bluuebunny/crossref_metadata_2025_split huggingface dataset:
DrLLPS: a data resource of liquid–liquid phase separation in eukaryotes
Authors: Ning Wanshan , Guo Yaping , Lin Shaofeng , Mei Bin , Wu Yu , Jiang Peiran , Tan Xiaodan , Zhang Weizhi , Chen Guowei , Peng Di , Chu Liang , Xue Yu 
Published: October 2019

Abstract
Here, we presented an integrative database named DrLLPS (http://llps.biocuckoo.cn/) for proteins involved in liquid–liquid phase separation (LLPS), which is a ubiquitous and crucial mechanism for spatiotemporal organization of various biochemical reactions, by creating membraneless organelles (MLOs) in eukaryotic cells. From the literature, we manually collected 150 scaffold proteins that are drivers of LLPS, 987 regulators that contribute in modulating LLPS, and 8148 potential client proteins that might be dispensable for the formation of MLOs, which were then categorized into 40 biomolecular condensates. We searched potential orthologs of these known proteins, and in total DrLLPS contained 437 887 known and potential LLPS-associated proteins in 164 eukaryotes. Furthermore, we carefully annotated LLPS-associated proteins in eight model organisms, by using the knowledge integrated from 110 widely used resources that covered 16 aspects, including protein disordered regions, domain annotations, post-translational modifications (PTMs), genetic variations, cancer mutations, molecular interactions, disease-associated information, drug-target relations, physicochemical property, protein functional annotations, protein expressions/proteomics, protein 3D structures, subcellular localizations, mRNA expressions, DNA & RNA elements, and DNA methylations. We anticipate DrLLPS can serve as a helpful resource for further analysis of LLPS.
Tobacco 21 Laws in Europe: A Policy Whose Time Has Come
Authors: Levy David T , Meza Rafael 
Published: October 2019

Abstract

Introduction
A 21 tobacco age of sale has been proposed for European nations.

Methods
We briefly review past studies of underage purchase policies and their enforcement.

Results
Past evaluations and modeling studies indicate important public health gains from 21 tobacco age of sale laws. However, further attention should be given to issues of compliance, the availability of social sources, and the breadth of coverage. In particular, the application of the law to e-cigarettes merits further attention.

Conclusions
Past literature indicates potential benefits of a 21 tobacco age of sale in terms of reducing tobacco use in European nations.

Implications
We review past studies of underage purchase laws, and the potential implications of applying that law to e-cigarettes. Past studies indicate the effectiveness of raising tobacco age of sale laws to 21. This law should be implemented and enforced in Europe.
Longitudinal, Nationwide, Cohort Study to Assess Incidence, Outcomes, and Costs Associated with Complicated Urinary Tract Infection
Authors: Carreno Joseph J , Tam Iris M , Meyers Juliana L , Esterberg Elizabeth , Candrilli Sean D , Lodise Thomas P 
Published: October 2019

AbstractAbstract

Introduction
Complicated urinary tract infections (cUTI) are common infections. Despite their frequency, limited data are available on the incidence and healthcare burden associated with cUTIs. This study details the epidemiology and 30-day health care resource utilization associated with cUTI in the US.

Methods
Retrospective study of PharmMetrics Plus database from 1/1/2013 to 12/31/2017. Inclusion criteria: age ≥ 18 years, ICD-9/10 cUTI diagnosis, and continuous enrollment for ≥ 6 months pre- and ≥ 30 days post-index dates. Two mutually exclusive study cohorts for cUTI patients were identified based on the setting of the first observed cUTI diagnosis (inpatient (IP) and outpatient (OP)).

Results
In total 543,502 adults with cUTI met the inclusion criteria (104,866 IP cohort; 438,636 OP cohort). Mean (SD) age was 48.1 (16.5) years and 68.1% were female. The overall incidence of cUTI was 1.01%, equating to approximately 2,882,195 annual cUTI cases in the US. In the IP cohort, overall median (IQR) 30-day health care costs were $13,028 ($4,855-$26,781). Median (IQR) costs for the initial admission were $9,441 ($2,079-$19,027), with median (IQR) length of stay (LOS) of 4 (3-8) days. Among IP patients, 12,933 (12.3%) had a subsequent readmission. In the OP cohort, median (IQR) 30-day health care costs were $1,531 ($305-$4,998). Of OP patients, 40,457 (9.2%) had a 30-day admission.

