bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resolving Cargo-motor-track Interactions in Living Cells with Bifocal Parallax Single Particle Tracking
Authors: Cheng Xiaodong , Chen Kuangcai , Dong Bin , Filbrun Seth L. , Wang Gufeng , Fang Ning 
Published: July 2020

AbstractResolving coordinated biomolecular interactions in living cellular environments is vital for understanding the mechanisms of molecular nanomachines. The conventional approach relies on localizing and tracking target biomolecules and/or subcellular organelles labeled with imaging probes. However, it is challenging to gain information on rotational dynamics, which can be more indicative of the work done by molecular motors and their dynamic binding status. Herein, a bifocal parallax single particle tracking method using half-plane point spread functions has been developed to resolve the full-range azimuth angle (0-360°), polar angle, and 3D displacement in real time under complex living cell conditions. Using this method, quantitative rotational and translational motion of the cargo in a 3D cell cytoskeleton was obtained. Not only well-known active intracellular transport and free diffusion were observed but new interactions, tight attachment and tethered rotation, were discovered for better interpretation of the dynamics of cargo-motor-track interactions at various types of microtubule intersections.Significance StatementTranslation and rotational motion of cargo during pauses at the microtubule intersections in living cells were revealed by high-accuracy three-dimensional single particle rotational tracking. The current study demonstrates the potential of studying coordinated interactions in living cellular environments by resolving characteristic rotational motions.
A two-step approach to testing overall effect of gene-environment interaction for multiple phenotypes
Authors: Majumdar Arunabha , Burch Kathryn S. , Sankararaman Sriram , Pasaniuc Bogdan , Gauderman W. James , Witte John S. 
Published: July 2020

AbstractWhile gene-environment (GxE) interactions contribute importantly to many different phenotypes, detecting such interactions requires well-powered studies and has proven difficult. To address this, we combine two approaches to improve GxE power: simultaneously evaluating multiple phenotypes and using a two-step analysis approach. Previous work shows that the power to identify a main genetic effect can be improved by simultaneously analyzing multiple related phenotypes. For a univariate phenotype, two-step methods produce higher power for detecting a GxE interaction compared to single step analysis. Therefore, we propose a two-step approach to test for an overall GxE effect for multiple phenotypes. Using simulations we demonstrate that, when more than one phenotype has GxE effect (i.e., GxE pleiotropy), our approach offers substantial gain in power (18% – 43%) to detect an aggregate-level GxE effect for a multivariate phenotype compared to an analogous two-step method to identify GxE effect for a univariate phenotype. We applied the proposed approach to simultaneously analyze three lipids, LDL, HDL and Triglyceride with the frequency of alcohol consumption as environmental factor in the UK Biobank. The method identified two independent genome-wide significant signals of an overall GxE effect on the vector of lipids.
Wild rice (O. latifolia) from natural ecosystems in the Pantanal region of Brazil: host toFusarium incarnatum-equisetispecies complex and highly contaminated by zearalenone
Authors: Tralamazza Sabina Moser , Piacentini Karim Cristina , Savi Geovana Dagostim , Carnielli-Queiroz Lorena , de Carvalho Fontes Lívia , Martins Camila Siedlarczyk , Corrêa Benedito , Rocha Liliana Oliveira 
Published: July 2020

