bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimally Invasive Transforaminal Interbody Fusion With Robotically Assisted Bilateral Pedicle Screw Fixation: 2-Dimensional Operative Video
Authors: Godzik Jakub , Walker Corey T , Theodore Nicholas , Uribe Juan S , Chang Steven W , Snyder Laura A 
Published: September 2018

Abstract
Minimally invasive surgery (MIS) techniques may enable faster patient recovery and reduce the incidence of postoperative infections. Image-guided approaches to spinal instrumentation and interbody fusion have gained popularity in MIS, reducing radiation exposure and improving screw placement accuracy. Use of a novel computed tomography (CT) navigation-based robotic arm provides for live image-guided surgery, with the potential for augmenting existing MIS approaches and improving the accuracy of instrumentation placement. We report on the surgical technique of MIS transforaminal lumbar interbody fusion (TLIF) performed with the assistance of a new robotic device (ExcelsiusGPS, Globus Medical Inc, Audubon, Pennsylvania) and intraoperative CT guidance in a patient with single-level lumbar spondylolisthesis. The patient gave written informed consent before treatment. Institutional review board approval was deemed unnecessary. The patient was positioned prone on the operating room table, and an intraoperative CT was obtained with stereotactic arrays placed bilaterally in the posterior superior iliac spine. Screw trajectories were planned using the ExcelsiusGPS software and placed percutaneously with the robotic arm without using a Kirschner wire. Interbody placement was performed via an expandable retractor after muscle dilation. Screw placement accuracy was determined with postoperative CT, which demonstrated good screw positioning without breach. The patient recovered well and was discharged home without complications. The combined use of the new robotic device and intraoperative CT enables accurate and safe fixation for the treatment of symptomatic lumbar spondylolisthesis. The operative video demonstrates the technical nuances of positioning, stereotactic marker placement, work flow, and screw placement.
Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Microsurgical Management of a Spinal Dural Arteriovenous Fistula With Shared Blood Supply to the Artery of Adamkiewicz: 3-Dimensional Operative Video
Authors: Cawley C Michael , Howard Brian M , Barrow Daniel L 
Published: September 2018

Abstract
The presented case is of a 65-yr-old gentleman referred for thoracic myelopathy. He developed bilateral, nondermatomal foot dysesthesia 14 mo prior to presentation, which progressed to numbness below the L3 level. He reported progressive gait instability, bilateral lower extremity weakness, and required a cane for ambulation. He subsequently developed urinary incontinence, while bowel function was spared. The neurological examination upon presentation revealed lower extremity strength was reduced to 4/5 in all major muscle groups bilaterally, while sensation and proprioception were reduced below the L3 level. Patellar and Achilles reflexes were not elicited and clonus was absent. Gait was unsteady and slow. The patient was not able to perform heel, toe and tandem gait. MRI revealed abnormal T2 hyper-intense signal and spinal cord expansion from T6 through the conus medullaris. Angiography revealed a dural arteriovenous fistula (dAVF) originating from the left T9 radicomedullary pedicle, which also supplied the Artery of Adamkiewicz (AoA). The patient underwent T8-10 laminectomies. Prior to disconnection of the fistula, an aneurysm clip was applied to the fistulous point and an indocyanine green video angiogram was completed to show that the fistula no longer opacified, but that the AoA remained patent, which was later confirmed with angiography. As of discharge, the patient's motor exam had improved substantially, though his sensory deficits persisted. This case demonstrates that surgical disconnection is requisite in the treatment of spinal dAVF that have a shared blood supply with the AoA, as embolization risks spinal cord infarction.
The patient consented to presentation of this case in a de-identified fashion.
Microtubules Gate Tau Condensation to Spatially Regulate Microtubule Functions
Authors: Tan Ruensern , Lam Aileen J. , Tan Tracy , Han Jisoo , Nowakowski Dan W. , Vershinin Michael , Simo Sergi , Ori-McKenney Kassandra M. , McKenney Richard J. 
Published: September 2018

