bluuebunny/crossref_metadata_2025_split huggingface dataset:
EvoFreq: Visualization of the Evolutionary Frequencies of Sequence and Model Data
Authors: Gatenbee Chandler D. , Schenck Ryan O. , Bravo Rafael , Anderson Alexander R.A. 
Published: August 2019

AbstractHigh throughput sequence data has provided in depth means of molecular characterization of populations. When recorded at numerous time steps, such data can reveal the evolutionary dynamics of the population under study by tracking the changes in genotype frequencies over time. This necessitates a simple and flexible means of visualizing an increasingly complex set of data. Here we offer EvoFreq as a comprehensive tool set to visualize the evolutionary and population frequency dynamics of clones at a single point in time or as population frequencies over time using a variety of informative methods. EvoFreq expands substantially on previous means of visualizing the clonal, temporal dynamics and offers users a range of options for displaying their sequence or model data. EvoFreq, implemented in R with robust user options and few dependencies, offers a high-throughput means of quickly building, and interrogating the temporal dynamics of hereditary information across many systems. EvoFreq is freely available viahttps://github.com/MathOnco/EvoFreq.
Severe Hyposmia Distinguishes Neuropathologically Confirmed Dementia with Lewy Bodies from Alzheimer’s Disease Dementia
Authors: Beach TG , Adler CH , Zhang N , Serrano GE , Sue LI , Driver-Dunckley Erika , Mehta Shayamal H. , Zamrini E , Sabbagh MN , Shill HA , Belden CM , Shprecher DR , Caselli RJ , Reiman EM , Davis KJ , Long KE , Nicholson LR , Intorcia AJ , Glass MJ , Walker JE , Callan M , Oliver JC , Arce R , Gerkin RC 
Published: August 2019

AbstractDue to the absence of core clinical features, many subjects with neuropathologically-confirmed dementia with Lewy bodies (DLB) are never diagnosed as such during life. Most of these are diagnosed with Alzheimer’s disease dementia (ADD) or unspecified dementia. Unrecognized DLB therefore is a critical impediment to clinical studies and treatment trials of both ADD and DLB. There are numerous published studies that suggest that olfactory function tests may be able to differentiate some neurodegenerative conditions from each other and from normal subjects, but there are very few studies with neuropathological confirmation of diagnosis. We compared University of Pennsylvania Smell Identification Test (UPSIT) results in 209 subjects: 1) 29 concurrently meeting intermediate or high consensus clinicopathological criteria for both DLB and ADD 2) 96 meeting criteria for ADD without DLB 3) 84 control subjects that were non-demented and without parkinsonism at death. The DLB subjects had significantly lower (one-way ANOVA p < 0.0001, pairwise Bonferroni p < 0.05) first and mean UPSIT scores (13.7 and 13.2) than ADD (23.3 and 22.2) or controls (29.6 and 28.9). For subjects with first and mean UPSIT scores less than 20 and 17, respectively, Firth logistic regression analysis, adjusted for age, gender and mean MMSE score, conferred statistically significant odds ratios of 17.5 and 18.0 for predicting a DLB vs ADD diagnosis, as compared to 3.3 for the presence or absence of visual hallucinations throughout the clinical observation period. To our knowledge, this is the largest study to date comparing olfactory function in subjects with neuropathologically confirmed DLB and ADD. Olfactory function testing may be a convenient and inexpensive strategy for enriching dementia studies or clinical trials with DLB subjects, or conversely, reducing the inclusion of DLB subjects in ADD studies or trials.
The maizeHairy Sheath Frayed1(Hsf1) mutant alters leaf patterning through increased cytokinin signaling
Authors: Muszynski Michael G. , Moss-Taylor Lindsay , Chudalayandi Sivanandan , Cahill James , Del Valle-Echevarria Angel R. , Alvarez-Castro Ignacio , Petefish Abby , Sakakibara Hitoshi , Krivosheev Dmitry M. , Lomin Sergey N. , Romanov Georgy A. , Thamotharan Subbiah , Li Bailin , Brugière Norbert 
Published: August 2019

