bluuebunny/crossref_metadata_2025_split huggingface dataset:
Group Similarity Constraint Functional Brain Network Estimation for Mild Congititive Impairment Classification
Authors: Gao Xin , Xu Xiaowen , Li Weikai , Li Rui 
Published: August 2019

AbstractFunctional brain network (FBN) provides an effective biomarker for understanding brain activation patterns, which also improve the diagnostic criteria for neurodegenerative diseases or the information transmission of brain. Unfortunately, despite its efficiency, FBN still suffers several challenges for accurately estimate the biological meaningful or discriminative FBNs, under the poor quality of functional magnetic resonance imaging (fMRI) data as well as the limited understanding of human brain. Hence, there still a motivation to alleviate those issues above, it is currently still an open field to discover. In this paper, a novel FBN estimation model based on group similarity constraints is proposed. In particular, we extend the FBN estimation model to the tensor form and incorporate the trace-norm regularizer for formulating the group similarity constraint. In order to verify the proposed method, we conduct experiments on identifying Mild Cognitive Impairments (MCIs) from normal controls (NCs) based on the estimated FBNs. The experimental results illustrated that the proposed method can construct a more discriminative brain network. Consequently, we achieved an 91.97% classification accuracy which outperforms the baseline methods. Thepost hocanalysis further shown more biologically meaningful functional brain connections obtained by our proposed method.
Mutational signatures in upper tract urothelial carcinoma define etiologically distinct subtypes with prognostic relevance
Authors: Li Xuesong , Lu Huan , Guan Bao , Xu Zhengzheng , Shi Yue , Li Juan , Kong Wenwen , Liu Jin , Fang Dong , Liu Libo , Shen Qi , Gong Yanqing , He Shiming , He Qun , Zhou Liqun , Ci Weimin 
Published: August 2019

AbstractParts of East Asia have a very high upper tract urothelial carcinoma (UTUC) prevalence, and an etiological link between the medicinal use of herbs containing aristolochic acid (AA) and UTUC has been established. The mutational signature of AA, which is characterized by a particular pattern of A:T to T:A transversions, can be detected by genome sequencing. Thus, integrating mutational signatures analysis with clinicopathological data may be a crucial step toward personalized treatment strategies for the disease. Therefore, we performed whole-genome sequencing (WGS) of 90 UTUC patients from China. Mutational signature analysis via nonnegative matrix factorization method defined three etiologically distinct subtypes with prognostic relevance: (i) AA, the typical AA mutational signature characterized by signature 22, had the highest tumor mutation burden, the best clinical outcomes; (ii) Age, an age-related group featured by signatures 1 and 5, had the lowest weighted genome instability index score, the worst clinical outcomes; and (iii) DSB, signature with deficiencies in DNA double strand break-repair featured by signatures 3, the intermediate clinical outcomes. Additionally, the distinct AA subtype was associated with AA exposure, the highest number of predicted neoantigens and heavier lymphocytes infiltrating. Thus, it may be good candidate for immune checkpoint blockade therapy. Notably, we showed AA-mutational signature was also identified in histologically “normal” urothelial cells. Thus, non-invasive urine test based on the AA-mutational signature could take advantage of this “field effect” to screen individuals at increased risk of recurrence due to exposure to herbal remedies containing the carcinogen AA. Collectively, the findings here may accelerate the development of novel prognostic markers and personalized therapeutic approaches for UTUC patients in China.
Analyzing combined eye-tracking/EEG experiments with (non)linear deconvolution models
Authors: Dimigen Olaf , Ehinger Benedikt V. 
Published: August 2019

ABSTRACTFixation-related potentials (FRPs), neural responses aligned to saccade offsets, are a promising tool to study the dynamics of attention and cognition under natural viewing conditions. In the past, four methodological problems have complicated the analysis of such combined eye-tracking/EEG experiments: (i) the synchronization of data streams, (ii) the removal of ocular artifacts, (iii) the condition-specific temporal overlap between the brain responses evoked by consecutive fixations, (iv) and the fact that numerous low-level stimulus and saccade properties also influence the post-saccadic neural responses. While effective solutions exist for the first two problems, the latter ones are only beginning to be addressed. In the current paper, we present and review a unified framework for FRP analysis that allows us to deconvolve overlapping potentials and control for linear and nonlinear confounds on the FRPs. An open software implementation is provided for all procedures. We then demonstrate the advantages of this approach for data from three commonly studied paradigms: face perception, scene viewing, and natural sentence reading. First, for a traditional ERP face recognition experiment, we show how deconvolution can separate stimulus-ERPs from overlapping muscle and brain potentials produced by small (micro)saccades on the face. Second, in scene viewing, we isolate multiple non-linear influences of saccade parameters on the FRP. Finally, for a natural sentence reading experiment using the boundary paradigm, we show how it is possible to study the neural correlates of parafoveal preview after removing spurious overlap effects caused by the associated difference in average fixation time. Our results suggest a principal way of measuring reliable fixation-related brain potentials during natural vision.
Regulatory kinase genetic interaction profiles differ between environmental conditions and cellular states
Authors: Sun Siyu , Baryshnikova Anastasia , Brandt Nathan , Gresham David 
Published: August 2019

