bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta-analysis of targeted metabolomics data from heterogeneous biological samples provides insights into metabolite dynamics
Authors: Lee Ho-Joon , Kremer Daniel M. , Sajjakulnukit Peter , Zhang Li , Lyssiotis Costas A. 
Published: January 2019

AbstractIntroductionMass spectrometry-based metabolomics coupled to liquid chromatography, or LC-MS metabolomics, has become the most popular tool for global metabolite abundance profiling to study metabolism. However, the physicochemical complexity of metabolites poses a major challenge for reliable measurements of metabolite abundance. One way to address the issue is to use multiple chromatographic methods to capture a greater range of molecular diversity. We previously developed a tandem mass spectrometry-based label-free targeted metabolomics analysis framework coupled to two distinct chromatographic methods, reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC), with dynamic multiple reaction monitoring (dMRM) for simultaneous detection of over 200 metabolites to study core metabolic pathways.ObjectivesWe aim to analyze a large-scale heterogeneous data compendium generated from our LC-MS/MS platform with both RPLC and HILIC methods to systematically assess measurement quality in biological replicate groups and to gain insights into metabolite dynamics across different biological conditions.MethodsOur metabolomics framework was applied in a wide range of experimental systems including cancer cell lines, tumors, extracellular media, primary cells, immune cells, organoids, organs (e.g. pancreata), tissues, and sera from human and mice. We also developed computational and statistical analysis pipelines, which include hierarchical clustering, replicate-group CV analysis, correlation analysis, and case-control paired analysis.ResultsWe generated a compendium of 42 heterogeneous deidentified datasets with 635 samples using both RPLC and HILIC methods. There exist signature metabolites that correspond to heterogeneous phenotypes, involved in several metabolic pathways. The RPLC method shows overall better reproducibility than the HILIC method for most metabolites including polar amino acids. Correlation analysis reveals high confidence metabolites irrespective of experimental systems such as methionine, phenylalanine, and taurine. We also identify homocystine, reduced glutathione, and phosphoenolpyruvic acid as highly dynamic metabolites across all case-control paired samples.ConclusionsOur study is expected to serve as a resource and a reference point for a systematic analysis of label-free LC-MS/MS targeted metabolomics data in both RPLC and HILIC methods with dMRM.
Detecting Circular RNA from High-throughput Sequence Data with de Bruijn Graph
Authors: Li Xin , Wu Yufeng 
Published: January 2019

AbstractCircular RNA is a type of non-coding RNA, which has a circular structure. Many circular RNAs are stable and contain exons, but are not translated into proteins. Circular RNA has important functions in gene regulation and plays an important role in some human diseases. Several biological methods, such as RNase R treatment, have been developed to identify circular RNA. Multiple bioinformatics tools have also been developed for circular RNA detection with high-throughput sequence data. In this paper, we present circDBG, a new method for circular RNA detection with de Bruijn graph. We conduct various experiments to evaluate the performance of CircDBG based on both simulated and real data. Our results show that CircDBG finds more reliable cir-cRNAs with low bias, has more efficiency in running time, and performs better in balancing accuracy and sensitivity than existing methods. As a byproduct, we also introduce a new method to classify circular RNAs based on reads alignment. Finally, we report a potential chimeric circular RNA that is found by CircDBG based on real sequence data. CircDBG can be downloaded from https://github.com/lxwgcool/CircDBG.
Molecular Landscape of Anti-Drug Antibodies Reveals the Mechanism of the Immune Response Following Treatment with TNFα Antagonists
Authors: Vaisman-Mentesh Anna , Rosenstein Shai , Yavzori Miri , Dror Yael , Fudim Ella , Ungar Bella , Kopylov Uri , Picard Orit , Kigel Aya , Ben-Horin Shomron , Benhar Itai , Wine Yariv 
Published: January 2019

