bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in brain network organization in adults with obesity as compared to healthy-weight individuals and seniors
Authors: Ottino-González J. , Baggio H.C. , Jurado M.A. , Segura B. , Caldú X. , Prats-Soteras X. , Tor C. , Sender-Palacios M.J. , Miró N. , Sánchez-Garre C. , Dadar M. , Dagher A. , García-García I. , Garolera M 
Published: June 2019

AbstractLife expectancy and obesity rates have drastically increased in recent years. An unhealthy weight is related to long-lasting biological deregulations that might compromise the normal course of aging. The aim of the current study was to test whether the network composition of young adults with obesity would show signs of premature aging. To this end, subjects with obesity (N = 30, mean age 32.8 ± 5.68), healthy-weight controls (N = 33, mean age 30.9 ± 6.24) as well as non-demented seniors (N = 30, mean age 67.1 ± 6.65) all underwent a resting-state MRI acquisition. Functional connectivity was studied by means of graph-theory measurements (i.e., small-world index, clustering coefficient, characteristic path length, and mean degree). Contrary to what expected, obesity in adults was related to disruptions in small-world properties driven by increases in network segregation (i.e., clustering coefficient) as compared to elders. Also, this group showed alterations in global and regional centrality metrics (i.e., degree) relative to controls and seniors. Despite not mimicking what was here shown by seniors, the topological organization linked to an obesity status may represent a flaw for cognitive functions depending on the rapid combination between different modular communities.
Ensemble-level organization of human kinetochores and evidence for distinct tension and attachment sensors
Authors: Roscioli Emanuele , Germanova Tsvetelina E. , Smith Christopher A. , Embacher Peter A. , Erent Muriel , Thompson Amelia I. , Burroughs Nigel J. , McAinsh Andrew D. 
Published: June 2019

SummaryKinetochores are multi-protein machines that form dynamic attachments to microtubules and generate the forces for chromosome segregation. High-fidelity is ensured because kinetochores can monitor attachment status and tension, using this information to activate checkpoints and error correction mechanisms. To explore how kinetochores achieve this we used two and three colour subpixel fluorescence localisation to define how six protein subunits from the major kinetochore complexes CCAN, MIS12, NDC80, KNL1, RZZ and the checkpoint proteins Bub1 and Mad2 are organised in the human kinetochore. This reveals how the kinetochore outer plate is a liquid crystal-like system with high nematic order and largely invariant to loss of attachment or tension except for two mechanical sensors. Firstly, Knl1 unravelling relays tension and secondly NDC80 jack-knifes under microtubule detachment, with only the latter wired up to the checkpoint signalling system. This provides insight into how kinetochores integrate mechanical signals to promote error-free chromosome segregation.
Endless Conflicts: Detecting Molecular Arms Races in Mammalian Genomes
Authors: Cooper Jacob C. , Leonard Christopher J. , Pedersen Brent S. , Carey Clayton M. , Quinlan Aaron R. , Elde Nels C. , Phadnis Nitin 
Published: June 2019

AbstractRecurrent positive selection at the codon level is often a sign that a gene is engaged in a molecular arms race – a conflict between the genome of its host and the genome of another species over mutually exclusive access to a resource that has a direct effect on the fitness of both individuals. Detecting molecular arms races has led to a better understanding of how evolution changes the molecular interfaces of proteins when organisms compete over time, especially in the realm of host-pathogen interactions. Here, we present a method for detection of gene-level recurrent positive selection across entire genomes for a given phylogenetic group. We deploy this method on five mammalian clades – primates, mice, deer mice, dogs, and bats – to both detect novel instances of recurrent positive selection and to compare the prevalence of recurrent positive selection between clades. We analyze the frequency at which individual genes are targets of recurrent positive selection in multiple clades. We find that coincidence of selection occurs far more frequently than expected by chance, indicating that all clades experience shared selective pressures. Additionally, we highlight Polymeric Immunoglobulin Receptor (PIGR) as a gene which shares specific amino acids under recurrent positive selection in multiple clades, indicating that it has been locked in a molecular arms race for ∼100My. These data provide an in-depth comparison of recurrent positive selection across the mammalian phylogeny, and highlights of the power of comparative evolutionary approaches to generate specific hypotheses about the molecular interactions of rapidly evolving genes.
The origin of the Gravettians: genomic evidence from a 36,000-year-old Eastern European
Authors: Bennett E. Andrew , Prat Sandrine , Péan Stéphane , Crépin Laurent , Yanevich Alexandr , Puaud Simon , Grange Thierry , Geigl Eva-Maria 
Published: June 2019

