bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cis-regulatory change underlying the motor neuron-specific loss of terminal selector gene expression in immotile tunicate larvae
Authors: Lowe Elijah K. , Racioppi Claudia , Peyriéras Nadine , Ristoratore Filomena , Christiaen Lionel , Swalla Billie J. , Stolfi Alberto 
Published: March 2019

AbstractThe evolutionary history of animal body plans cannot be fully reconstructed without considering the roles of both novelties and losses. Some of the more remarkable examples of massively parallel evolutionary losses in animals comes from many species in the tunicate genusMolgulathat have independently lost the swimming larva and instead develop as tail-less, immotile larvae that bypass the period of swimming and dispersal observed in other tunicates, marine invertebrate chordates that alternate between motile larval and sessile adult life cycle stages. The larvae ofMolgula occultaand other tail-less species do not fully develop structures that are essential for swimming behavior, including notochord, tail muscles, and otolith, and loss-of-function mutations have been identified in various genes required for the differentiation of these tissues. However, little is known about the extent of development of the larval nervous system inM. occulta. While differentiated neurons might in principle be entirely dispensable to the non-swimming larva, the adult has a fully functional nervous system like any other tunicate. To further investigate this conundrum, we studied the specification and patterning of theM. occultaMotor Ganglion, which is the key central nervous system compartment that drives the motor movements of swimming tunicate larvae. We found that the expression patterns of important regulators of MG neuron subtype specification are highly conserved during the development of the non-swimming larvae ofM. occulta, suggesting that the gene networks regulating their expression are largely intact in this species, despite the loss of swimming ability. However, we identified aM. occulta-specific reduction in expression of the important motor neuron terminal selector geneEbf (Collier/Olf/EBF or COE)in the Motor Ganglion. AlthoughM. occulta Ebfis predicted to encode a fully functional protein, its expression was reduced in developing motor neurons when compared to species with swimming larvae, which was corroborated by measuring allele-specific expression ofEbfin interspecific hybrid embryos produced by crossingM. occultawith the closely related swimming speciesM. oculata. Comparative reporter construct experiments also revealed a specificcis-regulatory sequence change that underlies the reduced expression ofM. occulta Ebfin motor neurons, but not in other tissues and cell types. This points to a potential mechanism for arresting larval motor neuron differentiation in the non-swimming larvae of this species.
FSTand the Triangle Inequality for Biallelic Markers
Authors: Arbisser Ilana M. , Rosenberg Noah A. 
Published: March 2019

AbstractThe population differentiation statisticFST, introduced by Sewall Wright, is often treated as a pairwise distance measure between populations. As was known to Wright, however,FSTis not a true metric because allele frequencies exist for which it does not satisfy the triangle inequality. We prove that a stronger result holds: for biallelic markers whose allele frequencies differ across three populations,FSTneversatisfies the triangle inequality. We study the deviation from the triangle inequality as a function of the allele frequencies of three populations, identifying frequency vectors at which the deviation is maximal. We also examine the implications of the failure of the triangle inequality for the four-point condition for groups of four populations. Next, we examine the extent to whichFSTfails to satisfy the triangle inequality in genome-wide data from human populations, finding that some loci have frequencies that produce deviations near the maximum. We discuss the consequences of the theoretical results for various types of data analysis, including multidimensional scaling and inference of neighbor-joining trees from pairwiseFSTmatrices.
Multiple constrained minimum variance beamformer (MCMV) performance in connectivity analyses
Authors: Nunes Adonay S. , Moiseev Alexander , Kozhemiako Nataliia , Cheung Teresa , Ribary Urs , Doesburg Sam M. 
Published: March 2019