AbstractDrugs formulated from monoclonal antibodies (mAbs) are clinically effective in various diseases. Repeated administration of mAbs, however, elicits an immune response in the form of anti-drug-antibodies (ADA), thereby reducing the drug’s efficacy. Notwithstanding their importance, the molecular landscape of ADA and the mechanisms involved in their formation are not fully understood. Using a newly developed quantitative bio-immunoassay, we found that ADA concentrations specific to TNFα antagonists can exceed extreme concentrations of 1 mg/ml with a wide range of neutralization capacity. Our data further suggest a preferential use of the λ light chain in a subset of neutralizing ADA. Moreover, we show that administration of TNFα antagonists result in a vaccine-like response whereby ADA formation is governed by the extrafollicular T cell-independent immune response. Our bio-immunoassay coupled with insights on the nature of the immune response can be leveraged to improve mAb immunogenicity assessment and facilitate improvement in therapeutic intervention strategies.
Birth-and-death evolution of the fatty acyl-CoA reductase (FAR) gene family and diversification of cuticular hydrocarbon synthesis in Drosophila
Authors: Finet Cédric , Slavik Kailey , Pu Jian , Carroll Sean B. , Chung Henry 
Published: January 2019

AbstractThe birth-and-death evolutionary model proposes that some members of a multigene family are phylogenetically stable and persist as a single copy over time whereas other members are phylogenetically unstable and undergo frequent duplication and loss. Functional studies suggest that stable genes are likely to encode essential functions, while rapidly evolving genes reflect phenotypic differences in traits that diverge rapidly among species. One such class of rapidly diverging traits are insect cuticular hydrocarbons (CHCs), which play dual roles in chemical communications as short-range recognition pheromones as well as protecting the insect from desiccation. Insect CHCs diverge rapidly between related species leading to ecological adaptation and/or reproductive isolation. Because the CHC and essential fatty acid biosynthetic pathways share common genes, we hypothesized that genes involved in the synthesis of CHCs would be evolutionary unstable, while those involved in fatty acid-associated essential functions would be evolutionary stable. To test this hypothesis, we investigated the evolutionary history of the fatty acyl-CoA reductases (FARs) gene family that encodes enzymes in CHC synthesis. We compiled a unique dataset of 200 FAR proteins across 12 Drosophila species. We uncovered a broad diversity in FAR content which is generated by gene duplications, subsequent gene losses, and alternative splicing. We also show that FARs expressed in oenocytes and presumably involved in CHC synthesis are more unstable than FARs from other tissues. We suggest that a comparative approach investigating the birth-and-death evolution of gene families can identify candidate genes involved in rapidly diverging traits between species.
Proximate causes and consequences of intergenerational influences of salient sensory experience
Authors: Aoued Hadj S , Sannigrahi Soma , Hunter Sarah C , Doshi Nandini , Chan Anthony , Walum Hasse , Dias Brian G 
Published: January 2019

ABSTRACTSalient sensory environments experienced by a parental generation can exert intergenerational influences on offspring, including offspring not conceived at the time of the parental experience. While these data provide an exciting new perspective on biological inheritance, questions remain about causes and consequences of intergenerational influences of salient sensory experience. We have previously shown that exposing male mice to a salient olfactory experience like olfactory fear conditioning results in offspring demonstrating a sensitivity to the odor used to condition the paternal generation and possessing an enhanced neuroanatomical representation for that odor. In this study, we first injected RNA extracted from sperm of male mice that underwent olfactory fear conditioning into naïve single cell zygotes and found that both male and female adults that develop from these embryos have increased sensitivity and enhanced neuroanatomical representation for the odor (Odor A) with which the paternal male had been conditioned. Next, we found that female, but not male offspring sired by males conditioned with Odor A show enhanced freezing when presented with Odor A after being exposed to a sub-threshold olfactory fear conditioning protocol that consisted of only a single Odor A + shock pairing. Our data provide evidence that RNA found in the paternal germline after exposure to salient sensory experiences can contribute to intergenerational influences of such experiences, and that such intergenerational influences confer an element of adaptation to the filial generation. In so doing, our work suggests that some causes (sperm RNA) and consequences (behavioral flexibility) of intergenerational influences of parental experiences are conserved across experiences as diverse as stressors, dietary manipulations, and sensory experiences.
Plasticity in evolutionary games
Authors: Dridi Slimane 
Published: January 2019