AbstractCell growth and quiescence in eukaryotic cells is controlled by an evolutionarily conserved network of signaling pathways. Signal transduction networks operate to modulate a wide range of cellular processes and physiological properties when cells exit proliferative growth and initiate a quiescent state. How signaling networks function to respond to diverse signals that result in cell cycle exit and establishment of a quiescent state is poorly understood. Here, we studied the function of signaling pathways in quiescent cells using global genetic interaction mapping in the model eukaryotic cell,Saccharomyces cerevisiae(budding yeast). We performed pooled analysis of genotypes using molecular barcode sequencing to test the role of ∼3,900 gene deletion mutants and ∼11,700 pairwise interactions between all non-essential genes and the protein kinasesTOR1, RIM15, PHO85in three different nutrient-restricted conditions in both proliferative and quiescent cells. We detect nearly five-fold more genetic interactions in quiescent cells compared to proliferative cells. We find that both individual gene effects and genetic interaction profiles vary depending on the specific pro-quiescence signal. The master regulator of quiescence,RIM15shows distinct genetic interaction profiles in response to different starvation signals. However, vacuole-related functions show consistent genetic interactions withRIM15in response to different starvation signals suggesting thatRIM15integrates diverse signals to maintain protein homeostasis in quiescent cells. Our study expands genome-wide genetic interaction profiling to additional conditions, and phenotypes, highlighting the conditional dependence of epistasis.
Cargo and Cell Specific Differences in Extracellular Vesicle Populations Identified by Multiplexed Immunofluorescent Analysis
Authors: Burbidge Kevin , Zwikelmaier Virginia , Cook Benjamin , Ispas Grace , Rademacher David J. , Campbell Edward M. 
Published: August 2019

AbstractExtracellular vesicles (EVs) are implicated in a wide variety of biological activities, have been implicated in the pathogenesis of numerous diseases, and have been proposed to serve as potential biomarkers of disease in human patients and animal models. However, characterization of EV populations is often performed using methods that do not account for heterogeneity of EV populations and require comparatively large sample sizes to facilitate analysis. Here, we describe an imaging-based method that allows for the multiplexed characterization of EV populations at the single EV level following centrifugation of EV populations directly onto cover slips, allowing comprehensive analysis of EV populations with relatively small samples. We observe that canonical EV markers are present on subsets of EVs which differ substantially in a producer cell and cargo specific fashion, including differences in EVs containing different HIV-1 proteins previously reported to be incorporated into pathogenic EVs. We also describe a lectin binding assay to interrogate EVs based on their glycan content, which we observe to change in response to pharmacological modulation of secretory autophagy pathways. These studies collectively reveal that multiplexed analysis of EV populations using fluorescent microscopy can reveal differences in specific EV populations that may be used to understand the biogenesis of specific EV populations or to interrogate small subsets of EVs of interest within larger EV populations.
Monosynaptic tracing success depends critically on helper virus concentrations
Authors: Lavin Thomas K. , Jin Lei , Lea Nicholas E. , Wickersham Ian R. 
Published: August 2019

ABSTRACTMonosynaptically-restricted transsynaptic tracing using deletion-mutant rabies virus has become a widely used technique in neuroscience, allowing identification, imaging, and manipulation of neurons directly presynaptic to a starting neuronal population. Its most common implementation is to use Cre mouse lines in combination with Cre-dependent “helper” adeno-associated viral vectors (AAVs) to supply the required genes to the targeted population before subsequent injection of a first-generation (ΔG) rabies viral vector. Here we show that the efficiency of transsynaptic spread and the degree of nonspecific labeling in wild-type control animals depend strongly on the concentrations of these helper AAVs. Our results suggest practical guidelines for achieving good results.
The impact of Hurricane Michael on longleaf pine habitats in Florida
Authors: Zampieri Nicole E. , Pau Stephanie , Okamoto Daniel K. 
Published: August 2019

