bluuebunny/crossref_metadata_2025_split huggingface dataset:
The amyloid structure of mouse RIPK3 (receptor interacting protein kinase 3) in cell necroptosis
Authors: Wu Xia-lian , Hu Hong , Dong Xing-qi , Zhang Jing , Wang Jian , Schwieters Charles D. , Liu Jing , Wu Guo-xiang , Li Bing , Lin Jing-yu , Wang Hua-yi , Lu Jun-xia 
Published: March 2021

AbstractRIPK3 amyloid complex plays crucial roles during TNF-induced necroptosis and in response to immune defense in both human and mouse. Here, we have structurally characterized mouse RIPK3 homogeneous self-assembly using solid-state NMR, revealing a well-ordered N-shaped amyloid core structure featured with 3 parallel in-register β-sheets. This structure differs from previously published human RIPK1/RIPK3 hetero-amyloid complex structure, which adopted a serpentine fold. Functional studies indicate both RIPK1-RIPK3 binding and RIPK3 amyloid formation are essential but not sufficient for TNF-induced necroptosis. The structural integrity of RIPK3 fibril with three β-strands is necessary for signaling. Molecular dynamics simulations with a mouse RIPK1/RIPK3 model indicate that the hetero-amyloid is less stable when adopting the RIPK3 fibril conformation, suggesting a structural transformation of RIPK3 from RIPK1-RIPK3 binding to RIPK3 amyloid formation. This structural transformation would provide the missing link connecting RIPK1-RIPK3 binding to RIPK3 homo-oligomer formation in the signal transduction.
Aptardi predicts polyadenylation sites in sample-specific transcriptomes using high-throughput RNA sequencing and DNA sequence
Authors: Lusk Ryan , Stene Evan , Banaei-Kashani Farnoush , Tabakoff Boris , Kechris Katerina , Saba Laura M. 
Published: March 2021

AbstractAnnotation of polyadenylation sites from short-read RNA sequencing alone is a challenging computational task. Other algorithms rooted in DNA sequence predict potential polyadenylation sites; however, in vivo expression of a particular site varies based on a myriad of conditions. Here, we introduce aptardi (alternative polyadenylation transcriptome analysis from RNA-Seq data and DNA sequence information), which leverages both DNA sequence and RNA sequencing in a machine learning paradigm to predict expressed polyadenylation sites. Specifically, as input aptardi takes DNA nucleotide sequence, genome-aligned RNA-Seq data, and an initial transcriptome. The program evaluates these initial transcripts to identify expressed polyadenylation sites in the biological sample and refines transcript 3′-ends accordingly. The average precision of the aptardi model is twice that of a standard transcriptome assembler. In particular, the recall of the aptardi model (the proportion of true polyadenylation sites detected by the algorithm) is improved by over three-fold. Also, the model—trained using the Human Brain Reference RNA commercial standard—performs well when applied to RNA-sequencing samples from different tissues and different mammalian species. Finally, aptardi’s input is simple to compile and its output is easily amenable to downstream analyses such as quantitation and differential expression.
Integrated cross-study datasets of genetic dependencies in cancer
Authors: Pacini Clare , Dempster Joshua M. , Boyle Isabella , Gonçalves Emanuel , Najgebauer Hanna , Karakoc Emre , van der Meer Dieudonne , Barthorpe Andrew , Lightfoot Howard , Jaaks Patricia , McFarland James M. , Garnett Mathew J. , Tsherniak Aviad , Iorio Francesco 
Published: March 2021

AbstractCRISPR-Cas9 viability screens are increasingly performed at a genome-wide scale across large panels of cell lines to identify new therapeutic targets for precision cancer therapy. Integrating the datasets resulting from these studies is necessary to adequately represent the heterogeneity of human cancers and to assemble a comprehensive map of cancer genetic vulnerabilities. Here, we integrated the two largest public independent CRISPR-Cas9 screens performed to date (at the Broad and Sanger institutes) by assessing, comparing, and selecting methods for correcting biases due to heterogeneous single-guide RNA efficiency, gene-independent responses to CRISPR-Cas9 targeting originated from copy number alterations, and experimental batch effects. Our integrated datasets recapitulate findings from the individual datasets, provide greater statistical power to cancer- and subtype-specific analyses, unveil additional biomarkers of gene dependency, and improve the detection of common essential genes. We provide the largest integrated resources of CRISPR-Cas9 screens to date and the basis for harmonizing existing and future functional genetics datasets.
Vulnerabilities of protected lands in the face of climate and human footprint changes
Authors: Shrestha Nawal , Xu Xiaoting , Meng Jiahui , Wang Zhiheng 
Published: March 2021

