bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural Correlates of Task-related Refixation Behaviour
Authors: Meghanathan Radha Nila , van Leeuwen Cees , Giannini Marcello , Nikolaev Andrey R. 
Published: September 2019

AbstractInformation uptake during scene viewing under free viewing conditions is crucially determined by the scanning plan. This plan is determined both by top-down and bottom-up factors. To capture top-down factors affecting saccade planning, we compared EEG between first fixations and refixations on items varying in task-relevance. First fixations and refixations impose different working memory costs because first fixations involve encoding of new items whereas refixations involve rehearsal of existing items in working memory. These memory requirements also differ with the task-relevance of the item being encoded. Together, these two factors of task-relevance and memory processes related to refixation behavior would affect saccade planning. In a visual task involving search and memorization of multiple targets, we compared saccade-related potentials (SRPs) between first fixations and refixations for task-relevant (target) and task-irrelevant (distractor) items. We assessed the interval preceding a saccade away from the fixation of interest. Studying this presaccadic interval revealed how mechanisms related to saccade preparation are affected by task-relevance and refixation behavior. We found higher SRP amplitudes for first fixations than refixations over the occipital region for task-relevant items only. Our findings indicate that saccade planning is modulated by both task-relevance of an item and working memory load.
A system for tracking whisker kinematics and whisker shape in three dimensions
Authors: Petersen Rasmus S. , Rodriguez Andrea Colins , Evans Mathew Hywel , Campagner Dario , Loft Michaela S. E. 
Published: September 2019

AbstractQuantification of behaviour is essential for systems neuroscience. Since the whisker system is a major model system for investigating the neural basis of behaviour, it is important to have methods for measuring whisker movements from behaving animals. Here, we developed a high-speed imaging system that measures whisker movements simultaneously from two vantage points. We developed an algorithm that uses the ‘stereo’ video data to track multiple whiskers by fitting 3D curves to the basal section of each target whisker. By using temporal information to constrain the fits, the algorithm is able to track multiple whiskers in parallel with low error rate. We used the output of the tracker to produce a 3D description of each tracked whisker, including its 3D orientation and 3D shape, as well as bending-related mechanical force. In conclusion, we present an automatic system to track whiskers in 3D from high-speed video, creating the opportunity for comprehensive 3D analysis of sensorimotor behaviour and its neural basis.Author summaryThe great ethologist Niko Tinbergen described a crucial challenge in biology to measure the “total movements made by the intact animal”. Advances in high-speed video and machine analysis of such data have made it possible to make profound advances. Here, we target the whisker system. The whisker system is a major experimental model in neurobiology and, since the whiskers are readily imageable, the system is ideally suited to machine vision. Rats and mice explore their environment by sweeping their whiskers to and fro. It is important to measure whisker movements in 3D, since whiskers move in 3D and since the mechanical forces that act on them are 3D. However, the problem of automatically tracking whiskers in 3D from video has generally been regarded as prohibitively difficult. Our innovation here is to extract 3D information about whiskers using a two-camera, high-speed imaging system and to develop computational methods to infer 3D whisker state from the imaging data. Our hope is that this study will facilitate comprehensive, 3D analysis of whisker behaviour and, more generally, contribute new insight into brain mechanisms of perception and behaviour.
C9orf72-associated arginine-rich dipeptide repeats induce RNA-dependent accumulation of Staufen in nucleus
Authors: Kim Eun Seon , Chung Chang Geon , Kim Yoon Ha , Cha In Jun , Park Jeong Hyang , Kim Jaekwang , Ha Chang Man , Kim Hyung-Jun , Lee Sung Bae 
Published: September 2019

