bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inferring the collective dynamics of neuronal populations from single-trial spike trains using mechanistic models
Authors: Donner Christian , Opper Manfred , Ladenbauer Josef 
Published: June 2019

AbstractMulti-neuronal spike-train data recorded in vivo often exhibit rich dynamics as well as considerable variability across cells and repetitions of identical experimental conditions (trials). Efforts to characterize and predict the population dynamics and the contributions of individual neurons require model-based tools. Abstract statistical models allow for principled parameter estimation and model selection, but possess only limited interpretive power because they typically do not incorporate prior biophysical constraints. Here we present a statistically principled approach based on a population of doubly-stochastic integrate-and-fire neurons, taking into account basic biophysics. This model class comprises an idealized description for the dynamics of the neuronal membrane voltage in response to fast independent and slower shared input fluctuations. To efficiently estimate the model parameters and compare different model variants we compute the likelihood of observed single-trail spike trains by leveraging analytical methods for spiking neuron models combined with inference techniques for hidden Markov models. This allows us to reconstruct the shared input variations, classify their dynamics, obtain precise spike rate estimates, and quantify how individual neurons couple to the low-dimensional overall population dynamics, all from a single trial. Extensive evaluations based on simulated data show that our method correctly identifies the dynamics of the shared input process and accurately estimates the model parameters. Validations on ground truth recordings of neurons in vitro demonstrate that our approach successfully reconstructs the dynamics of hidden inputs and yields improved fits compared to a typical phenomenological model. Finally, we apply the method to a neuronal population recorded in vivo, for which we assess the contributions of individual neurons to the overall spiking dynamics. Altogether, our work provides statistical inference tools for a class of reasonably constrained, mechanistic models and demonstrates the benefits of this approach to analyze measured spike train data.
Probabilistic representation in human visual cortex reflects uncertainty in serial decisions
Authors: van Bergen R.S. , Jehee J.F.M. 
Published: June 2019

AbstractHow does the brain represent the reliability of its sensory evidence? Here, we test whether sensory uncertainty is encoded in cortical population activity as the width of a probability distribution – a hypothesis that lies at the heart of Bayesian models of neural coding. We probe the neural representation of uncertainty by capitalizing on a well-known behavioral bias called serial dependence. Human observers of either sex reported the orientation of stimuli presented in sequence, while activity in visual cortex was measured with fMRI. We decoded probability distributions from population-level activity and found that serial dependence effects in behavior are consistent with a statistically advantageous sensory integration strategy, in which uncertain sensory information is given less weight. More fundamentally, our results suggest that probability distributions decoded from human visual cortex reflect the sensory uncertainty that observers rely on in their decisions, providing critical evidence for Bayesian theories of perception.
Archaeal ribosomal proteins possess nuclear localization signal-type motifs: implications for the origin of the cell nucleus
Authors: Melnikov Sergey , Kwok Hui-Si , Manakongtreecheep Kasidet , van den Elzen Antonia , Thoreen Carson C. , Söll Dieter 
Published: June 2019

AbstractEukaryotic cells are divided into the nucleus and the cytosol, and, to enter the nucleus, proteins typically possess short signal sequences, known as nuclear localization signals (NLSs). Although NLSs have long been considered as features unique to eukaryotic proteins, we show here that similar or identical protein segments are present in ribosomal proteins from the Archaea. Specifically, the ribosomal proteins uL3, uL15, uL18, and uS12 possess NLS-type motifs that are conserved across all major branches of the Archaea, including the most ancient groups Microarchaeota and Diapherotrites, pointing to the ancient origin of NLS-type motifs in the Archaea. Furthermore, by using fluorescence microscopy, we show that the archaeal NLS-type motifs can functionally substitute eukaryotic NLSs and direct the transport of ribosomal proteins into the nuclei of human cells. Collectively, these findings illustrate that the origin of NLSs preceded the origin of the cell nucleus, suggesting that the initial function of NLSs was not related to intracellular trafficking. Overall, our study reveals rare evolutionary intermediates among archaeal cells that can help elucidate the sequence of events that led to the origin of the eukaryotic cell.
Magnetic-alignment of polymer macro-nanodiscs enable residual dipolar couplings based high-resolution structural studies by NMR
Authors: Ravula Thirupathi , Ramamoorthy Ayyalusamy 
Published: June 2019