AbstractThe Gravettian technocomplex was present in Europe from more than 30,000 years ago until the Last Glacial Maximum, but the source of this industry and the people who manufactured it remain unsettled. We use genome-wide analysis of a ~36,000-year-old Eastern European individual (BuranKaya3A) from Buran-Kaya III in Crimea, the earliest documented occurrence of the Gravettian, to investigate relationships between population structures of Upper Palaeolithic Europe and the origin and spread of the culture. We show BuranKaya3A to be genetically close to both contemporary occupants of the Eastern European plain and the producers of the classical Gravettian of Central Europe 6,000 years later. These results support an Eastern European origin of an Early Gravettian industry practiced by members of a distinct population, who contributed ancestry to individuals from much later Gravettian sites to the west.
Enlarging the Scope of Randomization and Permutation Tests in Neuroimaging and Neuroscience
Authors: Maris Eric 
Published: June 2019

AbstractEspecially for the high-dimensional data collected in neuroscience, nonparametric statistical tests are an excellent alternative for parametric statistical tests. Because of the freedom to use any function of the data as a test statistic, nonparametric tests have the potential for a drastic increase in sensitivity by making a biologically-informed choice for a test statistic. In a companion paper (Geerligs & Maris, 2020), we demonstrate that such a drastic increase is actually possible. This increase in sensitivity is only useful if, at the same time, the false alarm (FA) rate can be controlled. However, for some study types (e.g., within-participant studies), nonparametric tests do not control the FA rate (see Eklund, Nichols, & Knutsson, 2016). In the present paper, we present a family of nonparametric randomization and permutation tests of which we prove exact FA rate control. Crucially, these proofs hold for a much larger family of study types than before, and they include both within-participant studies and studies in which the explanatory variable is not under experimental control. The crucial element of this statistical innovation is the adoption of a novel but highly relevant null hypothesis: statistical independence between the biological and the explanatory variable.
In vitroprototyping and rapid optimization of biosynthetic enzymes for cellular design
Authors: Karim Ashty S. , Dudley Quentin M. , Juminaga Alex , Yuan Yongbo , Crowe Samantha A. , Heggestad Jacob T. , Abdalla Tanus , Grubbe William , Rasor Blake , Coar Dave , Torculas Maria , Krein Michael , Liew FungMin (Eric) , Quattlebaum Amy , Jensen Rasmus O. , Stuart Jeff , Simpson Sean D. , Köpke Michael , Jewett Michael C. 
Published: June 2019

AbstractMicrobial cell factories offer an attractive approach for production of biobased products. Unfortunately, designing, building, and optimizing biosynthetic pathways remains a complex challenge, especially for industrially-relevant, non-model organisms. To address this challenge, we describe a platform forin vitroPrototyping andRapidOptimization ofBiosyntheticEnzymes (iPROBE). In iPROBE, cell lysates are enriched with biosynthetic enzymes by cell-free protein synthesis and then metabolic pathways are assembled in a mix-and-match fashion to assess pathway performance. We demonstrate iPROBE with two examples. First, we tested and ranked 54 different pathways for 3-hydroxybutyrate production, improvingin vivoproduction inClostridiumby 20-fold to 14.63 ± 0.48 g/L and identifying a new biosynthetic route to(S)-(+)-1,3-butanediol. Second, we used iPROBE and data-driven design to optimize a 6-stepn-butanol pathway, increasing titers 4-fold across 205 pathways, and showed strong correlation between cell-free and cellular performance. We expect iPROBE to accelerate design-build-test cycles for industrial biotechnology.
The SUMO Protease SENP3 regulates Mitochondrial Autophagy mediated by Fis1
Authors: Waters Emily , Wilkinson Kevin A. , Carmichael Ruth E. , Guo Chun 
Published: June 2019