ABSTRACTLeaf morphogenesis requires growth polarized along three axes - proximal-distal, medial-lateral and abaxial-adaxial. Grass leaves display a prominent proximal-distal (P-D) polarity consisting of a proximal sheath separated from the distal blade by the auricle and ligule. Although proper specification of the four segments is essential for normal morphology, our knowledge is incomplete regarding the mechanisms which influence P-D specification in monocots like maize (Zea mays). Here we report the identification of the gene underlying the semi-dominant, leaf patterning, maize mutantHairy Sheath Frayed1(Hsf1).Hsf1plants produce leaves with outgrowths consisting of proximal segments – sheath, auricle and ligule – emanating from the distal blade margin. Analysis of three independentHsf1alleles revealed gain-of-function missense mutations in the ligand binding domain of the maize cytokinin (CK) receptorZea mays Histidine Kinase1(ZmHK1)gene. Biochemical analysis and structural modeling suggest the mutated residues near the CK binding pocket affect CK binding affinity. Treatment of wild type seedlings with exogenous CK phenocopied theHsf1leaf phenotypes. Results from expression and epistatic analyses indicated theHsf1mutant receptor appears to be hypersignaling. Our results demonstrate that hypersignaling of CK in incipient leaf primordia can reprogram developmental patterns in maize.SummaryIncreased cytokinin signaling in the maizeHairy Sheath Frayed1mutant modifies leaf development leading to changes in pattering, growth and cell identity.
Crowding Reveals Fundamental Differences in Local vs. Global Processing in Humans and Machines
Authors: Doerig A. , Bornet A. , Choung O. H. , Herzog M. H. 
Published: August 2019

AbstractFeedforward Convolutional Neural Networks (ffCNNs) have become state-of-the-art models both in computer vision and neuroscience. However, human-like performance of ffCNNs does not necessarily imply human-like computations. Previous studies have suggested that current ffCNNs do not make use of global shape information. However, it is currently unclear whether this reflects fundamental differences between ffCNN and human processing or is merely an artefact of how ffCNNs are trained. Here, we use visual crowding as a well-controlled, specific probe to test global shape computations. Our results provide evidence that ffCNNs cannot produce human-like global shape computations for principled architectural reasons. We lay out approaches that may address shortcomings of ffCNNs to provide better models of the human visual system.
Photocontrol of endogenous glycine receptors in vivo
Authors: Gomila Alexandre M.J. , Rustler Karin , Maleeva Galyna , Nin-Hill Alba , Wutz Daniel , Bautista-Barrufet Antoni , Rovira Xavier , Bosch Miquel , Mukhametova Elvira , Mukhamedyarov Marat , Peiretti Frank , Alfonso-Prieto Mercedes , Rovira Carme , König Burkhard , Bregestovski Piotr , Gorostiza Pau 
Published: August 2019

ABSTRACTGlycine receptors (GlyRs) are indispensable to maintain excitatory/inhibitory balance in neuronal circuits controlling reflex and rhythmic motor behaviors. Here we have developed Glyght, the first GlyR ligand controlled with light. It is selective over other cys-loop receptors, active in vivo, and displays an allosteric mechanism of action. The photomanipulation of glycinergic neurotransmission opens new avenues to understand inhibitory circuits in intact animals, and to develop drug-based phototherapies.
Expectations affect the perception of material properties
Authors: Alley Lorilei M. , Schmid Alexandra C. , Doerschner Katja 
Published: August 2019

ABSTRACTMany objects that we encounter have ‘typical’ material qualities: spoons are hard, pillows are soft, and jell-O dessert is wobbly. Over a lifetime of experiences, strong associations between an object and its typical material properties may be formed, and these associations not only include how glossy, rough or pink an object is, but also how it behaves under force: we expect knocked over vases to shatter, popped bike tires to deflate, and gooey grilled cheese to hang between two slices of bread when pulled apart. Here we ask how such rich visual priors affect the visual perception of material qualities and present a particularly striking example of expectation violation. In a cue conflict design, we pair computer-rendered familiar objects with surprising material behaviors (a linen curtain shattering, a porcelain teacup wrinkling, etc.) and find that material qualities are not solely estimated from the object’s kinematics (i.e. its physical (atypical) motion while shattering, wrinkling, wobbling etc.); rather, material appearance is sometimes “pulled” towards the “native” motion, shape, and optical properties that are associated with this object. Our results, in addition to patterns we find in response time data, suggest that visual priors about materials can set up high-level expectations about complex future states of an object and show how these priors modulate material appearance.
SPAligner: Alignment of Long Diverged Molecular Sequences to Assembly Graphs
Authors: Dvorkina Tatiana , Antipov Dmitry , Korobeynikov Anton , Nurk Sergey 
Published: August 2019