AbstractAccumulation of RNA in the nucleus is one of the pathological features of C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD), yet its potential toxic cellular consequences remain largely undefined. RNA accumulated in the nucleus may interact with and increase nuclear localization of RNA-binding proteins (RBPs). Here, we show in C9-ALS/FTD Drosophila melanogaster model that Staufen, a double-stranded RBP normally localized in cytoplasm, accumulates in the nucleus, which is in contrast to many nuclear-localized RBPs, such as TDP-43 and FUS, whose cytoplasmic accumulation is thought to be a pathological hallmark of ALS/FTD. We found that in Drosophila neurons expressing arginine-rich dipeptide repeat proteins (DPRs), Staufen accumulated in the nucleus in an RNA-dependent manner. In the nucleus, Staufen localized closely to, and potentially interacts with, heterochromatin and nucleolus in Drosophila C4 da neurons expressing poly(PR), a proline-arginine (PR) DPR. PR toxicity in C4 da neurons increased Fibrillarin staining in the nucleolus, which was enhanced by stau heterozygous mutation. Furthermore, knockdown of fib exacerbated retinal degeneration mediated by PR toxicity, which suggests that increased amount of Fibrillarin by stau heterozygous mutation is protective. Heterozygotic mutation of stau could also mitigate retinal degeneration and rescue viability of flies exhibiting PR toxicity. Taken together, our data show that nuclear accumulation of cytoplasmic protein, such as Staufen, may also be an important pathological feature of C9-ALS/FTD.Author summaryCytoplasmic accumulation of nuclear RNA-binding proteins (RBPs) is one of the common pathological features of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In C9orf72-associated ALS/FTD fly model, we found that Staufen, a double-stranded (ds) RBP normally localized mostly in cytoplasm, accumulates in the nucleus in an RNA-dependent manner. Next, we checked wherein the nucleus Staufen accumulates and found that Staufen partially co-localizes with heterochromatin and nucleolus. Interestingly, the expression of Fibrillarin, a nucleolar protein, was significantly increased by C9orf72-derived PR toxicity and further augmented by reduction in stau dosage, the gene encoding Staufen. When we knocked down fib, the gene encoding Fibrillarin, PR-induced retinal degeneration was exacerbated. This indicates that increased Fibrillarin expression by stau dosage reduction is protective. Furthermore, when we reduced stau dosage in flies presenting PR toxicity, their retinal degeneration and viability were largely rescued. Based on these data, we suggest that nuclear accumulation of Staufen is an important feature of C9-ALS/FTD and suggest that reducing stau dosage is a promising therapeutic target.
Disentangling sound from syntax: electrophysiological analysis of linguistics expressions
Authors: Artoni Fiorenzo , d’Orio Piergiorgio , Catricalà Eleonora , Conca Francesca , Bottoni Franco , Pelliccia Veronica , Sartori Ivana , Russo Giorgio Lo , Cappa Stefano F. , Micera Silvestro , Moro Andrea 
Published: September 2019

AbstractSyntax is a species-specific component of human language combining a finite set of words in a potentially infinite number of sentences. Since words are by definition expressed by sound, factoring out syntactic information is normally impossible. Here, we circumvented this problem in a novel way by designing phrases with exactly the same acoustic content but different syntactic structures depending on the other words they occur with. By performing stereo- electroencephalographic (SEEG) recordings in epileptic patients we measured a different electrophysiological correlate of verb phrases vs. noun phrases by analyzing the high gamma band activity (150-300Hz frequency), in multiple cortical areas in both hemispheres, including language areas and their homologous in the non-dominant hemisphere. Our findings contribute to the ultimate goal of a complete neural decoding of linguistic structures from the brain.
Imaging plant germline differentiation within Arabidopsis flower by light sheet microscopy
Authors: Valuchova Sona , Mikulkova Pavlina , Pecinkova Jana , Klimova Jana , Krumnikl Michal , Bainar Petr , Heckmann Stefan , Tomancak Pavel , Riha Karel 
Published: September 2019

AbstractIn higher plants, germline differentiation occurs during a relatively short period within developing flowers. Understanding of the mechanisms that govern germline differentiation lags behind other plant developmental processes. This is largely because the germline is restricted to relatively few cells buried deep within floral tissues, which makes them difficult to study. To overcome this limitation, we have developed a methodology for live imaging of the germ cell lineage within floral organs of Arabidopsis using light sheet fluorescence microscopy. We have established reporter lines, cultivation conditions, and imaging protocols for high-resolution microscopy of developing flowers continuously for up to several days. We used multiview imagining to reconstruct a three-dimensional model of a flower at subcellular resolution. We demonstrate the power of this approach by capturing male and female meiosis, asymmetric pollen division, movement of meiotic chromosomes, and unusual restitution mitosis in tapetum cells. This method will enable new avenues of research into plant sexual reproduction.
Cyb5r3 links FoxO1-dependent mitochondrial dysfunction with β-cell failure
Authors: Fan Jason , Du Wen , Kim-Muller Ja Young , Son Jinsook , Kuo Taiyi , Larrea Delfina , Garcia Christian , Kitamoto Takumi , Kraakman Michael J. , Owusu-Ansah Edward , Cirulli Vincenzo , Accili Domenico 
Published: September 2019