AbstractProtected areas (PAs) play a pivotal role in maintaining viable populations of species and minimizing their habitat loss. Globally, there are currently over 200,000 PAs that cover approximately 15% of land area. The post-2020 global biodiversity framework aims to expand this coverage to 30% by 2030. However, focusing only on the percentage coverage of PAs without evaluating their effectiveness may fail to achieve conservation goals. Here, we use a multidimensional approach incorporating species, climate and anthropogenic vulnerabilities to assess the threat levels in over 2500 PAs in China. We identify nearly 10% of PAs as the most threatened PAs in China and about one-fifth PAs as hotspots of climate and anthropogenic vulnerabilities. We also find high climate instability in species vulnerability hotspots, suggesting an elevated likelihood of species’ extirpation therein. Our framework could be useful in assessing resiliency of global protected lands and also in selecting near optimal areas for their future expansion.
ADAR1 RNA editing enzyme regulates R-loop formation and genome stability at telomeres in cancer cells
Authors: Shiromoto Yusuke , Sakurai Masayuki , Minakuchi Moeko , Ariyoshi Kentaro , Nishikura Kazuko 
Published: March 2021

AbstractADAR1 is involved in adenosine-to-inosine RNA editing. The cytoplasmic ADAR1p150 edits 3’UTR double-stranded RNAs and thereby suppresses induction of interferons. Loss of this ADAR1p150 function underlies the embryonic lethality of Adar1 null mice, pathogenesis of the severe autoimmune disease Aicardi-Goutières syndrome, and the resistance developed in cancers to immune checkpoint blockade. In contrast, the biological functions of the nuclear-localized ADAR1p110 remain largely unknown. Here, we report that ADAR1p110 regulates R-loop formation and genome stability at telomeres in cancer cells carrying non-canonical variants of telomeric repeats. ADAR1p110 edits the A-C mismatches within RNA:DNA hybrids formed between canonical and non-canonical variant repeats. Editing of A-C mismatches to I:C matched pairs facilitates resolution of telomeric R-loops by RNase H2. This ADAR1p110-dependent control of telomeric R-loops is required for continued proliferation of telomerase-reactivated cancer cells, revealing the pro-oncogenic nature of ADAR1p110 and identifying ADAR1 as a promising therapeutic target of telomerase positive cancers.
Direct catalytic asymmetric synthesis of α-chiral bicyclo[1.1.1]pentanes
Authors: Wong Marie L. J. , Sterling Alistair J. , Mousseau James J. , Duarte Fernanda , Anderson Edward A. 
Published: March 2021

AbstractBicyclo[1.1.1]pentanes (BCPs) are important motifs in contemporary drug design as linear spacer units that improve pharmacokinetic profiles. The synthesis of BCPs featuring adjacent stereocenters is highly challenging, but desirable due to the fundamental importance of 3D chemical space in medicinal chemistry. Current methods to access these high-value chiral molecules typically involve transformations of pre-formed BCPs, and can display limitations in substrate scope. Here we describe an approach to synthesize α-chiral BCPs involving the direct, asymmetric addition of simple aldehydes to [1.1.1]propellane, the predominant BCP precursor. This is achieved by combining a photocatalyst and an organocatalyst to generate a chiral α-iminyl radical cation intermediate, which installs a stereocenter simultaneously with ring-opening of [1.1.1]propellane. The reaction proceeds under mild conditions, displays broad scope, and provides an array of α-chiral BCPs in high yield and enantioselectivity. We also present a theoretical model for stereoinduction in this mode of photoredox organocatalysis.
Fungi and insects compensate for lost vertebrate seed predation in an experimentally defaunated tropical forest
Authors: Williams Peter Jeffrey , Ong Robert C. , Brodie Jedediah F. , Luskin Matthew Scott 
Published: March 2021

