bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proton pump inhibitors inhibit PHOSPHO1 activity and matrix mineralisationin vitro
Authors: Staines Katherine A. , Myers Katherine , Little Kirsty , Ralston Stuart H. , Farquharson Colin 
Published: April 2021

AbstractProton pump inhibitors (PPIs) have been associated with an increased risk of fragility fractures in pharmaco-epidemiological studies. The mechanism is unclear but it has been speculated that by neutralising gastric acid, they may reduce intestinal calcium absorption, causing secondary hyperparathyroidism and bone loss. Here we investigated that hypothesis that the skeletal effects of PPI might be mediated by inhibitory effects on the bone-specific phosphatase PHOSPHO1. We found that the all PPI tested potential inhibited the activity of PHOSPHO1 with IC50 ranging between 0.73μM for esomeprazole to 19.27μM for pantoprazole. In contrast, these PPIs did not inhibit TNAP activity. We also found that mineralisation of bone matrix in primary osteoblast cultures inhibited by several PPI in a concentration dependent manner. In contrast, the histamine-2 receptor antagonists (H2RA) nizatidine, famotidine, cimetidine and ranitidine had no inhibitory effects on PHOSPHO1 activity. Our experiments shown for the first time that PPI inhibit PHOSPHO1 activity and matrix mineralisationin vitrorevealing a potential mechanism by which these widely used drugs are associated with the risk of fractures.
Chromoanagenesis landscape in 10,000 TCGA patients
Authors: Rasnic Roni , Linial Michal 
Published: April 2021

AbstractDuring the past decade, whole-genome sequencing of tumor biopsies and individuals with congenital disorders highlighted the phenomenon of chromoanagenesis, a single chaotic event of chromosomal rearrangement. Chromoanagenesis was shown to be frequent in many types of cancers, to occur in early stages of cancer development, and significantly impact the tumor’s nature. However, an in-depth, cancer-type dependent analysis has been somewhat incomplete due to the shortage in whole genome sequencing of cancerous samples. In this study, we extracted data from The Pan-Cancer Analysis of Whole Genome (PCAWG) and The Cancer Genome Atlas (TCGA) to construct a machine learning algorithm that can detect chromoanagenesis with high accuracy (86%). The algorithm was applied to ~10,000 TCGA cancer patients. We utilize the chromoanagenesis assignment results, to analyze cancer-type specific chromoanagenesis characteristics in 20 TCGA cancer types. Our results unveil prominent genes affected in either chromoanagenesis or non-chromoanagenesis tumorigenesis. The analysis reveals a mutual exclusivity relationship between the genes impaired in chromoanagenesis versus non-chromoanagenesis cases. We offer the discovered characteristics as possible targets for cancer diagnostic and therapeutic purposes.
Antimicrobial activity and degradation of superhydrophobic magnesium substrates in bacterial media
Authors: Emelyanenko Alexandre M. , Kaminsky Valery V. , Pytskii Ivan S. , Emelyanenko Kirill A. , Domantovsky Alexander G. , Chulkova Elizaveta V. , Shiryaev Andrei A. , Aleshkin Andrei V. , Boinovich Ludmila B. 
Published: April 2021

AbstractThe interest in magnesium-based materials is promoted by their biocompatibility, bioresorbability, and by their recently found antibacterial potential. Until now the widespread use of magnesium alloys in different corrosive environments was inhibited by their weakly controllable degradation rate and poorly understood microbiologically induced corrosion behavior. To better understand the degradation and usability of magnesium-based alloys, in this study we have fabricated the superhydrophobic coatings on top of magnesium-based alloy and analyzed the behavior of this alloy in bacterial dispersions ofPseudomonas aeruginosaandKlebsiella pneumoniaecells in phosphate buffered saline. It was shown that immersion of such coatings into bacterial dispersions causes notable changes in the morphology of the samples, dependent on the bacterial dispersion composition and the type of bacterial strain. The interaction of superhydrophobic coatings with the bacterial dispersion caused the formation of biofilms and sodium polyphosphate films, which provided enhanced barrier properties for magnesium dissolution and hence for dispersion medium alkalization, eventually leading to inhibition of magnesium substrate degradation. Electrochemical data obtained for superhydrophobic samples continuously contacted with the corrosive bacterial dispersions during 48 h indicated a high level of anti-corrosion protection.
Enhancing the dark side: Asymmetric gain of cone photoreceptors underpins discrimination of visual scenes based on their skewness
Authors: Yedutenko Matthew , Howlett Marcus H.C. , Kamermans Maarten 
Published: April 2021