AbstractThe longleaf pine (Pinus palustris) ecosystem of the North American Coastal Plain (NACP) is a global biodiversity hotspot. Disturbances such as tropical storms play an integral role in ecosystem maintenance in these systems. However, altered disturbance regimes as a result of climate change may be outside the historical threshold of tolerance. Hurricane Michael impacted the Florida panhandle as a Category 5 storm on October 10th, 2018. In this study, we estimate the extent of Florida longleaf habitat that was directly impacted by Hurricane Michael. We then quantify the impact of Hurricane Michael on tree density and size structure using a Before-After study design at four sites (two wet flatwood and two upland pine communities). Finally, we identify the most common type of tree damage at each site and community type. We found that 39% of the total remaining extent of longleaf pine habitat was affected by the storm in Florida alone. Tree mortality ranged from 1.3% at the site furthest from the storm center to 88.7% at the site closest. Most of this mortality was in mature sized trees (92% mortality), upon which much of the biodiversity in this habitat depends. As the frequency and intensity of extreme events increases, management plans that mitigate for climate change impacts need to account for large-scale stochastic mortality events in order to effectively preserve critical habitats.
Molecular assays to detect the presence and viability ofPhytophthora ramorumandGrosmannia clavigera
Authors: Wong Barbara , Leal Isabel , Feau Nicolas , Dale Angela , Uzunovic Adnan , Hamelin Richard C. 
Published: August 2019

Abstract/KeywordsTo determine if living microorganisms of phytosanitary concern are present in wood after eradication treatment and to evaluate the efficacy of such treatments, the method of choice is to grow microbes in petri dishes for subsequent identification. However, some plant pathogens are difficult or impossible to grow in axenic cultures. A molecular methodology capable of detecting living fungi and fungus-like organismsin situcan provide a solution. RNA represents the transcription of genes and can therefore only be produced by living organisms, providing a proxy for viability. We designed and used RNA-based molecular diagnostic assays targeting genes essential to vital processes and assessed their presence in wood colonized by fungi and oomycetes through reverse transcription and real-time polymerase chain reaction (PCR). A stability analysis was conducted by comparing the ratio of mRNA to gDNA over time following heat treatment of wood infected with the OomycetePhytophthora ramorumand the fungusGrosmannia clavigera. The real-time PCR results indicated that the DNA remained stable over a period of 10 days post treatment in heat-treated wood samples, whereas mRNA could not be detected after 24 hours forP. ramorumor 96 hours forG. clavigera. Therefore, this method provides a reliable way to evaluate the viability of these pathogens and test the effectiveness of existing and emerging wood treatments. This can have important phytosanitary impacts on assessing both timber and non-timber forest products of commercial value in international wood trade.
A simple CPG-based model to generate human hip moment pattern in walking by generating stiffness and equilibrium point trajectories
Authors: Bahramian Alireza , Towhidkhah Farzad , Jafari Sajad 
Published: August 2019

AbstractEquilibrium point hypothesis (its developed version named as referent control theory) presents a theory about how the central nerves system (CNS) generates human movements. On the other hand, it has been shown that nerves circuits known as central pattern generators (CPG) likely produce motor commands to the muscles in rhythmic motions. In the present study, we designed a bio-inspired walking model, by coupling double pendulum to CPGs that produces equilibrium and stiffness trajectories as reciprocal and co-activation commands. As a basic model, it is has been shown that this model can regenerate pattern of a hip moment in the swing phase by high correlation (ρ= 0.970) with experimental data. Moreover, it has been reported that a global electromyography (EMG) minima occurs in the mid-swing phase when the hip is more flexed in comparison with the other leg. Our model showed that equilibrium and actual hip angle trajectories match each other in mid-swing, similar to the mentioned posture, that is consistent with previous findings. Such a model can be used in active exoskeletons and prosthesis to make proper active stiffness and torque.
Using indication embeddings to represent patient health for drug safety studies
Authors: Melamed Rachel D. 
Published: August 2019

AbstractObjectiveThe electronic health record is a rising resource for quantifying medical practice, discovering adverse effects of drugs, and studying comparative effectiveness. One of the challenges of applying these methods to health care data is the high dimensionality of the health record. Methods to discover effects of drugs in health data must account for tens of thousands of potentially relevant confounders. Our goal in this work is to reduce the dimensionality of the health data with the aim of accelerating the application of retrospective cohort studies to this data.Materials and MethodsHere, we develop indication embeddings, a way to reduce the dimensionality of health data while capturing information relevant to treatment decisions. We evaluate these embeddings using external data on drug indications. Then, we use the embeddings as a substitute for medical history to match patients, and develop evaluation metrics for these matches.ResultsWe demonstrate that these embeddings recover therapeutic uses of drugs. We use embeddings as an informative representation of relationships between drugs, between health history events and drug prescriptions, and between patients at a particular time in their health history. We show that using embeddings to match cohorts improves the balance of the cohorts, even in terms of poorly measured risk factors like smoking.Discussion and ConclusionUnlike other embeddings inspired by word2vec, indication embeddings are specifically designed to capture the medical history leading to prescription of a new drug. For retrospective cohort studies, our low-dimensional representation helps in finding comparator drugs and constructing comparator cohorts.
Models of heterogeneous dopamine signaling in an insect learning and memory center
Authors: Jiang Linnie , Litwin-Kumar Ashok 
Published: August 2019

