bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro transcribed guide RNAs trigger an innate immune response via the RIG-I pathway
Authors: Wienert Beeke , Shin Jiyung , Zelin Elena , Pestal Kathleen , Corn Jacob E. 
Published: March 2018

AbstractCRISPR-Cas9 genome editing is revolutionizing fundamental research and has great potential for the treatment of many diseases. While editing of immortalized cell lines has become relatively easy, editing of therapeutically relevant primary cells and tissues can remain challenging. One recent advancement is the delivery of a Cas9 protein and an in vitro transcribed (IVT) guide RNA (gRNA) as a precomplexed ribonucleoprotein (RNP). This approach allows editing of primary cells such as T cells and hematopoietic stem cells, but the consequences beyond genome editing of introducing foreign Cas9 RNPs into mammalian cells are not fully understood. Here we show that the IVT gRNAs commonly used by many laboratories for RNP editing trigger a potent innate immune response that can be several thousand times stronger than benchmark immune stimulating ligands. IVT gRNAs are recognized in the cytosol through the RIG-I pathway but not the MDA5 pathway, thereby triggering a type I interferon response. Removal of the 5’-triphosphate from gRNAs ameliorates inflammatory signaling and prevents the loss of viability associated with genome editing in hematopoietic stem cells. The potential for Cas9 RNP editing to induce a potent antiviral response indicates that care must be taken when designing therapeutic strategies to edit primary cells.AbbreviationsCasCRISPR-associatedCIPcalf intestinal alkaline phosphataseCRISPRclustered, regularly interspaced, short palindromic repeatdCas9nuclease-dead Cas9HEK293Human embryonic kidney cells 293HEK293THuman embryonic kidney cells 293 SV40 large T antigenHeLaHenrietta Lacks cellsHSPCsCD34+ human hematopoietic stem and progenitor cellsIFNAR1Interferon Alpha And Beta Receptor Subunit 1IFNβ/IFNB1Interferon betaISG15Interferon-stimulated gene 15 IVT – in vitro transcribedKOknockoutMAVSmitochondrial activator of virus signalingMDA5/IFIH1melanoma differentiation-associated gene 5/ Interferon Induced with Helicase C Domain 1PAMPpathogen-associated molecular patternRIG-I/DDX58retinoic acid-inducible gene I/ DExD-H-box helicase 58gRNAguide RNASPRIsolid phase reversible immobilizationWTwild type
Co-option of neurotransmitter signaling for inter-organismal communication in C. elegans
Authors: Chute Christopher D. , DiLoreto Elizabeth M. , Zhang Ying K. , Rayes Diego , Coyle Veronica L. , Choi Hee June , Alkema Mark J. , Schroeder Frank C. , Srinivasan Jagan 
Published: March 2018

AbstractBiogenic amine neurotransmitters play a central role in metazoan biology, and both their chemical structures and cognate receptors are evolutionarily conserved. Their primary roles are in intra-organismal signaling, whereas biogenic amines are not normally recruited for communication between separate individuals. Here, we show that in C. elegans, a neurotransmitter-sensing G protein-coupled receptor, TYRA-2, is required for avoidance responses to osas#9, an ascaroside pheromone that incorporates the neurotransmitter octopamine. Neuronal ablation, cell-specific genetic rescue, and calcium imaging show that tyra-2 expression in the nociceptive neuron ASH is necessary and sufficient to induce osas#9 avoidance. Ectopic expression in the AWA neuron, which is generally associated with attractive responses, reverses the response to osas#9, resulting in attraction instead of avoidance behavior, confirming that TYRA-2 partakes in sensing osas#9. The TYRA-2/osas#9 signaling system thus represents an inter-organismal communication channel that evolved via co-option of a neurotransmitter and its cognate receptor.
Enterococcus faecalisAHG0090 is a genetically tractable bacterium and produces a secreted peptidic bioactive that suppresses NF-kB activation in human gut epithelial cells
Authors: Cuív Páraic Ó , Giria Rabina , Hoedt Emily C. , McGuckin Michael A. , Begun Jakob , Morrison Mark 
Published: March 2018