AbstractTau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer’s disease and other dementias, yet the physiological state of tau molecules within cells remains unclear. Using single molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of MT severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, controlled by the microtubule, is an important mechanism of tau’s biological functions, and that oligomerization of tau is a common property shared between the physiological and disease forms of the molecule.One Sentence Summary:Reversible tau oligomerization regulates microtubule functions.
Effects of altering histone post-translational modifications on mitotic chromosome structure and mechanics
Authors: Biggs Ronald , Liu Patrick , Stephens Andrew D. , Marko John F. 
Published: September 2018

AbstractDuring cell division chromatin is compacted into mitotic chromosomes to aid faithful segregation of the genome between two daughter cells. Post-translational modifications (PTM) of histones alter compaction of interphase chromatin, but it remains poorly understood how these modifications affect mitotic chromosome stiffness and structure. Using micropipette-based force measurements and epigenetic drugs, we probed the influence of canonical histone PTMs that dictate interphase euchromatin (acetylation) and heterochromatin (methylation) on mitotic chromosome stiffness. By measuring chromosome doubling force (the force required to double chromosome length), we find that histone methylation, but not acetylation, contributes to mitotic structure and stiffness. We discuss our findings in the context of chromatin gel modeling of the large-scale organization of mitotic chromosomes.
Multiple C2 domains and Transmembrane region Proteins (MCTPs) tether membranes at plasmodesmata
Authors: Brault Marie L. , Petit Jules D. , Immel Françoise , Nicolas William J. , Brocard Lysiane , Gaston Amélia , Fouché Mathieu , Hawkins Timothy J. , Crowet Jean-Marc , Grison Magali S. , Kraner Max , Alva Vikram , Claverol Stéphane , Deleu Magali , Lins Laurence , Tilsner Jens , Bayer Emmanuelle M. 
Published: September 2018

AbstractIn eukaryotes, membrane contact sites (MCS) allow direct communication between organelles. Plants have evolved unique MCS, the plasmodesmata intercellular pores, which combine endoplasmic reticulum (ER) - plasma membrane (PM) contacts with regulation of cell-to-cell signalling. The molecular mechanism and function of membrane tethering within plasmodesmata remains unknown.Here we show that the Multiple C2 domains and Transmembrane region Protein (MCTP) family, key regulators of cell-to-cell signalling in plants, act as ER - PM tethers specifically at plasmodesmata. We report that MCTPs are core plasmodesmata proteins that insert into the ER via their transmembrane region whilst their C2 domains dock to the PM through interaction with anionic phospholipids. A mctp3/4 loss-of-function mutant induces plant developmental defects while MCTP4 expression in a yeast Δtether mutant partially restores ER-PM tethering. Our data suggest that MCTPs are unique membrane tethers controlling both ER-PM contacts and cell-cell signalling.
Modeling neuronal avalanches and long-range temporal correlations at the emergence of collective oscillations: continuously varying exponents mimic M/EEG results
Authors: Porta Leonardo Dalla , Copelli Mauro 
Published: September 2018

AbstractWe revisit the CROS (“CRitical OScillations”) model which was recently proposed as an attempt to reproduce both scale-invariant neuronal avalanches and long-range time correlations. With excitatory and inhibitory stochastic neurons locally connected in a two-dimensional disordered network, the model exhibits a transition from an active to an oscillating state. Precisely at the transition, the fluctuations of the network activity have detrended fluctuation analysis (DFA) exponents close to one, and avalanches (defined as supra-threshold activity) have power law distributions of size and duration. By simulating larger system sizes, we show that, differently from previous results, the exponents governing the distributions of avalanche size and duration are not necessarily those of the mean-field directed percolation universality class (3/2 and 2, respectively). Instead, exponents obtained via a maximum-likelihood estimator vary continuously in a narrow region of parameter space. Around that critical region, moreover, the values of avalanche and DFA exponents display a spread with negative correlations, in qualitative agreement with the interindividual variability that was experimentally observed in M/EEG data.
Early Neural Correlates of an Auditory Pitch - Visual Size Cross-modal Association
Authors: Boyle Stephanie C. , Kayser Christoph , Ince Robin A. A. 
Published: September 2018