AbstractFunctional brain connectivity is increasingly being seen as critical for cognition, perception and motor control.Magnetoencephalography and electroencephalography are modalities that offer noninvasive mapping of electrophysiological interactions among brain regions, yet suffer from signal leakage and signal cancellation when estimating brain activity. This leads to biased connectivity values which complicate interpretation. In this study, we test the hypothesis that a Multiple Constrained Minimum Variance beamformer (MCMV) outperforms the more traditional Linearly Constrained Minimum Variance beamformer (LCMV) for estimation of electrophysiological connectivity. To this end, MCMV and LCMV performance is compared in task related analyses with both simulated data and human MEG recordings of visual steady state signals, and in resting state analyses with simulated data and human MEG data of 89 subjects. In task related scenarios connectivity was estimated using coherence and phase locking values, whereas envelope correlations were used for the resting state data. We also introduce a novel Augmented Pairwise MCMV (APW-MCMV) approach for signal leakage suppression in resting state analyses and assess its performance against LCMV and more conventional MCMV approaches. We demonstrate that with MCMV effects of signal mixing and coherent source cancellation are greatly reduced in both task related and resting state conditions, while in contrast to other approaches 0-and short time lag interactions are preserved. In addition, we demonstrate that in resting state analyses, APW-MCMV strongly reduces spurious connections while better controlling for false negatives compared to more conservative measures such as symmetrical orthogonalization.
A Novel Transfer Learning Approach for Toxoplasma Gondii Microscopic Image Recognition by Fuzzy Cycle Generative Adversarial Network
Authors: Li Sen , Li Aijia , Lara Diego Alejandro Molina , Marín Jorge Enrique Gómez , Juhas Mario , Zhang Yang 
Published: March 2019

AbstractToxoplasma gondii, one of the world’s most common parasites, can infect all types of warm-blooded animals, including one-third of the world’s human population. Most current routine diagnostic methods are costly, time-consuming, and labor-intensive. AlthoughT.gondiican be directly observed under the microscope in tissue or spinal fluid samples, this form of identification is difficult and requires well trained professionals. Nevertheless, the traditional identification of parasites under the microscope is still performed by a large number of laboratories. Novel, efficient and reliable methods ofT.gondiiidentification are therefore needed, particularly in developing countries. To this end, we developed a novel transfer learning based microscopic image recognition method forT.gondiiidentification. This approach employs Fuzzy Cycle Generative Adversarial Network (FCGAN) with transfer learning utilizing knowledge gained by the parasitologists that Toxoplasma is in banana or crescent shaped form. Our approach aims to build connection between micro and macro associated objects by embedding fuzzy C-means cluster algorithm into Cycle Generative Adversarial Network (Cycle GAN). Our approach achieves 93.1% and 94.0% detection accuracy for 400X and 1000X Toxoplasma microscopic images respectively. We show the high accuracy and effectiveness of our approach in the newly collected unlabeled Toxoplasma microscopic images, comparing to other current available deep learning methods. This novel method for Toxoplasma microscopic image recognition will open a new window for developing cost-effective and scalable deep learning based diagnostic solution, potentially enabling broader clinical access in developing countries.
Mutually suppressive roles of KMT2A and KDM5C in behaviour, neuronal structure, and histone H3K4 methylation
Authors: Vallianatos Christina N. , Raines Brynne , Porter Robert S. , Bonefas Katherine M. , Wu Michael C. , Garay Patricia M. , Collette Katie M. , Seo Young Ah , Dou Yali , Keegan Catherine E. , Tronson Natalie C. , Iwase Shigeki 
Published: March 2019

AbstractHistone H3 lysine 4 methylation (H3K4me) is extensively regulated by numerous writer and eraser enzymes in mammals. Nine H3K4me enzymes are associated with neurodevelopmental disorders to date, indicating their important roles in the brain. However, interplay among H3K4me enzymes during brain development remains largely unknown. Here, we show functional interactions of a writer-eraser duo,KMT2AandKDM5C, which are responsible for Wiedemann-Steiner Syndrome (WDSTS), and mental retardation X-linked syndromic Claes-Jensen type (MRXSCJ), respectively. Despite opposite enzymatic activities, the two mouse models deficient for eitherKmt2aorKdm5cshared reduced dendritic spines and increased aggression. Double mutation ofKmt2aandKdm5cclearly reversed dendritic morphology, key behavioral traits including aggression, and partially corrected altered transcriptomes and H3K4me landscapes. Thus, our study uncovers common yet mutually suppressive aspects of the WDSTS and MRXSCJ models and provides a proof of principle for balancing a single writer-eraser pair to ameliorate their associated disorders.
Comprehensive analysis of the internal structure and firmness in American cranberry (Vaccinium macrocarponAit.) fruit
Authors: Diaz-Garcia Luis , Rodriguez-Bonilla Lorraine , Phillips Matthew , Lopez-Hernandez Arnoldo , Grygleski Edward , Atucha Amaya , Zalapa Juan 
Published: March 2019