AbstractBackgroundGraph-based representation of genome assemblies has been recently used in different applications — from gene finding to haplotype separation. While most of these applications are based on the alignment of molecular sequences to assembly graphs, existing software tools for finding such alignments have important limitations.ResultsWe present a novel SPAligner tool for aligning long diverged molecular sequences to assembly graphs and demonstrate that SPAligner is an efficient solution for mapping third generation sequencing data and can also facilitate the identification of known genes in complex metagenomic datasets.ConclusionsOur work will facilitate accelerating the development of graph-based approaches in solving sequence to genome assembly alignment problem. SPAligner is implemented as a part of SPAdes tools library and is available on https://github.com/ablab/spades/archive/spaligner-paper.zip.
NRP2 as an emerging angiogenic player; promoting endothelial cell adhesion and migration by regulating recycling of α5 integrin
Authors: Alghamdi Abdullah AA , Benwell Christopher J , Atkinson Samuel J , Lambert Jordi , Robinson Stephen D 
Published: August 2019

AbstractAngiogenesis relies on the ability of endothelial cells (ECs) to migrate over the extracellular matrix via integrin receptors to respond to an angiogenic stimulus. Of the two neuropilin (NRP) orthologs to be identified, both have been reported to be expressed on normal blood and lymphatic ECs, and to play roles in the formation of blood and lymphatic vascular networks during angiogenesis. Whilst the role of NRP1 and its interactions with integrins during angiogenesis has been widely studied, the role of NRP2 in ECs is poorly understood. Here we demonstrate that NRP2 promotes Rac-1 mediated EC adhesion and migration over fibronectin (FN) matrices in a mechanistically distinct fashion to NRP1, showing no dependence on β3 integrin (ITGB3) expression, or VEGF stimulation. Furthermore, we highlight evidence of a regulatory crosstalk between NRP2 and α5 integrin (ITGA5) in ECs, with NRP2 depletion eliciting an upregulation of ITGA5 expression and disruptions in ITGA5 cellular organisation. Finally, we propose a mechanism whereby NRP2 promotes ITGA5 recycling in ECs; NRP2 depleted ECs were found to exhibit reduced levels of total ITGA5 subunit recycling compared to wild-type (WT) ECs. Our findings expose NRP2 as a novel angiogenic player by promoting ITGA5-mediated EC adhesion and migration on FN.
Structural distortions induced by Kinase Inhibiting RNase Attenuator (KIRA) compounds prevent the formation of face-to-face dimers of Inositol Requiring Enzyme 1α
Authors: Carlesso Antonio , Chintha Chetan , Gorman Adrienne M. , Samali Afshin , Eriksson Leif A. 
Published: August 2019

AbstractInositol-Requiring Enzyme 1α (IRE1α) is a transmembrane dual kinase/ribonuclease protein involved in propagation of the unfolded protein response (UPR). IRE1α is currently explored as a potential drug target due to growing evidence of its role in variety of disease conditions. Upon activation, IRE1 cleaves X-box Binding Protein 1 (XBP1) mRNA through its RNase domain. Small molecules targeting the kinase site are known to either increase or decrease RNase activity, but the allosteric relationship between the kinase and RNase domains of IRE1α is poorly understood. Subsets of IRE1 kinase inhibitors (known as “KIRA” compounds) bind to the ATP-binding site and allosterically impede the RNase activity. KIRA compounds are able to regulate the RNase activity by stabilizing monomeric form of IRE1α.In the present work, computational analysis, protein-protein and protein-ligand docking studies, and molecular dynamics simulations were applied to different IRE1 dimer systems to provide structural insights into the perturbation of IRE1 dimers by small molecules kinase inhibitors that regulate the RNase activity. By analyzing structural deviations, energetic components and number of hydrogen bonds in the interface region, we propose that the KIRA inhibitors act at an early stage of IRE1 activation by interfering with IRE1 face-to-face dimer formation, thus disabling the activation of the RNase domain. The work sheds light on the mechanism of action of KIRA compounds and may assist in development of further compounds in e.g. cancer therapeutics. The work also provides information on the sequence of events and protein-protein interactions initiating the unfolded protein response.Non-technical SummaryThe unfolded protein response is a protective feedback mechanism whereby cells regulate high levels of misfolded proteins in the endoplasmic reticulum. Due to its significance in cell survival, the UPR has become an interesting target in cancer therapy. A key pathway of the UPR is initiated by the activation of inositol requiring enzyme 1α (IRE1α), which must first dimerise in order to mediate the stress signal. Different inhibitors have been proposed in order to block the UPR at the level of IRE1α. We here unveil, through detailed computational studies, the mode of action of a set of IRE1α inhibitors targeting the kinase domain, which in turn helps us to further understand the mechanism of activation and progression of the UPR.
A novel machine learning based approach for iPS progenitor cell identification
Authors: Zhang Haishan , Shao Ximing , Peng Yin , Teng Yanning , Saravanan Konda Mani , Zhang Huiling , Li Hongchang , Wei Yanjie 
Published: August 2019

