Jaakko , Salomaa Veikko , Mäkelä Pia , Havulinna Aki S. , Ripatti Samuli 
Published: May 2019

AbstractObjectiveTo develop a highly polygenic risk score (PRS) for alcohol consumption and study whether it predicts alcohol-related morbidity and all-cause mortality.DesignBiobank-based prospective cohort studySettingFinnGen Study (Finland)Participants96,499 genotyped participants from the nationwide prospective FinnGen study and 36,499 participants from prospective cohorts (Health 2000, FINRISK, Twin Cohort) with detailed baseline data and up to 25 years of follow-up time.Main outcome measuresIncident alcohol-related morbidity and alcohol-related or all-cause mortality, based on hospitalizations, outpatient specialist care, drug purchases, and death reports.ResultsIn 96,499 FinnGen participants there were in total 4,785 first-observed incident alcohol-related health events. The PRS of alcohol consumption was associated with alcohol-related morbidity and the risk estimate (hazard ratio, HR) between the highest and lowest quintiles of the PRS was 1.67 [ 95 % confidence interval: 1.52-1.84], p=3.2*10−27). In 28,639 participants with comprehensive baseline data from prospective Health 2000 and FINRISK cohorts, 911 incident first alcohol-related events were observed. When adjusted for self-reported alcohol consumption, education, marital status, and gamma-glutamyl transferase blood levels, the risk estimate between the highest and lowest quintiles of the PRS was 1.58 (CI=[1.26-1.99], p=8.2*10−5). The PRS was also associated with all-cause mortality with a risk estimate of 1.33 between the highest and lowest quintiles (CI=[1.2-1.47], p=4.5e-08) in the adjusted model. In all 39,695 participants with self-reported alcohol consumption available, a 1 SD increase in the PRS was associated with 11.2 g (=0.93 drinks) higher weekly alcohol consumption (β=11.2 [9.85-12.58 g], p = 2.3*10−58).ConclusionsThe PRS for alcohol consumption associates for both alcohol-related morbidity and all-cause mortality. These findings underline the importance of heritable factors in alcohol-related behavior and the related health burden. The results highlight how measured genetic risk for an important behavioral risk factor can be used to predict related health outcomes.
IPSC-derived neuronal cultures expressing the Alzheimer’s disease associated rare TREM2 R47H variant enables the construction of an Aβ-induced gene regulatory network
Authors: Martins Soraia , Müller-Schiffmann Andreas , Bohndorf Martina , Wruck Wasco , Sleegers Kristel , Van Broeckhoven Christine , Korth Carsten , Adjaye James 
Published: May 2019

AbstractRecently, genes associated with immune response and inflammation have been identified as genetic risk factors for late-onset Alzheimer’s disease (LOAD). One of them is the rare p.Arg47His (R47H) variant within triggering receptor expressed on myeloid cells 2 (TREM2), which has been shown to increase the risk for developing AD 2-3-fold. Here, we report the generation and characterization of a model of LOAD using lymphoblast-derived iPSCs from patients harbouring the R47H mutation in TREM2 (AD TREM2 iPSCs), as well as from control individuals without dementia (CON iPSCs). iPSCs efficiently differentiate into mature neuronal cultures and comparative global transcriptome analysis identified a distinct gene expression profile in AD TREM2 neuronal cultures. Furthermore, manipulation of the iPSC-derived functional neuronal cultures with an Aβ-S8C dimer highlighted metabolic pathways, phagosome and immune response as the most perturbed pathways in AD TREM2 neuronal cultures. Through the construction of an Aβ-induced gene regulatory network, we were able to identify an Aβ signature linked to protein processing in the endoplasmic reticulum (ER) which emphasised ER-stress, as a potential causal role in LOAD. Overall, this study has shown that our AD-iPSC based model can be used for in-depth studies to better understand the molecular mechanisms underlying the etiology of LOAD and provides new opportunities for screening of potential therapeutic targets.
Membrane domains and phosphatase exclusion produce robust signaling responses in B cells engaged with natural ligands and artificial cross-linkers presented on lipid bilayers
Authors: Núñez Marcos Francisco , Wisser Kathleen , Veatch Sarah L 
Published: May 2019