AbstractCranberry (Vaccinium macrocarponAit.) fruit quality traits encompass many properties. Among these, fruit firmness has become a quality standard due to the recent demand increase for sweetened and dried cranberries (SDC). Traditionally, this trait has been measured by the cranberry industry using compression tests; however, it is poorly understood how fruit firmness is influenced by other characteristics. In this study, we developed a high-throughput computer-vision method to measure the internal structure of cranberry fruit, which may in turn influence cranberry fruit firmness. We measured the internal structure of 16 cranberry cultivars measured over a 40-day period. Internal structure data paired with fruit firmness values at each evaluation period allowed us to explore the correlations between firmness and internal morphological characteristics.
Evolutionary changes of an intestinalLactobacillus reuteriduring probiotic manufacture
Authors: López Lázaro , Cardenas Paúl , Prado María B. , Trueba Gabriel 
Published: March 2019

ABSTRACTProbiotic bacteria are frequently used to treat intestinal (and other types of diseases) or to improve health, however little is known about the evolutionary changes of these bacteria during probiotic manufacture. It has been observed that when bacteria adapt to a new environment, they lose the skills to thrive in the original niche. In this study, a strain ofLactobacillus reuteriwas isolated from the duodenum of a mouse and subjected to 150 serial passes in milk to simulate industrial propagation of probiotic bacteria. The strain adapted to milk outperformed its ancestor in milk, but it showed reduced aptitude to grow culture media, and possibly in mouse intestines. Bacterial adaptation to milk seemed to select a number of non-synonymous mutations in metabolic genes.IMPORTANCEBacteria in the microbiota must endure hostile conditions including antagonism from other members of the microbial community. Little is known about the evolution of probiotic bacteria in the dairy industry. We show that repeated growth ofL. reuteriin milk results in reduced ability to grow in culture medium and possibly colonize the mammalian intestine. Our results contribute to the notion that probiotic bacteria colonize only transiently intestines.
The phytopathogenic nature ofDickeya aquatica174/2 and the dynamic early evolution ofDickeyapathogenicity
Authors: Duprey Alexandre , Taib Najwa , Leonard Simon , Garin Tiffany , Flandrois Jean-Pierre , Nasser William , Brochier-Armanet Céline , Reverchon Sylvie 
Published: March 2019

AbstractOriginality-Significance statementAlthough the reach of large-scale comparative studies has spread exponentially over the years, the phytopathogenicDickeyagroup remains overlooked. In this work, we sequence the complete genome ofDickeya aquaticatype strain, a species isolated from water that was first assumed to be non-phytopathogenic. We show that the proteome ofD. aquaticacontains a wide number of proteins involved inDickeyavirulence, including plant cell wall degrading enzymes, suggesting that this species could be in fact pathogenic. Using experimental approaches, we confirm this prediction and uncover the particular affinity ofD. aquaticafor acidic fruits. In-depth phylogenomic analyses reveal thatDickeyaspecies display a great degree of genetic plasticity in the pathogenicity determinants, explaining how this bacterial group was able to colonize a wide variety of plants growing in different climates. These observations greatly advance our understanding of how bacteria adapt to new ecological niches.SummaryDickeyais a genus of phytopathogenic enterobacterales causing soft rot in a variety of plants (e.g. potato, chicory, maize). Among the species affiliated to this genus,Dickeya aquatica, described in 2014, remained particularly mysterious because it had no known host. Furthermore, whileD. aquaticawas proposed to represent a deep-branching species amongDickeyagenus, its precise phylogenetic position remained elusive.Here, we report the complete genome sequence of theD. aquaticatype strain 174/2. We demonstrate the affinity ofD. aquaticaTfor acidic fruits such as tomato and cucumber, and show that exposure of this bacterium to acidic pH induces twitching motility. An in-depth phylogenomic analysis of all availableDickeyaproteomes pinpointsD. aquaticaas the second deepest branching lineage within this genus and reclassifies two lineages that likely correspond to new genomospecies (gs.):Dickeyags. poaceaephila (Dickeyasp NCPPB 569) andDickeyags. undicola (Dickeyasp 2B12), together with a new putative genus, tentatively namedProdigiosinella. Finally, from comparative analyses ofDickeyaproteomes we infer the complex evolutionary history of this genus, paving the way to study the adaptive patterns and processes ofDickeyato different environmental niches and hosts. In particular, we hypothetize that the lack of xylanases and xylose degradation pathways inD. aquaticacould reflects adaptation to aquatic charophyte hosts which, in contrast to land plants, do not contain xyloglucans.
Genomic investigation reveals contaminated detergent as the source of an ESBL-producing Klebsiella michiganensis outbreak in a neonatal unit
Authors: Chapman Paul , Forde Brian M. , Roberts Leah W. , Bergh Haakon , Vesey Debra , Jennison Amy V. , Moss Susan , Paterson David L. , Beatson Scott A. , Harris Patrick N. A. 
Published: March 2019

