bluuebunny/crossref_metadata_2025 huggingface dataset:
Arsenic alters nitric oxide signaling similar to autism spectrum disorder and Alzheimer’s disease-associated mutations
Authors: Tripathi Manish Kumar , Kartawy Maryam , Ginzburg Shelly , Amal Haitham
Published: March 2022

Epidemiological studies have proven that exposure to Arsenic (AS) leads to the development of many neurological disorders. However, few studies have investigated its molecular mechanisms in the brain. Our previous work has revealed nitric oxide (NO)-mediated apoptosis and SNO reprogramming in the cortex following arsenic treatment, yet the role of NO and S-nitrosylation (SNO) in AS-mediated neurotoxicity has not been investigated. Therefore, we have conducted a multidisciplinary in-vivo study in mice with two different doses of Sodium Arsenite (SA) (0.1 ppm and 1 ppm) in drinking water. We used the novel SNOTRAP-based mass spectrometry method followed by the bioinformatics analysis, Western blot validation, and five different behavioral tests. Bioinformatics analysis of SA-treated mice showed significant SNO-enrichment of processes involved in mitochondrial respiratory function, endogenous antioxidant systems, transcriptional regulation, cytoskeleton maintenance, and regulation of apoptosis. Western blotting showed increased levels of cleaved PARP-1 and cleaved caspase-3 in SA-treated mice consistent with SA-induced apoptosis. Behavioral studies showed significant cognitive dysfunctions similar to those of Autism spectrum disorder (ASD) and Alzheimer’s disease (AD). A comparative analysis of the SNO-proteome of SA-treated mice with two transgenic mouse strains, models of ASD and AD, showed molecular convergence of SA environmental neurotoxicity and the genetic mutations causing ASD and AD. This is the first study to show the effects of AS on SNO-signaling in the striatum and hippocampus and its effects on behavioral characteristics. Finally, further investigation of the NO-dependent mechanisms of AS-mediated neurotoxicity may reveal new drug targets for its prevention.
Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder
Authors: Xue Xiangning , Zong Wei , Glausier Jill R. , Kim Sam-Moon , Shelton Micah A. , Phan BaDoi N. , Srinivasan Chaitanya , Pfenning Andreas R. , Tseng George C. , Lewis David A. , Seney Marianne L. , Logan Ryan W.
Published: March 2022

Severe and persistent disruptions to sleep and circadian rhythms are common in people with opioid use disorder (OUD). Preclinical evidence suggests altered molecular rhythms in the brain modulate opioid reward and relapse. However, whether molecular rhythms are disrupted in the brains of people with OUD remained an open question, critical to understanding the role of circadian rhythms in opioid addiction. Using subjects’ times of death as a marker of time of day, we investigated transcriptional rhythms in the brains of subjects with OUD compared to unaffected comparison subjects. We discovered rhythmic transcripts in both the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc), key brain areas involved in OUD, that were largely distinct between OUD and unaffected subjects. Fewer rhythmic transcripts were identified in DLPFC of subjects with OUD compared to unaffected subjects, whereas in the NAc, nearly double the number of rhythmic transcripts was identified in subjects with OUD. In NAc of subjects with OUD, rhythmic transcripts peaked either in the evening or near sunrise, and were associated with an opioid, dopamine, and GABAergic neurotransmission. Associations with altered neurotransmission in NAc were further supported by co-expression network analysis which identified OUD-specific modules enriched for transcripts involved in dopamine, GABA, and glutamatergic synaptic functions. Additionally, rhythmic transcripts in DLPFC and NAc of subjects with OUD were enriched for genomic loci associated with sleep-related GWAS traits, including sleep duration and insomnia. Collectively, our findings connect transcriptional rhythm changes in opioidergic, dopaminergic, GABAergic signaling in the human brain to sleep-related traits in opioid addiction.
APOE-ε4 modulates the association among plasma Aβ42/Aβ40, vascular diseases, neurodegeneration and cognitive decline in non-demented elderly adults
Authors: Shi Dai , Xie Siwei , Li Anqi , Wang Qingyong , Guo Hongbo , Han Ying , Xu Huaxi , Gan Wen-Biao , Zhang Lei , Guo Tengfei ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2022