AbstractOverhunting reduces important plant-animal interactions such as vertebrate seed dispersal and seed predation, thereby altering plant regeneration and even above-ground biomass. It remains unclear, however, if non-hunted species can compensate for lost vertebrates in defaunated ecosystems. We use a nested exclusion experiment to isolate the effects of different seed enemies in a Bornean rainforest. In four of five tree species, vertebrates kill many seeds (13–66%). Nonetheless, when large mammals are excluded, seed mortality from insects and fungi fully compensates for the lost vertebrate predation, such that defaunation has no effect on seedling establishment. The switch from seed predation by generalist vertebrates to specialist insects and fungi in defaunated systems may alter Janzen–Connell effects and density-dependence in plants. Previous work using simulation models to explore how lost seed dispersal will affect tree species composition and carbon storage may require reevaluation in the context of functional redundancy within complex species interactions networks.
Computational analysis of fused co-expression networks for the identification of candidate cancer gene biomarkers
Authors: Pidò Sara , Ceddia Gaia , Masseroli Marco 
Published: March 2021

AbstractThe complexity of cancer has always been a huge issue in understanding the source of this disease. However, by appreciating its complexity, we can shed some light on crucial gene associations across and in specific cancer types. In this study, we develop a general framework to infer relevant gene biomarkers and their gene-to-gene associations using multiple gene co-expression networks for each cancer type. Specifically, we infer computationally and biologically interesting communities of genes from kidney renal clear cell carcinoma, liver hepatocellular carcinoma, and prostate adenocarcinoma data sets of The Cancer Genome Atlas (TCGA) database. The gene communities are extracted through a data-driven pipeline and then evaluated through both functional analyses and literature findings. Furthermore, we provide a computational validation of their relevance for each cancer type by comparing the performance of normal/cancer classification for our identified gene sets and other gene signatures, including the typically-used differentially expressed genes. The hallmark of this study is its approach based on gene co-expression networks from different similarity measures: using a combination of multiple gene networks and then fusing normal and cancer networks for each cancer type, we can have better insights on the overall structure of the cancer-type-specific network.
Defining the root cause of reduced H1N1 live attenuated influenza vaccine effectiveness: low viral fitness leads to inter-strain competition
Authors: Dibben Oliver , Crowe Jonathan , Cooper Shaun , Hill Laura , Schewe Katarzyna E. , Bright Helen 
Published: March 2021

AbstractIn the 2013–14 and 2015–16 influenza seasons, reduced vaccine effectiveness (VE) was observed for the H1N1 component of the FluMist quadrivalent live attenuated influenza vaccine (QLAIV) in the USA, leading to loss of Advisory Committee on Immunization Practices recommendation. Here we demonstrate in ferrets that 2015–16A/H1N1pdm09 vaccine strain A/Bolivia/559/2013 (A/BOL13) is outcompeted in trivalent (TLAIV) and QLAIV formulations, leading to reduced protection from wild-type challenge. While monovalent (MLAIV) A/BOL13 provided significant protection from wild-type virus shedding and fever at doses as low as 3.0 log10 fluorescent focus units (FFU), it failed to provide a similar level of protection in TLAIV or QLAIV formulation, even at a 6.0 log10 FFU dose. Conversely, clinically effective H1N1 strain A/New Caledonia/20/1999 provided significant protection in MLAIV, TLAIV, and QLAIV formulations. In conclusion, reduced A/BOL13 replicative fitness rendered it susceptible to inter-strain competition in QLAIV, contributing to its reduced VE in the 2015–16 season.
Easing COVID-19 lockdown measures while protecting the older restricts the deaths to the level of the full lockdown
Authors: Fokas A. S. , Cuevas-Maraver J. , Kevrekidis P. G. 
Published: March 2021

AbstractGuided by a rigorous mathematical result, we have earlier introduced a numerical algorithm, which using as input the cumulative number of deaths caused by COVID-19, can estimate the effect of easing of the lockdown conditions. Applying this algorithm to data from Greece, we extend it to the case of two subpopulations, namely, those consisting of individuals below and above 40 years of age. After supplementing the Greek data for deaths with the data for the number of individuals reported to be infected by SARS-CoV-2, we estimated the effect on deaths and infections in the case that the easing of the lockdown measures is different for these two subpopulations. We found that if the lockdown measures are partially eased only for the young subpopulation, then the effect on deaths and infections is small. However, if the easing is substantial for the older population, this effect may be catastrophic.
Trumpet sounds emitted by male sperm whales in the Mediterranean Sea
Authors: Pace D. S. , Lanfredi C. , Airoldi S. , Giacomini G. , Silvestri M. , Pavan G. , Ardizzone D. 
Published: March 2021