AbstractBackgroundKlebsiella species are problematic pathogens in neonatal units and may cause outbreaks, for which sources of transmission can be challenging to elucidate. We describe the use of whole genome sequencing (WGS) to investigate environmental sources of transmission during an outbreak of extended-spectrum-β-lactamase (ESBL)-producing Klebsiella michiganensis colonizing neonates.MethodsCeftriaxone-resistant Klebsiella spp. isolated from neonates (or their mothers) and the hospital environment were included. Short-read (Illumina) and long-read (MinION, Oxford Nanopore Technologies) sequencing was used to confirm species taxonomy, define antimicrobial resistance genes and determine phylogenetic relationships using single nucleotide polymorphism (SNP) profiling.ResultsA total of 21 organisms (10 patient-derived and 11 environmental isolates) were sequenced. Standard laboratory methods identified the outbreak strain as an ESBL-producing Klebsiella oxytoca, but taxonomic assignment from WGS data suggested closer identity to Klebsiella michiganensis. Strains isolated from baby bath drains and multiple detergent dispensing bottles were either identical or closely related by SNP comparison. Detergent bottles contaminated by K. michiganensis had been used for washing milk-expressing equipment. No new cases were identified once the detergent bottles were removed and the baby baths decommissioned.ConclusionsEnvironmental reservoirs may be an important source in outbreaks of multi-drug resistant organisms. WGS, in conjunction with traditional epidemiological investigation, can be instrumental in revealing routes of transmission and guiding infection control responses.Key pointsK. michiganensis can be misidentified as K. oxytoca and is probably under-recognized as a nosocomial pathogenWhole genome sequencing of neonatal and environmental isolates during an outbreak of ESBL-producing K. michiganensis confirmed contaminated detergent and sinks to be the source
Integrating deep and radiomics features in cancer bioimaging
Authors: Bizzego A. , Bussola N. , Salvalai D. , Chierici M. , Maggio V. , Jurman G. , Furlanello C. 
Published: March 2019

AbstractAlmost every clinical specialty will use artificial intelligence in the future. The first area of practical impact is expected to be the rapid and accurate interpretation of image streams such as radiology scans, histo-pathology slides, ophthalmic imaging, and any other bioimaging diagnostic systems, enriched by clinical phenotypes used as outcome labels or additional descriptors. In this study, we introduce a machine learning framework for automatic image interpretation that combines the current pattern recognition approach (“radiomics”) with Deep Learning (DL). As a first application in cancer bioimaging, we apply the framework for prognosis of locoregional recurrence in head and neck squamous cell carcinoma (N=298) from Computed Tomography (CT) and Positron Emission Tomography (PET) imaging. The DL architecture is composed of two parallel cascades of Convolutional Neural Network (CNN) layers merging in a softmax classification layer. The network is first pretrained on head and neck tumor stage diagnosis, then finetuned on the prognostic task by internal transfer learning. In parallel, radiomics features (e.g., shape of the tumor mass, texture and pixels intensity statistics) are derived by predefined feature extractors on the CT/PET pairs. We compare and mix deep learning and radiomics features into a unifying classification pipeline (RADLER), where model selection and evaluation are based on a data analysis plan developed in the MAQC initiative for reproducible biomarkers. On the multimodal CT/PET cancer dataset, the mixed deep learning/radiomics approach is more accurate than using only one feature type, or image mode. Further, RADLER significantly improves over published results on the same data.
RexAB is essential for the mutagenic repair ofStaphylococcus aureusDNA damage caused by co-trimoxazole
Authors: Clarke Rebecca S. , Bruderer Maya S. , Ha Kam Pou , Edwards Andrew M. 
Published: March 2019