Including apolipoprotein E-ε4 (APOE-ε4) status and older age into consideration may increase the accuracy of plasma Aβ42/Aβ40 detecting Aβ+ individuals, but the rationale behind this remains to be fully understood. Besides, both Aβ pathology and vascular diseases are related to neurodegeneration and cognitive decline, but it is still not fully understood how APOE-ε4 modulates these relationships. In this study, we examined 241 non-demented Alzheimer’s Disease Neuroimaging Initiative participants to investigate the associations among age, white matter hyperintensities (WMH), hypertension, hyperlipidemia, body mass index (BMI), plasma Aβ42/Aβ40 measured by liquid chromatography tandem mass spectrometry, and 18F-florbetapir Aβ PET as well as their prediction of longitudinal adjusted hippocampal volume (aHCV) and cognition in APOE-ε4 carriers and non-carriers. We found older age predicted faster WMH increase (p = 0.024) and cortical Aβ accumulation (p = 0.043) in APOE-ε4 non-carriers only, whereas lower plasma Aβ42/Aβ40 predicted faster cortical Aβ accumulation (p < 0.018) regardless of APOE-ε4 status. While larger WMH and underweight predicted (p < 0.05) faster decreases in aHCV and cognition in APOE-ε4 non-carriers, lower plasma Aβ42/Aβ40 predicted (p < 0.031) faster decreases in aHCV and cognition in APOE-ε4 carriers. Higher Aβ PET also predicted faster rates of aHCV (p = 0.010) in APOE-ε4 carriers only, but was related to faster rates of cognitive decline (p < 0.022) regardless of APOE-ε4 status. These findings may provide novel insights into understanding different mechanisms underlie neurodegeneration and cognitive decline in non-demented elderly adults with and without APOE-ε4 allele, which may help the design of anti-Alzheimer’s clinical trials.
Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice
Authors: Zhang Yuan , Chen Yuling , Zhang Zhao , Tao Xiang , Xu Sha , Zhang Xinyan , Zurashvili Tinatin , Lu Zhouping , Bayascas José Ramon , Jin Liping , Zhao Jianyuan , Zhou Xiangyu
Published: March 2022

Acyl-CoA oxidase 2 (Acox2) is an enzyme involved in peroxisomal bile acid synthesis and branched-chain fatty acid degradation. Acox2 knockout (−/−) mice spontaneously developed liver cancer with marked lymphocytic infiltrate. Tandem-affinity purification coupled with mass spectrometry analysis revealed that Acox2 interacted with methylcrotonoyl-CoA carboxylase followed by co-immunoprecipitation confirmation. Here we reported that non-histone lysine crotonylation (Kcr) levels were downregulated in Acox2−/− mice livers. Interestingly, Kcr signals were concentrated in the nucleus of tumor cells but mostly located in the cytoplasm of adjacent normal liver cells of Acox2−/− mice. Quantitative analysis of the global crotonylome further revealed that 54% (27/50) of downregulated non-histone Kcr sites were located in mitochondrial (11/50) and peroxisomal (17/50) enzymes including Ehhadh, Scp2, Hsd17b4, Crot, Etfa, Cpt1a, Eci1/2, Hadha, Etfdh, and Idh2. Subsequent site-directed mutagenesis and transcriptome analysis revealed that Ehhadh K572cr might have site-specific regulatory roles by downregulating TOP3B expression that lead to increased DNA damage in vitro. Our findings suggested Acox2 is a regulator of Kcr that might play critical role on hepatic metabolic homeostasis.
The world-wide waste web
Authors: Martínez Johann H. , Romero Sergi , Ramasco José J. , Estrada Ernesto
Published: March 2022