Conclusions
This study demonstrates that the economic burden associated with cUTIs is substantial, especially among patients requiring hospitalization. These findings highlight the need for new treatment approaches and antibiotics that avert hospitalization and reduce LOS.
Effects of the Your Family, Your Neighborhood Intervention on Neighborhood Social Processes
Authors: Brisson Daniel , Lechuga Peña Stephanie , Mattocks Nicole , Plassmeyer Mark , McCune Sarah 
Published: October 2019

AbstractThe objective of this study was to ascertain whether participation in the Your Family, Your Neighborhood (YFYN) intervention, an intervention for families living in low-income neighborhoods, leads to improved perceptions of neighborhood social cohesion and informal neighborhood social control. Fifty-two families in three low-income, urban neighborhoods participated in the manualized YFYN intervention. In this quasi-experimental study treatment families (n = 37) in two low-income neighborhoods received YFYN and control families (n = 15) from one separate low-income neighborhood did not. Families receiving YFYN attended 10 two-hour skills-based curriculum sessions during which they gathered for a community dinner and participated in parent- and child-specific skills-based groups. Treatment families reported increases in both neighborhood social cohesion and informal neighborhood social control after receiving YFYN. However, families receiving YFYN did not experience statistically significant improvements in perceptions of neighborhood social cohesion or informal neighborhood social control compared with nontreatment families. In conclusion, the delivery of YFYN in low-income neighborhoods may improve perceptions of neighborhood social cohesion. Further testing, with randomization and a larger sample, should be conducted to provide a more robust understanding of the impact of YFYN.
Exploring the relationship between grapheme colour-picking consistency and mental imagery
Authors: Spiller Mary Jane , Harkry Lee , McCullagh Fintan , Thoma Volker , Jonas Clare 
Published: October 2019

Previous research has indicated a potential link between mental imagery and synaesthesia. However, these findings are mainly based on imagery self-report measures and recruitment of self-selected synaesthetes. To avoid issues of self-selection and demand effects, we recruited participants from the general population, rather than synaesthetes specifically, and used colour-picking consistency tests for letters and numbers to assess a ‘synaesthete-like’ experience. Mental imagery ability and mental rotation ability were assessed using both self-report measures and behavioural assessments. Consistency in colour-picking for letters (but not numbers) was predicted by performance on the visual mental imagery task but not by a mental rotation task or self-report measures. Using the consistency score as a proxy measure of grapheme-colour synaesthesia, we provide more evidence for the suggestion that synaesthetic experience is associated with enhanced mental imagery, even when participants are naive to the research topic.
This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’.
DNA Break-Induced Epigenetic Drift as a Cause of Mammalian Aging
Authors: Hayano Motoshi , Yang Jae-Hyun , Bonkowski Michael S. , Amorim Joao A. , Ross Jaime M. , Coppotelli Giuseppe , Griffin Patrick T. , Chew Yap Ching , Guo Wei , Yang Xiaojing , Vera Daniel L. , Salfati Elias L. , Das Abhirup , Thakur Sachin , Kane Alice E. , Mitchell Sarah J. , Mohri Yasuaki , Nishimura Emi K. , Schaevitz Laura , Garg Neha , Balta Ana-Maria , Rego Meghan A. , Gregory-Ksander Meredith , Jakobs Tatjana C. , Zhong Lei , Wakimoto Hiroko , Mostoslavsky Raul , Wagers Amy J. , Tsubota Kazuo , Bonasera Stephen J. , Palmeira Carlos M. , Seidman Jonathan G. , Seidman Christine E. , Wolf Norman S. , Kreiling Jill A. , Sedivy John M. , Murphy George F. , Oberdoerffer Philipp , Ksander Bruce R. , Rajman Luis A. , Sinclair David A. 
Published: October 2019

SUMMARYThere are numerous hallmarks of aging in mammals, but no unifying cause has been identified. In budding yeast, aging is associated with a loss of epigenetic information that occurs in response to genome instability, particularly DNA double-strand breaks (DSBs). Mammals also undergo predictable epigenetic changes with age, including alterations to DNA methylation patterns that serve as epigenetic “age” clocks, but what drives these changes is not known. Using a transgenic mouse system called “ICE” (for induciblechanges to theepigenome), we show that a tissue’s response to non-mutagenic DSBs reorganizes the epigenome and accelerates physiological, cognitive, and molecular changes normally seen in older mice, including advancement of the epigenetic clock. These findings implicate DSB-induced epigenetic drift as a conserved cause of aging from yeast to mammals.One Sentence SummaryDNA breaks induce epigenomic changes that accelerate the aging clock in mammals
Correlating STED and synchrotron XRF nano-imaging unveils the co-segregation of metals and cytoskeleton proteins in dendrites
Authors: Domart Florelle , Cloetens Peter , Roudeau Stéphane , Carmona Asuncion , Verdier Emeline , Choquet Daniel , Ortega Richard 
Published: October 2019