AbstractEnterococcus faecalisis an early coloniser of the human infant gut and contributes to the development of intestinal immunity. To better understand the functional capacity ofE. faecaliswe constructed a broad host range RP4 mobilisable vector, pEHR513112, that confers chloramphenicol resistance and used a metaparental mating approach to isolateE. faecalisAHG0090 from a faecal sample collected from a healthy human infant. We demonstrated thatE. faecalisAHG0090 is genetically tractable and could be manipulated using traditional molecular microbiology approaches.E. faecalisAHG0090 was comparable to the gold-standard anti-inflammatory bacteriumFaecalibacterium prausnitziiA2-165 in its ability to suppress cytokine mediated NF-КB activation in human gut derived LS174T goblet cell-like and Caco-2 enterocyte-like cell lines.E. faecalisAHG0090 andF. prausnitziiA2-165 produced secreted low molecular weight NF-КB suppressive peptidic bioactives. Both bioactives were sensitive to heat and proteinase K treatments although theE. faecalisAHG0090 bioactive was more resilient to both forms of treatment. As expected,E. faecalisAHG0090 suppressed IL-1β induced NF-КB-p65 subunit nuclear translocation and expression of the NF-КB regulated genes IL-6, IL-8 and CXCL-10. Finally, we determined thatE. faecalisAHG0090 is distantly related to other commensal strains and likely encodes niche factors that support effective colonisation of the infant gut.
The latency of a visual evoked potential tracks the onset of decision making
Authors: Nunez Michael D. , Gosai Aishwarya , Vandekerckhove Joachim , Srinivasan Ramesh 
Published: March 2018

AbstractEncoding of a sensory stimulus is believed to be the first step in perceptual decision making. Previous research has shown that electrical signals recorded from the human brain track evidence accumulation during perceptual decision making (Gold and Shadlen, 2007; O’Connell et al., 2012; Philiastides et al., 2014). In this study we directly tested the hypothesis that the latency of the N200 recorded by EEG (a negative peak occurring between 150 and 275 ms after stimulus presentation in human participants) reflects the visual encoding time (VET) required for completion of figure-ground segregation before evidence accumulation. We show that N200 latencies vary across individuals, are modulated by external visual noise, and increase response time byxmilliseconds when they increase byxmilliseconds, reflecting a linear regression slope of 1. Simulations of cognitive decision-making theory show that variation in human response times not related to evidence accumulation (including VET) are tracked by the fastest response times. A relationship with a slope of 1 between N200 latencies and VET was found by fitting a linear model between trial-averaged N200 latencies and the 10th percentiles of response times. A slope of 1 was also found between single-trial N200 latencies and response times. Fitting a novel neuro-cognitive model of decision-making also yielded a slope of 1 between N200 latency and non-decision time in multiple visual noise conditions, indicating that N200 latencies track the completion of visual encoding and the onset of evidence accumulation. The N200 waveforms were localized to the cortical surface at distributed temporal and extrastriate locations, consistent with a distributed network engaged in figure-ground segregation of the target stimulus.Significance StatementEncoding of a sensory stimulus is believed to be the first step in perceptual decision making. In this study, we report evidence that visual evoked potentials (EPs) around 200 ms after stimulus presentation track the time of visual figure-ground segregation before the onset of evidence accumulation during decision making. These EP latencies vary across individuals, are modulated by external visual noise, and increase response time byxmilliseconds when they increase byxmilliseconds. Hierarchical Bayesian model-fitting was also used to relate these EPs to a specific cognitive parameter that tracks time related to visual encoding in a decision-making model of response time. This work adds to the growing literature that suggests that EEG signals can track the component cognitive processes of decision making.
Task-evoked pupil responses reflect internal belief states
Authors: Colizoli O. , de Gee J.W. , Urai A.E. , Donner T.H. 
Published: March 2018