Countries globally trade with tons of waste materials every year, some of which are highly hazardous. This trade admits a network representation of the world-wide waste web, with countries as vertices and flows as directed weighted edges. Here we investigate the main properties of this network by tracking 108 categories of wastes interchanged in the period 2001–2019. Although, most of the hazardous waste was traded between developed nations, a disproportionate asymmetry existed in the flow from developed to developing countries. Using a dynamical model, we simulate how waste stress propagates through the network and affects the countries. We identify 28 countries with low Environmental Performance Index that are at high risk of waste congestion. Therefore, they are at threat of improper handling and disposal of hazardous waste. We find evidence of pollution by heavy metals, by volatile organic compounds and/or by persistent organic pollutants, which are used as chemical fingerprints, due to the improper handling of waste in several of these countries.
Predictive models for the selection of thermally tolerant corals based on offspring survival
Authors: Quigley K. M. , van Oppen M. J. H.
Published: March 2022

Finding coral reefs resilient to climate warming is challenging given the large spatial scale of reef ecosystems. Methods are needed to predict the location of corals with heritable tolerance to high temperatures. Here, we combine Great Barrier Reef-scale remote sensing with breeding experiments that estimate larval and juvenile coral survival under exposure to high temperatures. Using reproductive corals collected from the northern and central Great Barrier Reef, we develop forecasting models to locate reefs harbouring corals capable of producing offspring with increased heat tolerance of an additional 3.4° heating weeks (~3 °C). Our findings predict hundreds of reefs (~7.5%) may be home to corals that have high and heritable heat-tolerance in habitats with high daily and annual temperature ranges and historically variable heat stress. The locations identified represent targets for protection and consideration as a source of corals for use in restoration of degraded reefs given their potential to resist climate change impacts and repopulate reefs with tolerant offspring.
Trade-off between reducing mutational accumulation and increasing commitment to differentiation determines tissue organization
Authors: Demeter Márton , Derényi Imre , Szöllősi Gergely J.
Published: March 2022

Species-specific differences control cancer risk across orders of magnitude variation in body size and lifespan, e.g., by varying the copy numbers of tumor suppressor genes. It is unclear, however, how different tissues within an organism can control somatic evolution despite being subject to markedly different constraints, but sharing the same genome. Hierarchical differentiation, characteristic of self-renewing tissues, can restrain somatic evolution both by limiting divisional load, thereby reducing mutation accumulation, and by increasing cells’ commitment to differentiation, which can “wash out” mutants. Here, we explore the organization of hierarchical tissues that have evolved to limit their lifetime incidence of cancer. Estimating the likelihood of cancer in the presence of mutations that enhance self-proliferation, we demonstrate that a trade-off exists between mutation accumulation and the strength of washing out. Our results explain differences in the organization of widely different hierarchical tissues, such as colon and blood.
Large-scale cryovolcanic resurfacing on Pluto
Authors: Singer Kelsi N. , White Oliver L. , Schmitt Bernard , Rader Erika L. , Protopapa Silvia , Grundy William M. , Cruikshank Dale P. , Bertrand Tanguy , Schenk Paul M. , McKinnon William B. , Stern S. Alan , Dhingra Rajani D. , Runyon Kirby D. , Beyer Ross A. , Bray Veronica J. , Ore Cristina Dalle , Spencer John R. , Moore Jeffrey M. , Nimmo Francis , Keane James T. , Young Leslie A. , Olkin Catherine B. , Lauer Tod R. , Weaver Harold A. , Ennico-Smith Kimberly
Published: March 2022

The New Horizons spacecraft returned images and compositional data showing that terrains on Pluto span a variety of ages, ranging from relatively ancient, heavily cratered areas to very young surfaces with few-to-no impact craters. One of the regions with very few impact craters is dominated by enormous rises with hummocky flanks. Similar features do not exist anywhere else in the imaged solar system. Here we analyze the geomorphology and composition of the features and conclude this region was resurfaced by cryovolcanic processes, of a type and scale so far unique to Pluto. Creation of this terrain requires multiple eruption sites and a large volume of material (>104 km3) to form what we propose are multiple, several-km-high domes, some of which merge to form more complex planforms. The existence of these massive features suggests Pluto’s interior structure and evolution allows for either enhanced retention of heat or more heat overall than was anticipated before New Horizons, which permitted mobilization of water-ice-rich materials late in Pluto’s history.
Electric control of a canted-antiferromagnetic Chern insulator
Authors: Cai Jiaqi , Ovchinnikov Dmitry , Fei Zaiyao , He Minhao , Song Tiancheng , Lin Zhong , Wang Chong , Cobden David , Chu Jiun-Haw , Cui Yong-Tao , Chang Cui-Zu , Xiao Di , Yan Jiaqiang , Xu Xiaodong
Published: March 2022

