bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive evolution among cytoplasmic piRNA proteins leads to decreased genomic auto-immunity
Authors: Wang Luyang , Barbash Daniel A. , Kelleher Erin S. 
Published: January 2019

AbstractIn metazoan germlines, the piRNA pathway acts as a genomic immune system, employing small RNA-mediated silencing to defend host DNA from the harmful effects of transposable elements (TEs). In response to dynamic changes in TE content, host genomes are proposed to alter the piRNAs that they produce in order to silence the most active TE families. Surprisingly, however, piRNA pathway proteins, which execute piRNA biogenesis and enforce silencing of targeted sequences, also evolve rapidly and adaptively in animals. If TE silencing evolves through changes in piRNAs, what necessitates changes in piRNA pathway proteins? Here we used interspecific complementation to test for functional differences betweenDrosophila melanogasterandD. simulansalleles of three adaptively evolving piRNA pathway proteins: Armitage, Aubergine and Spindle-E. Surprisingly, we observed interspecific divergence in the regulation of only a handful of TE families, which were more robustly silenced by the heterospecific piRNA pathway protein. This suggests that positive selection does not act on piRNA effector proteins to enhance their function in TE repression, but rather that TEs may evolve to “escape” silencing by homospecific alleles. We also discovered thatD. simulansalleles ofaubandarmiexhibit enhanced off-target effects on host transcripts in aD. melanogasterbackground, suggesting the avoidance of genomic auto-immunity as a critical target of selection. Our observations suggest that piRNA effector proteins are subject to an evolutionary trade-off between defending the host genome from the harmful effect of TEs while also minimizing friendly fire against host genes.Author SummaryTransposable elements are mobile fragments of selfish DNA that burden host genomes with deleterious mutations and incite genome instability. Host cells employ a specialized small-RNA mediated silencing pathway, the piRNA pathway, to act as a genomic immune system suppressing the mobilization of TEs. Changes in genomic TE content are met with rapid changes in the piRNA pool, thereby maintain host control over transposition. However, piRNA pathway proteins—which enact piRNA biogenesis and silence target TEs—also evolve adaptively. To isolate forces that underlie this adaptive evolution, we examined functional divergence between twoDrosophilaspecies for three adaptively evolving piRNA pathway proteins. To our surprise, we found very few differences in TE regulation, suggesting that evolution has not generally acted to enhance control of TE parasites. Rather, we discovered interspecific differences in the regulation of host mRNAs for two proteins, which suggested that proteins evolve to avoid off-target silencing of host transcripts. We propose that the avoidance of such “genomic autoimmunity” is an important and underappreciated force driving the adaptive evolution of piRNA proteins.
SHARQnet - Sophisticated Harmonic Artifact Reduction in Quantitative Susceptibility Mapping using a Deep Convolutional Neural Network
Authors: Bollmann Steffen , Kristensen Matilde Holm , Larsen Morten Skaarup , Olsen Mathias Vassard , Pedersen Mads Jozwiak , Østergaard Lasse Riis , O’Brien Kieran , Langkammer Christian , Fazlollahi Amir , Barth Markus 
Published: January 2019

AbstractQuantitative susceptibility mapping (QSM) reveals pathological changes in widespread diseases such as Parkinson’s disease, Multiple Sclerosis, or hepatic iron overload. QSM requires multiple processing steps after the acquisition of magnetic resonance imaging (MRI) phase measurements such as unwrapping, background field removal and the solution of an ill-posed field-to-source-inversion. Current techniques utilize iterative optimization procedures to solve the inversion and background field correction, which are computationally expensive and lead to suboptimal or over-regularized solutions requiring a careful choice of parameters that make a clinical application of QSM challenging. We have previously demonstrated that a deep convolutional neural network can invert the magnetic dipole kernel with a very efficient feed forward multiplication not requiring iterative optimization or the choice of regularization parameters. In this work, we extended this approach to remove background fields in QSM. The prototype method, called SHARQnet, was trained on simulated background fields and tested on 3T and 7T brain datasets. We show that SHARQnet outperforms current background field removal procedures and generalizes to a wide range of input data without requiring any parameter adjustments. In summary, we demonstrate that the solution of ill-posed problems in QSM can be achieved by learning the underlying physics causing the artifacts and removing them in an efficient and reliable manner and thereby will help to bring QSM towards clinical applications.
Hippocampal morphometry in sudden and unexpected death in epilepsy (SUDEP)
Authors: Somani Alyma , Zborovschi Anita-Beatrix , Liu Yan , Patodia Smriti , Michalak Zuzanna , Sisodiya Sanjay M , Thom Maria 
Published: January 2019