AbstractPerceptual decisions about the state of the environment are often made in the face of uncertain evidence. Internal uncertainty signals are considered important regulators of learning and decision-making. A growing body of work has implicated the brain’s arousal systems in uncertainty signaling. Here, we found that two specific computational variables, postulated by recent theoretical work, evoke boosts of arousal at different times during a perceptual decision: decision confidence (the observer’s internally estimated probability that a choice was correct given the evidence) before feedback, and prediction errors (deviations from expected reward) after feedback. We monitored pupil diameter, a peripheral marker of central arousal state, while subjects performed a challenging perceptual choice task with a delayed monetary reward. We quantified evoked pupil responses during decision formation and after reward-linked feedback. During both intervals, decision difficulty and accuracy had interacting effects on pupil responses. Pupil responses negatively scaled with decision confidence prior to feedback and scaled with uncertainty-dependent prediction errors after feedback. This pattern of pupil responses during both intervals was in line with a model using the observer’s graded belief about choice accuracy to anticipate rewards and compute prediction errors. We conclude that pupil-linked arousal systems are modulated by internal belief states.
Differences in cognitive functions between cytomegalovirus-infected and cytomegalovirus-free university students: a case control study
Authors: Chvátalová Veronika , Šebánková Blanka , Hrbáčková Hana , Tureček Petr , Flegr Jaroslav 
Published: March 2018

AbstractCytomegalovirus (CMV) is the herpetic virus, which infects 45 – 100% people worldwide. Many reports suggest that CMV could impair cognitive functions of infected subjects. Here we searched for indices of effects of CMV on infected subjects’ intelligence and knowledge. The Intelligence Structure Test I-S-T 2000 R was used to compare IQ of 148 CMV-infected and 135 CMV-free university students. Infected students expressed higher intelligence. Paradoxically, their IQ decreased with decreasing concentration of anti-CMV antibodies, which can be used, statistically, as a proxy of the time passed from the moment of infection in young subjects when the age of subjects is statistically controlled. The paradox of seemingly higher intelligence of CMV infected subjects could be explained by the presence of the subpopulation of about 5 – 10 % CMV-positive individuals in the population of “CMV-negative students”. These false negative subjects had probably not only the oldest infections and therefore the lowest concentration of anamnestic antibodies, but also the lowest intelligence among the infected students. Prevalence of CMV infection in all countries is very high, approaching sometimes 90 %. Therefore, the total impact of CMV on human intelligence may be large.
Depressiveness and Neuroticism in Bartonella Seropositive and Seronegative Subjects – Preregistered Case-Controls Study
Authors: Flegr Jaroslav , Preiss Marek , Balatova Pavla 
Published: March 2018

AbstractSeveral recent studies have demonstrated the association of cat-related injuries with major depression and with depressiveness in the general population. It was suggested that cat-scratch disease, the infection with the bacteriumBartonella henselae, can be responsible for the observed association. However, no direct evidence for the role of theBartonellainfection in this association has been published until now. In this preregistered case-controls study performed on 250 healthy subjects tested earlier for the presence of anti-ToxoplasmaIgG antibodies, we searched for the positive association between presence of anamnestic anti-BartonellaIgG antibodies and depressiveness measured with Beck II inventory, depression subscale of neuroticism measured with N-70 questionnaire, and self-reported health problems. We found that thatBartonella-seropositivity was positively correlated with Beck depression only inToxoplasma-seronegative men and negatively correlated with health inToxoplasma-seronegative women.Bartonellaseropositivity expressed protective effects againstToxoplasmaseropositivity-associated increased neuroticism in men whileToxoplasma-seropositivity expressed protective effects againstBartonellaseropositivity-associated health problems in women. A comparison of the patterns of association of mental and physical health problems withBartonellaseropositivity and with reported cat-related injury suggests that different factor, possibly infection with different pathogen transmitted by cat related-injuries than theBartonella henselae, is responsible for the observed association of cat related-injuries with depressiveness and major depression. The existence of complex interactions betweenBartonellaseropositivity,Toxoplasmaseropositivity, and sex also suggest that the effect of symbionts on the host’s phenotype must by always studied in the context of other infections, and separately for men and women.
Task-induced deactivation in diverse brain systems correlates with interindividual differences in distinct autonomic indices
Authors: Iacovella Vittorio , Faes Luca , Hasson Uri 
Published: March 2018