AbstractZinc and copper are involved in neuronal differentiation and synaptic plasticity but the molecular mechanisms behind these processes are still elusive due in part to the difficulty of imaging trace metals together with proteins at the synaptic level. We correlate stimulated emission depletion (STED) microscopy of proteins and synchrotron X-ray fluorescence (SXRF) imaging of trace metals, both performed with 40 nm spatial resolution, on primary rat hippocampal neurons. We achieve a detection limit for zinc of 14 zeptogram (10-21 g) per pixel. We reveal the co-localization at the nanoscale of zinc and tubulin in dendrites with a molecular ratio of about one zinc atom per tubulin-αβ dimer. We observe the co-segregation of copper and F-actin within the nano-architecture of dendritic protrusions. In addition, zinc chelation causes a decrease in the expression of cytoskeleton proteins in dendrites and spines. Overall, these results indicate new functions for zinc and copper in the modulation of the cytoskeleton morphology in dendrites, a mechanism associated to neuronal plasticity and memory formation.
Rapid multicomponent bioluminescence imaging via substrate unmixing
Authors: Rathbun Colin M. , Ionkina Anastasia A. , Yao Zi , Jones Krysten A. , Porterfield William B. , Prescher Jennifer A. 
Published: October 2019

ABSTRACTEngineered luciferases and luciferins have dramatically expanded the scope of bioluminescence imaging in recent years. Multicomponent tracking remains challenging, though, due to a lack of streamlined methods to visualize combinations of bioluminescent reporters. Here we report a strategy for rapid, multiplexed imaging with a wide range of luciferases and luciferins. Sequential addition of orthogonal luciferins, followed by substrate unmixing, enabled facile detection of multiple luciferases in vitro and in vivo. Multicomponent imaging in mice was also achieved on the minutes-to-hours time scale, a vast improvement over conventional protocols.
Inhibitory signaling in mammalian olfactory transduction potentially mediated by Gαo
Authors: Corey Elizabeth A. , Ukhanov Kirill , Bobkov Yuriy V. , McIntyre Jeremy C. , Martens Jeffrey R. , Ache Barry W. 
Published: October 2019

AbstractOlfactory GPCRs (ORs) in mammalian olfactory receptor neurons (ORNs) mediate excitation through the Gαsfamily member Gαolf. Here we tentatively associate a second G protein, Gαo, with inhibitory signalling in mammalian olfactory transduction by first showing that odor evoked phosphoinositide 3-kinase (PI3K)-dependent inhibition of signal transduction is absent in the native ORNs of mice carrying a conditional OMP-Cre based knockout of Gαo. We then identify an OR from native rat ORNs that are activated by octanol through cyclic nucleotide signaling and inhibited by citral in a PI3K-dependent manner. We show that the OR activates cyclic nucleotide signaling and PI3K signaling in a manner that reflects its functionality in native ORNs. Our findings lay the groundwork to explore the interesting possibility that ORs can interact with two different G proteins in a functionally identified, ligand-dependent manner to mediate opponent signaling in mature mammalian ORNs.
Multiple ribonuclease A family members cleave transfer RNAs in response to stress
Authors: Akiyama Yasutoshi , Lyons Shawn , Fay Marta M. , Abe Takaaki , Anderson Paul , Ivanov Pavel 
Published: October 2019

ABSTRACTDuring stress, changes in gene expression are critical for cell survival. Stress-induced tRNA cleavage has been implicated in various cellular processes, where tRNA fragments play diverse regulatory roles. Angiogenin (ANG), a member of the RNase A superfamily, induces cleavage of tRNAs resulting in the formation of tRNA-derived stress-induced RNAs (tiRNAs) that contribute to translational reprogramming aiming at cell survival. The role of other stress-induced RNases in tRNA cleavage is poorly understood. Using gene editing and biochemical approaches, we show that other members of the RNase A family are capable of targeting tRNAs in stress-responsive manner. We show that in the absence of ANG, these RNases also promote the production of tiRNAs. Moreover, specific stresses (such as treatment with sodium arsenite) activate cleavage of universal 3’-CCA termini of tRNAs in ANG-independent fashion in living cells. We conclude that multiple RNase A family members are capable of targeting tRNAs in a stress-specific mannerin vivo.
Amygdalostriatal coupling underpins positive but not negative coloring of ambiguous affect
Authors: Kim M. Justin , Mattek Alison M. , Shin Jin 
Published: October 2019