ABSTRACTResidual dipolar couplings (RDCs) have been shown to be valuable for the structural studies of systems ranging from small molecules to large proteins. Here we demonstrate the lyotropic liquid crystal behavior of polymer macro-nanodiscs (> 20 nm in diameter) and enable the measurement of RDCs using high resolution NMR.
Reversal learning performance in the XY* mouse model of Klinefelter and Turner Syndromes
Authors: Aarde Shawn M. , Hrncir Haley , Arnold Arthur P. , Jentsch J. David 
Published: June 2019

ABSTRACTKlinefelter syndrome (KS; 47, XXY) and Turner syndrome (TS; 45, XO) are caused by two relatively common sex chromosome aneuploidies. These conditions are associated with an increased odds of neuropsychiatric disorders, including attention deficit/hyperactivity disorder (ADHD), as well as impairments in cognition that include learning delays, attentional dysfunction and impulsivity. We studied cognitive functions in the XY* mouse model, which allows comparison of XXY to XY males (KS model), and XO to XX females (TS model). We evaluated adult mice with and without gonads, using a version of an operant reversal-learning task (RLT) that can be used to measure various facets of learning, impulsivity and attention. In the KS model, only one measure related to impulsivity – perseverative responding under reversal conditions – reliably discriminated gonadally intact XXY and XY mice. In contrast, a fundamental learning impairment (more trials to criterion in acquisition phase) in XXY mice, as compared to XY, was observed in gonadectomized subjects. No other task measures showed differences consistent with KS. In the TS mouse model, XO mice did not show a pattern of results consistent with TS, similar to past observations. Thus, the application of this RLT to these XY* models reveals only limited behavioral impairments relevant to KS.
A neurally plausible model for online recognition and postdiction in a dynamical environment
Authors: Wenliang Li Kevin , Sahani Maneesh 
Published: June 2019

AbstractHumans and other animals are frequently near-optimal in their ability to integrate noisy and ambiguous sensory data to form robust percepts, which are informed both by sensory evidence and by prior experience about the causal structure of the environment. It is hypothesized that the brain establishes these structures using an internal model of how the observed patterns can be generated from relevant but unobserved causes. In dynamic environments, such integration often takes the form of postdiction, wherein later sensory evidence affects inferences about earlier percepts. As the brain must operate in current time, without the luxury of acausal propagation of information, how does such postdictive inference come about? Here, we propose a general framework for neural probabilistic inference in dynamic models based on the distributed distributional code (DDC) representation of uncertainty, naturally extending the underlying encoding to incorporate implicit probabilistic beliefs about both present and past. We show that, as in other uses of the DDC, an inferential model can be learned efficiently using samples from an internal model of the world. Applied to stimuli used in the context of psychophysics experiments, the framework provides an online and plausible mechanism for inference, including postdictive effects.
Challenging the boundaries of the physical self: purely distal cues in the environment impact body ownership
Authors: Grechuta Klaudia , De La Torre Javier , Ballester Belén Rubio , Verschure Paul F.M.J. 
Published: June 2019