AbstractSperm whale trumpets are sounds only occasionally documented, with a well recognisable and stereotyped acoustic arrangement. This study investigated the acoustic features of the trumpets and the context in which these sounds were recorded, using acoustic data collected over 22 years, in the Pelagos Sanctuary area (North-Western Mediterranean Sea). Analysed trumpets (n = 230), recorded at the beginning of a dive after the whale fluke-up, comprised a series of acoustic units organized in short sequences. Acoustic parameters were derived for the entire trumpet and for each distinguishable unit in a trumpet. Overall, trumpet durations and their initial frequencies were higher in recordings collected when multiple whales were visually or acoustically detected in the observation area. The identity of 68 whales was assessed through photo-identification, with 29 individuals producing trumpets within and between years. The variability of the acoustic parameters appeared to be higher within the same individuals rather than between different individuals, suggesting an individual plasticity in composing and arranging units in a trumpet. Different click patterns were observed before and after the trumpets, with more complex sequences when (1) other whales were visually/acoustically detected, and (2) individuals were in suitable foraging sites (i.e., canyon areas). Trumpets were commonly followed or preceded by click patterns suited for communication, such as codas and/or slow clicks. Significant relations between the trumpet emission and the male-only long-range communication click pattern (i.e. slow clicks) emerged, supporting the hypothesis that a trumpet is a sound emitted by maturing/mature males in feeding grounds. This study provides the first evidence that trumpets were conserved in the sperm whale acoustic repertoire at the decadal timescale, persisting across years and individuals in the same area. This persistence may be functionally specific to foraging activities performed by males in a well-established feeding area.
Determine neighboring region spatial effect on dengue cases using ensemble ARIMA models
Authors: Thiruchelvam Loshini , Dass Sarat Chandra , Asirvadam Vijanth Sagayan , Daud Hanita , Gill Balvinder Singh 
Published: March 2021

AbstractThe state of Selangor, in Malaysia consist of urban and peri-urban centres with good transportation system, and suitable temperature levels with high precipitations and humidity which make the state ideal for high number of dengue cases, annually. This study investigates if districts within the Selangor state do influence each other in determining pattern of dengue cases. Study compares two different models; the Autoregressive Integrated Moving Average (ARIMA) and Ensemble ARIMA models, using the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) measurement to gauge their performance tools. ARIMA model is developed using the epidemiological data of dengue cases, whereas ensemble ARIMA incorporates the neighbouring regions’ dengue models as the exogenous variable (X), into traditional ARIMA model. Ensemble ARIMA models have better model fit compared to the basic ARIMA models by incorporating neighbuoring effects of seven districts which made of state of Selangor. The AIC and BIC values of ensemble ARIMA models to be smaller compared to traditional ARIMA counterpart models. Thus, study concludes that pattern of dengue cases for a district is subject to spatial effects of its neighbouring districts and number of dengue cases in the surrounding areas.
Scaling laws for ion irradiation effects in iron-based superconductors
Authors: Torsello Daniele , Gozzelino Laura , Gerbaldo Roberto , Tamegai Tsuyoshi , Ghigo Gianluca 
Published: March 2021

AbstractWe report on ion irradiation experiments performed on compounds belonging to the $$\hbox {BaFe}_2\hbox {As}_2$$

BaFe
2

As
2

family, each one involving the partial substitution of an atom of the parent compound (K for Ba, Co for Fe, and P for As), with an optimal composition to maximize the superconducting critical temperature $$T_c$$

T
c

. Employed ion beams were 3.5-MeV protons, 250-MeV Au ions, and 1.2-GeV Pb ions, but additional data from literature are also considered, thus covering a wide range of ions and energies. Microwave characterization based on the use of a coplanar waveguide resonator allowed us to investigate the irradiation-induced $$T_c$$

T
c

degradation, as well as the increase of normal state resistivity and London penetration depth. The damage was quantified in terms of displacements per atom (dpa). From this broad and comprehensive set of experimental data, clear scaling laws emerge, valid in the range of moderate irradiation-induced disorder (dpa up to 5 $$\times$$
×
10 $$^{-3}$$