AbstractIdentification of induced pluripotent stem (iPS) progenitor cells, the iPS forming cells in early stage of reprogramming, could provide valuable information for studying the origin and underlying mechanism of iPS cells. However, it is very difficult to identify experimentally since there are no biomarkers known for early progenitor cells, and only about 6 days after reprogramming initiation, iPS cells can be experimentally determined via fluorescent probes. What is more, the ratio of progenitor cells during early reprograming period is below 5%, which is too low to capture experimentally in the early stage.In this paper, we propose a novel computational approach for the identification of iPS progenitor cells based on machine learning and microscopic image analysis. Firstly, we record the reprogramming process using a live cell imaging system after 48 hours of infection with retroviruses expressing Oct4, Sox2 and Klf4, later iPS progenitor cells and normal murine embryonic fibroblasts (MEFs) within 3 to 5 days after infection are labeled by retrospectively tracing the time-lapse microscopic image. We then calculate 11 types of cell morphological and motion features such as area, speed, etc., and select best time windows for modeling and perform feature selection. Finally, a prediction model using XGBoost is built based on the selected six types of features and best time windows. Our model allows several missing values/frames in the sample datasets, thus it is applicable to a wide range of scenarios.Cross-validation, holdout validation and independent test experiments showed that the minimum precision is above 52%, that is, the ratio of predicted progenitor cells within 3 to 5 days after viral infection is above 52%. The results also confirmed that the morphology and motion pattern of iPS progenitor cells is different from that of normal MEFs, which helps with the machine learning methods for iPS progenitor cell identification.Author SummaryIdentification of induced pluripotent stem (iPS) progenitor cells could provide valuable information for studying the origin and underlying mechanism of iPS cells. However, it is very difficult to identify experimentally since there are no biomarkers known for early progenitor cells, and only after about 6 days of induction, iPS cells can be experimentally determined via fluorescent probes. What is more, the percentage of the progenitor cells during the early induction period is below 5%, too low to capture experimentally in early stage. In this work, we proposed an approach for the identification of iPS progenitor cells, the iPS forming cells, based on machine learning and microscopic image analysis. The aim is to help biologists to enrich iPS progenitor cells during the early stage of induction, which allows experimentalists to select iPS progenitor cells with much higher probability, and furthermore to study the biomarkers which trigger the reprogramming process.
Differentiation of Human Colon Tissue In Culture: Effects of calcium on trans-epithelial electrical resistance and tissue cohesive properties
Authors: McClintock Shannon D , Dame Michael K , Richter Aliah , Attili Durga , Silvestri Sabrina S , Berner Maliha M , Bohm Margaret S , Karpoff Kateryna , McCarthy Caroline , Spence Jason R , Varani James , Aslam Muhammad N 
Published: August 2019