AbstractWe assessed the mycobiota diversity and mycotoxin levels present in wild rice (Oryza latifolia) from the Pantanal region of Brazil; fundamental aspects of which are severely understudied as an edible plant from a natural ecosystem. We found a variety of fungal species contaminating the rice samples; the most frequent genera beingFusarium, NigrosporaandCladosporium(35.9%, 26.1% and 15%, respectively). Within theFusariumgenus, the wild rice samples were mostly contaminated by theFusarium incarnatum-equisetispecies complex (FIESC) (80%) along withFusarium fujikuroispecies complex (20%). Phylogenetic analysis supported multiple FIESC species and gave strong support to the presence of two previously uncharacterized lineages within the complex (LN1 and LN2). Deoxynivalenol (DON) and zearalenone (ZEA) chemical analysis showed that most of the isolates were DON/ZEA producers and some were defined as high ZEA producers, displaying abundant ZEA levels over DON (over 19 times more). Suggesting that ZEA likely has a key adaptive role for FIESC in wild rice (O. latifolia). Mycotoxin determination in the rice samples revealed high frequency of ZEA, and 85% of rice samples had levels >100 μg/kg; the recommended limit set by regulatory agencies. DON was only detected in 5.2% of the samples. Our data shows that FIESC species are the main source of ZEA contamination in wild rice and the excessive levels of ZEA found in the rice samples raises considerable safety concerns regarding wild rice consumption by humans and animals.
MATHEMATICAL MODELING OF RETINAL DEGENERATION: AEROBIC GLYCOLYSIS IN A SINGLE CONE
Authors: Camacho Erika , Dobreva Atanaska , Larripa Kamila , Rǎdulescu Anca , Schmidt Deena , Trejo Imelda 
Published: July 2020

ABSTRACTCell degeneration, including that resulting in retinal diseases, is linked to metabolic issues. In the retina, photoreceptor degeneration can result from imbalance in lactate production and consumption as well as disturbances to pyruvate and glucose levels. To identify the key mechanisms in metabolism that may be culprits of this degeneration, we use a nonlinear system of differential equations to mathematically model the metabolic pathway of aerobic glycolysis in a healthy cone photoreceptor. This model allows us to analyze the levels of lactate, glucose, and pyruvate within a single cone cell. We perform numerical simulations, use available metabolic data to estimate parameters and fit the model to this data, and conduct a sensitivity analysis using two different methods (LHS/PRCC and eFAST) to identify pathways that have the largest impact on the system. Using bifurcation techniques, we find that the system has a bistable regime, biologically corresponding to a healthy versus a pathological state. The system exhibits a saddle node bifurcation and hysteresis. This work confirms the necessity for the external glucose concentration to sustain the cell even at low initial internal glucose levels. It also validates the role ofβ-oxidation of fatty acids which fuel oxidative phosphorylation under glucose- and lactate-depleted conditions, by showing that the rate ofβ-oxidation of ingested outer segment fatty acids in a healthy cone cell must be low. Model simulations reveal the modulating effect of external lactate in bringing the system to steady state; the bigger the difference between external lactate and initial internal lactate concentrations, the longer the system takes to achieve steady state. Parameter estimation for metabolic data demonstrates the importance of rerouting glucose and other intermediate metabolites to produce glycerol 3-phosphate (G3P), thus increasing lipid synthesis (a precursor to fatty acid production) to support their high growth rate. While a number of parameters are found to be significant by one or both of the methods for sensitivity analysis, the rate ofβ-oxidation of ingested outer segment fatty acids is shown to consistently play an important role in the concentration of glucose, G3P, and pyruvate, whereas the extracellular lactate level is shown to consistently play an important role in the concentration of lactate and acetyl coenzyme A. The ability of these mechanisms to affect key metabolites’ variability and levels (as revealed in our analyses) signifies the importance of inter-dependent and inter-connected feedback processes modulated by and affecting both the RPE’s and cone’s metabolism.
The global and local distribution of RNA structure throughout the SARS-CoV-2 genome
Authors: Tavares Rafael de Cesaris Araujo , Mahadeshwar Gandhar , Pyle Anna Marie 
Published: July 2020

AbstractSARS-CoV-2 is the causative viral agent of COVID-19, the disease at the center of the current global pandemic. While knowledge of highly structured regions is integral for mechanistic insights into the viral infection cycle, very little is known about the location and folding stability of functional elements within the massive, ~30kb SARS-CoV-2 RNA genome. In this study, we analyze the folding stability of this RNA genome relative to the structural landscape of other well-known viral RNAs. We present an in-silico pipeline to locate regions of high base pair content across this long genome and also identify well-defined RNA structures, a method that allows for direct comparisons of RNA structural complexity within the several domains in SARS-CoV-2 genome. We report that the SARS-CoV-2 genomic propensity to stable RNA folding is exceptional among RNA viruses, superseding even that of HCV, one of the most highly structured viral RNAs in nature. Furthermore, our analysis reveals varying levels of RNA structure across genomic functional regions, with accessory and structural ORFs containing the highest structural density in the viral genome. Finally, we take a step further to examine how individual RNA structures formed by these ORFs are affected by the differences in genomic and subgenomic contexts. The conclusions reported in this study provide a foundation for structure-function hypotheses in SARS-CoV-2 biology, and in turn, may guide the 3D structural characterization of potential RNA drug targets for COVID-19 therapeutics.
It matters who you know, down below: Different mycorrhizal fungal communities differentially affect plant phenolic defences against herbivory
Authors: Frew Adam , Wilson Bree A. L. 
Published: July 2020