AbstractB cells respond to a wide variety of antigens with varying valiancy and mode of presentation to the highly expressed B cell receptor (BCR). We previously demonstrated that clustering the IgM isotype of BCR with an artificial soluble cross-linker led to the stabilization of an ordered phase-like domain. This domain sorted minimal peptides and full-length proteins to generate local hot-spots for tyrosine phosphorylation at receptor clusters, facilitating receptor activation. BCR can also be activated through interactions with natural ligands or artificial cross-linkers presented at bilayer surfaces, where it is proposed that alternate mechanisms play important roles in receptor clustering and activation, including one mechanism involving the exclusion phosphatases due to their bulky extracellular domains. The goals of the current study are to determine if markers of membrane phases are sorted by BCR clusters formed through engagement with bilayer-presented natural ligands or cross-linkers, and to estimate the contribution that membrane phase partitioning plays in organizing regulatory proteins with respect to BCR clusters under these stimulation conditions. We use super-resolution fluorescence localization microscopy to find that BCR engagement with either a bilayer-presented natural ligand or artificial cross-linker generates ordered phase-like domains that are more robust than those observed with soluble cross-linkers. In addition, we provide evidence that interactions between regulatory proteins and BCR are partially determined through their preference for ordered membrane domains and present a minimal model of receptor activation that incorporates both ordered domains and steric exclusion mechanisms to produce a more sensitive response. Overall, this work highlights that cells are capable of integrating multiple interaction modalities to give rise to cellular functions, likely conferring flexibility and robustness to cellular responses.
Practical universalk-mer sets for minimizer schemes
Authors: DeBlasio Dan , Gbosibo Fiyinfoluwa , Kingsford Carl , Marçais Guillaume 
Published: May 2019

AbstractMinimizer schemes have found widespread use in genomic applications as a way to quickly predict the matching probability of large sequences. Most methods for minimizer schemes use randomized (or close to randomized) ordering ofk-mers when finding minimizers, but recent work has shown that not all non-lexicographic orderings perform the same. One way to findk-mer orderings for minimizer schemes is through the use of universalk-mer sets, which are subsets ofk-mers that are guaranteed to cover all windows. The smaller this set the fewer false positives (where two poorly aligned sequences being identified as possible matches) are identified. Current methods for creating universalk-mer sets are limited in the length of thek-mer that can be considered, and cannot compute sets in the range of lengths currently used in practice. We take some of the first steps in creating universalk-mer sets that can be used to construct minimizer orders for large values ofkthat are practical. We do this using iterative extension of thek-mers in a set, and guided contraction of the set itself. We also show that this process will be guaranteed to never increase the number of distinct minimizers chosen in a sequence, and thus can only decrease the number of false positives over using the current sets on smallk-mers.
Intragenic repeat expansions control yeast chronological aging
Authors: Barré Benjamin P , Hallin Johan , Yue Jia-Xing , Persson Karl , Mikhalev Ekaterina , Irizar Agurtzane , Thompson Dawn , Molin Mikael , Warringer Jonas , Liti Gianni 
Published: May 2019

ABSTRACTAging varies among individuals due to both genetics and environment but the underlying molecular mechanisms remain largely unknown. Using a highly recombinedSaccharomyces cerevisiaepopulation, we found 30 distinct Quantitative Trait Loci (QTLs) that control chronological life span (CLS) in calorie rich and calorie restricted environments, and under rapamycin exposure. Calorie restriction and rapamycin extended life span in virtually all genotypes, but through different genetic variants. We tracked the two major QTLs to massive expansions of intragenic tandem repeats in the cell wall glycoproteinsFLO11andHPF1, which caused a dramatic life span shortening. Life span impairment by N-terminalHPF1repeat expansion was partially buffered by rapamycin but not by calorie restriction. TheHPF1repeat expansion shifted yeast cells from a sedentary to a buoyant state, thereby increasing their exposure to surrounding oxygen. The higher oxygenation perturbed methionine, lipid, and purine metabolism, which likely explains the life span shortening. We conclude that fast evolving intragenic repeat expansions can fundamentally change the relationship between cells and their environment with profound effects on cellular life style and longevity.
Genomic potential for photoferrotrophy in a seasonally anoxic Boreal Shield lake
Authors: Tsuji JM , Tran N , Schiff SL , Venkiteswaran JJ , Molot LA , Tank M , Hanada S , Neufeld JD 
Published: May 2019

