bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between toothbrushing and non-alcoholic fatty liver disease
Authors: Kim Ji-Youn , Park Yong-Moon , Lee Gyu-Na , Song Hyun Chul , Ahn Yu-Bae , Han Kyungdo , Ko Seung-Hyun 
Published: December 2020

AbstractNon-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Periodontitis, as chronic inflammatory destructive disease, is associated metabolic syndomes bidirectionally. Toothbrushing is an essential and important way to manage periodontitis through mechanical removal of biofilm at periodontal tissue. We aimed to assess the association between toothbrushing frequency and the prevalent NAFLD in nationally representative Korean adults. Among adults aged 19 years and older who participated in the Korea National Health and Nutrition Examination Survey in 2010, a total of 6,352 subjects were analyzed. NAFLD was defined as fatty liver index ≥60. Multiple logistic regression analysis was used to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). An inverse association between toothbrushing frequency and NAFLD was found. The adjusted ORs (95% CIs) of NALFD was 0.56 (0.35 - 0.90) in the group who performed toothbrushing ≥ 3 per day compared to the group that performed toothbrushing ≤ 1 per day. For those with toothbrushing frequency ≤1 per day, the adjusted OR (95% CIs) of NAFLD was 2.27 (1.22-4.23) in smokers and 4.55 (1.98 – 10.44) in subjects with diabetes mellitus (DM), compared to those without the disease and with toothbrushing frequency ≥2 per day, respectively. Our results indicate that higher frequency of toothbrushing is inversely associated with NAFLD. As a modifiable oral habit, regular toothbrushing may be recommended to lower risk of NAFLD, especially in high risk groups such as smokers and diabetic patients.
Human major infections: tuberculosis, treponematoses, leprosy – a paleopathological perspective of their evolution
Authors: Henneberg Maciej , Holloway-Kew Kara , Lucas Teghan 
Published: December 2020

AbstractObjectiveThe key to evolution is reproduction. Pathogens can either kill the human host or can invade the host without causing death, thus ensuring their own survival, reproduction and spread. Tuberculosis, treponematoses and leprosy are widespread chronic infectious diseases whereby the host is not immediately killed. These diseases are examples of the co-evolution of host and pathogen. They can be well studied as the paleopathological record is extensive, spanning over 200 human generations.MethodsThe paleopathology of each disease has been well documented in the form of published synthetic analyses recording each known case and case frequencies in the samples they were derived from. Here the data from these synthetic analyses were re-analysed to show changes in the prevalence of each disease over time. A total of 69,379 skeletons are included in this study.ResultsThere was ultimately a decline in the prevalence of each disease over time, this decline was statistically significant (Chi-squared, p<0.001). A trend may start with the increase in the disease’s prevalence before the prevalence declines, in tuberculosis the decline is monotonic.ConclusionsIncrease in skeletal changes resulting from the respective diseases appears in the initial period of host-disease contact, followed by a decline resulting from co-adaptation that is mutually beneficial for the disease (spread and maintenance of pathogen) and host (less pathological reactions to the infection). Eventually either the host may become immune or tolerant, or the pathogen tends to be commensalic rather than parasitic.
Characterization of genetic diversity and population structure withinStaphylococcus chromogenesby multilocus sequence typing
Authors: Huebner Rebeca , Mugabi Robert , Hetesy Gabriella , Fox Lawrence , De Vliegher Sarne , De Visscher Anneleen , Barlow John W , Sensabaugh George 
Published: December 2020

AbstractStaphylococcus chromogenesis a common skin commensal in cattle and has been identified as a frequent cause of bovine mastitis and intramammary infections. To better understand the extent of strain diversity within this species and to facilitate study of strain variation as a factor in pathogenicity, we have developed a seven locus Multilocus Sequence Typing (MLST) scheme. The scheme was tested on 120 isolates collected from three geographic locations, Vermont and Washington State in the United States and Belgium. A total of 46 sequence types (STs) were identified with most of the STs being location specific. The utility of the typing scheme is indicated by a discrimination power of 95.6% for all isolates and greater than 90% for isolates from each of the three locations. Phylogenetic analysis placed 39 of the 46 STs into single core group consistent with a common genetic lineage; the STs in this group differ by less than 0.5% at the nucleotide sequence level. Most of the diversification in this lineage group can be attributed to mutation; recombination plays a limited role. This lineage group includes two clusters of single nucleotide variants in starburst configurations indicative of recent clonal expansion; nearly 50% of the isolates sampled in this study are in these two clusters. The remaining seven STs were set apart from the core group by having alleles with highly variable sequences at one or more loci. Recombination had a higher impact than mutation in the diversification of these outlier STs. Alleles with hypervariable sequences were detected at five of the seven loci used in the MLST scheme; the average sequence distances between the hypervariable alleles and the common core alleles ranged from 12 to 34 nucleotides. The extent of these sequence differences suggests the hypervariable alleles may be remnants of an ancestral genotype.
A dynamic spike threshold with correlated noise predicts observed patterns of negative interval correlations in neuronal spike trains
Authors: Sidhu Robin S. , Johnson Erik C. , Jones Douglas L. , Ratnam Rama 
Published: December 2020