ABSTRACTArbuscular mycorrhizal (AM) fungi are ubiquitous symbionts of most terrestrial plants. These fungi not only provide their host plants with access to nutrients and resources but are known to augment plant defences against insect herbivores. Relatively little is known about the role of AM fungal diversity and community assembly on the expression of plant defence traits. Here, we report how plant (Triticum aestivum) phenolic-based resistance to insect herbivory is differentially affected by different AM fungal communities. An inoculant of four AM fungal species and a field-sourced native AM fungal community increased plant phenolics by 47.9% and 50.2%, respectively, compared to plants inoculated with only one fungal species. Correspondingly, the performance (relative growth rate) of the insect herbivore was 36% and 61.3% lower when feeding on plants associated with these AM fungal communities. Furthermore, there was a negative correlation between foliar phenolics and herbivore growth. We propose that AM fungal community assembly can drive insect herbivore performance by affecting phenolic-based defence mechanisms.
Three hallmarks of malaria-induced selection in human genomes
Authors: Tennessen Jacob A. , Duraisingh Manoj T. 
Published: July 2020

AbstractMalaria has plausibly been the single strongest selective pressure on our species. Many of the best-characterized cases of adaptive evolution in humans are in genes tied to malaria resistance. However, the complex evolutionary patterns at these genes are poorly captured by standard scans for non-neutral evolution. Here we present three new statistical tests for selection based on population genetic patterns that are observed more than once among key malaria resistance loci. We assess these tests using forward-time evolutionary simulations and apply them to global whole-genome sequencing data from humans, and thus we show that they are effective at distinguishing selection from neutrality. Each test captures a distinct evolutionary pattern, here called Divergent Haplotypes, Repeated Shifts, and Arrested Sweeps, associated with a particular period of human prehistory. We clarify the selective signatures at known malaria-relevant genes and identify additional genes showing similar adaptive evolutionary patterns. Among our top outliers, we see a particular enrichment for genes involved in erythropoiesis and for genes previously associated with malaria resistance, consistent with a major role for malaria in shaping these patterns of genetic diversity. Polymorphisms at these genes are likely to impact resistance to malaria infection and contribute to ongoing host-parasite coevolutionary dynamics.
Auditory detection is modulated by theta phase of silent lip movements
Authors: Biau Emmanuel , Wang Danying , Park Hyojin , Jensen Ole , Hanslmayr Simon 
Published: July 2020

ABSTRACTAudiovisual speech perception relies, among other things, on our expertise to map a speaker’s lip movements with speech sounds. This multimodal matching is facilitated by salient syllable features that align lip movements and acoustic envelope signals in the 4 - 8 Hz theta band. Although non-exclusive, the predominance of theta rhythms in speech processing has been firmly established by studies showing that neural oscillations track the acoustic envelope in the primary auditory cortex. Equivalently, theta oscillations in the visual cortex entrain to lip movements, and the auditory cortex is recruited during silent speech perception. These findings suggest that neuronal theta oscillations may play a functional role in organising information flow across visual and auditory sensory areas. We presented silent speech movies while participants performed a pure tone detection task to test whether entrainment to lip movements directs the auditory system and drives behavioural outcomes. We showed that auditory detection varied depending on the ongoing theta phase conveyed by lip movements in the movies. In a complementary experiment presenting the same movies while recording participants’ electro-encephalogram (EEG), we found that silent lip movements entrained neural oscillations in the visual and auditory cortices with the visual phase leading the auditory phase. These results support the idea that the visual cortex entrained by lip movements filtered the sensitivity of the auditory cortex via theta phase synchronisation.
A fluorescent l-2-hydroxyglutarate biosensor
Authors: Kang Zhaoqi , Zhang Manman , Gao Kaiyu , Zhang Wen , Liu Yidong , Xiao Dan , Guo Shiting , Ma Cuiqing , Gao Chao , Xu Ping 
Published: July 2020