AbstractThe unique ability to identify one’s own body and experience it as one’s own is fundamental in goal-oriented behavior and survival. However, the mechanisms underlying the so-called body ownership are yet not fully understood. The plasticity of body ownership has been studied using two experimental methods or their variations. Specifically, the Rubber Hand Illusion (RHI), where the tactile stimuli are externally generated, or the moving RHI which implies self-initiated movements. Grounded in these paradigms, evidence has demonstrated that body ownership is a product of bottom-up reception of self- and externally-generated multisensory information and top-down comparison between the predicted and the actual sensory stimuli. Crucially, provided the design of the current paradigms, where one of the manipulated cues always involves the processing of a proximal modality sensing the body or its surface (e.g., touch), the contribution of sensory signals which pertain to the environment remain elusive. Here we propose that, as any robust percept, body ownership depends on the integration and prediction of all the sensory stimuli, and therefore it will depend on the consistency of purely distal sensory signals pertaining to the environment. To test our hypothesis, we create an embodied goal-oriented task and manipulate the predictability of the surrounding environment by changing the congruency of purely distal multisensory cues while preserving bodily and action-driven signals entirely predictable. Our results empirically reveal that the way we represent our body is contingent upon all the sensory stimuli including purely distal and action-independent signals which pertain to the environment.
Nitrogen Fertilisers Shape the Composition and Predicted Functions of the Microbiota of Field-Grown Tomato Plants
Authors: Caradonia Federica , Ronga Domenico , Catellani Marcello , Azevedo Cleber Vinícius Giaretta , Terrazas Rodrigo Alegria , Robertson-Albertyn Senga , Francia Enrico , Bulgarelli Davide 
Published: June 2019

ABSTRACTThe microbial communities thriving at the root-soil interface have the potential to improve plant growth and sustainable crop production. Yet, how agricultural practices, such as the application of either mineral or organic nitrogen fertilisers, impact on the composition and functions of these communities remains to be fully elucidated. By deploying a two-pronged 16S rRNA gene sequencing and predictive metagenomics approach we demonstrated that the bacterial microbiota of field-grown tomato (Solanum lycopersicum) plants is the product of a selective process that progressively differentiates between rhizosphere and root microhabitats. This process initiates as early as plants are in a nursery stage and it is then more marked at late developmental stages, in particular at harvest. This selection acts on both the bacterial relative abundances and phylogenetic assignments, with a bias for the enrichment of members of the phylum Actinobacteria in the root compartment. Digestate-based and mineral-based nitrogen fertilisers trigger a distinct bacterial enrichment in both rhizosphere and root microhabitats. This compositional diversification mirrors a predicted functional diversification of the root-inhabiting communities, manifested predominantly by the differential enrichment of genes associated to ABC transporters and the two-component system. Together, our data suggest that the microbiota thriving at the tomato root-soil interface is modulated by and in responses to the type of nitrogen fertiliser applied to the field.
Impact of narrow spectrum Penicillin V on the oral and fecal resistome in a young child treated for otitis media
Authors: Sturød Kjersti , Dhariwal Achal , Dahle Ulf R , Vestrheim Didrik F , Petersen Fernanda C 
Published: June 2019

AbstractBackgroundAntibiotic overuse has led to a global emergence of resistant bacteria, and children are among the frequent users. Most studies with broad-spectrum antibiotics show severe impact on the resistome development of patients. Although narrow-spectrum antibiotics are believed to have less side-effects, their impact on the microbiome and resistome is mostly unknown. The aim of this study was to investigate the impact of the narrow-spectrum antibiotic phenoxymethylpenicillin (Penicillin V) on the microbiome and resistome of a child treated for acute otitis media (OM).MethodsOral and fecal samples were collected from a one-year child before (day 0) and after (day 5 and 30) receiving Penicillin V against OM. Metagenomic sequencing data was analysed to determine taxonomic profiling, using Kraken and Bracken software, and resistance profiling, using KMA in combination with the ResFinder database.ResultsIn the oral samples, 11 antimicrobial resistance genes (ARGs), belonging to four classes, were identified at baseline. At day 5, the abundance of some ARGs was increased, some remained unchanged, while others disappeared. At day 30, most ARGs had returned to baseline levels, or lower. In the fecal samples we observed seven ARGs at baseline and five at day 5, with only one gene observed at day 5 being present at baseline. At day 30 the number of ARGs increased to 21 ARGs from 7 different classes.ConclusionsPenicillin V had a remarkable impact on the fecal resistome indicating that even narrow-pectrum antibiotics may have important consequences in selecting for a more resistant microbiome.
Multiple conformations facilitate PilT function in the type IV pilus
Authors: McCallum Matthew , Benlekbir Samir , Nguyen Sheryl , Tammam Stephanie , Rubinstein John L. , Burrows Lori L. , Howell P. Lynne 
Published: June 2019