AbstractNegative correlations in the sequential evolution of interspike intervals (ISIs) are a signature of memory in neuronal spike-trains. They provide coding benefits including firing-rate stabilization, improved detectability of weak sensory signals, and enhanced transmission of information by improving signal-to-noise ratio. Primary electrosensory afferent spike-trains in weakly electric fish fall into two categories based on the pattern of SCCs: non-bursting units have negative SCCs which remain negative but decay to zero with increasing lags (Type I SCCs), and bursting units have oscillatory (alternating sign) SCCs which damp to zero with increasing lags (Type II SCCs). Here, we predict and match observed ISI serial correlations in these afferents using a stochastic dynamic threshold model. We determine SCCs as a function of an arbitrary discrete noise correlation functionRk, wherekis a multiple of the mean ISI. The function permits forward and inverse calculations of SCCs. Both types of SCCs can be generated by adding colored noise to the spike threshold with Type I SCCs generated with slow noise and Type II SCCs generated with fast noise. We show that a first-order autoregressive (AR) process with a single parameter is sufficient to predict and accurately match both types of afferent SCCs, the type being determined by the sign of the AR parameter. The predicted and experimentally observed SCCs are in geometric progression. The theory predicts that the limiting sum of SCCs is −0.5 yielding a perfect DC-block in the power spectrum of the spike train. Observed SCCs from afferents have a limiting sum that is slightly larger at −0.475 ± 0.04 (mean ± s.d.). We conclude that the underlying process for generating ISIs may be a simple combination of low-order autoregressive (AR) processes, and discuss the results from the perspective of optimal coding.
Accurate detection and tracking of ants in indoor and outdoor environments
Authors: Wu Meihong , Cao Xiaoyan , Guo Shihui 
Published: December 2020

AbstractMonitoring social insects’ activity is critical for biologists researching their group mechanism. Manually labelling individual insects in a video is labour-intensive. Automated tracking social insects is particularly challenging: (1) individuals are small and similar in appearance; (2) frequent interactions with each other cause severe and long-term occlusion. We propose a detection and tracking framework for ants by: (1) adopting a two-stage object detection framework using ResNet-50 as backbone and coding the position of regions of interest to locate ants accurately; (2) using the ResNet model to develop the appearance descriptors of ants; (3) constructing long-term appearance sequences and combining them with motion information to achieve online tracking. To validate our method, we build a video database of ant colony captured in both indoor and outdoor scenes. We achieve a state-of-the-art performance of 95.7% mMOTA and 81.1% mMOTP in indoor videos, 81.8% mMOTA and 81.9% mMOTP in outdoor videos. Our method runs 6-10 times faster than existing methods for insect tracking. The datasets and code are made publicly available, we aim to contribute to an automated tracking tool for biologists in relevant domains.Author summaryThe research on the group behavior of social insects is in great favor with biologists. But before analysis, each insect needs to be tracked separately in a video. Obviously, that is a time-consuming and labor-intensive work. In this manuscript, we introduce a detection and tracking framework that can automatically track the movement of ants in a video scene. The software first uses a residual network to detect the positions of ants, then learns the appearance descriptor of each ant as appearance information via another residual network. Furthermore, we obtain motion information of each ant by using the Kalman filter. Combining with appearance and motion information, we can accurately track every ant in the ant colony. We validate the performance of our framework using 4 indoor and 5 outdoor videos, including multiple ants. We invite interested readers to apply these methods using our freely available software.
Reconstitution of β-adrenergic regulation of CaV1.2: Rad-dependent and Rad-independent protein kinase A mechanisms
Authors: Katz Moshe , Subramaniam Suraj , Chomsky-Hecht Orna , Tsemakhovich Vladimir , Belkacemi Anouar , Flockerzi Veit , Klussmann Enno , Hirsch Joel A. , Weiss Sharon , Dascal Nathan 
Published: December 2020