AbstractObjectiveDiabetes is characterized by pancreatic β-cell dedifferentiation. Dedifferentiating β-cells inappropriately metabolize lipids over carbohydrates and exhibit impaired mitochondrial oxidative phosphorylation. However, the mechanism linking the β-cell’s response to an adverse metabolic environment with impaired mitochondrial function remains unclear.MethodsHere we report that the oxidoreductase cytochrome b5 reductase 3 (Cyb5r3) links FoxO1 signaling to β-cell stimulus/secretion coupling by regulating mitochondrial function, reactive oxygen species generation, and NAD/NADH ratios.ResultsExpression of Cyb5r3 is decreased in FoxO1-deficient β-cells. Mice with β-cell-specific deletion of Cyb5r3 have impaired insulin secretion resulting in glucose intolerance and diet-induced hyperglycemia. Cyb5r3-deficient β-cells have a blunted respiratory response to glucose and display extensive mitochondrial and secretory granule abnormalities, consistent with altered differentiation. Moreover, FoxO1 is unable to maintain expression of key differentiation markers in Cyb5r3-deficient β-cells, suggesting that Cyb5r3 is required for FoxO1-dependent lineage stability.ConclusionsThe findings highlight a pathway linking FoxO1 to mitochondrial dysfunction that can mediate β-cell failure.
Adaptive Tuning Curve Widths Improve Sample Efficient Learning
Authors: Meier Florian , Dang-Nhu Raphaël , Steger Angelika 
Published: September 2019

AbstractNatural brains perform miraculously well in learning new tasks from a small number of samples, whereas sample efficient learning is still a major open problem in the field of machine learning. Here, we raise the question, how the neural coding scheme affects sample efficiency, and make first progress on this question by proposing and analyzing a learning algorithm that uses a simple reinforce-type plasticity mechanism and does not require any gradients to learn low dimensional mappings. It harnesses three bio-plausible mechanisms, namely, population codes with bell shaped tuning curves, continous attractor mechanisms and probabilistic synapses, to achieve sample efficient learning. We show both theoretically and by simulations that population codes with broadly tuned neurons lead to high sample efficiency, whereas codes with sharply tuned neurons account for high final precision. Moreover, a dynamic adaptation of the tuning width during learning gives rise to both, high sample efficiency and high final precision. We prove a sample efficiency guarantee for our algorithm that lies within a logarithmic factor from the information theoretical optimum. Our simulations show that for low dimensional mappings, our learning algorithm achieves comparable sample efficiency to multi-layer perceptrons trained by gradient descent, although it does not use any gradients. Furthermore, it achieves competitive sample efficiency in low dimensional reinforcement learning tasks. From a machine learning perspective, these findings may inspire novel approaches to improve sample efficiency. From a neuroscience perspective, these findings suggest sample efficiency as a yet unstudied functional role of adaptive tuning curve width.
Probing glioblastoma and its microenvironment using single-nucleus and single-cell sequencing
Authors: Peng Sen , Rath Sanhita , Vuong Connor , Bollam Saumya , Eschbacher Jenny , Dong Xishuang , Mehta Shwetal , Sanai Nader , Berens Michael , Kim Seungchan , Dhruv Harshil 
Published: September 2019