AbstractHumans routinely integrate affective information from multiple sources. For example, we rarely interpret an emotional facial expression devoid of context. Here, we describe the neural correlates of an affective computation that involves integrating multiple sources, by leveraging the ambiguity and subtle feature-based valence signals found in surprised faces. Using functional magnetic resonance imaging, participants reported the valence of surprised faces modulated by positive or negative sentences. Amygdala activity corresponded to the valence value assigned to each contextually modulated face, with greater activity reflecting more negative ratings. Amygdala activity did not track the valence of the faces or sentences per se. Moreover, the amygdala was functionally coupled with the nucleus accumbens only during face trials preceded by positive contextual cues. These data suggest 1) valence-related amygdala activity reflects the integrated valence values rather than the valence values of each individual component, and 2) amygdalostriatal coupling underpins positive but not negative coloring of ambiguous affect.
Low-dimensional learned feature spaces quantify individual and group differences in vocal repertoires
Authors: Goffinet Jack , Brudner Samuel , Mooney Richard , Pearson John 
Published: October 2019

SUMMARYIncreases in the scale and complexity of behavioral data pose an increasing challenge for data analysis. A common strategy involves replacing entire behaviors with small numbers of handpicked, domain-specific features, but this approach suffers from several crucial limitations. For example, handpicked features may miss important dimensions of variability, and correlations among them complicate statistical testing. Here, by contrast, we apply the variational autoencoder (VAE), an unsupervised learning method, to learn features directly from data and quantify the vocal behavior of two model species: the laboratory mouse and the zebra finch. The VAE converges on a parsimonious representation that outperforms handpicked features on a variety of common analysis tasks, enables the measurement of moment-by-moment vocal variability on the timescale of tens of milliseconds in the zebra finch, provides strong evidence that mouse ultrasonic vocalizations do not cluster as is commonly believed, and captures the similarity of tutor and pupil birdsong with qualitatively higher fidelity than previous approaches. In all, we demonstrate the utility of modern unsupervised learning approaches to the quantification of complex and high-dimensional vocal behavior.
Among-individual diet variation within a lake trout ecotype: lack of stability of niche use
Authors: Chavarie L. , Howland K.L. , Harris L.N. , Gallagher C.P. , Hansen M.J. , Tonn W.M. , Muir A.M. , Krueger C.C. 
Published: October 2019

AbstractIn a polymorphic species, stable differences in resource use are expected among ecotypes, and homogeneity in resource use is predicted within an ecotype. Yet, using a broad resource spectrum has been identified as a strategy for fishes living in unproductive northern environments, where food is patchily distributed and ephemeral. We investigated whether individual specialization of trophic resources occurred within the generalist piscivore ecotype of lake trout from Great Bear Lake, Canada, reflective of a form of diversity. Four distinct dietary patterns of resource use within the lake trout ecotype were detected from fatty acid composition, with some variation linked to spatial patterns within Great Bear Lake. Feeding habits of different groups within the ecotype were not associated with detectable morphological or genetic differentiation, suggesting that behavioral plasticity caused the trophic differences. A low level of genetic differentiation was detected between exceptionally large-sized individuals and other individuals. Investigating a geologically young system that displays high levels of intraspecific diversity and focusing on individual variation in diet suggested that individual trophic specialization can occur within an ecotype. The characterization of niche use among individuals, as done in this study, is necessary to understand the role that individual variation can play at the beginning of differentiation processes.
CellProfiler: A fit tool for image analysis in droplet microfluidics
Authors: Bartkova Simona , Vendelin Marko , Sanka Immanuel , Pata Pille , Scheler Ott 
Published: October 2019