AbstractNeuroimaging research has shown that different cognitive tasks induce relatively specific activation patterns, as well as less task-specific deactivation patterns. Here we examined whether individual differences in Autonomic Nervous System (ANS) activity during task performance correlate with the magnitude of task-induced deactivation. In an fMRI study, participants performed a continuous mental arithmetic task in a task/rest block design, while undergoing combined fMRI and heart / respiration rate acquisitions using photoplethysmograph and respiration belt. As expected, task performance increased heart-rate and reduced the RMSSD, a cardiac index related to vagal tone. Across participants, higher heart rate during task was linked to increased activation in fronto-parietal regions, as well as to stronger deactivation in ventromedial prefrontal regions. Respiration frequency during task was associated with similar patterns, but in different regions than those identified for heart-rate. Finally, in a large set of regions, almost exclusively limited to the Default Mode Network, lower RMSSD was associated with greater deactivation, and furthermore, the vast majority of these regions were task-deactivated at the group level. Together, our findings show that inter-individual differences in ANS activity are strongly linked to task-induced deactivation. Importantly, our findings suggest that deactivation is a multifaceted construct potentially linked to ANS control, because distinct ANS measures correlate with deactivation in different regions. We discuss the implications for current theories of cortical control of the ANS and for accounts of deactivation, with particular reference to studies documenting a “failure to deactivate” in multiple clinical states.
Automatic Instrument Segmentation in Robot-Assisted Surgery Using Deep Learning
Authors: Shvets Alexey A. , Rakhlin Alexander , Kalinin Alexandr A. , Iglovikov Vladimir I. 
Published: March 2018

AbstractSemantic segmentation of robotic instruments is an important problem for the robot-assisted surgery. One of the main challenges is to correctly detect an instrument’s position for the tracking and pose estimation in the vicinity of surgical scenes. Accurate pixel-wise instrument segmentation is needed to address this challenge. In this paper we describe our deep learning-based approach for robotic instrument segmentation. Our approach demonstrates an improvement over the state-of-the-art results using several novel deep neural network architectures. It addressed the binary segmentation problem, where every pixel in an image is labeled as an instrument or background from the surgery video feed. In addition, we solve a multi-class segmentation problem, in which we distinguish between different instruments or different parts of an instrument from the background. In this setting, our approach outperforms other methods for automatic instrument segmentation thereby providing state-of-the-art results for these problems. The source code for our solution is made publicly available.
The Rumen Metatranscriptome Landscape Reflects Dietary Adaptation and Methanogenesis in Lactating Dairy Cows
Authors: Hornung Bastian , den Bogert Bartholomeus van , Davids Mark , Martins dos Santos Vitor A.P. , Plugge Caroline M. , Schaap Peter J. , Smidt Hauke 
Published: March 2018

AbstractMethane eructed by ruminant animals is a main contributor to greenhouse gas emissions and is solely produced by members of the phylumEuryarchaeotawithin the domainArchaea. Methanogenesis depends on the availability of hydrogen, carbon dioxide, methanol and acetate produced, which are metabolic products of anaerobic microbial degradation of feed-derived fibers. Changing the feed composition of the ruminants has been proposed as a strategy to mitigate methanogenesis of the rumen microbiota.We investigated the impact of corn silage enhanced diets on the rumen microbiota of rumen-fistulated dairy cows, with a special focus on carbohydrate breakdown and methanogenesis. Metatranscriptome analysis of rumen samples taken from animals fed corn silage enhanced diets revealed that genes involved in starch metabolism were significantly more expressed while archaeal genes involved in methanogenesis showed lower expression values. The nutritional intervention also influenced the cross-feeding betweenArchaeaandBacteria.The results indicate that the ruminant diet is important in methanogenesis. The diet-induced changes resulted in a reduced methane emission. The metatranscriptomic analysis provided insights into key underlying mechanisms and opens the way for new rational methods to further reduce methane output of ruminant animals.
Integrating cross-linking experiments withab initioprotein-protein docking
Authors: Vreven Thom , Schweppe Devin K. , Chavez Juan D. , Weisbrod Chad R. , Shibata Sayaka , Zheng Chunxiang , Bruce James E. , Weng Zhiping 
Published: March 2018