AbstractThe ability to respond appropriately to environmental cues is fundamental to the success of all forms of life, but previous theoretical studies of the evolution of plasticity make so diverse assumptions that the conditions under which plasticity can emerge in evolving populations are unclear when fitness is frequency-dependent. We study the effect of adding plastic types to symmetric evolutionary games. Since frequency-dependence induces an evolutionary change in the environment of players, one might expect that plastic individuals who can adapt their phenotypes to the environment could have a fitness advantage over simpler purely genetically determined phenotypes. In our model, plastic individuals can detect the type of their opponent before an interaction and condition their action on it. Even though it might appear as an outstanding advantage, such an ability cannot guarantee global stability in all games for even the smallest positive plasticity costs. We identify classes of games where plasticity can or cannot be globally or locally stable. In games where the standard replicator dynamics converge to a pure state, costly plasticity cannot invade an equilibrium population. Costly plasticity can however be locally stable, but the way to achieve this is not to play the best-response to any possible encountered type. Rather, part of the stability success of plastic types is based on establishing Pareto-efficiency as residents; in certain social dilemma games such as the Prisoner’s Dilemma and the Snowdrift game, this implies that plastic types need to cooperate with a strictly positive probability in order to ensure their stability against invasion by pure types. Zero-sum games always allow for the global stability of plastic types. This study offers a more principled way of thinking about the evolutionary emergence of plasticity in social scenarios, and helps demonstrate that such an emergence is strongly dependent on the type of game individuals are faced with.
Spring-loaded inverted pendulum goes through two contraction-extension cycles during the single stance phase of walking
Authors: Antoniak Gabriel , Biswas Tirthabir , Cortes Nelson , Sikdar Siddhartha , Chun Chanwoo , Bhandawat Vikas 
Published: January 2019

AbstractDespite the overall complexity of legged locomotion, the motion of the center of mass (COM) itself is relatively simple, and can be qualitatively described by simple mechanical models. The spring-loaded inverted pendulum (SLIP) is one such model, and describes both the COM motion and the ground reaction forces (GRFs) during running. Similarly, walking can be modeled by two SLIP-like legs (double SLIP or DSLIP). However, DSLIP has many limitations and is unlikely to serve as a quantitative model for walking. As a first step to obtaining a quantitative model for walking, we explored the ability of SLIP to model the single stance phase of walking across the entire range of walking speeds. We show that SLIP can be employed to quantitatively model the single stance phase except for two exceptions: first, it predicts larger horizontal GRFs than empirically observed. A new model - angular and radial spring-loaded inverted pendulum (ARSLIP) can overcome this deficit. Second, even the single stance phase has active elements, and therefore a quantitative model of locomotion would require active elements. Surprisingly, the leg spring undergoes a contraction-extension-contraction-extension (CECE) during walking; this cycling is partly responsible for the M-shaped GRFs produced during walking. The CECE cycle also lengthens the stance duration allowing the COM to travel passively for a longer time, and decreases the velocity redirection between the beginning and end of a step. A combination of ARSLIP along with active mechanisms during transition from one step to the next is necessary to describe walking.
Cognitive vulnerability to sleep deprivation is robustly associated with two dynamic connectivity states
Authors: Teng James , Ong Ju Lynn , Patanaik Amiya , Tandi Jesisca , Zhou Juan Helen , Chee Michael W.L. , Lim Julian 
Published: January 2019