AbstractIntroductionCardiac L-type voltage-gated CaV1.2 channels are crucial in physiological regulation of cardiac excitation-contraction coupling. Adrenergic modulation of CaV1.2 starts with activation of β-adrenergic receptors (AR) and culminates in protein kinase A (PKA) - induced increase of calcium influx through CaV1.2 channels. To date, this cascade has never been fully reconstituted in heterologous systems; even partial reconstitution proved challenging and controversial. A recent study identified Rad, a calcium channel inhibitory protein, as an essential component of the adrenergic signaling cascade. We corroborated this finding, further characterized, and fully reconstituted, the complete β-AR CaV1.2 modulation cascade in a heterologous expression system.ObjectiveOur primary goal was to heterologously reconstitute the complete β-adrenergic cascade, and to investigate the role of Rad and additional molecular determinants in adrenergic regulation of cardiac CaV1.2.Methods and ResultsWe utilized theXenopusoocyte heterologous expression system. We expressed CaV1.2 channel subunits, without or with Rad and β1-AR or β2-AR. To activate PKA, we injected cyclic AMP (cAMP) into the oocytes, or extracellularly applied isoproterenol (Iso) to stimulate β-AR. Whole-cell Ba2+currents served as readout. We find and distinguish between two distinct pathways of PKA modulation of CaV1.2: Rad-dependent (~80% of total) and Rad-independent. We separate the two mechanisms by showing distinct requirements for the cytosolic N- and distal C- termini of α1Cand for the CaVβ subunit. Finally, for the first time, we reconstitute the complete pathway using agonist activation of either β1-AR or β2-AR. The reconstituted system reproduces the known features of β-AR regulation in cardiomyocytes, such as a >2-fold increase in CaV1.2 current, a hyperpolarizing shift in activation curve, and a high constitutive activity of β2-AR.ConclusionsThe adrenergic modulation of CaV1.2 is composed of two distinct pathways, Rad-independent and Rad-dependent. The latter contributes most of the β-AR-induced enhancement of CaV1.2 activity, crucially depends on CaVβ subunit, and is differently regulated by β1-AR and β2-AR. The reconstitution of the full β-AR cascade provides the means to address central unresolved issues related to roles of auxiliary proteins in the cascade, CaV1.2 isoforms, and will help to develop therapies for catecholamine-induced cardiac pathologies.
Complex history of aerobic respiration and phototrophy in the Chloroflexota class Anaerolineae revealed by high-quality draft genome ofCa. Roseilinea mizusawaensis AA3_104
Authors: Ward Lewis M. , Li-Hau Fátima , Kakegawa Takeshi , McGlynn Shawn E. 
Published: December 2020

AbstractThe candidate genus Roseilinea is a novel lineage in the Chloroflexota (formerly Chloroflexi or green nonsulfur bacteria) phylum known so far only from very incomplete metagenome-assembled genomes and preliminary enrichments. Roseilinea is notable for appearing capable of anoxygenic photoheterotrophy despite being only distantly related to well-known phototrophic Chloroflexota in the Chloroflexia class such asChloroflexusandRoseiflexus.Here, we present a high quality metagenome-assembled genome of a member of Roseilinea, greatly improving our understanding of the metabolic capacity and taxonomic assignment of this genus. These data allow us to confidently describe the genetic basis for photoheterotrophy in these organisms as well as propose a candidate family for these organisms,Ca.Roseilineaceae, within the Anaerolineae class of Chloroflexota.
Differential Requirements for the CENP-O Complex Reveal Parallel PLK1 Kinetochore Recruitment Pathways
Authors: Nguyen Alexandra L. , Fadel Marie Diane , Cheeseman Iain M. 
Published: December 2020