AbstractCo-trimoxazole (SXT) is a combination therapeutic that consists of sulfamethoxazole and trimethoprim that is increasingly used to treat skin and soft-tissue infections caused by methicillin-resistantStaphylococcus aureus(MRSA). However, the use of SXT is limited to the treatment of low-burden, superficialS. aureusinfections and its therapeutic value is compromised by the frequent emergence of resistance. As a first step towards the identification of approaches to enhance the efficacy of SXT, we examined the role of bacterial DNA repair in antibiotic susceptibility and mutagenesis. This revealed that SXT caused DNA damage inS. aureusvia both thymidine limitation and the generation of reactive oxygen species. Then, using mutants defective for DNA repair, it was found that repair of this damage required the RexAB nuclease/helicase complex, indicating that SXT causes DNA double-strand breaks. Furthermore, RexAB-mediated DNA repair led to induction of the SOS response, which resulted in an increased mutation rate and may explain the frequent emergence of resistant strains during SXT therapy. In summary, this work determined that SXT causes DNA damage inS. aureusvia both thymidine limitation and oxidative stress, which is repaired by the RexAB complex, leading to induction of the mutagenic SOS response. Small molecule inhibitors of RexAB could therefore have therapeutic value by increasing the efficacy of SXT and decreasing the emergence of drug-resistance during treatment of infections caused byS. aureus.
Effect of task and attention on neural tracking of speech
Authors: Vanthornhout Jonas , Decruy Lien , Francart Tom 
Published: March 2019

AbstractEEG-based measures of neural tracking of natural running speech are becoming increasingly popular to investigate neural processing of speech and have applications in audiology. When the stimulus is a single speaker, it is usually assumed that the listener actively attends to and understands the stimulus. However, as the level of attention of the listener is inherently variable, we investigated how it affected neural envelope tracking. Using a movie as a distractor, we varied the level of attention while we estimated neural envelope tracking. We varied the intelligibility level by adding stationary noise. We found a significant difference in neural envelope tracking between the condition with maximal attention and the movie condition. This difference was most pronounced in the right-frontal region of the brain. The degree of neural envelope tracking was highly correlated with the stimulus signal-to-noise ratio, even in the movie condition. This could be due to residual neural resources to passively attend to the stimulus. When envelope tracking is used to objectively measure speech understanding this means that the procedure can be made more enjoyable and feasible by letting participants watch a movie during stimulus presentation.
Temperature accounts for the biodiversity of a hyperdiverse group of insects in urban Los Angeles
Authors: McGlynn Terrence P. , Meineke Emily K. , Bahlai Christie A. , Li Enjie , Hartop Emily A. , Adams Benjamin J. , Brown Brian V. 
Published: March 2019

AbstractThe urban heat island effect is a worldwide phenomenon that has been linked to species’ distributions and abundances in cities. However, effects of urban heat on biotic communities are nearly impossible to disentangle from effects of land cover in most cases because hotter urban sites also have less vegetation and more impervious surfaces than cooler sites within cities. We sampled phorid flies, one of the largest, most biologically diverse families of true flies (Insecta: Diptera: Phoridae), at 30 sites distributed within the central Los Angeles Basin, where we found that temperature and the density of urban land cover are decoupled. Abundance, richness, and community composition of phorids inside urban Los Angeles were most parsimoniously accounted for by mean air temperature in the week preceding sampling. Sites with intermediate mean temperatures had more phorid fly individuals and higher richness. Communities were more even at urban sites with lower minimum temperatures and sites located further away from natural areas, suggesting that communities separated from natural source populations may be more homogenized. Species composition was best explained by minimum temperature. Inasmuch as warmer areas within cities can predict future effects of climate change, phorid fly communities are likely to shift non-linearly under future climates in more natural areas. Exhaustive surveys of biotic communities within cities, such as the one we describe here, can provide baselines for determining the effects of urban and global climate warming as they intensify.