AbstractMitochondria are unavoidably subject to organellar stress resulting from exposure to a range of reactive molecular species. Consequently, cells operate a poorly understood quality control programme of mitophagy to facilitate elimination of dysfunctional mitochondria. Here we use a model stressor, deferiprone (DFP), to investigate the molecular basis for stress-induced mitophagy. We show that mitochondrial fission 1 protein (Fis1) is required for DFP-induced mitophagy and that Fis1 is SUMOylated at K149, an amino acid residue critical for Fis1 mitochondrial localization. We find that DFP treatment leads to the stabilisation of the SUMO protease SENP3, which is mediated by downregulation of the E3 ubiquitin (Ub) ligase CHIP. SENP3 is responsible for Fis1 deSUMOylation and depletion of SENP3 abolishes DFP-induced mitochondrial mitophagy. Furthermore, preventing Fis1 SUMOylation by conservative K149R mutation enhances Fis1 mitochondrial localization. Critically, expressing a Fis1 K149R mutant restores DFP-induced mitophagy in SENP3 depleted cells. Thus, we propose a model in which SENP3-mediated deSUMOylation facilitates Fis1 mitochondrial localization to underpin stress-induced mitophagy.
Evolutionary implementation of Bayesian computations
Authors: Czégel Dániel , Giaffar Hamza , Zachar István , Tenenbaum Joshua B. , Szathmáry Eörs 
Published: June 2019

AbstractThe Bayesian framework offers a flexible language for the consistent modular assembly of statistical models used by both minds and machines. Another algorithmic domain capable of adaptation in potentially high-dimensional and uncertain environments is Darwinian evolution. The equivalence of their fundamental dynamical equations, replicator dynamics and Bayesian update, hints at a deeper algorithmic analogy. Here we show, based on a unified mathematical discussion of evolutionary dynamics and statistical learning in terms of Bayesian graphical models, that this is indeed the case. Building blocks of Bayesian computations, such as inference in hierarchical models, filtering in hidden Markov models, gradient likelihood optimization, and expectation-maximization dynamics of mixture models, map naturally to fundamental concepts of evolution: multilevel selection, quasispecies dynamics, phenotypic adaptation and ecological competition, respectively. We believe that these correspondences point towards a more comprehensive understanding of flavors of adaptive computation observed in Nature, as well as suggesting new ways to combine insights from the two domains in engineering applications.
De novo protein design enables precise induction of functional antibodies in vivo
Authors: Sesterhenn Fabian , Yang Che , Bonet Jaume , Cramer Johannes T , Wen Xiaolin , Wang Yimeng , Chiang Chi-I , Abriata Luciano A , Kucharska Iga , Castoro Giacomo , Vollers Sabrina S , Galloux Marie , Dheilly Elie , Rosset Stéphane , Corthésy Patricia , Georgeon Sandrine , Villard Mélanie , Richard Charles-Adrien , Descamps Delphyne , Delgado Teresa , Oricchio Elisa , Rameix-Welti Marie-Anne , Más Vicente , Ervin Sean , Eléouët Jean-François , Riffault Sabine , Bates John T , Julien Jean-Phillipe , Li Yuxing , Jardetzky Theodore , Krey Thomas , Correia Bruno E 
Published: June 2019

AbstractDe novo protein design has been successful in expanding the natural protein repertoire. However, most de novo proteins lack biological function, presenting a major methodological challenge. In vaccinology, the induction of precise antibody responses remains a cornerstone for next-generation vaccines. Here, we present a novel protein design algorithm, termed TopoBuilder, with which we engineered epitope-focused immunogens displaying complex structural motifs. Both in mice and non-human primates, cocktails of three de novo designed immunogens induced robust neutralizing responses against the respiratory syncytial virus. Furthermore, the immunogens refocused pre-existing antibody responses towards defined neutralization epitopes. Overall, our de novo design approach opens the possibility of targeting specific epitopes for vaccine and therapeutic antibody development, and more generally will be applicable to design de novo proteins displaying complex functional motifs.
Diverse cell junctions with unique molecular composition in tissues of a sponge (Porifera)
Authors: Mitchell Jennyfer M. , Nichols Scott A. 
Published: June 2019