AbstractType IV pilus-like systems are protein complexes that polymerize a fibre of pilins. They are critical for virulence in many pathogens. Pilin polymerization and depolymerization are powered by motor PilT-like ATPases thought to possess C2 symmetry. However, most PilT-like ATPases crystallize with either C3 or C6 symmetry and the relevance of these conformations is unclear. Here we determined the X-ray structures of PilT in four unique conformations and used these structures to classify the conformation of available PilT-like ATPase structures. Single particle electron cryomicroscopy (cryoEM) structures of PilT revealed condition-dependent preferences for C2,C3, and C6 conformations. The physiologic importance of these conformations was validated by co-evolution analysis and functional studies of point mutants, identifying a rare gain-of-function mutation that favours the C2 conformation. With these data we propose a comprehensive model of PilT function with broad implications for PilT-like ATPases.
siQ-ChIP: A reverse-engineered quantitative framework for ChIP-sequencing
Authors: Dickson Bradley M , Tiedemann Rochelle L , Chomiak Alison A , Vaughan Robert M , Cornett Evan M , Rothbart Scott B 
Published: June 2019

AbstractChromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) is a key technique for mapping the distribution and relative abundance of histone posttranslational modifications (PTMs) and chromatin-associated factors across genomes. There is a perceived challenge regarding the ability to quantitatively plot ChIP-seq data, and as such, approaches making use of exogenous additives, or “spike-ins” have recently been developed. Relying on the fact that the IP step of ChIP-seq is a competitive binding reaction, we present a quantitative framework for ChIP-seq analysis that circumvents the need to modify standard sample preparation pipelines with spike-in reagents. We also introduce a visualization technique that, when paired with our formal developments, produces a much more rich characterization of sequencing data.
Barcoding biological reactions with DNA-functionalized vesicles
Authors: Peruzzi Justin A. , Jacobs Miranda L. , Vu Timothy Q. , Kamat Neha P. 
Published: June 2019

AbstractTargeted vesicle fusion is a promising approach to selectively control interactions between vesicle compartments and would enable the initiation of biological reactions in complex aqueous environments. Here, we explore how two features of vesicle membranes, DNA tethers and phase-segregated membranes, promote fusion between specific vesicle populations. We show that membrane phase-segregation provides an energetic driver for membrane fusion that increases the efficiency of DNA-mediated fusion events. Using this system, we show that orthogonality provided by DNA tethers allows us to direct fusion and delivery of DNA cargo to specific vesicle populations. We then demonstrate that vesicle fusion between DNA-tethered vesicles can be used to initiatein vitroprotein expression that leads to the synthesis of model soluble and membrane proteins. The ability to engineer orthogonal fusion events between DNA-tethered vesicles will provide a new strategy to control the spatio-temporal dynamics of cell-free reactions, expanding opportunities to engineer artificial cellular systems.
Topoisomerases modulate the timing of meiotic DNA breakage and chromosome morphogenesis inSaccharomyces cerevisiae
Authors: Heldrich Jonna , Sun Xiaoji , Vale-Silva Luis A. , Markowitz Tovah E. , Hochwagen Andreas 
Published: June 2019