AbstractSimilar to other core biological processes, the vast majority of cell division components are essential for viability across human cell lines. However, genome-wide screens have identified a number of proteins that exhibit cell line-specific essentiality. Defining the behaviors of these proteins is critical to our understanding of complex biological processes. Here, we harness differential essentiality to reveal the contributions of the 4-subunit centromere-localized CENP-O complex, whose precise function has been difficult to define. Our results support a model in which the CENP-O complex and BUB1 act in parallel pathways to recruit a threshold level of PLK1 to mitotic kinetochores, ensuring accurate chromosome segregation. We demonstrate that targeted changes to either pathway sensitizes cells to the loss of the other component, resulting in cell-state dependent requirements. This approach also highlights the advantage of comparing phenotypes across diverse cell lines to define critical functional contributions and behaviors that could be exploited for the targeted treatment of disease.
Understanding the Evolutionary Games in NSCLC Microenvironment
Authors: Bhattacharya Ranjini , Velde Robert Vander , Marusyk Viktoriya , Desai Bina , Kaznatcheev Artem , Marusyk Andriy , Basanta David 
Published: December 2020

AbstractWhile initially highly successful, targeted therapies eventually fail as populations of tumor cells evolve mechanisms of resistance, leading to resumption of tumor growth. Historically, cell-intrinsic mutational changes have been the major focus of experimental and clinical studies to decipher origins of therapy resistance. While the importance of these mutational changes is undeniable, a growing body of evidence suggests that non-cell autonomous interactions between sub-populations of tumor cells, as well as with non-tumor cells within tumor microenvironment, might have a profound impact on both short term sensitivity of cancer cells to therapies, as well as on the evolutionary dynamics of emergent resistance. In contrast to well established tools to interrogate the functional impact of cell-intrinsic mutational changes, methodologies to understand non-cell autonomous interactions are largely lacking.Evolutionary Game Theory (EGT) is one of the main frameworks to understand the dynamics that drive frequency changes in interacting competing populations with different phenotypic strategies. However, despite a few notable exceptions, the use of EGT to understand evolutionary dynamics in the context of evolving tumors has been largely confined to theoretical studies. In order to apply EGT towards advancing our understanding of evolving tumor populations, we decided to focus on the context of the emergence of resistance to targeted therapies, directed against EML4-ALK fusion gene in lung cancers, as clinical responses to ALK inhibitors represent a poster child of limitations, posed by evolving resistance. To this end, we have examined competitive dynamics between differentially labelled therapy-naïve tumor cells, cells with cell-intrinsic resistance mechanisms, and cells with cell-extrinsic resistance, mediated by paracrine action of hepatocyte growth factor (HGF), withinin vitrogame assays in the presence or absence of front-line ALK inhibitor alectinib. We found that producers of HGF were the fittest in every pairwise game, while also supporting the proliferation of therapy-naïve cells. Both selective advantage of these producer cells and their impact on total population growth was a linearly increasing function of the initial frequency of producers until eventually reaching a plateau. Resistant cells did not significantly interact with the other two phenotypes. These results provide insights on reconciling selection driven emergence of subpopulations with cell non-cell autonomous resistance mechanisms, with lack of evidence of clonal dominance of these subpopulations. Further, our studies elucidate mechanisms for co-existence of multiple resistance strategies within evolving tumors. This manuscript serves as a technical report and will be followed up with a research paper in a different journal.
u-track 3D: measuring and interrogating dense particle dynamics in three dimensions
Authors: Roudot Philippe , Legant Wesley R. , Zou Qiongjing , Dean Kevin M. , Isogai Tadamoto , Welf Erik S. , David Ana F. , Gerlich Daniel W. , Fiolka Reto , Betzig Eric , Danuser Gaudenz 
Published: December 2020

AbstractParticle tracking is a ubiquitous task in the study of dynamic molecular and cellular processes through microscopy. Light-sheet microscopy has opened a path to acquiring complete cell volumes for investigation in 3-dimensions (3D). However, hypothesis formulation and quantitative analysis have remained difficult due to fundamental challenges in the visualization and the verification of large and dense sets of 3D particle trajectories. Here we describe u-track 3D, a software package that addresses these two challenges. Building on the established framework of particle association in space and time implemented for 2D time-lapse sequences, we first report a complete and versatile pipeline for particle tracking in 3D. We then present the concept of dynamic region of interest (dynROI), which allows an experimenter to interact with dynamic 3D processes in 2D views amenable to visual inspection. Third, we present an estimator of trackability which defines a score for every trajectory, thereby overcoming the challenges of trajectory validation by visual inspection. With these combined strategies, u-track 3D provides a framework for the unbiased study of molecular processes in complex volumetric sequences.
SINE Retrotransposons Import Polyadenylation Signals to 3’UTRs in Dog (Canis familiaris)
Authors: Choi Jessica D. , Del Pinto Lelani A. , Sutter Nathan B. 
Published: December 2020

