bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seeker: Alignment-free identification of bacteriophage genomes by deep learning
Authors: Auslander Noam , Gussow Ayal B. , Benler Sean , Wolf Yuri I. , Koonin Eugene V. 
Published: April 2020

SummaryAdvances in metagenomics enable massive discovery of diverse, distinct microbes and viruses. Bacteriophages, the most abundant biological entity on Earth, evolve rapidly, and therefore, detection of unknown bacteriophages in sequence datasets is a challenge. The existing methods rely on sequence similarity to known bacteriophage sequences, impeding the identification and characterization of distinct bacteriophage families. We present Seeker, a deep-learning tool for reference-free identification of phage sequences. Seeker allows rapid detection of phages in sequence datasets and clean differentiation of phage sequences from bacterial ones, even for phages with little sequence similarity to established phage families. We comprehensively validate Seeker’s ability to identify unknown phages and employ Seeker to detect unknown phages, some of which are highly divergent from known phage families. We provide a web portal (seeker.pythonanywhere.com) and a user-friendly python package (https://github.com/gussow/seeker) allowing researchers to easily apply Seeker in metagenomic studies, for the detection of diverse unknown bacteriophages.
Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease
Authors: Leng Kun , Li Emmy , Eser Rana , Piergies Antonia , Sit Rene , Tan Michelle , Neff Norma , Li Song Hua , Rodriguez Roberta Diehl , Suemoto Claudia Kimie , Paraizo Leite Renata Elaine , Pasqualucci Carlos A. , Seeley William W. , Spina Salvatore , Heinsen Helmut , Grinberg Lea T. , Kampmann Martin 
Published: April 2020

ABSTRACTAlzheimer’s disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus – brain regions where neurofibrillary inclusions and neuronal loss occur early and late in AD, respectively – from postmortem brains spanning the progression of AD-type tau neurofibrillary pathology. We identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex, and subsequently validated their depletion and selective susceptibility to neurofibrillary inclusions during disease progression using quantitative neuropathological methods. We also discovered an astrocyte subpopulation, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions. Our characterization of selectively vulnerable neurons in AD paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience.
Antibiotics shift the temperature response curve ofEscherichia coligrowth
Authors: Cruz-Loya Mauricio , Tekin Elif , Kang Tina Manzhu , Rodriguez-Verdugo Alejandra , Savage Van M. , Yeh Pamela J. 
Published: April 2020

AbstractTemperature variation—through time and across climatic gradients—affects individuals, populations, and communities. Yet how the thermal response of biological systems is altered by environmental stressors is poorly understood. Here we quantify two key features—optimal temperature and temperature breadth—to investigate how temperature responses vary in the presence of antibiotics. We use high-throughput screening to measure growth ofEscherichia coliunder single and pairwise combinations of 12 antibiotics across seven temperatures that range from 22°C to 46°C. We find that antibiotic stress often results in considerable changes in the optimal temperature for growth and a narrower temperature breadth. The direction of the optimal temperature shifts can be explained by the similarities between antibiotic-induced and temperature-induced damage to the physiology of the bacterium. We also find that the effects of pairs of stressors in the temperature response can often be explained by just one antibiotic out of the pair. Our study has implications for a general understanding of how ecological systems adapt and evolve to environmental changes.
Signaling mechanism of phytochromes in solution
Authors: Isaksson Linnéa , Gustavsson Emil , Persson Cecilia , Brath Ulrika , Vrhovac Lidija , Karlsson Göran , Orekhov Vladislav , Westenhoff Sebastian 
Published: April 2020

AbstractPhytochrome proteins guide the red/far-red photoresponse of plants, fungi, and bacteria. The proteins change their structure in response to light, thereby altering their biochemical activity. Crystal structures suggest that the mechanism of signal transduction from the chromophore to the output domains involves refolding of the so-called PHY tongue. It is currently not clear how the two other notable structural features of the phytochrome superfamily, the helical spine and a figure-of-eight knot, are involved in photoconversion. Here, we present solution NMR data of the complete photosensory core module fromD. radiodurans(DrBphP). Photoswitching between the resting and active states induces changes in amide chemical shifts, residual dipolar couplings, and relaxation dynamics. All observables indicate a photoinduced structural change in the knot region and lower part of the helical spine. This implies that a conformational signal is transduced from the chromophore to the helical spine through the PAS and GAF domains. The new pathway underpins functional studies of plant phytochromes and may explain photo-sensing by phytochromes under biological conditions.
Quantifying relative virulence: When μmaxfails and AUC alone just isn’t enough
Authors: Ceballos Ruben Michael , Stacy Carson Len 
Published: April 2020