AbstractDuring meiotic prophase, concurrent transcription, recombination, and chromosome synapsis, place substantial topological strain on chromosomal DNA, but the role of topoisomerases in this context remains poorly defined. Here, we analyzed the roles topoisomerases I and II (Top1 and Top2) during meiotic prophase inSaccharomyces cerevisiae. We show that both topoisomerases accumulate primarily in promoter-containing intergenic regions of actively transcribing genes. Enrichment partially overlaps meiotic double-strand break (DSB) hotspots, but disruption of either topoisomerase has different effects during meiotic recombination.TOP1disruption delays DSB induction and shortens the window of DSB accumulation by an unknown mechanism. By contrast, temperature-sensitivetop2-1mutants accumulate DSBs on synapsed chromosomes and exhibit a marked delay in meiotic chromosome remodeling. This defect results from a delay in recruiting the meiotic chromosome remodeler Pch2/TRIP13 but, unexpectedly, is not due to a loss of Top2 catalytic activity. Instead, mutant Top2-1 protein has reduced contact with chromatin but remains associated with meiotic chromosomes, and we provide evidence that this altered binding is responsible for the delay in chromosome remodeling. Our results imply independent roles for topoisomerases I and II in modulating meiotic recombination.
One-shot tagging during wake and cueing during sleep with spatiotemporal patterns of transcranial electrical stimulation can boost long-term metamemory of individual episodes in humans
Authors: Pilly Praveen K. , Skorheim Steven W. , Hubbard Ryan J. , Ketz Nicholas A. , Roach Shane M. , Jones Aaron P. , Robert Bradley , Bryant Natalie B. , Lerner Itamar , Hartholt Arno , Mullins Teagan S. , Choe Jaehoon , Clark Vincent P. , Howard Michael D. 
Published: June 2019

AbstractTargeted memory reactivation (TMR) during slow-wave oscillations (SWOs) in non-rapid eye movement (NREM) sleep has been demonstrated with sensory cues to achieve about 5-12% improvement in post-nap memory performance on simple laboratory tasks. But prior work has neither addressed the one-shot aspect of episodic memory acquisition, nor dealt with the presence of interference from ambient environmental cues in real-world settings for the sensory cues. Moreover, TMR with sensory cues may not be scalable to the multitude of experiences over one’s lifetime. We designed a novel non-invasive paradigm that tags one-shot experiences of minute-long naturalistic episodes within immersive virtual reality (VR) with unique spatiotemporal amplitude-modulated patterns (STAMPs) of transcranial electrical stimulation (tES) and cues them during SWOs. In particular, we demonstrate that these STAMPs can be re-applied as brief pulses to temporally coincide with UP states of SWOs (0.4167 – 1 s) on two consecutive nights to achieve about 20% improvement in the metamemory of targeted episodes at 48 hours after the one-shot viewing, compared to the control episodes. Post-sleep metamemory of the targeted episodes was driven by an interaction between their pre-sleep metamemory and the number of STAMP applications for those episodes during sleep. Overnight metamemory improvements were mediated by spectral power increases from 6.18 to 6.7 s following the offset of STAMPs in the slow-spindle band (9-12 Hz) for left temporal areas in the scalp electroencephalography (EEG) during sleep. These results prescribe an optimal strategy to leverage STAMPs for boosting metamemory and suggest that real-world episodic memories can be modulated in a targeted manner even with coarser, non-invasive spatiotemporal stimulation.
DNA Punch Cards: Storing Data on Native DNA Sequences via Nicking
Authors: Tabatabaei S Kasra , Wang Boya , Athreya Nagendra Bala Murali , Enghiad Behnam , Hernandez Alvaro Gonzalo , Fields Christopher J. , Leburton Jean-Pierre , Soloveichik David , Zhao Huimin , Milenkovic Olgica 
Published: June 2019

AbstractSynthetic DNA-based data storage systems have received significant attention due to the promise of ultrahigh storage density and long-term stability. However, all platforms proposed so far suffer from high cost, read-write latency and error-rates that render them noncompetitive with modern optical and magnetic storage devices. One means to avoid synthesizing DNA and to reduce the system error-rates is to use readily available native DNA. As the symbol/nucleotide content of native DNA is fixed, one may adopt an alternative recording strategy that modifies the DNA topology to encode desired information. Here, we report the first macromolecular storage paradigm in which data is written in the form of “nicks (punches)” at predetermined positions on the sugar-phosphate backbone of native dsDNA. The platform accommodates parallel nicking on multiple “orthogonal” genomic DNA fragments and paired nicking and disassociation for creating “toehold” regions that enable single-bit random access and strand displacement in-memory computations. As a proof of concept, we used the programmable restriction enzyme Pyrococcus furiosus Argonaute to punch two files into the PCR products of Escherichia coli genomic DNA. The encoded data is accurately reconstructed through high-throughput sequencing and read alignment.