AbstractBackgroundMessenger RNA 3’ untranslated regions (3’UTRs) control many aspects of gene expression and determine where the transcript will terminate. The polyadenylation signal (PAS) AAUAAA is a key regulator of transcript termination and this hexamer, or a similar sequence, is very frequently found within 30 bp of 3’UTR ends. Short interspersed element (SINE) retrotransposons are found throughout genomes in high copy number. When inserted into genes they can disrupt expression, alter splicing, or cause nuclear retention of mRNAs. The genomes of the domestic dog and other carnivores carry hundreds of thousands Can-SINEs, a tRNA-related SINE with transcription termination potential. Because of this we asked whether Can-SINEs may help terminate transcript in some dog genes.ResultsDog 3’UTRs have several peaks of AATAAA PAS frequency within 40 bp of the 3’UTR end, including four bp-interval peaks at 28, 32, and 36 bp from the end. The periodicity is partly explained by TAAA(n) repeats within Can-SINE AT-rich tails. While density of antisense-oriented Can-SINEs in 3’UTRs is fairly constant with distances from 3’end, sense-oriented Can-SINEs are common at the 3’end but nearly absent farther upstream. There are nine Can-SINE sub-types in the dog genome and the consensus sequence sense strands (head to tail) all carry at least three PASs while antisense strands usually have none. We annotated all repeat-masked Can-SINE copies in the Boxer reference genome and found that the young SINEC_Cf type has a mode of 15 bp for target site duplications (TSDs). We find that all Can-SINE types favor integration at TSDs beginning with A(4). The count of AATAAA PASs differs significantly between sense and antisense-oriented retrotransposons in transcripts. Can-SINEs near 3’UTR ends are very likely to carry AATAAA on the mRNA sense strand while those farther upstream are not. We also identified loci where Can-SINE insertion has truncated or altered a dog 3’UTR compared to the human ortholog.ConclusionDog Can-SINE activity has imported AATAAA PASs into gene transcripts and led to alteration of 3’UTRs. AATAAA sequences are selectively removed from Can-SINEs in introns and upstream 3’UTR regions but are retained at the far downstream end of 3’UTRs, which we infer reflects their role as termination sequences for these transcripts.
Lipid Droplets Promote Phase Separation of Ago2 to Accelerate Dicer1 Loss and Decelerate miRNA Activity in Lipid Exposed Hepatic Cells
Authors: Bandyopadhyay Diptankar , Basu Sudarshana , Mukherjee Ishita , Chakraborty Ritobrita , Mukherjee Kamalika , Chattopadhyay Krishnananda , Chakrabarti Saikat , Chakrabarti Partha , Bhattacharyya Suvendra N. 
Published: December 2020

AbstractmiR-122 is a liver specific miRNA that plays an important role in controlling metabolic homeostasis in mammalian liver cells. Interestingly, miR-122 on exposure to lipotoxic stress is reduced in liver cells. To fight stress, miRNA processor Dicer1 is depleted to cause reduced miR-122 production and the lowering of miRNA level ensures a better stress response in hepatocytes under lipotoxic stress. Interestingly, lipid droplets, formed in the liver cells on exposure to high fat, ensure cytoplasmic phase separation of Ago2 and prevent interaction of Ago2 with Dicer1. Lipid droplets bind miRNA and enhance miRNA-Ago2 uncoupling and Ago2 phase separation. Loss of interaction between Ago2 and Dicer1 eventually facilitates export and lowering of cellular Dicer1, a process also dependent on the endosomal maturation controller protein Alix, thereby ceasing pre-miRNA processing by Dicer1 in lipid exposed cells. Depletion of lipid droplets by downregulation of Perilipins with siRNAs resulted in a rescue of cellular Dicer1 level and Ago2-Dicer1 interaction. This is a novel mechanism that liver cells adopt to restrict cellular miRNA levels under stress condition. Thus, lipid droplets prevent cell death upon exposure to high fat by reducing intra and extracellular pool of miR-122 in hepatic tissue.