ABSTRACTObjectiveTo determine hippocampal morphometric parameters, including granule cell dispersion and features of malrotation, as potential biomarkers for SUDEP from an archival post-mortem series.MethodsIn a retrospective study of 187 archival post-mortems from three groups, SUDEP (68; 14 with hippocampal sclerosis (HS)), non-SUDEP epilepsy controls (EP-C =66; 25 with HS) and non-epilepsy controls (NEC= 53), Nissl/H&E stained sections from left and right hippocampus from five coronal levels were digitised. Image analysis was carried out for granule cell layer (GCL) thickness and measurements of hippocampal dimensions (HD) for shape [width (HD1), height (HD2)] and medial hippocampal positioning in relation to the parahippocampal gyrus (PHG) length (HD3). A qualitative evaluation of hippocampal malrotational (HMAL) features, dentate gyrus invaginations (DGI) and subicular/CA1 folds (SCF) was also made.ResultsGCL thickness was increased in HS more than those without (p<0.001). In non-HS cases increased GCL thickness was noted in EP-C compared to NEC (p<0.05) but not between SUDEP and NEC. There was no significant difference in the frequency of DGI, SCF, measurements of hippocampal shape (HD1, HD2 or ratio) or medial positioning between SUDEP, EP-C and NEC groups, when factoring in HS, coronal level and age at death. Comparison between left and right sides within cases showed significantly greater PHG lengths (HD3) on the right side in the SUDEP group only (p=0.018)ConclusionsNo hippocampal morphometric features were identified in support of either excessive granule cell dispersion or features of HMAL as biomarkers for SUDEP. Asymmetries in PHG measurements in SUDEP warrant further investigation as they may indicate abnormal central autonomic networks.
The time course of updating in running span
Authors: Kaur Shraddha , Norris Dennis , Gathercole Susan E 
Published: January 2019

AbstractRunning span can be performed by either passively listening to to-be-remembered items or actively updating the target set during presentation. This choice of strategy is influenced by the rate of presentation in the task. Previous research suggests that the active updating process is demanding and time-consuming. It is favored at relatively slow rates of presentation, while the passive strategy is more successful when applied at fast rates. In two experiments the time course of resource demand during task performance and its sensitivity to presentation rate was examined. We hypothesized that running span imposes a high cognitive load only when active updating is employed. Participants performed running span simultaneously with a spatial reaction time (RT) task, and RTs on the concurrent task were used to index the resource demands of the memory task. A slow-paced running span exhibited a large overall resource demand in comparison with the serial recall tasks (Experiment 1) and fast-paced running span (Experiment 2). This demand was observed from the position in the list from which participants are presumed to start updating, suggesting a cognitive shift to a demanding mode of updating. In addition, a demand burst was found approximately 1000ms following item onset at these later positions. These data establish that the process of active updating in running span task is slow and cognitively demanding and indicate that this limits its application during fast presentation rates.
Excessive deliberation in social anxiety
Authors: Hunter Lindsay E. , Meer Elana A. , Gillan Claire M. , Hsu Ming , Daw Nathaniel D. 
Published: January 2019

AbstractA goal of computational psychiatry is to ground symptoms in more fundamental computational mechanisms. Theory suggests that rumination and other symptoms in mood disorders reflect dysregulated mental simulation, a process that normally serves to evaluate candidate actions. If so, these covert symptoms should have observable consequences: excessively deliberative choices, specifically about options related to the content of rumination. In two large general population samples, we examined how symptoms of social anxiety disorder (SAD) predict choices in a socially framed reinforcement learning task, the Patent Race game. Using a computational learning model to assess learning strategy, we found that self-reported social anxiety was indeed associated with an increase in deliberative evaluation. The effect was specific to learning from a particular (“upward counterfactual”) subset of feedback, broadly matching the biased content of rumination in SAD. It was also robust to controlling for other psychiatric symptoms. These results ground the symptoms of SAD, such as overthinking and paralysis in social interactions, in well characterized neuro-computational mechanisms and offer a rare example of enhanced function in disease
R-loops and regulatory changes in chronologically ageing fission yeast cells drive non-random patterns of genome rearrangements
Authors: Ellis David A. , Reyes-Martín Félix , Rodríguez-López María , Cotobal Cristina , Sun Xi-Ming , Jeffares Daniel C. , Marguerat Samuel , Tallada Víctor A. , Bähler Jürg 
Published: January 2019