AbstractOne of the more challenging aspects in quantitative virology is quantifying relative virulence between two (or more) viruses that have different replication dynamics in a given susceptible host. Host growth curve analysis is often used to detail virus-host interactions and to determine the impact of viral infection on a host. Quantifying relative virulence using canonical parameters such as maximum specific growth rate (μmax) can fail to provide accurate information regarding experimental infection, especially for non-lytic viruses. Although area-under-the-curve (AUC) can be more robust by through calculation of a percent inhibition (PIAUC), this metric can be sensitive to limit selection. In this study, using empirical and extrapolated data from Sulfolobus Spindle-shaped Virus (SSV) infections, we introduce a novel, simple metric that is proven to be more robust and less sensitive than traditional measures for determining relative virulence. This metric (ISC) more accurately aligns biological phenomena with quantified metrics from growth curve analysis to determine trends in relative virulence. It also addresses a major gap in virology by allowing comparisons between non-lytic single-virus/single-host (SVSH) infections and between non-lytic versus lytic virus infection on a given host. HowISCmay be applied to polymicrobial infection – both coinfection of a host culture and superinfection of a single cell with more than one virus (or other pathogen type) is a topic of ongoing investigation.
Detection of Static, Dynamic, and No Tactile Friction Based on Non-linear dynamics of EEG Signals: A Preliminary Study
Authors: Baghdadi Golnaz , Amiri Mahmood 
Published: April 2020

ABSTRACTTouching an object leads to a frictional interaction between the skin and the object. There are two kinds of friction: the first contact that leads to static friction and the dragging phase that leads to dynamic friction. No study has been performed to show the effect of friction type on EEG signals. The main goal of the current study is to investigate the effect of tactile friction on non-linear features of EEG signals.Participants performed a tactile task that each of its trials had three states: the sensation of 1) static friction, 2) dynamic friction, and 3) no friction. During the experiment, EEG signals were recorded, and different linear and non-linear EEG indices were extracted and analyzed to find the effect of the tactile friction on EEG signals.Linear features such as spectral features were not a good choice to distinguish between the states. However, non-linear features such as Lyapunov exponent, Higuchi’s dimension, and Hurst exponent had the potential to separate the mentioned states. Results also showed signs of predictability (negative Lyapunov exponent) in the signals recorded during dynamic friction and the existence of long-range dependency (memory) in EEG signals recorded during all states. The complexity of the tactile system in Theta band was also higher than the Delta band. The results of this research not only increase our knowledge about brain non-linear dynamics in response to tactile friction but also lead to a design of a preliminary system that can automatically detect friction between the skin and surfaces.
Neural computation underlying rapid learning and dynamic memory recall for sensori-motor control in insects
Authors: Rapp Hannes , Nawrot Martin Paul 
Published: April 2020

AbstractForaging is a vital behavioral task for living organisms. Behavioral strategies and abstract mathematical models thereof have been described in detail for various species. To explore the link between underlying nervous systems and abstract computational principles we present how a biologically detailed neural circuit model of the insect mushroom body implements sensory processing, learning and motor control. We focus on cast & surge strategies employed by flying insects when foraging within turbulent odor plumes. Using a synaptic plasticity rule the model rapidly learns to associate individual olfactory sensory cues paired with food in a classical conditioning paradigm. Without retraining, the system dynamically recalls memories to detect relevant cues in complex sensory scenes. Accumulation of this sensory evidence on short timescales generates cast & surge motor commands. Our systems approach is generic and predicts that population sparseness facilitates learning, while temporal sparseness is required for dynamic memory recall and precise behavioral control.
Synchronized infection identifies early rate-limiting steps in the hepatitis B virus life cycle
Authors: Chakraborty Anindita , Ko Chunkyu , Henning Christin , Lucko Aaron , Zhuang Xiaodong , Wettengel Jochen M. , Protzer Ulrike , McKeating Jane A 
Published: April 2020