AbstractSingle-cell (scSeq) and single-nucleus sequencing (snSeq) are powerful tools to investigate cancer genomics at single cell resolution. Multiple studies have recently illuminated intratumoral heterogeneity in glioblastoma, however, the majority focused on molecular complexity of tumor cells, without considering unexplored host cell types that contribute to the microenvironment around tumor. To address the glioblastoma microenvironment composition and potential tumor-host interactions, we performed deep coverage sequencing of freshly resected primary GBM patient tissue without implementing any tumor enrichment strategies. The sequencing resulted in 902 cells and 1186 nuclei, respectively, passing quality control and with low mitochondrial gene percentage. We customized reference transcriptome by listing gene transcript loci as exons to take into account immature RNA, which greatly improved the alignment rate for single-nucleus data. We applied Cell Ranger pipelines (Version 3.0.2) and Seurat package (Version 2.3.1) and discovered 10 clusters in both scSeq and snSeq. Pathway analysis of each cluster signature in scSeq data along with known GBM microenvironment cell signatures revealed glioma tumor population along with surrounding microglia/macrophages, astrocytes, pericytes, oligodendrocytes, T cells and endothelial cells. The analysis of snSeq was able to capture the majority of cell types from patient tissues (tumor and microenvironment cells), but interestingly presented different cell type composition in microenvironment cell types such as microglia/macrophages. Integrating single-cell and single-nucleus transcriptomic data using canonical correlation analysis facilitated a comparison of snSeq and scSeq, contrasting depiction for certain cell types (e.g. NKX6-2 gene in Oligodendrocytes). Differential analysis of pathways between tumor and microenvironment cells unveiled potentially rewired pathways such as double strand break repair pathway. Our results demonstrate the cellular diversity of brain tumor microenvironment and lay a foundation to further investigate the individual tumor and host cell transcriptomes that are influenced not only by their cell identity but also by their interaction with surrounding microenvironment.
FANCY: Fast Estimation of Privacy Risk in Functional Genomics Data
Authors: Gürsoy Gamze , Brannon Charlotte M. , Navarro Fabio C.P. , Gerstein Mark 
Published: September 2019

AbstractFunctional genomics data is becoming clinically actionable, raising privacy concerns. However, quantifying the privacy leakage by genotyping is difficult due to the heterogeneous nature of sequencing techniques. Thus, we present FANCY, a tool that rapidly estimates number of leaking variants from raw RNA-Seq, ATAC-Seq and ChIP-Seq reads, without explicit genotyping. FANCY employs supervised regression using overall sequencing statistics as features and provides an estimate of the overall privacy risk before data release. FANCY can predict the cumulative number of leaking SNVs with a 0.95 average R2 for all independent test sets. We acknowledged the importance of accurate prediction even when the number of leaked variants is low, so we developed a special version of model, which can make predictions with higher accuracy for only a few leaking variants. A python and MATLAB implementation of FANCY, as well as custom scripts to generate the features can be found at https://github.com/gersteinlab/FANCY. We also provide jupyter notebooks so that users can optimize the parameters in the regression model based on their own data. An easy-to-use webserver that takes inputs and displays results can be found at fancy.gersteinlab.org.
A Subcutaneous Implant of Tenofovir Alafenamide Fumarate Causes Local Inflammation and Tissue Necrosis in Rabbits and Macaques
Authors: Su Jonathan T. , Simpson Solange M , Sung Samuel , Tfaily Ewa Bryndza , Veazey Ronald , Marzinke Mark , Qiu Jiang , Watrous David , Widanapathirana Lakmini , Pearson Elizabeth , Peet M. Melissa , Karunakaran Dipu , Grasperge Brooke , Dobek Georgina , Cain Charlette M. , Hope Thomas , Kiser Patrick F. 
Published: September 2019

ABSTRACTWe describe the in vitro and in vivo evaluation of a subcutaneous reservoir implant delivering tenofovir alafenamide hemifumarate (TAF) for the prevention of HIV infection. These long-acting reservoir implants were able to deliver antiretroviral drug for over 90 days in vitro and in vivo. We evaluated the implants for implantation site histopathology and pharmacokinetics in plasma and tissues for up to 12 weeks in New Zealand White rabbits and rhesus macaque models. A dose-ranging study in rabbits demonstrated dose-dependent pharmacokinetics and local inflammation up to severe necrosis around the active implants. The matched placebos showed normal wound healing and fibrous tissue encapsulation of the implant. We designed a second implant with a lower release rate and flux of TAF and achieved a median cellular level of tenofovir diphosphate of 42 fmol per 106 rhesus macaque peripheral blood mononuclear cells at a dose of 10 µg/kg/day. This dose and flux of TAF also resulted in adverse local inflammation and necrosis near the implant in rhesus macaques. Inflammation in the primates was markedly lower in the placebo group than the active implant. The histological inflammatory response to the TAF implant at 4 and 12 weeks in primates was graded as a severe reaction. Thus, while we were able to achieve sustained target dose we observed unacceptable inflammatory response locally at the implant tissue interface.
Reduced frontal white matter microstructure in healthy older adults with low tactile recognition performance
Authors: Higgen Focko L. , Braaß Hanna , Schulz Robert , Xue Gui , Gerloff Christian 
Published: September 2019