AbstractAberrant repair of DNA double-strand breaks can recombine distant pairs of chromosomal breakpoints. Such chromosomal rearrangements are a hallmark of ageing and compromise the structure and function of genomes. Rearrangements are challenging to detect in non-dividing cell populations, because they reflect individually rare, heterogeneous events. The genomic distribution ofde novorearrangements in non-dividing cells, and their dynamics during ageing, remain therefore poorly characterized. Studies of genomic instability during ageing have focussed on mitochondrial DNA, small genetic variants, or proliferating cells. To gain a better understanding of genome rearrangements during cellular ageing, we focused on a single diagnostic measure – DNA breakpoint junctions – allowing us to interrogate the changing genomic landscape in non-dividing cells of fission yeast (Schizosaccharomyces pombe). Aberrant DNA junctions that accumulated with age were associated with microhomology sequences and R-loops. Global hotspots for age-associated breakpoint formation were evident near telomeric genes and linked to remote breakpoints on the same or different chromosomes, including the mitochondrial chromosome. An unexpected mechanism of genomic instability caused more local hotspots: age-associated reduction in an RNA-binding protein could trigger R-loop formation at target loci. This finding suggests that biological processes other than transcription or replication can drive genome rearrangements. Notably, we detected similar signatures of genome rearrangements that accumulated in old brain cells of humans. These findings provide insights into the unique patterns and potential mechanisms of genome rearrangements in non-dividing cells, which can be triggered by ageing-related changes in gene-regulatory proteins.
A Pipeline for Faecal Host DNA Analysis by Absolute Quantification of LINE-1 and Mitochondrial Genomic Elements Using ddPCR
Authors: He Kuang , Fujiwara Hideaki , Zajac Cynthia , Sandford Erin , Reddy Pavan , Choi Sung Won , Tewari Muneesh 
Published: January 2019

AbstractStool contains DNA shed from cells of the gastrointestinal (GI) tract and has great potential as a bio-specimen for non-invasive, nucleic acid-based detection of GI diseases. Whereas methods for studying faecal microbiome DNA are plentiful, there is a lack of well-characterised procedures for stabilisation, isolation, and quantitative analysis of faecal host DNA. We report an optimised pipeline for faecal host DNA analysis from the point-of-collection to droplet digital PCR (ddPCR) absolute quantification of host-specific gene targets. We evaluated multiple methods for preservation and isolation of host DNA from stool to identify the highest performing methods. To quantify host DNA even if present in partially degraded form, we developed sensitive, human-specific short-amplicon ddPCR assays targeting repetitive nuclear genomic elements (LINE-1) and mitochondrial genes. We validated the ability of these optimised methods to perform absolute quantification of host DNA in 200 stool DNA extracts from samples that were serially collected from three healthy individuals and three hospitalised patients. These specimens allowed assessment of host DNA day-to-day variability in stool specimens with widely varying physical characteristics (i.e., Bristol scores). We further extended this approach to mouse stool analysis, to enable faecal host DNA studies in animal disease models as well.
X-ray structures of two active secreted Bacteroides thetaiotaomicron C11 proteases in complex with peptide-based inhibitors
Authors: Roncase Emily J. , González-Páez Gonzalo E. , Wolan Dennis W. 
Published: January 2019

ABSTRACTCommensal bacteria secrete proteins and metabolites to influence host intestinal homeostasis and proteases represent a significant constituent of the components at the host:microbiome interface. Here, we determined the structures of the two secreted C11 cysteine proteases encoded by the established gut commensal Bacteroides thetaiotaomicron. We employed mutational analysis to demonstrate the two proteases, termed “thetapain” and “iotapain”, undergo in trans self-maturation after lysine and/or arginine residues, as observed for other C11 proteases. We determined the structures of the active forms of thetapain and iotapain in complex with irreversible peptide inhibitors, Ac-VLTK-AOMK and biotin-VLTK-AOMK, respectively. Structural comparisons revealed key active-site interactions important for peptide recognition are more extensive for thetapain; however, both proteases employ a glutamate residue to preferentially bind small polar residues at the P2 position. Our results will aid in the design of protease-specific probes to ultimately understand the biological role of C11 proteases in bacterial fitness, elucidate their host and/or microbial substrates, and interrogate their involvement in microbiome-related diseases.
High genetic diversity of Plasmodium falciparum in the low transmission setting of the Kingdom of Eswatini
Authors: Roh Michelle E. , Tessema Sofonias K. , Murphy Maxwell , Nhlabathi Nomcebo , Mkhonta Nomcebo , Vilakati Sibonakaliso , Ntshalintshali Nyasatu , Saini Manik , Maphalala Gugu , Chen Anna , Wilheim Jordan , Prach Lisa , Gosling Roly , Kunene Simon , Hsiang Michelle , Greenhouse Bryan 
Published: January 2019