AbstractDroplet microfluidic assays are rapidly gaining popularity as the result of the ability to manipulate and monitor single biological molecules, individual cells or small populations of bacteria in pico- and nanoliter droplets, with high sensitivity, precision and accuracy in a high-throughput manner. Nonetheless, there is a demand for user-friendly and low-cost droplet analysis technology. In this article we meet this demand with free open-source software CellProfiler (CP). To illustrate the competence of CP as a droplet analysis tool, we show droplet digital quantification of viable fluorescent bacteria.
Neto-α controls synapse organization and homeostasis at the Drosophila neuromuscular junction
Authors: Han Tae Hee , Vicidomini Rosario , Ramos Cathy Isaura , Wang Qi , Nguyen Peter , Jarnik Michal , Li Moyi , Stawarski Michal , Hernandez Roberto X. , Macleod Gregory T. , Serpe Mihaela 
Published: October 2019

SummaryGlutamate receptor auxiliary proteins control receptor distribution and function, ultimately controlling synapse assembly, maturation and plasticity. At the Drosophila neuromuscular junction (NMJ), a synapse with both pre- and post-synaptic kainate-type glutamate receptors (KARs), we show that the auxiliary protein Neto evolved functionally distinct isoforms to modulate synapse development and homeostasis. Using genetics, cell biology and electrophysiology we demonstrate that Neto-α functions on both sides of the NMJ. In muscle, Neto-α limits the size of the postsynaptic receptors field. In motor neurons, Neto-α controls neurotransmitter release in a KAR-dependent manner. Furthermore, Neto-α is both required and sufficient for the presynaptic increase in neurotransmitter release in response to reduced postsynaptic sensitivity. This KAR-independent function of Neto-α is involved in activity-induced cytomatrix remodeling. We propose that Drosophila ensured NMJ functionality by acquiring two Neto isoforms with differential expression patterns and activities.
AutoTuner: High fidelity, robust, and rapid parameter selection for metabolomics data processing
Authors: McLean Craig , Kujawinski Elizabeth B. 
Published: October 2019

AbstractUntargeted metabolomics experiments provide a snapshot of cellular metabolism, but remain challenging to interpret due to the computational complexity involved in data processing and analysis. Prior to any interpretation, raw data must be processed to remove noise and to align mass-spectral peaks across samples. This step requires selection of dataset-specific parameters, as erroneous parameters can result in noise inflation. While several algorithms exist to automate parameter selection, each depends on gradient descent optimization functions. In contrast, our new parameter optimization algorithm, AutoTuner, obtains parameter estimates from raw data in a single step as opposed to many iterations. Here, we tested the accuracy and the run time of AutoTuner in comparison to isotopologue parameter optimization (IPO), the most commonly-used parameter selection tool, and compared the resulting parameters’ influence on the quality of feature tables after processing. We performed a Monte Carlo experiment to test the robustness of AutoTuner parameter selection, and found that AutoTuner generated similar parameter estimates from random subsets of samples. We conclude that AutoTuner is a desirable alternative to existing tools, because it is scalable, highly robust, and very fast (∼100-1000X speed improvement from other algorithms going from days to minutes). AutoTuner is freely available as an R package through BioConductor.
New analysis framework incorporating mixed mutual information and scalable Bayesian networks for multimodal high dimensional genomic and epigenomic cancer data
Authors: Wang Xichun , Branciamore Sergio , Gogoshin Grigoriy , Ding Shuyu , Rodin Andrei S 
Published: October 2019

AbstractWe propose a novel two-stage analysis strategy to discover candidate genes associated with the particular cancer outcomes in large multimodal genomic cancers databases, such as The Cancer Genome Atlas (TCGA). During the first stage, we use mixed mutual information to perform variable selection; during the second stage, we use scalable Bayesian network (BN) modeling to identify candidate genes and their interactions. Two crucial features of the proposed approach are (i) the ability to handle mixed data types (continuous and discrete, genomic, epigenomic, etc.), and (ii) a flexible boundary between the variable selection and network modeling stages --- the boundary that can be adjusted in accordance with the investigators’ BN software scalability and hardware implementation. These two aspects result in high generalizability of the proposed analytical framework. We apply the above strategy to three different TCGA datasets (LGG, Brain Lower Grade Glioma; HNSC, Head and Neck Squamous Cell Carcinoma; STES, Stomach and Esophageal Carcinoma), linking multimodal molecular information (SNPs, mRNA expression, DNA methylation) to two clinical outcome variables (tumor status and patient survival). We identify 11 candidate genes, of which 6 have already been directly implicated in the cancer literature. One novel LGG prognostic factor suggested by our analysis, methylation of TMPRSS11F type II transmembrane serine protease, presents intriguing direction for the follow-up studies.