-
3

were investigated). In these conditions, linear trends with dpa were found for all the modification rates, while a power law dependence on the ion energy was found for heavy-ion irradiation. All these scaling laws are reported and discussed throughout the paper.
Wild whale faecal samples as a proxy of anthropogenic impact
Authors: Marangi Marianna , Airoldi Sabina , Beneduce Luciano , Zaccone Claudio 
Published: March 2021

AbstractThe occurrence of protozoan parasite, bacterial communities, organic pollutants and heavy metals was investigated in free-ranging species of fin (Balaenoptera physalus, n. 2) and sperm (Physeter macrocephalus, n. 2) whales from the Pelagos Sanctuary, Corsican-Ligurian Provencal Basin (Northern-Western Mediterranean Sea). Out of four faecal samples investigated, two from fin whales and one from sperm whale were found positive to Blastocystis sp. A higher number of sequences related to Synergistetes and Spirochaetae were found in sperm whales if compared with fin whales. Moreover, As, Co and Hg were found exclusively in sperm whale faecal samples, while Pb was found only in fin whale faecal samples. The concentration of both PAH and PCB was always below the limit of detection. This is the first report in which the presence of these opportunistic pathogens, bacteria and chemical pollutants have been investigated in faecal samples of free-ranging whale species and the first record of Blastocystis in fin and sperm whales. Thus, this study may provide baseline data on new anthropozoonotic parasite, bacterial records and heavy metals in free-ranging fin and sperm whales, probably as a result of an increasing anthropogenic activity. This survey calls for more integrated research to perform regular monitoring programs supported by national and/or international authorities responsible for preservation of these still vulnerable and threatened whale species in the Mediterranean Sea.
Bilayer ventilated labyrinthine metasurfaces with high sound absorption and tunable bandwidth
Authors: Du Jiayuan , Luo Yuezhou , Zhao Xinyu , Sun Xiaodong , Song Yanan , Hu Xinhua 
Published: March 2021

AbstractThe recent advent of acoustic metamaterials offers unprecedented opportunities for sound controlling in various occasions, whereas it remains a challenge to attain broadband high sound absorption and free air flow simultaneously. Here, we demonstrated, both theoretically and experimentally, that this problem can be overcome by using a bilayer ventilated labyrinthine metasurface. By altering the spacing between two constituent single-layer metasurfaces and adopting asymmetric losses in them, near-perfect (98.6%) absorption is achieved at resonant frequency for sound waves incident from the front. The relative bandwidth of absorption peak can be tuned in a wide range (from 12% to 80%) by adjusting the open area ratio of the structure. For sound waves from the back, the bilayer metasurface still serves as a sound barrier with low transmission. Our results present a strategy to realize high sound absorption and free air flow simultaneously, and could find applications in building acoustics and noise remediation.
On ab initio-based, free and closed-form expressions for gravitational waves
Authors: Tiglio Manuel , Villanueva Aarón 
Published: March 2021

AbstractWe introduce a new approach for finding high accuracy, free and closed-form expressions for the gravitational waves emitted by binary black hole collisions from ab initio models. More precisely, our expressions are built from numerical surrogate models based on supercomputer simulations of the Einstein equations, which have been shown to be essentially indistinguishable from each other. Distinct aspects of our approach are that: (i) representations of the gravitational waves can be explicitly written in a few lines, (ii) these representations are free-form yet still fast to search for and validate and (iii) there are no underlying physical approximations in the underlying model. The key strategy is combining techniques from Artificial Intelligence and Reduced Order Modeling for parameterized systems. Namely, symbolic regression through genetic programming combined with sparse representations in parameter space and the time domain using Reduced Basis and the Empirical Interpolation Method enabling fast free-form symbolic searches and large-scale a posteriori validations. As a proof of concept we present our results for the collision of two black holes, initially without spin, and with an initial separation corresponding to 25–31 gravitational wave cycles before merger. The minimum overlap, compared to ground truth solutions, is 99%. That is, 1% difference between our closed-form expressions and supercomputer simulations; this is considered for gravitational (GW) science more than the minimum required due to experimental numerical errors which otherwise dominate. This paper aims to contribute to the field of GWs in particular and Artificial Intelligence in general.