AbstractTheDrosophilamushroom body exhibits dopamine dependent synaptic plasticity that underlies the acquisition of associative memories. Recordings of dopamine neurons in this system have identified signals related to external reinforcement such as reward and punishment. However, other factors including locomotion, novelty, reward expectation, and internal state have also recently been shown to modulate dopamine neurons. This heterogeneity is at odds with typical modeling approaches in which these neurons are assumed to encode a global, scalar error signal. How is dopamine dependent plasticity coordinated in the presence of such heterogeneity? We develop a modeling approach that infers a pattern of dopamine activity sufficient to solve defined behavioral tasks, given architectural constraints informed by knowledge of mushroom body circuitry. Model dopamine neurons exhibit diverse tuning to task parameters while nonetheless producing coherent learned behaviors. Our results provide a mechanistic framework that accounts for the heterogeneity of dopamine activity during learning and behavior.
Haplotype genetic score analysis in 10,734 mother/infant pairs reveals complex maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes and adult phenotypes
Authors: Chen Jing , Bacelis Jonas , Navais Pol Sole , Srivastava Amit , Juodakis Julius , Rouse Amy , Hallman Mikko , Teramo Kari , Melbye Mads , Feenstra Bjarke , Freathy Rachel M. , Davey-Smith George , Lawlor Deborah A. , Murray Jeffrey C. , Williams Scott M. , Jacobsson Bo , Muglia Louis J. , Zhang Ge 
Published: August 2019

ABSTRACTMany maternal traits are associated with a neonate’s gestational duration, birth weight and birth length. These birth outcomes are subsequently associated with late onset health conditions. Based on 10,734 mother/infant duos of European ancestry, we constructed haplotype genetic scores to dissect the maternal and fetal genetic effects underlying these observed associations. We showed that maternal height and fetal growth jointly affect the duration of gestation – maternal height positively influences the gestational duration, while faster fetal growth reduces gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: tall maternal stature and higher blood glucose causally increase birth size; in the fetus, the height and metabolic risk increasing alleles can lead to increased and decreased birth size respectively; birth weight-raising alleles in fetus may reduce gestational duration and increase maternal blood pressure. These maternal and fetal genetic effects can largely explain the observed associations between the studied maternal phenotypes and birth outcomes as well as the life-course associations between these birth outcomes and adult phenotypes.
IRBIT Directs Differentiation of Intestinal Stem Cell Progeny to Maintain Tissue Homeostasis
Authors: Arnaoutov Alexei , Lee Hangnoh , Haase Karen Plevock , Aksenova Vasilisa , Jarnik Michal , Oliver Brian , Serpe Mihaela , Dasso Mary 
Published: August 2019

SummaryThe maintenance of the intestinal epithelium is ensured by the controlled proliferation of intestinal stem cells (ISCs) and differentiation of their progeny into various cell types, including enterocytes (ECs) that both mediate nutrient absorption and provide a barrier against pathogens. The signals that regulate transition of proliferative ISCs into differentiated ECs are not fully understood. IRBIT is an evolutionarily conserved protein that regulates ribonucleotide reductase (RNR), an enzyme critical for the generation of DNA precursors. Here, we show that IRBIT expression in ISC progeny within the Drosophila midgut epithelium cells is essential for their differentiation via suppression of RNR activity. Disruption of this IRBIT-RNR regulatory circuit causes a rapid, premature loss of intestinal tissue integrity as flies age. This age-related dysplasia can be reversed by suppression of RNR activity in ISC progeny. Collectively, our findings demonstrate an unexpected and novel role of the IRBIT-RNR pathway in gut homeostasis.
A DNA G-quadruplex/i-motif hybrid
Authors: Chu Betty , Zhang Daoning , Paukstelis Paul J. 
Published: August 2019

AbstractDNA can form many structures beyond the canonical Watson-Crick double helix. It is now clear that noncanonical structures are present in genomic DNA and have biological functions. G-rich G-quadruplexes and C-rich i-motifs are the most well-characterized noncanonical DNA motifs that have been detectedin vivowith either proscribed or postulated biological roles. Because of their independent sequence requirements, these structures have largely been considered distinct types of quadruplexes. Here, we describe the crystal structure of the DNA oligonucleotide, d(CCAGGCTGCAA), that self-associates to form a quadruplex structure containing two central antiparallel G-tetrads and six i-motif C-C+base pairs. Solution studies suggest a robust structural motif capable of assembling as a tetramer of individual strands or as a dimer when composed of tandem repeats. This hybrid structure highlights the growing structural diversity of DNA and suggests that biological systems may harbor many functionally important non-duplex structures.