AbstractPhotoferrotrophy, the light-induced oxidation of ferrous iron, is thought to have contributed to primary production within Earth’s early anoxic oceans yet is presumed to be of little modern environmental relevance. Here we use genome-resolved metagenomics and enrichment cultivation to explore the potential for photoferrotrophy in the anoxic water columns of globally abundant Boreal Shield lakes. We recovered four high-completeness and low-contamination draft genome bins assigned to the class Chlorobia (formerly phylum Chlorobi) from environmental metagenome data and enriched two novel sulfide-oxidizing species, also from the Chlorobia. The sequenced genomes of both enriched species, including the novel “Candidatus Chlorobium canadense”, encoded the cyc2 candidate gene marker for iron oxidation, suggesting the potential for photoferrotrophic growth. Surprisingly, one of the environmental genome bins encoded cyc2 and lacked sulfur oxidation gene pathways altogether. Despite the presence of cyc2 in the corresponding draft genome, we were unable to induce photoferrotrophy in “Ca. Chlorobium canadense”, suggesting that yet-unexplored mechanisms regulate expression of sulfide and ferrous iron oxidation gene systems, or that previously unrecognized functions for this outer membrane cytochrome exist. Doubling the known diversity of Chlorobia-associated cyc2 genes, metagenome data showed that putative photoferrotrophic populations occurred in one lake but that only sulfide-oxidizing populations were present in a neighboring lake, implying that strong ecological or geochemical controls govern the favourability of photoferrotrophy in aquatic environments. These results indicate that anoxygenic photoautotrophs in Boreal Shield lakes could have unexplored metabolic diversity that is controlled by ecological and biogeochemical drivers pertinent to understanding Earth’s early microbial communities.
Humans can efficiently look for but not select multiple visual objects
Authors: Ort Eduard , Fahrenfort Johannes J. , ten Cate Tuomas , Eimer Martin , Olivers Christian N.L. 
Published: May 2019

AbstractThe human brain recurrently prioritizes task-relevant over task-irrelevant visual information. A central, question is whether multiple objects can be prioritized simultaneously. To answer this, we let observers search for two colored targets among distractors. Crucially, we independently varied the number of target colors that observers anticipated, and the number of target colors actually used to distinguish the targets in the display. This enabled us to dissociate the preparation of selection mechanisms from the actual engagement of such mechanisms. Multivariate classification of electroencephalographic activity allowed us to track selection of each target separately across time. The results revealed only small neural and behavioral costs associated with preparing for selecting two objects, but substantial costs when engaging in selection. Further analyses suggest this cost is the consequence of neural competition resulting in limited parallel processing, rather than a serial bottleneck. The findings bridge diverging theoretical perspectives on capacity limitations of feature-based attention.
Evolutionary forces on different flavors of intrinsic disorder in the human proteome
Authors: Forcelloni Sergio , Giansanti Andrea 
Published: May 2019