Abstractl-2-Hydroxyglutarate (l-2-HG) plays important roles in diverse physiological processes, such as carbon starvation response, tumorigenesis, and hypoxic adaptation. Despite its importance and intensively studied metabolism, regulation ofl-2-HG metabolism remains poorly understood and a regulator specifically responded tol-2-HG has never been identified. Based on the genomic neighborhood analysis of the gene encodingl-2-HG oxidase (LhgO), LhgR, which represses the transcription oflhgO, was identified inPseudomonas putidaW619 in this study. LhgR was demonstrated to recognizel-2-HG as its specific effector molecule, and this allosteric transcription factor was then used as a biorecognition element for construction ofl-2-HG-sensing FRET sensor. The newly developedl-2-HG sensor can conveniently monitor the concentrations ofl-2-HG in various biological samples. In addition to bacteriall-2-HG generation during carbon starvation, biological functions of thel-2-HG dehydrogenase and hypoxia inducedl-2-HG accumulation were also revealed by using thel-2-HG sensor in human cells.
The impact of plasma membrane lipid composition on flagella-mediated adhesion of enterohemorrhagicEscherichia coli
Authors: Cazzola Hélène , Lemaire Laurine , Acket Sébastien , Prost Elise , Duma Luminita , Erhardt Marc , Čechová Petra , Trouillas Patrick , Mohareb Fady , Rossi Claire , Rossez Yannick 
Published: July 2020

AbstractEnterohemorrhagicEscherichia coli(EHEC) O157:H7 is a major cause of foodborne gastrointestinal illness. The adhesion of EHEC on host tissues is the first step enabling bacterial colonization. Adhesins like fimbriae and flagella mediate this mechanism. Here, we studied the interaction of the bacterial flagellum with the host cell’s plasma membrane using Giant Unilamellar Vesicles (GUVs) as a biologically relevant model. Cultured cell lines contain many different molecular components including proteins and glycoproteins. In contrast, with GUVs we can characterize the bacterial mode of interaction solely with a defined lipid part of the cell membrane. Bacterial adhesion on GUVs was dependent on the presence of the flagellar filament and its motility. By testing different phospholipid head groups, the nature of the fatty acid chains or the liposome curvature, we found that lipid packing is a key parameter to enable bacterial adhesion. Using HT-29 cells grown in the presence of polyunsaturated fatty acid (α-linolenic acid) or saturated fatty acid (palmitic acid), we found that α-linolenic acid reduced adhesion of wild type EHEC but not of a non-flagellated mutant. Finally, our results reveal that the presence of flagella is advantageous for the bacteria to bind to lipid rafts. We speculate that polyunsaturated fatty acids prevent flagellar adhesion on membrane bilayers and play a clear role for optimal host colonization. Flagella-mediated adhesion to plasma membranes has broad implications to host-pathogen interactions.ImportanceBacterial adhesion is a crucial step to allow bacteria to colonize their hosts, invade tissues and form biofilm. EnterohemorrhagicE. coliO157:H7 is a human pathogen and the causative agent of diarrhea and hemorrhagic colitis. Here, we use biomimetic membrane models and cell lines to decipher the impact of lipid content of the plasma membrane on enterohemorrhagic E.coliflagella-mediated adhesion. Our findings provide evidence that polyunsaturated fatty acid (α-linolenic acid) inhibits E.coliflagella adhesion to the plasma membrane in a mechanism separate from its antimicrobial and anti-inflammatory functions. In addition, we confirm that cholesterol-enriched lipid microdomains, often called lipid rafts are important in bacterial adhesion. These findings significantly strengthen plasma membrane adhesion via bacterial flagella in an important human pathogen. This mechanism represents a promising target for the development of novel anti-adhesion therapies.
Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation
Authors: Bastos André M. , Donoghue Jacob A. , Brincat Scott L. , Mahnke Meredith , Yanar Jorge , Correa Josefina , Waite Ayan S. , Lundqvist Mikael , Roy Jefferson , Brown Emery N. , Miller Earl K. 
Published: July 2020