AbstractResearch has shown participants associate high pitch tones with small objects, and low pitch tones with large objects. Yet it remains unclear when these associations emerge in neural signals, and whether or not they are likely the result of predictive coding mechanisms being influenced by multisensory priors. Here we investigated these questions using a modified version of the implicit association task, 128-channel human EEG, and two approaches to single-trial analysis (linear discriminant and mutual information). During two interlaced discrimination tasks (auditory high/low tone and visual small/large circle), one stimulus was presented per trial and the auditory stimulus-response assignment was manipulated. On congruent trials preferred pairings (high tone, small circle) were assigned to the same response key, and on incongruent trials non-preferred pairings were (low tone, small circle). The results showed participants (male and female) responded faster during auditory congruent than incongruent trials. The EEG results showed that acoustic pitch and visual size were represented early in the trial (~100 ms and ~220 ms), over temporal and frontal regions. Neural signals were also modulated by congruency early in the trial for auditory (<100ms) and visual modalities (~200ms). For auditory trials, EEG components were predictive of reaction times, but for visual trials they were not. These EEG results were consistent across analysis methods, demonstrating they are robust to the statistical methodology used. Overall, our data support an early origin of cross-modal associations, and suggest that these may originate during early sensory processing potentially due to predictive coding mechanisms.
Coalescent-based phylogenetic inference from genes with unequivocal historical signal suggests a polytomy at the root of the placental mammal tree of life
Authors: Moreira Filipe R. R. , Schrago Carlos G. 
Published: September 2018

AbstractFinding the correct place of the root of the Placentalia tree of life is an unsolved problem in mammalian systematics. Three major competing hypotheses were proposed, alternating the position of the supraordinal taxa Afrotheria, Xenarthra, or Atlantogenata as sister lineages to the remaining placentals. While all three phylogenetic associations were inferred by studies conducted so far, recent assessments applying heterogeneous models and coalescent-based phylogenetic methods found robust support for the Atlantogenata hypothesis. Current developments in theoretical phylogenetics, such as the demonstration that concatenating genes may bias the likelihood function, and that summary coalescent-based phylogenetic methods are sensitive to errors in gene tree estimation, calls for a reevaluation of the early placental split problem. We investigated the phylogenetic relationships between placental superorders by restricting the analysis to subsets of genes with unequivocal phylogenetic signal. In contrast to previous works, we show that the hypothesis of a polytomy at the placental root could not be rejected under the multispecies coalescent model. This result endorses conclusions from analyses of retroposon insertion patterns. We provide an analytical framework to access empirical polytomies employing summary coalescent methods and topological tests, helping the investigation of poorly resolved nodes in the tree of life.
Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes
Authors: Siahaan Valerie , Krattenmacher Jochen , Hernandez-Vega Amayra , Hyman Anthony A. , Diez Stefan , Lansky Zdenek , Braun Marcus 
Published: September 2018

AbstractTau is an intrinsically disordered protein, which diffuses on microtubules. In neurodegenerative diseases collectively termed tauopathies, tau malfunction and its detachment from axonal microtubules is correlated with microtubule degradation. It is known that tau can protect microtubules from microtubule-degrading enzymes, such as katanin. However, how tau can fulfill such regulative function is still unclear. Using in vitro reconstitution, we here show that tau molecules on microtubules cooperatively form islands of an ordered layer with regulatory qualities distinct from a comparably dense layer of diffusible tau. These islands shield the microtubules from katanin and kinesin-1 but are penetrable by kinesin-8 which causes the islands to disassemble. Our results indicate a new phase of tau, constituting an adjustable protective sheath around microtubules.
GPR17 is an Essential Component of the Negative Feedback Loop of the Sonic Hedgehog Signalling Pathway in Neural Tube Development
Authors: Yatsuzuka Atsuki , Hori Akiko , Kadoya Minori , Matsuo-Takasaki Mami , Kondo Toru , Sasai Noriaki 
Published: September 2018