AbstractAging leads to a reduction of connectivity in large-scale structural brain networks. Sensory processing and other cognitive processes rely on information flow between distant brain areas. However, data linking age-related structural brain alterations to cognitive functioning, especially sensory processing, is sparse.Aiming to determine group differences in sensory processing between older and younger participants, we implemented a complex tactile recognition task and investigated to what extent changes in microstructural white matter integrity of large-scale brain networks might reflect success in task performance. Structural brain integrity was accessed by means of diffusion-weighted imaging and fractional anisotrophy.The data revealed that poor performance in complex tactile recognition in older, neurologically healthy individuals is related to decreased structural integrity pronounced in the anterior corpus callosum. This region was strongly connected to the prefrontal cortex. Our data suggests decreased fractional anisotrophy in the anterior corpus callosum as a surrogate marker for progressed brain aging, leading to disturbances in networks relevant for higher-order cognitive processing. Complex tactile recognition might be a sensitive marker for identifying these starting cognitive impairments in older adults.
Spatio-temporal control of DNA replication by the pneumococcal cell cycle regulator CcrZ
Authors: Gallay Clement , Sanselicio Stefano , Anderson Mary E. , Soh Young Min , Liu Xue , Stamsås Gro A. , Pelliciari Simone , van Raaphorst Renske , Dénéréaz Julien , Kjos Morten , Murray Heath , Gruber Stephan , Grossman Alan D. , Veening Jan-Willem 
Published: September 2019

AbstractMost bacteria replicate and segregate their DNA concomitantly while growing, before cell division takes place. How bacteria synchronize these different cell cycle events to ensure faithful chromosome inheritance is poorly understood. Here, we identified a conserved and essential protein in pneumococci and related Firmicutes named CcrZ (for Cell Cycle Regulator protein interacting with FtsZ) that couples cell division with DNA replication by controlling the activity of the master initiator of DNA replication, DnaA. The absence of CcrZ causes mis-timed and reduced initiation of DNA replication, which subsequently results in aberrant cell division. We show that CcrZ from Streptococcus pneumoniae directly interacts with the cytoskeleton protein FtsZ to place it in the middle of the newborn cell where the DnaA-bound origin is positioned. Together, this work uncovers a new mechanism for the control of the bacterial cell cycle in which CcrZ controls DnaA activity to ensure that the chromosome is replicated at the right time during the cell cycle.
Interactions ofPlasmodium falciparumETRAMP14.1 with PfEMP1, translocon components and other ETRAMP members at the interface of host-parasite
Authors: Sindhe Kirthana Mysore Vasudevarao , Ray Ananya , Kumar Sanjeev , Surolia Namita 
Published: September 2019

AbstractThe Early Transcribed Membrane Proteins (ETRAMPs) belong to a multigene family which are conserved, are specific toPlasmodiumspecies, and abundantly present in parasitophorous vacuolar membrane (PVM). The functions of the members of this family are poorly understood.PfETRAMP14.1 (PF3D7_1401400) is a member of this family, present only inPlasmodium falciparum. In this study, we report the potential interacting partners ofPfETRAMP14.1 by using immunoprecipitation (IP) LC-MS/MS as well as protein-interaction network reconstructed onin vivoarray analyses of severe malaria inflicted patients from malaria endemic Indian regions. We findPfETRAMP14.1 to be the most highly transcribed gene in severe infection. Our studies with western blot analysis and Immuno-flurorescence show thatPfETRAMP14.1 is expressed at PVM during all the intraerythrocytic stages ofP.falciparumwith maximum expression at early trophozoite stage. Further, our results reveal interactions of ETRAMP14.1 withPlasmodium falciparumerythrocyte membrane protein 1(PfEMP1), thioredoxin (TRX2), export protein 2 (EXP2), heat shock protein 70-1 (Hsp70-1) and some of the ETRAMP family members. We propose that ETRAMP14.1 helps trafficking of PfEMP1 to the host RBC surface in conjunction with translocon machinery and the chaperone HSP 70-1.