AbstractPsychophysical data indicates humans can discriminate visual scenes based on their skewness – the ratio of dark and bright patches within a visual scene. It was also shown that on a phenomenological level this skew discrimination is described by the so-called Blackshot mechanism, which accentuates strong negative contrasts within a scene. Here we demonstrate that the underlying computation starts as early as the cone phototransduction cascade whose gain is higher for strong negative contrasts than for strong positive contrasts. We recorded from goldfish cone photoreceptors and found that the asymmetry in the phototransduction gain leads to higher amplitude of the responses to negatively than to positively skewed light stimuli. This asymmetry in the amplitude was present in the photocurrent, voltage response and cone synaptic output. These results highlight the importance of the early photoreceptor non-linearity for perception. Additionally, we found that stimulus skewness leads to a subtle change in photoreceptor kinetics. For negatively skewed stimuli, the cone’s impulse response functions peak later than for positively skewed stimulus. However, stimulus skewness does not affect the cone’s overall integration time.
Mechanical Metric for Skeletal Biomechanics Derived from Spectral Analysis of Stiffness matrix
Authors: Henyš Petr , Kuchař Michal , Hájek Petr , Hammer Niels 
Published: April 2021

AbstractA new metric for the quantitative and qualitative evaluation of bone stiffness is introduced. It is based on the spectral decomposition of stiffness matrix computed with finite element method. The here proposed metric is defined as an amplitude rescaled eigenvalues of stiffness matrix. The metric contains unique information on the principal stiffness of bone and reflects both bone shape and material properties. The metric was compared with anthropometrical measures and was tested for sex sensitivity on pelvis bone. Further, the smallest stiffness of pelvis was computed under a certain loading condition and analyzed with respect to sex and direction. The metric complements anthropometrical measures and provides a unique information about the smallest bone stiffness independent from the loading configuration and can be easily computed by state-of-the-art subject specified finite element algorithms.
Interpreting Neural Networks for Biological Sequences by Learning Stochastic Masks
Authors: Linder Johannes , La Fleur Alyssa , Chen Zibo , Ljubetič Ajasja , Baker David , Kannan Sreeram , Seelig Georg 
Published: April 2021

AbstractSequence-based neural networks can learn to make accurate predictions from large biological datasets, but model interpretation remains challenging. Many existing feature attribution methods are optimized for continuous rather than discrete input patterns and assess individual feature importance in isolation, making them ill-suited for interpreting non-linear interactions in molecular sequences. Building on work in computer vision and natural language processing, we developed an approach based on deep generative modeling - Scrambler networks - wherein the most salient sequence positions are identified with learned input masks. Scramblers learn to generate Position-Specific Scoring Matrices (PSSMs) where unimportant nucleotides or residues are ‘scrambled’ by raising their entropy. We apply Scramblers to interpret the effects of genetic variants, uncover non-linear interactions between cis-regulatory elements, explain binding specificity for protein-protein interactions, and identify structural determinants ofde novodesigned proteins. We show that interpretation based on a generative model allows for efficient attribution across large datasets and results in high-quality explanations, often outperforming state-of-the-art methods.
Large-scale deployment and establishment ofWolbachiainto theAedes aegyptipopulation in Rio de Janeiro, Brazil
Authors: Moledo Gesto João Silveira , Pinto Sofia , Stehling Dias Fernando Braga , Peixoto Julia , Costa Guilherme , Kutcher Simon , Montgomery Jacqui , Green Benjamin R. , Anders Katherine L. , Ryan Peter A. , Simmons Cameron P. , O’Neill Scott L. , Moreira Luciano Andrade 
Published: April 2021