AbstractDorsal-ventral pattern formation of the neural tube is regulated by temporal and spatial activities of extracellular signalling molecules. Sonic hedgehog (Shh) assigns ventral neural subtypes via activation of the Gli transcription factors. Shh activity changes dynamically during neural differentiation, but the mechanisms responsible for regulating this dynamicity are not fully understood. Here we show that the P2Y-type G-protein coupled receptor GPR17 is involved in temporal regulation of the Shh signal. GPR17 was expressed in the ventral progenitor regions of the neural tube and acted as a negative regulator of the Shh signal in chick embryos. While the activation of the GPR17-related signal inhibited ventral identity, perturbation ofGPR17expression led to aberrant expansion of ventral neural domains. Notably, perturbation ofGPR17expression partially inhibited the negative feedback of Gli activity. Moreover, GPR17 increased cAMP activity, suggesting that it exerts its function by inhibiting the processing of Gli3 protein. GPR17 also negatively regulated Shh signalling in neural cells differentiated from mouse embryonic stem cells, suggesting that GPR17 function is conserved among different organisms. Our results demonstrate that GPR17 is a novel negative regulator of Shh signalling in a wide range of cellular contexts.Author SummaryDuring neural development, determination of cell fate and the progress of differentiation are regulated by extracellular signal molecules, including Sonic Hedgehog (Shh). Shh forms a gradient within the embryonic organ of the central nervous system, or the neural tube, and a variety of cells are produced corresponding to the concentration. While the signal concentration is critical for cell fate, recent studies have revealed that the intracellular signal intensity does not always correspond to the Shh concentration. Rather, the intracellular signal intensity changes over time. Importantly, the signal intensity peaks and gradually decreases thereafter, and the half-life of the Shh signal contributes to the cell fate determination. However, the mechanisms for this temporal change are not fully understood.By using chick embryos and mouse embryonic stem cells as model systems, we demonstrate that the G-protein coupled receptor, GPR17, is an essential regulator for the negative feedback of the Shh signal during neural development. WhileGPR17gene expression is induced by the Shh signal, GPR17 perturbs the Shh signalling pathway. This negative function of GPR17 on the Shh signal is conserved among different vertebrate species. The collective data demonstrate that GPR17 is a negative regulator for the Shh signalling pathway in a wide range of the cellular contexts.
Genome-wide identification and expression analysis of the FAR gene family in hexaploid wheat (Triticum aestivum L.)
Authors: Shi Shandang , Chai Guaiqiang , Ren Hui , Nan Wenzhi , Wu Hongqi , Wang Yong , Li Chunlian , Wang Zhonghua 
Published: September 2018

AbstractFatty acyl-CoA reductase (FAR) is involved in the biosynthesis of primary alcohols, which are waxy constituents that play an important role in plant stress. Previous studies have shown that primary alcohol is the most important component in the wheat seeding stage and accounts for more than 80% of the total composition. To date, eight FAR genes have been identified in wheat, but there has not been a systematic analysis. In this study, a comprehensive overview of the TaFAR gene family was performed, including analyses of the phylogenetic relationship, the multiple sequence alignment, the conserved motif distribution and the expression pattern. The result showed that a total of 41 wheat FAR genes were identified and designated TaFAR1-A–TaFAR22-D; all FAR genes were divided into six classes according to their phylogenetic relationship, and most of the FAR genes might be related to wheat cuticular wax synthesis. The analysis of the promoter binding site showed that TaFAR genes could be regulated by the MYB transcription factor and could be used as target genes for hormone regulation under adverse conditions, especially during a drought. This study provides a basis for further analyses of the TaFAR gene function and of upstream regulatory genes.
High-throughput targeted long-read single cell sequencing reveals the clonal and transcriptional landscape of lymphocytes
Authors: Singh Mandeep , Al-Eryani Ghamdan , Carswell Shaun , Ferguson James M. , Blackburn James , Barton Kirston , Roden Daniel , Luciani Fabio , Phan Tri , Junankar Simon , Jackson Katherine , Goodnow Christopher C. , Smith Martin A. , Swarbrick Alexander 
Published: September 2018