AbstractThe integrity and organization of animal tissues depends upon specialized protein complexes that mediate adhesion between cells with each other (cadherin-based adherens junctions), and with the extracellular matrix (integrin-based focal adhesions). Reconstructing how and when these cell junctions evolved is central to understanding early tissue evolution in animals. We examined focal adhesion protein homologs in tissues of the freshwater sponge,Ephydatia muelleri(phylum Porifera). We found that sponge homologs of focal adhesion proteins co-precipitate as a complex and localize to cell junctions in sponge tissues. These data support that the adhesion roles of these proteins evolved early, prior to the divergence of sponges and other animals. However, in contrast to the spatially partitioned distribution of cell junctions in epithelia of other animals, focal adhesion proteins were found to be co-distributed with the adherens junction protein Emβ-catenin in sponge tissues; both at certain cell-cell and cell-extracellular matrix (ECM) adhesions. Sponge adhesion structures were found to be unique in other ways, too. The basopinacoderm (substrate-attachment epithelium) lacks typical polarity in that cell-ECM adhesions form on both basal and apical surfaces, and compositionally unique cell junctions form at the interface between cells with spicules (siliceous skeletal elements) and between cells and environmental bacteria. These results clarify the diversity, distribution and molecular composition of cell junctions in tissues ofE. muelleri, but raise new questions about their function and homology with cell junctions in other animals.
Maternal glucocorticoid levels during incubation predict breeding success, but not reproductive investment, in a free-ranging bird
Authors: Fischer Devin , Marrotte Robby R. , Chin Eunice H. , Coulson Smolly , Burness Gary 
Published: June 2019

ABSTRACTThe hormone corticosterone (CORT)) has been hypothesized to be linked with fitness, but the directionality of the relationship is unclear. The “CORT-fitness hypothesis” proposes that high levels of CORT arise from challenging environmental conditions, resulting in lower reproductive success (a negative relationship). In contrast, the “CORT-adaptation hypothesis” suggests that, during energetically demanding periods, CORT will mediate physiological or behavioural changes that result in increased reproductive investment and success (a positive relationship). During two breeding seasons, we experimentally manipulated circulating CORT levels in female tree swallows (Tachycineta bicolor) prior to egg laying, and measured subsequent reproductive effort, breeding success, and maternal survival. When females were recaptured during egg incubation and again during the nestling stage, the CORT levels were similar among individuals in each treatment group, and maternal treatment had no effect on indices of fitness. By considering variation among females, we found support for the “CORT-adaptation hypothesis”; there was a significant positive relationship between CORT levels during incubation and hatching and fledging success. During the nestling stage CORT levels were unrelated to any measure of investment or success. Within the environmental context of our study, relationships between maternal glucocorticoid levels and indices fitness vary across reproductive stages.SUMMARY STATEMENTMaternal corticosterone levels predict breeding success of female tree swallows.
Dynamics and variability of neuronal subtype responses during growth, degrowth, and regeneration
Authors: Havrilak Jamie A. , Al-Shaer Layla , Baban Noor , Akinci Nesli , Layden Michael J. 
Published: June 2019

AbstractBackgroundWe are interested in nervous system dynamics in adult and regenerating animals. Preliminary studies suggest that some species alter neuronal number to scale with changes in body size. Similarly, in some species regenerates resulting from wholebody axis regeneration are smaller than their pre-amputated parent, but they maintain the correct proportionality, suggesting that tissue and neuronal scaling also occurs in regenerates. The cell dynamics and responses of neuronal subtypes during nervous system regeneration, scaling, and whole-body axis regeneration are not well understood in any system. The cnidarian sea anemone Nematostella vectensis is capable of wholebody axis regeneration, and its transparent, “simple” body plan and the availability of fluorescent reporter transgenic lines allow neuronal subtypes to be tracked in vivo in adult and regenerating animals. A number of observations suggest this anemone is able to alter its size in responses to changes in feeding. We utilized the NvLWamide-like::mCherry neuronal subtype transgenic reporter line to determine the in vivo response of neuronal subtypes during growth, degrowth, and regeneration.ResultsNematostella alters its size in response to caloric intake, and the nervous system responds by altering neuronal number to scale as the animal changes in size. Neuronal numbers in both the endodermal and ectodermal nerve nets decreased as animals shrunk, increased as they grew, and the changes were reversible. Whole-body axis regeneration resulted in regenerates that were smaller than their pre-amputated size, and the regenerated nerve nets were reduced in neuronal number. Different neuronal subtypes had several distinct responses during regeneration that included consistent, no, and conditional increases in number. Conditional responses were regulated, in part, by the size of the remnant fragment and the position of the amputation site. Regenerates and adults with reduced nerve nets displayed normal behaviors, indicating that the nerve net retains functionality as it scales.ConclusionThese data suggest that the Nematostella nerve net is dynamic, capable of scaling with changes in body size, and that neuronal subtypes display differential regenerative responses, which we propose may be linked to the scale state of the regenerating animals.
Experience shapes activity dynamics and stimulus coding of VIP inhibitory and excitatory cells in visual cortex
Authors: Garrett Marina E. , Manavi Sahar , Roll Kate , Ollerenshaw Douglas R. , Groblewski Peter A. , Kiggins Justin , Jia Xiaoxuan , Casal Linzy , Mace Kyla , Williford Ali , Leon Arielle , Mihalas Stefan , Olsen Shawn R. 
Published: June 2019