AbstractTraditional methods of vector control have proven insufficient to reduce the alarming incidence of Dengue, Zika and chikungunya in endemic countries. The bacterium symbiontWolbachiahas emerged as an efficient pathogen-blocking and self-dispersing agent that reduces the vectorial potential ofAedes aegyptipopulations and potentially impairs arboviral disease transmission. In this work, we report the results of a large-scaleWolbachiaintervention in Ilha do Governador, Rio de Janeiro, Brazil.wMel-infected adults were released across residential areas between August 2017 and March 2020. Over 131 weeks, including release and post-release phases, we monitored thewMel prevalence in field specimens, and analyzed introgression profiles of two assigned intervention areas, RJ1 and RJ2. Our results revealed thatwMel successfully invaded both areas, reaching overall infection rates of 50-70% in RJ1, and 30-60% in RJ2 by the end of the monitoring period. At the neighborhood-level,wMel introgression was heterogeneous in both RJ1 and RJ2, with some profiles sustaining a consistent increase in infection rates and others failing to elicit the same. Correlation analysis revealed a weak overall association between RJ1 and RJ2 (r= 0.2849,P= 0.0236), and an association at a higher degree when comparing different deployment strategies, vehicle or backpack-assisted, within RJ1 (r= 0.4676,P< 0.0001) or RJ2 (r= 0.6263,P< 0.0001). The frequencyknockdown resistance(kdr) alleles inwMel-infected specimens from both areas was consistently high over this study. Altogether, these findings corroborate thatwMel can be successfully deployed at large-scale as part of vector control intervention strategies, and provide the basis for imminent disease impact studies in Southeastern Brazil.
Tubulin Acetylation Promotes Penetrative Capacity of Cells Undergoing Radial Intercalation
Authors: Collins Caitlin , Kim Sun K. , Ventrella Rosa , Mitchell Jen W. , Mitchell Brian 
Published: April 2021

AbstractThe post-translational modification of tubulin provides a wide diversity of differential functions to microtubule networks. Here we address the role of tubulin acetylation on the penetrative capacity of cells undergoing radial intercalation in the skin ofXenopusembryos. Radial intercalation is the process by which cells move apically and penetrate the epithelial barrier via inserting into the outer epithelium. As such there are two opposing forces that regulate the ability of cells to intercalate: the restrictive forces of the epithelial barrier versus the penetrative forces of the intercalating cell. By positively and negatively modulating tubulin acetylation specifically in the intercalating cells, the timing of intercalation can be altered such that cells with more acetylated microtubules penetrate the epithelium faster. Moreover, theXenopusepithelium is a complex array of variable types of vertices and we find that intercalating cells preferentially penetrate at higher order “rosette” vertices as opposed to the more prevalent tricellular vertices. We observed differential timing in the ability of cells to penetrate different types of vertices, indicating lower order vertices represent more restrictive sites of insertion. Interestingly, we are able to shift the accessibility of early intercalating cells towards the more restrictive tricellular junctions by modulating the level of tubulin acetylation and the subsequent penetrative capacity of intercalating cells. Overall our data implicate tubulin acetylation in driving tissue penetration of intercalating cells.
Embryo-to-embryo variability in RNAi knockdown efficiency of dKDM5/lid in Drosophila melanogaster
Authors: Albright Ashley , Eisen Michael 
Published: April 2021

AbstractWe used the maternal-Gal4 shRNA system to knock down expression of dKDM5/lid in Drosophila melanogaster embryos, and analyzed the efficacy of the knockdown by qRT-PCR. Although average relative expression of lid was significantly lower in knockdown conditions compared to the driver-only control, we observed a wide and overlapping range of relative gene expression between individual control and knockdown embryos.
Hematopoietic differentiation is characterized by a transient peak of entropy at a single cell level
Authors: Dussiau Charles , Boussaroque Agathe , Gaillard Mathilde , Bravetti Clotilde , Zaroili Laila , Knosp Camille , Friedrich Chloé , Asquier Philippe , Willems Lise , Quint Laurent , Bouscary Didier , Fontenay Michaela , Espinasse Thibault , Plesa Adriana , Sujobert Pierre , Gandrillon Olivier , Kosmider Olivier 
Published: April 2021