AbstractHigh-throughput single-cell RNA-Sequencing is a powerful technique for gene expression profiling of complex and heterogeneous cellular populations such as the immune system. However, these methods only provide short-read sequence from one end of a cDNA template, making them poorly suited to the investigation of gene-regulatory events such as mRNA splicing, adaptive immune responses or somatic genome evolution. To address this challenge, we have developed a method that combines targeted long-read sequencing with short-read based transcriptome profiling of barcoded single cell libraries generated by droplet-based partitioning. We use Repertoire And Gene Expression sequencing (RAGE-seq) to accurately characterize full-length T cell (TCR) and B cell (BCR) receptor sequences and transcriptional profiles of more than 7,138 lymphocytes sampled from the primary tumour and draining lymph node of a breast cancer patient. With this method we show that somatic mutation, alternate splicing and clonal evolution of T and B lymphocytes can be tracked across these tissue compartments. Our results demonstrate that RAGE-Seq is an accessible and cost-effective method for high-throughput deep single cell profiling, applicable to a wide range of biological challenges.
Middle-way flexible docking: Pose prediction using mixed-resolution Monte Carlo in estrogen receptorα
Authors: Spiriti Justin , Subramanian Sundar Raman , Palli Rohith , Wu Maria , Zuckerman Daniel M. 
Published: September 2018

AbstractThere is a vast gulf between the two primary strategies for simulating protein-ligand interactions. Docking methods significantly limit or eliminate protein flexibility to gain great speed at the price of uncontrolled inaccuracy, whereas fully flexible atomistic molecular dynamics simulations are expensive and often suffer from limited sampling. We have developed a flexible docking approach geared especially for highly flexible or poorly resolved targets based on mixed-resolution Monte Carlo (MRMC), which is intended to offer a balance among speed, protein flexibility, and sampling power. The binding region of the protein is treated with a standard atomistic force field, while the remainder of the protein is modeled at the residue level with a Gō model that permits protein flexibility while saving computational cost. Implicit solvation is used. Here we assess three facets of the MRMC approach with implications for other docking studies: (i) the role of receptor flexibility in cross-docking pose prediction; (ii) the use of non-equilibrium candidate Monte Carlo (NCMC) and (iii) the use of pose-clustering in scoring. We examine 61 co-crystallized ligands of estrogen receptorα, an important cancer target known for its flexibility. We also compare the performance of the MRMC approach with Autodock smina, a docking program. [1] Adding protein flexibility, not surprisingly, leads to significantly lower total energies and stronger interactions between protein and ligand, but notably we document the important role of backbone flexibility in the improvement. The improved backbone flexibility also leads to improved performance relative to smina. Somewhat unexpectedly, our implementation of NCMC leads to only modestly improved sampling of ligand poses. Overall, the addition of protein flexibility improves the performance of docking, as measured by energy-ranked poses, but we do not find significant improvements based on cluster information or the use of NCMC.
Covariate Assisted Principal Regression for Covariance Matrix Outcomes
Authors: Zhao Yi , Wang Bingkai , Mostofsky Stewart H. , Caffo Brian S. , Luo Xi 
Published: September 2018

AbstractModeling variances in data has been an important topic in many fields, including in financial and neuroimaging analysis. We consider the problem of regressing covariance matrices on a vector covariates, collected from each observational unit. The main aim is to uncover the variation in the covariance matrices across units that are explained by the covariates. This paper introducesCovariate Assisted Principal(CAP) regression, an optimization-based method for identifying the components predicted by (generalized) linear models of the covariates. We develop computationally efficient algorithms to jointly search the projection directions and regression coefficients, and we establish the asymptotic properties. Using extensive simulation studies, our method shows higher accuracy and robustness in coefficient estimation than competing methods. Applied to a resting-state functional magnetic resonance imaging study, our approach identifies the human brain network changes associated with age and sex.