ABSTRACTAb initioprotein-protein docking algorithms often rely on experimental data to identify the most likely complex structure. We integrated protein-protein docking with the experimental data of chemical cross-linking followed by mass spectrometry. We tested our approach using 12 cases that resulted from an exhaustive search of the Protein Data Bank for protein complexes with cross-links identified in our experiments. We implemented cross-links as constraints based on Euclidean distance or void-volume distance. For most test cases the rank of the top-scoring near-native prediction was improved by at least two fold compared with docking without the cross-link information, and the success rates for the top 5 and top 10 predictions doubled. Our results demonstrate the delicate balance between retaining correct predictions and eliminating false positives. Several test cases had multiple components with distinct interfaces, and we present an approach for assigning cross-links to the interfaces. Employing the symmetry information for these cases further improved the performance of complex structure prediction.HighlightsIncorporating low-resolution cross-linking experimental data in protein-protein docking algorithms improves performance more than two fold.Integration of protein-protein docking with chemical cross-linking reveals information on the configuration of higher order complexes.Symmetry analysis of protein-protein docking results improves the predictions of multimeric complex structures
Age differences in head motion and estimates of cortical morphology
Authors: Madan Christopher R. 
Published: March 2018

AbstractCortical morphology is known to differ with age, as measured by cortical thickness, fractal dimensionality, and gyrification. However, head motion during MRI scanning has been shown to influence estimates of cortical thickness as well as increase with age. Studies have also found task-related differences in head motion and relationships between body-mass index (BMI) and head motion. Here I replicated these prior findings, as well as several others, within a large, open-access dataset (Centre for Ageing and Neuroscience, CamCAN). This is a larger dataset than these results have been demonstrated previously, within a sample size of more than 600 adults across the adult lifespan. While replicating prior findings is important, demonstrating these key findings concurrently also provides an opportunity for additional related analyses: Critically, I test for the influence of head motion on cortical fractal dimensionality and gyrification; effects were statistically significant in some cases, but small in magnitude.
Bacterial swarming reducesProteus mirabilisandVibrio parahaemolyticuscell stiffness and increases β-lactam susceptibility
Authors: Auer George K. , Oliver Piercen M. , Rajendram Manohary , Lin Ti-Yu , Yao Qing , Jensen Grant J. , Weibel Douglas B. 
Published: March 2018

AbstractSwarmer cells of the gram-negative pathogenic bacteriaProteus mirabilisandVibrio parahaemolyticusbecome long (>10-100 μm) and multinucleate during their growth and motility on polymer surfaces. We demonstrate increasing cell length is accompanied by a large increase in flexibility. Using a microfluidic assay to measure single-cell mechanics, we identified large differences in swarmer cell stiffness of (bending rigidity ofP. mirabilis, 9.6 × 10−22N m2;V. parahaemolyticus, 9.7 × 10−23N m2) compared to vegetative cells (1.4 × 10−20N m2and 3.2 × 10−22N m2, respectively). The reduction in bending rigidity (~3-15 fold) was accompanied by a decrease in the average polysaccharide strand length of the peptidoglycan layer of the cell wall from 28-30 to 19-22 disaccharides. Atomic force microscopy revealed a reduction inP. mirabilispeptidoglycan thickness from 1.5 nm (vegetative) to 1.0 nm (swarmer) and electron cryotomography indicated changes in swarmer cell wall morphology.P. mirabilisandV. parahaemolyticusswarmer cells became increasingly sensitive to osmotic pressure and susceptible to cell wall-modifying antibiotics (compared to vegetative cells)—they were ~30% more likely to die after 3 h of treatment with minimum inhibitory concentrations of the β-lactams cephalexin and penicillin G. The adaptive cost of swarming is offset by the increase in cell susceptibility to physical and chemical changes in their environment, thereby suggesting the development of new chemotherapies for bacteria that leverage swarming for colonization of hosts and survival.ImportanceProteus mirabilisandVibrio parahaemolyticusare bacteria that infect humans. To adapt to environmental changes, these bacteria alter their cell morphology and move collectively to access new sources of nutrients in a process referred to as ‘swarming’. We found that a change in the composition and thickness of the peptidoglycan layer of the cell wall makes swarmer cells ofP. mirabilisandV. parahaemolyticusmore flexible (i.e., reduced cell stiffness) and increases their sensitivity to osmotic pressure and cell-wall targeting antibiotics (e.g., β-lactams). These results highlight the importance of assessing the extracellular environment in determining antibiotic doses and the use of β-lactams antibiotics for treating infections caused by swarmer cells ofP. mirabilisandV. parahaemolyticus.