The interplay between band topology and magnetism can give rise to exotic states of matter. For example, magnetically doped topological insulators can realize a Chern insulator that exhibits quantized Hall resistance at zero magnetic field. While prior works have focused on ferromagnetic systems, little is known about band topology and its manipulation in antiferromagnets. Here, we report that MnBi2Te4 is a rare platform for realizing a canted-antiferromagnetic (cAFM) Chern insulator with electrical control. We show that the Chern insulator state with Chern number C = 1 appears as the AFM to canted-AFM phase transition happens. The Chern insulator state is further confirmed by observing the unusual transition of the C = 1 state in the cAFM phase to the C = 2 orbital quantum Hall states in the magnetic field induced ferromagnetic phase. Near the cAFM-AFM phase boundary, we show that the dissipationless chiral edge transport can be toggled on and off by applying an electric field alone. We attribute this switching effect to the electrical field tuning of the exchange gap alignment between the top and bottom surfaces. Our work paves the way for future studies on topological cAFM spintronics and facilitates the development of proof-of-concept Chern insulator devices.
Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against poxvirus infection
Authors: Yang Ning , Luna Joseph M. , Dai Peihong , Wang Yi , Rice Charles M. , Deng Liang
Published: March 2022

The pulmonary immune system consists of a network of tissue-resident cells as well as immune cells that are recruited to the lungs during infection and/or inflammation. How these immune components function during an acute poxvirus infection is not well understood. Intranasal infection of mice with vaccinia virus causes lethal pneumonia and systemic dissemination. Here we report that vaccinia C7 is a crucial virulence factor that blocks activation of the transcription factor IRF3. We provide evidence that type II alveolar epithelial cells (AECIIs) respond to pulmonary infection of vaccinia virus by inducing IFN-β and IFN-stimulated genes via the activation of the MDA5 and STING-mediated nucleic acid-sensing pathways and the type I IFN positive feedback loop. This leads to the recruitment and activation of CCR2+ inflammatory monocytes in the infected lungs and subsequent differentiation into Lyve1− interstitial macrophages (Lyve1− IMs), which efficiently engulf viral particles and block viral replication. Our results provide insights into how innate immune sensing of viral infection by lung AECIIs influences the activation and differentiation of CCR2+ inflammatory monocytes to defend against pulmonary poxvirus infection.
A hierarchical transcriptional network activates specific CDK inhibitors that regulate G2 to control cell size and number in Arabidopsis
Authors: Nomoto Yuji , Takatsuka Hirotomo , Yamada Kesuke , Suzuki Toshiya , Suzuki Takamasa , Huang Ying , Latrasse David , An Jing , Gombos Magdolna , Breuer Christian , Ishida Takashi , Maeo Kenichiro , Imamura Miyu , Yamashino Takafumi , Sugimoto Keiko , Magyar Zoltán , Bögre László , Raynaud Cécile , Benhamed Moussa , Ito Masaki
Published: March 2022

How cell size and number are determined during organ development remains a fundamental question in cell biology. Here, we identified a GRAS family transcription factor, called SCARECROW-LIKE28 (SCL28), with a critical role in determining cell size in Arabidopsis. SCL28 is part of a transcriptional regulatory network downstream of the central MYB3Rs that regulate G2 to M phase cell cycle transition. We show that SCL28 forms a dimer with the AP2-type transcription factor, AtSMOS1, which defines the specificity for promoter binding and directly activates transcription of a specific set of SIAMESE-RELATED (SMR) family genes, encoding plant-specific inhibitors of cyclin-dependent kinases and thus inhibiting cell cycle progression at G2 and promoting the onset of endoreplication. Through this dose-dependent regulation of SMR transcription, SCL28 quantitatively sets the balance between cell size and number without dramatically changing final organ size. We propose that this hierarchical transcriptional network constitutes a cell cycle regulatory mechanism that allows to adjust cell size and number to attain robust organ growth.
An adaptive synaptic array using Fowler–Nordheim dynamic analog memory
Authors: Mehta Darshit , Rahman Mustafizur , Aono Kenji , Chakrabartty Shantanu
Published: March 2022