AbstractRobustly linking dynamic functional connectivity (DFC) states to behaviour is an important goal of the fledgling research using these methods. Previously, using a sliding window approach, we identified two dynamic connectivity states (DCS) linked to arousal. Here, in an independent dataset, 32 healthy participants underwent two sets of resting-state functional magnetic resonance imaging (fMRI) scans, once in a well-rested state and once after a single night of total sleep deprivation. Using a temporal differencing method, DFC and clustering analysis on the resting state fMRI data revealed five centroids that were highly correlated with those found in previous work, including the two states associated with high and low arousal. Individual differences in cognitive vulnerability to sleep deprivation were measured using changes in Psychomotor Vigilance Test (PVT) performance (lapses and median reaction speed), Changes in the percentage of time spent in the arousal states from the well-rested to the sleep-deprived condition specifically were correlated with declines in PVT performance. Our results provide good evidence of the validity and reproducibility of DFC measures, particularly with regard to measuring arousal and attention, and are an encouraging base from which to build a chronnectome mapping DCS to cognition.
Exploring Frequency-dependent Brain Networks from ongoing EEG using Spatial ICA during music listening
Authors: Zhu Yongjie , Zhang Chi , Toiviainen Petri , Huotilainen Minna , Mathiak Klaus , Ristaniemi Tapani , Cong Fengyu 
Published: January 2019

AbstractRecently, exploring brain activity based on functional networks during naturalistic stimuli especially music and video represents an attractive challenge because of the low signal-to-noise ratio in collected brain data. Although most efforts focusing on exploring the listening brain have been made through functional magnetic resonance imaging (fMRI), sensor-level electro- or magnetoencephalography (EEG/MEG) technique, little is known about how neural rhythms are involved in the brain network activity under naturalistic stimuli. This study exploited cortical oscillations through analysis of ongoing EEG and musical feature during free-listening to music. We used a data-driven method that combined music information retrieval with spatial Independent Components Analysis (ICA) to probe the interplay between the spatial profiles and the spectral patterns. We projected the sensor data into cortical space using a minimum-norm estimate and applied the Short Time Fourier Transform (STFT) to obtain frequency information. Then, spatial ICA was made to extract spatial-spectral-temporal information of brain activity in source space and five long-term musical features were computationally extracted from the naturalistic stimuli. The spatial profiles of the components whose temporal courses were significantly correlated with musical feature time series were clustered to identify reproducible brain networks across the participants. Using the proposed approach, we found brain networks of musical feature processing are frequency-dependent and three plausible frequency-dependent networks were identified; the proposed method seems valuable for characterizing the large-scale frequency-dependent brain activity engaged in musical feature processing.
Chandipura virus requires pro-survival RelA NF-κB function for its propagation
Authors: Bais Sachendra S. , Ratra Yashika , Kushawaha Pramod K. , Basak Soumen 
Published: January 2019

SummaryIn response to infection by RNA viruses, mammalian cells typically activate RelA-containing NF-κB heterodimers, which induce genes encoding interferon-β and other antiviral mediators. Therefore, RelA is commonly thought to function as an anti-viral transcription factor. Notably, virus-specific mechanisms often modify mainstay immune pathways. Despite its human health relevance, how Chandipura virus (CHPV) per se interacts with the cellular signaling machinery has not been investigated. Here, we report that RelA deficiency abrogated antiviral gene expressions and yet surprisingly caused diminished growth of CHPV in mouse embryonic fibroblasts. Our experimental studies clarified that RelA-dependent synthesis of pro-survival factors restrained infection-inflicted cell death, and that exacerbated cell death processes prevented multiplication of CHPV in RelA-deficient cells. In sum, we identify a pro-viral function of the immune-activating transcription factor RelA NF-κB linked to its pro-survival properties.HighlightsLack of RelA NF-κB leads to reduced growth of CHPV ex vivoRelA deficiency exacerbates cell-death processes upon CHPV infectionInhibition of cell-death processes restores CHPV multiplication in RelA-deficient MEFs
Context-specific modulation of intrinsic coupling modes shapes multisensory processing
Authors: Galindo-Leon Edgar E. , Stitt Iain , Pieper Florian , Stieglitz Thomas , Engler Gerhard , Engel Andreas K. 
Published: January 2019