AbstractBackground and aimsHuman colonoid cultures maintained under low-calcium (0.25 mM) conditions undergo differentiation spontaneously and, concomitantly, express a high level of tight junction proteins, but not desmosomal proteins. When calcium is included to a final concentration of 1.5 – 3.0 mM (provided either as a single agent or as a combination of calcium and minerals), there is little change in tight junction proteins but a strong up-regulation of desmosomal proteins and an increase in desmosome formation. The aim of this study was to assess functional consequences of the differences in calcium-mediated barrier protein expression.MethodsHuman colonoid-derived epithelial monolayers were interrogated in transwell culture under low- or high-calcium conditions. Ion permeability and monolayer integrity were assessed by measuring trans-epithelial electrical resistance (TEER) across the confluent monolayer. Colonoid cohesiveness was assessed in parallel.ResultsTEER values were high in the low-calcium environment and increased only modestly in response to calcium. In contrast, colonoid cohesiveness increased substantially with calcium supplementation. In both assays, the response to Aquamin was greater than the response to calcium alone. However, differences between interventions were small and only compared to the 0.25 mM calcium were they statistically significant. Consistent with these findings, occludin expression (a measure of tight junctions) was high at 0.25 mM calcium and did not increase with supplementation. Cadherin-17 and desmoglein-2 were weakly-expressed under low calcium conditions but increased with intervention.ConclusionsThese findings indicate that low ambient calcium levels are sufficient to support formation of a permeability barrier in the colonic epithelium. Higher calcium levels are necessary to promote tissue cohesion and enhance barrier function. These findings may help explain how an adequate daily intake of calcium contributes to colonic health by improving barrier function, even though there is little change in colonic histological features over a wide range of calcium intake levels.
Repeated noninvasive stimulation of the ventromedial prefrontal cortex reveals cumulative amplification of pleasant compared to unpleasant scene processing: a single subject pilot study
Authors: Winker Constantin , Rehbein Maimu A. , Sabatinelli Dean , Junghofer Markus 
Published: August 2019

AbstractThe ventromedial prefrontal cortex (vmPFC) is a major hub of the reward system and has been shown to activate specifically in response to pleasant / rewarding stimuli. Previous studies demonstrate enhanced pleasant cue reactivity after single applications of transcranial direct current stimulation (tDCS) to the vmPFC. Here we present a pilot case study in which we assess the cumulative impact of multiple consecutive vmPFC-tDCS sessions on the processing of visual emotional stimuli in an event-related MEG recording design. The results point to stable modulation of increased positivity biases (pleasant > unpleasant stimulus signal strength) after excitatory vmPFC stimulation and a reversed pattern (pleasant < unpleasant) after inhibitory stimulation across five consecutive tDCS sessions. Moreover, cumulative effects of these emotional bias modulations were observable for several source-localized spatio-temporal clusters, suggesting an increase in modulatory efficiency by repeated tDCS sessions. This pilot study provides evidence for improvements in the effectiveness and utility of a novel tDCS paradigm in the context of emotional processing.
Two roles for the yeast transcription coactivator SAGA and a set of genes redundantly regulated by TFIID and SAGA
Authors: Donczew Rafal , Warfield Linda , Pacheco Derek , Erijman Ariel , Hahn Steven 
Published: August 2019

AbstractDeletions within genes coding for subunits of the transcription coactivator SAGA caused strong genome-wide defects in transcription and SAGA-mediated chromatin modifications. In contrast, rapid SAGA depletion produced only modest transcription defects at 13% of protein-coding genes – genes that are generally more sensitive to rapid TFIID depletion. However, transcription of these “coactivator-redundant” genes is strongly affected by rapid depletion of both factors, showing the overlapping functions of TFIID and SAGA at this gene set. We suggest that this overlapping function is linked to TBP-DNA recruitment. The remaining 87% of expressed genes that we term “TFIID-dependent” are highly sensitive to rapid TFIID depletion and insensitive to rapid SAGA depletion. Genome-wide mapping of SAGA and TFIID found binding of both factors at many genes independent of gene class. DNA analysis suggests that the distinction between the gene classes is due to multiple components rather than any single regulatory factor or promoter sequence motif.
One-shot gesture recognition with attention-based DTW for human-robot collaboration
Authors: Kuang Yiqun , Cheng Hong , Zheng Yali , Cui Fang , Huang Rui 
Published: August 2019

Purpose
This paper aims to present a one-shot gesture recognition approach which can be a high-efficient communication channel in human–robot collaboration systems.

Design/methodology/approach
This paper applies dynamic time warping (DTW) to align two gesture sequences in temporal domain with a novel frame-wise distance measure which matches local features in spatial domain. Furthermore, a novel and robust bidirectional attention region extraction method is proposed to retain information in both movement and hold phase of a gesture.

Findings
The proposed approach is capable of providing efficient one-shot gesture recognition without elaborately designed features. The experiments on a social robot (JiaJia) demonstrate that the proposed approach can be used in a human–robot collaboration system flexibly.

Originality/value
According to previous literature, there are no similar solutions that can achieve an efficient gesture recognition with simple local feature descriptor and combine the advantages of local features with DTW.