In this paper we present an adaptive synaptic array that can be used to improve the energy-efficiency of training machine learning (ML) systems. The synaptic array comprises of an ensemble of analog memory elements, each of which is a micro-scale dynamical system in its own right, storing information in its temporal state trajectory. The state trajectories are then modulated by a system level learning algorithm such that the ensemble trajectory is guided towards the optimal solution. We show that the extrinsic energy required for state trajectory modulation can be matched to the dynamics of neural network learning which leads to a significant reduction in energy-dissipated for memory updates during ML training. Thus, the proposed synapse array could have significant implications in addressing the energy-efficiency imbalance between the training and the inference phases observed in artificial intelligence (AI) systems.
Exploring a blue-light-sensing transcription factor to double the peak productivity of oil in Nannochloropsis oceanica
Authors: Zhang Peng , Xin Yi , He Yuehui , Tang Xianfeng , Shen Chen , Wang Qintao , Lv Nana , Li Yun , Hu Qiang , Xu Jian
Published: March 2022

Oleaginous microalgae can produce triacylglycerol (TAG) under stress, yet the underlying mechanism remains largely unknown. Here, we show that, in Nannochloropsis oceanica, a bZIP-family regulator NobZIP77 represses the transcription of a type-2 diacylgycerol acyltransferase encoding gene NoDGAT2B under nitrogen-repletion (N+), while nitrogen-depletion (N−) relieves such inhibition and activates NoDGAT2B expression and synthesis of TAG preferably from C16:1. Intriguingly, NobZIP77 is a sensor of blue light (BL), which reduces binding of NobZIP77 to the NoDGAT2B-promoter, unleashes NoDGAT2B and elevates TAG under N−. Under N+ and white light, NobZIP77 knockout fully preserves cell growth rate and nearly triples TAG productivity. Moreover, exposing the NobZIP77-knockout line to BL under N− can double the peak productivity of TAG. These results underscore the potential of coupling light quality to oil synthesis in feedstock or bioprocess development.
Highly efficient prime editing by introducing same-sense mutations in pegRNA or stabilizing its structure
Authors: Li Xiaosa , Zhou Lina , Gao Bao-Qing , Li Guangye , Wang Xiao , Wang Ying , Wei Jia , Han Wenyan , Wang Zixian , Li Jifang , Gao Runze , Zhu Junjie , Xu Wenchao , Wu Jing , Yang Bei , Sun Xiaodong , Yang Li , Chen Jia
Published: March 2022

Prime editor (PE), which is developed by combining Cas9 nickase and an engineered reverse transcriptase, can mediate all twelve types of base substitutions and small insertions or deletions in living cells but its efficiency remains low. Here, we develop spegRNA by introducing same-sense mutations at proper positions in the reverse-transcription template of pegRNA to increase PE’s base-editing efficiency up-to 4,976-fold (on-average 353-fold). We also develop apegRNA by altering the pegRNA secondary structure to increase PE’s indel-editing efficiency up-to 10.6-fold (on-average 2.77-fold). The spegRNA and apegRNA can be combined to further enhance editing efficiency. When spegRNA and apegRNA are used in PE3 and PE5 systems, the efficiencies of sPE3, aPE3, sPE5 and aPE5 systems are all enhanced significantly. The strategies developed in this study realize highly efficient prime editing at certain previously uneditable sites.
Crystal structure and cellular functions of uPAR dimer
Authors: Yu Shujuan , Sui Yaqun , Wang Jiawei , Li Yongdong , Li Hanlin , Cao Yingping , Chen Liqing , Jiang Longguang , Yuan Cai , Huang Mingdong
Published: March 2022