ABSTRACTIn this study, we perform a systematic analysis of evolutionary forces (i.e., mutational bias and natural selection) that shape the codon usage bias of human genes encoding for different structural and functional variants of proteins. Well-structured proteins are expected to be more under control by natural selection than intrinsically disordered proteins because one or few mutations (even synonymous) in the genes can result in a protein that no longer folds correctly. On the contrary, intrinsically disordered proteins are generally thought to evolve more rapidly than well-folded proteins, primarily attributed to relaxed purifying natural selection due to the lack of structural constraints. Using different genetic tools, we find compelling evidence that intrinsically disordered proteins are the variant of human proteins on which both mutational bias and natural selection act more effectively, corroborating their essential role for evolutionary adaptability and protein evolvability. We speculate that intrinsically disordered proteins have a high tolerance to mutations (both neutral and adaptive) but also a selective propensity to preserve their structural disorder, i.e., flexibility and conformational dynamics under physiological conditions. Additionally, we confirm not only that intrinsically disordered proteins are preferentially encoded by GC-rich genes, but also that they are characterized by the highest fraction of CpG-sites in the sequences, implying a higher susceptibility to methylation resulting in C-T transition mutations. Our results provide new insight about protein evolution and human genetic diseases identifying intrinsically disordered proteins as reservoirs for evolutionary innovations.
Partial-resistance against aphids in wild barley reduces the oviposition success of the generalist parasitoid,Aphidius colemaniViereck
Authors: Leybourne Daniel. J. , Valentine Tracy. A. , Bos Jorunn. I. B. , Karley Alison. J. 
Published: May 2019

AbstractAphids are significant agricultural pests of cereal crops with a worldwide distribution. The control of aphids in agricultural systems is currently heavily reliant on insecticidal compounds, but it is becoming increasingly apparent that chemical-based control of agricultural pests has far-reaching unintended consequences on agro-ecosystems. As a result, more sustainable means of aphid control are becoming increasingly desirable. Potential options include increasing plant resistance against aphids, promoting biocontrol, and the combined use of both strategies. When used together it is important to understand how, and to what extent, increased plant resistance against aphids affects the success of biocontrol agents. In this current study, we examine how partial-resistance against cereal aphids in a wild relative of barley,Hordeum spontaneum 5(Hsp5), affects the success of the common parasitoid of cereal aphids,Aphidius colemani. We show that the parasitism success ofA. colemaniattacking nymphs of the bird cherry-oat aphid,Rhopalosiphum padi, contained on Hsp5 is reduced compared with the parasitism success of wasps attackingR. padinymphs feeding on a susceptible modern cultivar of barley,H. vulgarecv. Concerto.Explantaparasitism assays showed that the in parasitoid success is a direct effect of the plant environment (such as differential architectural traits), rather than an indirect effect dur to a decrease in aphid suitability resulting from increased resistance against aphids in Hsp5. Our study highlights the importance of understanding the direct and indirect effects of plant resistance against aphids on biocontrol strategies.
Learning lexical-syntactic biases: An fMRI study on how we connect words and syntactic information
Authors: Weber K. , Meyer A. , Hagoort P. 
Published: May 2019

AbstractLanguage processing often involves learning new words and how they relate to each other. These relations are realized through syntactic information connected to a word, e.g. a word can be verb or a noun, or both, like the word ‘run’. In a behavioral and an fMRI task we showed that words and their syntactic properties, i.e. lexical items which were either syntactically ambiguous or unambiguous, can be learned through the probabilities of co-occurrence in an exposure session and subsequently used in a production task. Novel words were processed within regions of the language network (left inferior frontal and posterior middle temporal gyrus) and more syntactic options led to higher activations herein, even when the words were shown in isolation, suggesting combined lexical-syntactic representation. When words were shown in untrained grammatical contexts, activation in left inferior frontal cortex increased. This might reflect competition between the newly learned representation and the presented information. The results elucidate the lexical nature of the neural representations of lexical-syntactic information within the language network and the specific role of the left inferior frontal cortex in unification of the novel words with the surrounding context.
Auditory processing atypicalities for pure tones and complex speech sounds in Rett Syndrome – towards neuromarkers of disease progression
Authors: Sysoeva Olga V. , Molholm Sophie , Djukic Aleksandra , Frey Hans-Peter , Foxe John J. 
Published: May 2019