ABSTRACTHepatitis B virus (HBV) is an enveloped DNA virus that contains a partially double-stranded relaxed circular (rc) DNA. Upon infection, rcDNA is delivered to the nucleus where it is repaired to covalently closed circular (ccc) DNA that serves as the transcription template for all viral RNAs. Our understanding of HBV particle entry dynamics and host pathways regulating intracellular virus trafficking and cccDNA formation is limited. The discovery of sodium taurocholate co-transporting peptide (NTCP) as the primary receptor allows studies on these early steps in viral life cycle. We employed a synchronized infection protocol to quantify HBV entry kinetics. HBV attachment to cells at 4°C is independent of NTCP, however, subsequent particle uptake is NTCP-dependent and reaches saturation at 12h post-infection. HBV uptake is clathrin- and dynamin dependent with actin and tubulin playing a role in the first 6h of infection. Cellular fractionation studies demonstrate HBV DNA in the nucleus within 6h of infection and cccDNA was first detected at 24h post-infection. Our studies show the majority (83%) of cell bound particles enter HepG2-NTCP cells, however, only a minority (<1%) of intracellular rcDNA was converted to cccDNA, highlighting this as a rate-limiting in establishing infectionin vitro. This knowledge highlights the deficiencies in ourin vitrocell culture systems and will inform the design and evaluation of physiologically relevant models that support efficient HBV replication.
APenicillium rubensplatform strain for secondary metabolite production
Authors: Pohl Carsten , Polli Fabiola , Schütze Tabea , Viggiano Annarita , Mózsik László , Jung Sascha , de Vries Maaike , Bovenberg Roel A.L. , Meyer Vera , Driessen Arnold J.M. 
Published: April 2020

AbstractWe present aPenicillium rubensstrain with an industrial background in which the four highly expressed biosynthetic gene clusters (BGC) required to produce penicillin, roquefortine, chrysogine and fungisporin were removed. This resulted in a minimal secondary metabolite background. Amino acid pools under steady-state growth conditions showed reduced levels of methionine and increased intracellular aromatic amino acids. Expression profiling of remaining BGC core genes and untargeted mass spectrometry did not identify products from uncharacterized BGCs. This platform strain was repurposed for expression of the recently identified polyketide calbistrin gene cluster and achieved high yields of decumbenone A, B and C. The penicillin BGC could be restored throughin vivoassembly with eight DNA segments with short overlaps. Our study paves the way for fast combinatorial assembly and expression of biosynthetic pathways in a fungal strain with low endogenous secondary metabolite burden.
The order Tethyida (Porifera) in California: taxonomy, systematics, and the first member of the family Hemiasterellidae in the Eastern Pacific
Authors: Turner Thomas L. 
Published: April 2020

AbstractSponges (phylum Porifera) are ubiquitous inhabitants of marine ecosystems and have been shown to provide substantial ecosystem services. Despite this ecological importance, the sponge fauna in California has received little study. Here I use a collection of kelp forest sponges to describe the diversity of the order Tethyida in California. This order contains the genus Tethya, which has been included in long-term ecological monitoring projects. I show that Tethya vacua is a junior synonym of Tethya californiana, and thus all Tethya populations known in California belong to a single species. Genetic data from California’s only Timeidae, Timea authia, indicate that this species is in fact in the Tethyidae and is the third known member of the genus Tethytimea. I also describe the first member of the family Hemiasterellidae from the Eastern Pacific, Galaxia gaviotensis gen. nov. sp. nov. By combining field photographs, morphological taxonomy, and phylogenetic analysis of these samples, this work will facilitate future efforts to understand the evolution of this order and the ecological role of sponges in the California kelp forest.
Mutational profiling of micro-dissected pre-malignant lesions from archived specimens
Authors: Nachmanson Daniela , Steward Joseph , Yao Huazhen , Officer Adam , Jeong Eliza , O’Keefe Thomas J. , Hasteh Farnaz , Jepsen Kristen , Hirst Gillian L. , Esserman Laura J. , Borowsky Alexander D. , Harismendy Olivier 
Published: April 2020