Receptor dimerization of urokinase-type plasminogen activator receptor (uPAR) was previously identified at protein level and on cell surface. Recently, a dimeric form of mouse uPAR isoform 2 was proposed to induce kidney disease. Here, we report the crystal structure of human uPAR dimer at 2.96 Å. The structure reveals enormous conformational changes of the dimer compared to the monomeric structure: D1 of uPAR opens up into a large expanded ring that captures a β-hairpin loop of a neighboring uPAR to form an expanded β-sheet, leading to an elongated, highly intertwined dimeric uPAR. Based on the structure, we identify E49P as a mutation promoting dimer formation. The mutation increases receptor binding to the amino terminal fragment of its primary ligand uPA, induces the receptor to distribute to the basal membrane, promotes cell proliferation, and alters cell morphology via β1 integrin signaling. These results reveal the structural basis for uPAR dimerization, its effect on cellular functions, and provide a basis to further study this multifunctional receptor.
Estimation of the bidirectional relationship between schizophrenia and inflammatory bowel disease using the mendelian randomization approach
Authors: Qian Li , He Xiaoyan , Gao Fengjie , Fan Yajuan , Zhao Binbin , Ma Qingyan , Yan Bin , Wang Wei , Ma Xiancang , Yang Jian
Published: March 2022

It has been reported that schizophrenia (SCZ) and inflammatory bowel disease (IBD) are related. However, whether there is a bidirectional interaction between them remains unclear. The aim of this study was to conduct a bidirectional Mendelian randomization (MR) analysis to elucidate the causal relationship between SCZ and IBD and its subtypes, including Crohn’s disease (CD) and ulcerative colitis (UC). Single-nucleotide polymorphisms (SNPs) extracted from the summary data of genome-wide association studies were used as genetic instruments. MR was performed using the inverse-variance-weighted method. The MR-Egger and weighted median methods were used for sensitivity analyses. Analysis using 70 SNPs as genetic instruments showed that SCZ was associated with an increased risk of IBD (OR = 1.14, 95% CI: 1.09–1.20, P = 9.21 × 10−8), CD (OR = 1.16, 95% CI: 1.07–1.25, P = 1.42 × 10−4), and UC (OR = 1.14, 95% CI: 1.07–1.21, P = 2.72 × 10−5). The results of the sensitivity analyses were robust and no evidence of pleiotropy was observed. Bidirectional MR analyses showed no causal effects of IBD, CD, or UC on SCZ. This study suggests that SCZ has causal effects on IBD and its subtypes, whereas IBD has no effect on SCZ. Brain-gut axis interactions may help clarify the causal relationship between SCZ and IBD. However, further studies are needed to elucidate the biological mechanisms behind the brain-gut interactions.
Native range estimates for red-listed vascular plants
Authors: Borgelt Jan , Sicacha-Parada Jorge , Skarpaas Olav , Verones Francesca
Published: March 2022

Besides being central for understanding both global biodiversity patterns and associated anthropogenic impacts, species range maps are currently only available for a small subset of global biodiversity. Here, we provide a set of assembled spatial data for terrestrial vascular plants listed at the global IUCN red list. The dataset consists of pre-defined native regions for 47,675 species, density of available native occurrence records for 30,906 species, and standardized, large-scale Maxent predictions for 27,208 species, highlighting environmentally suitable areas within species’ native regions. The data was generated in an automated approach consisting of data scraping and filtering, variable selection, model calibration and model selection. Generated Maxent predictions were validated by comparing a subset to available expert-drawn range maps from IUCN (n = 4,257), as well as by qualitatively inspecting predictions for randomly selected species. We expect this data to serve as a substitute whenever expert-drawn species range maps are not available for conducting large-scale analyses on biodiversity patterns and associated anthropogenic impacts.
Comprehensive spectral libraries for various rabbit eye tissue proteomes
Authors: Qin Guoting , Zhang Pengzhi , Sun Mingxia , Fu Wenjiang , Cai Chengzhi
Published: March 2022