AbstractHematopoietic differentiation has been metaphorically represented as linear trajectories with discrete steps from hematopoietic stem cells to mature cells. While the transcriptional state of cells at the beginning or at the end of these trajectories are well described from bulk analysis, what happens in the intermediate states has remained elusive until the use of single cell approaches. Applying Shannon entropy to measure cell-to-cell variability among cells at the same stage of differentiation, we observed a transient peak of gene expression variability in all the hematopoietic differentiation pathways. Strikingly, genes with the highest entropy variation in a given differentiation pathway matched genes known as pathway-specific, whereas genes with the highest expression variation were common to all pathways. Finally, we showed that the level of cell-to-cell variation is increased in the most immature compartment of hematopoiesis in myelodysplastic syndromes. These data suggest that differentiation could be better conceptualized as a dynamical stochastic process with a transient stage of cellular indetermination.
Germline Sex Determination regulates sex-specific signaling between germline stem cells and their niche
Authors: Bhaskar Pradeep Kumar , Southard Sheryl , Baxter Kelly , Van Doren Mark 
Published: April 2021

SummaryThe establishment of sexual identity in germ cells is critical for the development of male and female germline stem cells (GSCs) and production of sperm vs. eggs. Thus, this process is essential for sexual reproduction and human fertility. Germ cells depend on signals from the somatic gonad to determine their sex, but in organisms such as flies, mice and humans, the sex chromosome genotype of the germ cells is also important for germline sexual development. How somatic signals and germ cell-intrinsic cues act together to regulate germline sex determination is a key question about which little is known. We have found that JAK/STAT signaling in the GSC niche promotes male identity in germ cells and GSCs, in part by activating expression of the epigenetic reader Phf7. We have also found that JAK/STAT signaling is blocked in XX (female) germ cells through the intrinsic action of the sex determination geneSex lethal, which preserves female identity. Thus, an important function of germline sexual identity is to control how GSCs respond to signals in their niche environment.
Volumetric Semantic Instance Segmentation of the Plasma Membrane of HeLa Cells
Authors: Karabağ Cefa , Jones Martin L. , Reyes-Aldasoro Constantino Carlos 
Published: April 2021

AbstractIn this work, the unsupervised volumetric semantic segmentation of the plasma membrane of HeLa cells as observed with Serial Block Face Scanning Electron Microscopy is described. The resin background of the images was segmented at different slices of a 3D stack of 518 slices with 8, 192 × 8, 192 pixels each. The background was used to create a distance map which helped identify and rank the cells by their size at each slice. The centroids of the cells detected at different slices were linked to identify them as a single cell that spanned a number of slices. A subset of these cells, i.e., largest ones and those not close to the edges were selected for further processing. The selected cells were then automatically cropped to smaller regions of interest of 2, 000 × 2, 000 × 300 voxels that were treated as cell instances. Then, for each of these volumes the nucleus was segmented and the cell was separated from any neighbouring cells through a series of traditional image processing steps that followed the plasma membrane. The segmentation process was repeated for all the regions selected. For one cell for which the ground truth was available, the algorithm provided excellent results in Accuracy (AC) and Jaccard Index (JI): Nucleus: JI = 0.9665, AC= 0.9975, Cell and Nucleus JI = 0.8711, AC = 0.9655, Cell only JI = 0.8094, AC = 0.9629. A limitation of the algorithm for the plasma membrane segmentation was the presence of background, as in cases of tightly packed cells. When tested for these conditions, the segmentation of the nuclear envelope was still possible. All the code and data are released openly through GitHub, Zenodo and EMPIAR.
Analytical model for rock effective elastic properties with aligned elliptical cracks embedded in transversely isotropic background
Authors: Guo Junxin , Zhao Luanxiao , Yang Zhifang , Li Hongbing 
Published: April 2021