ABSTRACTDue to severe motor impairments and the lack of expressive language abilities seen in most patients with Rett Syndrome (RTT), it has proven extremely difficult to obtain accurate measures of auditory processing capabilities in this population. Here, we examined early auditory cortical processing of pure tones and more complex phonemes females with confirmed mutation of the MECP2 gene. We recorded high-density auditory evoked potentials (AEP), which allow for objective evaluation of the timing and severity of processing deficits along the auditory processing hierarchy. We compared AEPs of 12 females with RTT to those of 21 typically developing (TD) peers aged 4-21 years, interrogating the first four major components of the AEP (P1: 60-90ms; N1: 100-130ms; P2: 135-165ms; N2: 245-275ms). Atypicalities were evident in RTT at the initial stage of processing. Whereas the initial P1 showed increased amplitude to phonemic inputs relative to tones in TD participants, this modulation by stimulus complexity was absent in RTT. Interestingly, the subsequent N1 did not differ between groups, whereas the following P2 was hugely diminished in RTT, regardless of stimulus complexity. The N2 was similarly smaller in RTT, and did not differ as a function of stimulus type. The P2 effect was remarkably robust in differentiating between groups with near perfect separation between the two groups despite the wide age range of our samples. Given this robustness, along with the observation that P2 amplitude was significantly associated with RTT symptom severity, the P2 has the potential to serve as a biomarker of treatment efficacy.Significance statementOur study points to dramatic reduction of the P2 component of the auditory evoked potential (AEP) as a potentially reliable biomarker of Rett Syndrome severity, with prospective applicability as an objective readout (neuromarker) of change in functional brain activity following therapeutic interventions administered in the context of clinical trials. Compellingly, the reduction of P2 amplitude in patients with RTT mimics findings in animal models of RTT, providing a translational bridge between pre-clinical and human research.
Investigating Transfusion-Related Sepsis using Culture-Independent Metagenomic Sequencing
Authors: Crawford Emily , Kamm Jack , Miller Steve , Li Lucy M. , Caldera Saharai , Lyden Amy , Yokoe Deborah , Nichols Amy , Tran Nam K. , Barnard Sarah E. , Conner Peter M. , Nambiar Ashok , Zinter Matt S. , Moayeri Morvarid , Serpa Paula Hayakawa , Prince Brian C. , Quan Jenai , Sit Rene , Tan Michelle , Phelps Maira , DeRisi Joseph L. , Tato Cristina M. , Langelier Charles 
Published: May 2019

AbstractBackgroundTransfusion-related sepsis remains an important hospital infection control challenge. Investigating septic transfusion events is often restricted by the limitations of bacterial culture in terms of time requirements and low yield in the setting of prior antibiotic administration.MethodsIn three Gram-negative septic transfusion cases, we performed mNGS of direct clinical blood specimens in addition to standard culture-based approaches utilized for infection control investigations. Pathogen detection leveraged IDSeq, a new open-access microbial bioinformatics portal. Phylogenetic analysis was performed to assess microbial genetic relatedness and understand transmission events.ResultsmNGS of direct clinical blood specimens afforded precision detection of pathogens responsible for each case of transfusion-related sepsis, and enabled discovery of a novel Acinetobacter species in a platelet product that had become contaminated despite photochemical pathogen reduction. In each case, longitudinal assessment of pathogen burden elucidated the temporal sequence of events associated with each transfusion-transmitted infection. We found that informative data could be obtained from culture-independent mNGS of residual platelet products and leftover blood specimens that were either unsuitable or unavailable for culture, or that failed to grow due to prior antibiotic administration. We additionally developed methods to enhance accuracy for detecting transfusion-associated pathogens sharing taxonomic similarity to contaminants commonly found in mNGS library preparations.ConclusionsCulture-independent mNGS of blood products afforded rapid and precise assessment of pathogen identity, abundance and genetic relatedness. Together, these challenging cases demonstrated the potential for metagenomics to advance existing methods for investigating transfusion-transmitted infections.