AbstractThe specific circuit mechanisms through which anesthetics induce unconsciousness have not been completely characterized. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with the anesthetic propofol. Unconsciousness was marked by slow frequency (~1 Hz) oscillations in local field potentials, entrainment of local spiking to Up states alternating with Down states of little spiking, and decreased coherence in frequencies above 4 Hz. Thalamic stimulation “awakened” anesthetized NHPs and reversed the electrophysiologic features of unconsciousness. Unconsciousness is linked to cortical and thalamic slow frequency synchrony coupled with decreased spiking, and loss of higher-frequency dynamics. This may disrupt cortical communication/integration.
Adaptation of theRomanomermis culicivoraxCCA-adding enzyme to miniaturized armless tRNA substrates
Authors: Hennig Oliver , Philipp Susanne , Bonin Sonja , Rollet Kévin , Kolberg Tim , Jühling Tina , Betat Heike , Sauter Claude , Mörl Mario 
Published: July 2020

AbstractThe mitochondrial genome of the nematodeRomanomermis culicivoraxencodes for miniaturized hairpin-like tRNA molecules that lack D- as well as T-arms, strongly deviating from the consensus cloverleaf. The single tRNA nucleotidyltransferase of this organism is fully active on armless tRNAs, while the human counterpart is not able to add a complete CCA-end. Transplanting single regions of theRomanomermisenzyme into the human counterpart, we identified a beta-turn element of the catalytic core that – when inserted into the human enzyme - confers full CCA-adding activity on armless tRNAs. This region, originally identified to position the 3’-end of the tRNA primer in the catalytic core, dramatically increases the enzyme’s substrate affinity. While conventional tRNA substrates bind to the enzyme by interactions with the T-arm, this is not possible in the case of armless tRNAs, and the strong contribution of the beta-turn compensates for an otherwise too weak interaction required for the addition of a complete CCA-terminus. This compensation demonstrates the remarkable evolutionary plasticity of the catalytic core elements of this enzyme to adapt to unconventional tRNA substrates.
Listeners with congenital amusia are sensitive to context uncertainty in melodic sequences
Authors: Quiroga-Martinez D. R. , Tillmann B. , Brattico E. , Cholvy F. , Fornoni L. , Vuust P. , Caclin A. 
Published: July 2020

AbstractIn typical listeners, the perceptual salience of a surprising auditory event depends on the uncertainty of its context. For example, in melodies, pitch deviants are more easily detected and generate larger neural responses when the context is highly predictable than when it is less so. However, it is not known whether amusic listeners with abnormal pitch processing are sensitive to the degree of uncertainty of pitch sequences and, if so, whether they are to a different extent than typical non-musician listeners. To answer this question, we manipulated the uncertainty of short melodies while participants with and without congenital amusia underwent EEG recordings in a passive listening task. Uncertainty was manipulated by presenting melodies with different levels of complexity and familiarity, under the assumption that simpler and more familiar patterns would enhance pitch predictability. We recorded mismatch negativity (MMN) responses to pitch, intensity, timbre, location, and rhythm deviants as a measure of auditory surprise. In both participant groups, we observed reduced MMN amplitudes and longer peak latencies for all sound features with increasing levels of complexity, and putative familiarity effects only for intensity deviants. No significant group-by-complexity or group-by-familiarity interactions were detected. However, in contrast to previous studies, pitch MMN responses in amusics were disrupted in high complexity and unfamiliar melodies. The present results thus indicate that amusics are sensitive to the uncertainty of melodic sequences and that preattentive auditory change detection is greatly spared in this population across sound features and levels of predictability. However, our findings also hint at pitch-specific impairments in this population when uncertainty is high, thus suggesting that pitch processing under high uncertainty conditions requires an intact frontotemporal loop.