AbstractIntrinsically generated patterns of coupled neuronal activity are associated with the dynamics of specific brain states. Sensory inputs are extrinsic factors that can perturb these intrinsic coupling modes, creating a complex scenario in which forthcoming stimuli are processed. Studying this intrinsic-extrinsic interplay is necessary to better understand perceptual integration and selection. Here, we show that this interplay leads to a reconfiguration of functional cortical connectivity that acts as a mechanism to facilitate stimulus processing. Using audiovisual stimulation in anesthetized ferrets, we found that this reconfiguration of coupling modes is context-specific, depending on long-term modulation by repetitive sensory inputs. These reconfigured coupling modes, in turn, lead to changes in latencies and power of local field potential responses that support multisensory integration. Our study demonstrates that this interplay extends across multiple time scales and involves different types of intrinsic coupling. These results suggest a novel large-scale mechanism that facilitates multisensory integration.
Fanconi anemia proteins are required to maintain nucleolar homeostasis
Authors: Gueiderikh Anna , Rouvet Guillaume , Souquère-Besse Sylvie , Apcher Sébastien , Diaz Jean-Jacques , Rosselli Filippo 
Published: January 2019

AbstractThe majority of inherited bone marrow failure (iBMF) syndromes are associated to nucleolar and/or ribosomal abnormalities, but Fanconi anemia (FA), the most common iBMF, is attributed to alterations in DNA damage responses. However, the involvement, if any, of the FA (FANC) proteins in the maintenance of nucleolar functions and/or ribosome biogenesis is yet unexplored. Here, we report that FANC pathway loss-of-function is associated to a loss of the nucleolar homeostasis, demonstrating increased rDNA rearrangements, accumulation of nucleolar DNA damage, nucleolar protein mislocalization, and a p53-independent induction of the growth inhibitory protein p21. Moreover, specifically associated to FANCA loss-of-function, which is responsible for approximately 65% of FA cases, we observed reduced rDNA transcription and rRNA processing as well as alteration in protein synthesis and polysome profiles. Thus, we have identified nucleolar consequences associated with FANC pathway deficiency, challenging current hypothesis on the physiopathology of FA.
Fecal microbiota dysbiosis in macaques and humans within a shared environment
Authors: Grant Erica , Kyes Randall C. , Kyes Pensri , Trinh Pauline , Ramirez Vickie , Tanee Tawatchai , Pinlaor Porntip , Dangtakot Rungtiwa , Rabinowitz Peter M. 
Published: January 2019

AbstractTraditional zoonotic disease research focuses on detection of recognized pathogens and may miss opportunities to understand broader microbial transmission dynamics between humans, animals, and the environment. We studied human-macaque microbiome overlap in Kosum Phisai District, Maha Sarakham Province, Thailand, where a growing population of long-tailed macaques (Macaca fascicularis) in Kosumpee Forest Park interact with humans from an adjacent village. We surveyed workers in or near the park with elevated exposure to macaques to characterize tasks resulting in exposure to macaque feces in addition to dietary and lifestyle factors that influence gut microbiome composition. Fecal samples were collected from 12 exposed workers and 6 controls without macaque exposure, as well as 8 macaques from Kosumpee Forest Park and 4 from an isolated forest patch with minimal human contact. The V4 region of the 16S rRNA gene from fecal sample extracted DNA was amplified and sequenced using Illumina HiSeq to characterize the microbial community. A permuted betadisper test on the weighted UniFrac distances revealed significant differences in the dispersion patterns of gut microbiota from exposed and control macaques (p=0.03). The high variance in gut microbiota composition of macaques in contact with humans has potential implications for gut microbiome stability and susceptibility to disease, described by the Anna Karenina principle (AKP). Human samples had homogenous variance in beta diversity but different spatial medians between groups (p=0.02), indicating a shift in microbial composition that may be explained by fundamental lifestyle differences between the groups unrelated to exposure status. SourceTracker was used to estimate the percent of gut taxa in exposed humans that was contributed by macaques. While one worker showed evidence of elevated contribution, the overall trend was not significant. Task observations among workers revealed opportunities to employ protective measures or training to reduce exposure to occupational hazards. These results suggest the potential for hygiene measures to mitigate negative aspects of contact between humans and macaques in order to optimize the health of both populations.