ABSTRACTCortical circuits are flexible and can change with experience and learning. However, the effects of experience on specific cell types, including distinct inhibitory types, are not well understood. Here we investigated how excitatory and VIP inhibitory cells in layer 2/3 of mouse visual cortex were impacted by visual experience in the context of a behavioral task. Mice learned to perform an image change detection task with a set of eight natural scene images, viewing these images thousands of times. Subsequently, during 2-photon imaging experiments, mice performed the task with these familiar images and three additional sets of novel images. Novel images evoked stronger overall activity in both excitatory and VIP populations, and familiar images were more sparsely coded by excitatory cells. The temporal dynamics of VIP activity differed markedly between novel and familiar images: VIP cells were stimulus-driven by novel images but displayed ramping activity during the inter-stimulus interval for familiar images. Moreover, when a familiar stimulus was omitted from an expected sequence, VIP cells showed extended ramping activity until the subsequent image presentation. This prominent shift in response dynamics suggests that VIP cells may adopt different modes of processing during familiar versus novel conditions.HIGHLIGHTSExperience with natural images in a change detection task reduces overall activity of cortical excitatory and VIP inhibitory cellsEncoding of natural images is sharpened with experience in excitatory neuronsVIP cells are stimulus-driven by novel images but show pre-stimulus ramping for familiar imagesVIP cells show strong ramping activity during the omission of an expected stimulus
Hash-based core genome multi-locus sequencing typing for Clostridium difficile
Authors: Eyre David W , Peto Tim EA , Crook Derrick W , Walker A Sarah , Wilcox Mark H 
Published: June 2019

AbstractBackgroundPathogen whole-genome sequencing has huge potential as a tool to better understand infection transmission. However, rapidly identifying closely-related genomes among a background of thousands of other genomes is challenging.MethodsWe describe a refinement to core-genome multi-locus sequence typing (cgMLST) where alleles at each gene are reproducibly converted to a unique hash, or short string of letters (hash-cgMLST). This avoids the resource-intensive need for a single centralised database of sequentially-numbered alleles. We test the reproducibility and discriminatory power of cgMLST/hash-cgMLST compared to mapping-based approaches in Clostridium difficile using repeated sequencing of the same isolates (replicates) and data from consecutive infection isolates from six English hospitals.ResultsHash-cgMLST provided the same results as standard cgMLST with minimal performance penalty. Comparing 272 pairs of replicate sequences, using reference-based mapping there were 0, 1 or 2 SNPs between 262(96%), 5(2%) and 1(<1%) pairs respectively. Using hash-cgMLST or standard cgMLST, 197(72%) replicate pairs had zero gene differences, 37(14%), 8(3%) and 30(11%) pairs had 1, 2 and >2 differences respectively. False gene differences were clustered in specific genes and associated with fragmented assemblies. Considering 413 pairs of infections within ≤2 SNPS, i.e. consistent with recent transmission, 266(64%) had ≤2 gene differences and 50(12%) ≥5 differences. Comparing a genome to 100,000 others took <1 minute using hash-cgMLST.ConclusionHash-cgMLST is an effective surveillance tool that can rapidly identify clusters of related genomes. However, cgMLST/hash-cgMLST generates potentially more false variants than mapping-based analysis. Refined mapping-based variant calling is likely required to precisely define close genetic relationships.