AbstractBackgroundSystematic cancer screening has led to the increased detection of pre-malignant lesions (PMLs). The absence of reliable prognostic markers has led mostly to over treatment resulting in potentially unnecessary stress, or potentially insufficient treatment and avoidable progression. Importantly, most mutational profiling studies have relied on PML synchronous to invasive cancer, or performed in patients without outcome information, hence limiting their utility for biomarker discovery. The limitations in comprehensive mutational profiling of PMLs are in large part due to the significant technical and methodological challenges: most PML specimens are small, fixed in formalin and paraffin embedded (FFPE) and lack matching normal DNA.MethodsUsing test DNA from a highly degraded FFPE specimen, multiple targeted sequencing approaches were evaluated, varying DNA input amount (3-200 ng), library preparation strategy (BE: Blunt-End, SS: Single-Strand, AT: A-Tailing) and target size (whole exome vs cancer gene panel). Variants in high-input DNA from FFPE and mirrored frozen specimens were used for PML-specific variant calling training and testing, respectively. The resulting approach was applied to profile and compare multiple regions micro-dissected (mean area 5 mm2) from 3 breast ductal carcinoma in situ (DCIS).ResultsUsing low-input FFPE DNA, BE and SS libraries resulted in 4.9 and 3.7 increase over AT libraries in the fraction of whole exome covered at 20x (BE:87%, SS:63%, AT:17%). Compared to high-confidence somatic mutations from frozen specimens, PML-specific variant filtering increased recall (BE:85%, SS:80%, AT:75%) and precision (BE:93%, SS:91%, AT:84%) to levels expected from sampling variation. Copy number alterations were consistent across all tested approaches and only impacted by the design of the capture probe-set. Applied to DNA extracted from 9 micro-dissected regions (8 PML, 1 normal epithelium), the approach achieved comparable performance, illustrated the data adequacy to identify candidate driver events(GATA3 mutations, ERBB2orFGFR1 gains, TP53 loss)and measure intra-lesion genetic heterogeneity.ConclusionAlternate experimental and analytical strategies increased the accuracy of DNA sequencing from archived micro-dissected PML regions, supporting the deeper molecular characterization of early cancer lesions and achieving a critical milestone in the development of biology-informed prognostic markers and precision chemo-prevention strategies.
Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts
Authors: Berdiel-Acer Mireia , Maia Ana , Hristova Zhivka , Borgoni Simone , Vetter Martina , Burmester Sara , Becki Corinna , Abnaof Khalid , Binenbaum Ilona , Bethmann Daniel , Chatziioannou Aristotelis , Hasmann Max , Thomssen Christoph , Espinet Elisa , Wiemann Stefan 
Published: April 2020

AbstractHER3 is highly expressed in luminal breast cancer subtypes. Its activation by NRG1 promotes activation of AKT and ERK1/2, contributing to tumour progression and therapy resistance. HER3-targeting agents that block this activation, are currently under phase 1/2 clinical studies, and although they have shown favorable tolerability, their activity as a single agent has proven to be limited. Here we show that phosphorylation and activation of HER3 in luminal breast cancer cells occurs in a paracrine manner and is mediated by NRG1 expressed by cancer-associated fibroblasts (CAFs). Moreover, we uncover an autocrine role of NRG1 in CAFs. This occurs independently of HER3 and results in the induction of a strong migratory and pro-fibrotic phenotype, describing a subset of CAFs with elevated expression of NRG1 and an associated transcriptomic profile that determines their functional properties. Finally, we identified Hyaluronan Synthase 2(HAS2), a targetable molecule strongly correlated withNRG1, as an attractive player supporting NRG1 - autocrine signaling in CAFs.
Causal relationships between substance use and insomnia
Authors: Pasman Joëlle A. , Smit Dirk J.A. , Kingma Lilian , Vink Jacqueline M. , Treur Jorien L. , Verweij Karin J.H. 
Published: April 2020