ABSTRACTSeismic methods are often used for fracture detection and characterization, for which many analytical rock physics models have been developed to link fracture parameters to rock elastic properties. However, most of these models are limited to isotropic background and circular (penny‐shaped) fractures. In this work, we derived a more general analytical model for effective elastic properties of rocks embedded with aligned elliptical cracks in transversely isotropic background. The solutions for the case with dry cracks parallel to isotropic plane of transversely isotropic background were first derived using the corresponding Eshelby's tensor. Then, the results were extended to the case with inclined and rotated cracks under the assumption of constant crack opening displacement tensor. Finally, to obtain the results for fluid‐filled crack case, the Brown–Korringa equation was applied. To investigate the controlling factors on rock elastic properties, we studied one fractured tight sandstone sample with transversely isotropic background. The results show that rock elastic properties are insensitive to crack spin angle, but sensitive to crack inclination angle. Depending on crack inclination angle and fluid saturation, background anisotropy can either amplify or reduce the anisotropy of seismic wave velocity. Crack density and aspect ratio are found to be controlling crack parameters for rock elastic properties. The crack plane shape has negligible direct influence on rock elastic properties, whereas it has indirect influence by affecting values of crack density and aspect ratio. Compared with the numerical model and the previous analytical model for the special case with circular cracks, our model agrees well with them, which validates the accuracy of our model.
Closing the life cycle of forest trees: The difficult dynamics of seedling‐to‐sapling transitions in a subtropical rainforest
Authors: Chang‐Yang Chia‐Hao , Needham Jessica , Lu Chia‐Ling , Hsieh Chang‐Fu , Sun I‐Fang , McMahon Sean M. 
Published: April 2021

Abstract

Experimental and observational studies on seedling dynamics posit mechanisms that can influence forest diversity, structure and function. However, high mortality and slow growth of seedlings make it difficult to evaluate the importance of this life‐history filter to total tree life history. Quantifying the duration and transition of the seedling phase would help us understand this ‘black box’ in tree population biology.

We used a 16‐year dataset of comprehensive seedling‐to‐sapling demography from a subtropical rainforest to construct population models that capture temporal demographic fluctuations for eight major tree species. We used data‐driven demographic models and simulations to estimate the transition ratios from newly recruited seedlings to saplings of 2‐m height and the time taken to attain 2‐m height for a newly recruited seedling conditional on its survival.

Projections among species estimated that as few as 57 to more than 40,000 seedlings (with a median of 2,087) were required to make a single 2‐m high sapling. Furthermore, it would take 22–200 years (with a median of 47) for a newly recruited seedling to become a 2‐m high sapling. We found that temporal variation in demographic rates could greatly reduce the number of seedlings per established sapling, but not passage times (PTs). We also identified the importance of consistently fast growth rates for seedlings to escape the high mortality of early stages.

Synthesis. Our findings demonstrate that high mortality in the very early seedling stage severely limits the probability that a newly recruited seedling will transition to the sapling stage. Although the PTs vary, we found this to be true across species with a range of life‐history strategies. Only seedlings with consistently fast growth rates are expected to pass through this life‐history filter. Findings from seedling studies should consider how short‐term studies of seedling demography might capture the rare exceptional individuals and exceptional conditions that might define the dynamics of this seedling bottleneck.
Antifibrinolytics reduces blood loss in thoracic surgery: a systematic review and meta‐analysis
Authors: Leow Lowell , Ng Josiah , Luo Hai Dong , Choong Andrew M. T. L. , Mithiran Harish , Kofidis Theo , Tam John Kit Chung 
Published: April 2021

AbstractBackgroundThe purpose of this systematic review is to evaluate the efficacy of antifibrinolytics in non‐cardiac thoracic surgery.MethodsWe searched for all randomized controlled trials on this topic. A set of strict inclusion and exclusion criteria was developed. Six studies were meta‐analysed together then in subgroups of topical tranexamic acid and intravenous aprotinin. We compared postoperative chest drain output, transfusions requirements and duration of hospital stay where available to determine the efficacy of topical tranexamic acid or intravenous aprotinin in reducing blood loss.ResultsThe use of antifibrinolytics reduces 24‐h chest drain output (−290.21 mL [−524.75, −55.66], P = 0.02, I2 = 98%), red blood cell transfusion requirements (−1.27 units [−2.24, −0.30], P = 0.01, I2 = 100%) and shortened duration of hospital stay (−1.81 days [−3.25, −0.36], P = 0.01, I2 = 96%). The subgroup analysis also supported this trend.ConclusionWe conclude that the use of antifibrinolytics appears to reduce postoperative blood loss by reducing chest drain output, transfusion requirements and length of stay after thoracic surgery.