ABSTRACTBackgroundTo better understand transmission dynamics, we characterized Plasmodium falciparum (Pf) genetic diversity in Eswatini, where transmission is low and sustained by importation.Methods26 Pf microsatellites were genotyped in 66% of all confirmed cases from 2014-2016 (n=582). Population and within-host diversity were used to characterize differences between imported and locally-acquired infections, as determined by travel history. Logistic regression was used to assess the added value of diversity metrics to classify imported and local infections beyond epidemiology data alone.ResultsThe parasite population in Eswatini was highly diverse (HE=0.75) and complex, with 67% polyclonal infections, a mean MOI of 2.2, and mean FWS of 0.84. Imported cases had comparable diversity to local cases, but exhibited higher MOI (2.4 versus 2.0; p=0.004) and lower mean FWS (0.82 vs. 0.85; p=0.03). Addition of MOI and FWS to multivariate analyses did not increase discrimination between imported and local infections.DiscussionIn contrast to the commonly held perception that Pf diversity declines with decreasing transmission intensity, isolates from Eswatini exhibited high parasite diversity consistent with high rates of malaria importation and limited local transmission. Estimates of malaria transmission intensity from genetic data need to consider the effect of importation, especially as countries near elimination.
Systemic signalling throughTCTP1controls lateral root formation in Arabidopsis
Authors: Branco Rémi , Masle Josette 
Published: January 2019

AbstractAs in animals, the plant body plan and primary organs are established during embryogenesis. However, plants have the ability to generate new organs and functional units throughout their whole life. These are produced through the specification, initiation and differentiation of secondary meristems, governed by the intrinsic genetic program and cues from the environment. They give plants an extraordinary developmental plasticity to modulate their size and architecture according to environmental constraints and opportunities. How this plasticity is regulated at the whole organism level is still largely elusive. In particular the mechanisms regulating the iterative formation of lateral roots along the primary root remain little known. A pivotal role of auxin is well established and recently the role of local mechanical signals and oscillations in transcriptional activity has emerged. Here we provide evidence for a role of Translationally Controlled Tumor Protein (TCTP), a vital ubiquitous protein in eukaryotes. We show that Arabidopsis AtTCTP1 controls root system architecture through a dual function: as a general constitutive growth promoter locally, and as a systemic signalling agent via mobility from the shoot. Our data indicate that this signalling function is specifically targeted to the pericycle and modulates the frequency of lateral root initiation and emergence sites along the primary root, and the compromise between branching and elongating, independent of shoot size. Plant TCTP genes show high similarity among species. TCTP messengers and proteins have been detected in the vasculature of diverse species. This suggests that the mobility and extracellular signalling function ofAtTCTP1to control root organogenesis might be widely conserved within the plant kingdom, and highly relevant to a better understanding of post-embryonic formation of lateral organs in plants, and the elusive coordination of shoot and root morphogenesis.
Comparative analysis of ionic strength tolerance between freshwater and marine Caulobacterales adhesins
Authors: Chepkwony Nelson K. , Berne Cécile , Brun Yves V. 
Published: January 2019

ABSTRACTBacterial adhesion is affected by environmental factors, such as ionic strength, pH, temperature, and shear forces, and therefore marine bacteria must have developed holdfasts with different composition and structures than their freshwater counterparts to adapt to their natural environment. The dimorphicα-proteobacteriumHirschia balticais a marine budding bacterium in the Caulobacterales clade.H.balticauses a polar adhesin, the holdfast, located at the cell pole opposite the reproductive stalk for surface attachment and cell-cell adhesion. The holdfast adhesin has been best characterized inCaulobacter crescentus, a freshwater member of the Caulobacterales, and little is known about holdfast composition and properties in marine Caulobacterales. Here we useH. balticaas a model to characterize holdfast properties in marine Caulobacterales. We show that freshwater and marine Caulobacterales use similar genes in holdfast biogenesis and that these genes are highly conserved among the two genera. We also determine thatH. balticaproduces larger holdfast thanC. crescentusand that those holdfasts have a different chemical composition, as they contain N-acetylglucosamine and galactose monosaccharide residues and proteins, but lack DNA. Finally, we show thatH. balticaholdfasts tolerate higher ionic strength than those ofC. crescentus. We conclude that marine Caulobacterales holdfasts have physicochemical properties that maximize binding in high ionic strength environments.IMPORTANCEMost bacteria spend a large amount of their lifespan attached to surfaces, forming complex multicellular communities called biofilms. Bacteria can colonize virtually any surface, therefore they have adapted to bind efficiently in very different environments. In this study, we compare the adhesive holdfasts produced by the freshwater bacteriumC. crescentusand a relative, the marine bacteriumH. baltica. We show thatH. balticaholdfasts have a different morphology and chemical composition, and tolerate high ionic strength. Our results show thatH. balticaholdfast is an excellent model to study the effect of ionic strength on adhesion and providing insights on the physicochemical properties required for adhesion in the marine environment.