AbstractBackgroundPoor sleep quality and insomnia have been associated with the use of tobacco, alcohol, and cannabis, but it is unclear if there is a causal link. In this Mendelian Randomization (MR) study we examine if insomnia causes substance use and/or if substance use causes insomnia.MethodsMR uses summary effect estimates from a genome-wide association study (GWAS) to create a genetic instrumental variable for a proposed ‘exposure’ variable and then identifies that same genetic instrument in an ‘outcome’ GWAS. With data of GWAS of insomnia, smoking (initiation, heaviness, cessation), alcohol use (drinks per week, dependence), and cannabis initiation, bi-directional causal effects were tested. Multiple sensitivity analyses were applied to assess the robustness of the findings.ResultsThere was strong evidence for positive causal effects of insomnia on all substance use phenotypes (smoking traits, alcohol dependence, cannabis initiation), except alcohol per week. The effects on alcohol dependence and cannabis initiation were attenuated after filtering out pleiotropic SNPs. In the other direction, there was strong evidence that smoking initiation increased chances of insomnia (smoking heaviness and cessation could not be tested as exposures). We found no evidence that alcohol use per week, alcohol dependence, or cannabis initiation causally affect insomnia.ConclusionsThere were unidirectional effects of insomnia on alcohol dependence and cannabis initiation, and bidirectional effects between insomnia and smoking measures. Bidirectional effects between smoking and insomnia might give rise to a vicious circle. Future research should investigate if interventions aimed at insomnia are beneficial for substance use treatment.
Fast multi-directional DSLM for confocal detection without striping artifacts
Authors: Ricci Pietro , Sancataldo Giuseppe , Gavryusev Vladislav , Franceschini Alessandra , Müllenbroich Marie Caroline , Silvestri Ludovico , Pavone Francesco Saverio 
Published: April 2020

AbstractIn recent years light-sheet fluorescence microscopy (LSFM) has become a cornerstone technology for neuroscience, improving quality and capabilities of 3D imaging. By selectively illuminating a single plane, it provides intrinsic optical sectioning and fast image recording, while minimizing out of focus fluorescence background, sample photo-damage and photo-bleaching. However, images acquired with LSFM are often affected by light absorption or scattering effects, leading to un-even illumination and striping artifacts. In this work we present an optical solution to this problem, via fast multi-directional illumination of the sample, based on an acousto-optical deflector (AOD). We demonstrate that this pivoting system is compatible with confocal detection in digital scanned laser light-sheet fluorescence microscopy (DSLM) by using a pivoted elliptical-Gaussian beam. We tested its performance by acquiring signals emitted by specific fluorophores in several mouse brain areas, comparing the pivoting beam illumination and a traditional static one, measuring the point spread function response and quantifying the striping reduction. We observed real-time shadow suppression, while preserving the advantages of confocal detection for image contrast.
A two-stage homogenization for modelling of elastic-plastic functionally graded composites
Authors: Ogierman Witold 
Published: April 2020

Purpose
The purpose of this study is to develop a homogenization approach that ensures both high accuracy and time-efficient solution for elastic-plastic functionally graded composites.

Design/methodology/approach
The paper presents a novel two-stage hybrid homogenization approach that combines advantages of the mean field homogenization and homogenization based on the finite element method (FEM). The groundbreaking nature of the developed approach is associated with division of the hybrid homogenization procedure into two stages, which allows to very efficiently determine the solution for arbitrary volume fraction of the reinforcement. This paper concerns also on modelling of composites with randomly distributed prolate and oblate particles. For this purpose, the hybrid homogenization was implemented in the framework of the discrete orientation averaging procedure involving pseudo-grain discretization method.

Findings
Agreement between the results obtained using the proposed approach and the standard FEM-based homogenization is very good (up to the volume fraction of 0.3).

Originality/value
The proposed two-stage homogenization approach allows to obtain the solution for materials with arbitrary volume fraction of the reinforcement very efficiently; therefore, it is highly beneficial for the two-scale modeling of nonlinear functionally graded materials and structures.