Rabbits have been widely used for studying ocular physiology and pathology due to their relatively large eye size and similar structures with human eyes. Various rabbit ocular disease models, such as dry eye, age-related macular degeneration, and glaucoma, have been established. Despite the growing application of proteomics in vision research using rabbit ocular models, there is no spectral assay library for rabbit eye proteome publicly available. Here, we generated spectral assay libraries for rabbit eye compartments, including conjunctiva, cornea, iris, retina, sclera, vitreous humor, and tears using fractionated samples and ion mobility separation enabling deep proteome coverage. The rabbit eye spectral assay library includes 9,830 protein groups and 113,593 peptides. We present the data as a freely available community resource for proteomic studies in the vision field. Instrument data and spectral libraries are available via ProteomeXchange with identifier PXD031194.
A worldwide epidemiological database for COVID-19 at fine-grained spatial resolution
Authors: Guidotti Emanuele
Published: March 2022

This database provides the daily time-series of COVID-19 cases, deaths, recovered people, tests, vaccinations, and hospitalizations, for more than 230 countries, 760 regions, and 12,000 lower-level administrative divisions. The geographical entities are associated with identifiers to match with hydrometeorological, geospatial, and mobility data. The database includes policy measures at the national and, when available, sub-national levels. The data acquisition pipeline is open-source and fully automated. As most governments revise the data retrospectively, the database always updates the complete time-series to mirror the original source. Vintage data, immutable snapshots of the data taken each day, are provided to ensure research reproducibility. The latest data are updated on an hourly basis, and the vintage data are available since April 14, 2020. All the data are available in CSV files or SQLite format. By unifying the access to the data, this work makes it possible to study the pandemic on a global scale with high resolution, taking into account within-country variations, nonpharmaceutical interventions, and environmental and exogenous variables.
Application of the effective diameters of porous media to the non-Darcy flow analyses
Authors: Shin Chang-Hoon
Published: March 2022

Non-Darcy flows are a vital event leading to the inaccuracy in flow performance evaluation, particularly in the fractured wells in shale gas and tight oil deposits. The internal flow commonly indicates high flow rates at the early period of production, owing to the large geometric size of hydraulic fracture and high porosity in proppant packs. After that, the production flow rate decays steeply until the Darcy flow regime is attained. Therefore, accurate porous flow analyses from the Darcy to Forchheimer and then turbulent flow regimes are essential for optimal facility designs and economic productions in the unconventional deposits. The Comiti capillary model is recognised as the leading non-Darcy flow correlation for simple packed beds comprising mono-size grains. However, in actual hydraulic fractures, various types of proppants are used simultaneously and generally combined with numerous soil grains of different sizes and shapes. In this study, the Comiti model is modified by incorporating the effective diameters of the porous media and then examined for mixed complex multi-size packs. Subsequently, a novel type of non-Darcy flow equation is presented according to the logarithmic turbulent friction factor based on the physical variables determined only in the Darcy flow regime. The new equation presents accurate results for all the types of proppant packs under wide porosity and permeability ranges. The generalised non-Darcy flow correlation, which can be extensively employed from the Darcy to non-Darcy flow analyses, particularly beyond the Forchheimer regime, is presented for the accurate flow evaluation of the fractured reservoirs.
In silico analysis of SARS-CoV-2 proteins as targets for clinically available drugs
Authors: Chan Wallace K. B. , Olson Keith M. , Wotring Jesse W. , Sexton Jonathan Z. , Carlson Heather A. , Traynor John R.
Published: March 2022

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires treatments with rapid clinical translatability. Here we develop a multi-target and multi-ligand virtual screening method to identify FDA-approved drugs with potential activity against SARS-CoV-2 at traditional and understudied viral targets. 1,268 FDA-approved small molecule drugs were docked to 47 putative binding sites across 23 SARS-CoV-2 proteins. We compared drugs between binding sites and filtered out compounds that had no reported activity in an in vitro screen against SARS-CoV-2 infection of human liver (Huh-7) cells. This identified 17 “high-confidence”, and 97 “medium-confidence” drug-site pairs. The “high-confidence” group was subjected to molecular dynamics simulations to yield six compounds with stable binding poses at their optimal target proteins. Three drugs—amprenavir, levomefolic acid, and calcipotriol—were predicted to bind to 3 different sites on the spike protein, domperidone to the Mac1 domain of the non-structural protein (Nsp) 3, avanafil to Nsp15, and nintedanib to the nucleocapsid protein involved in packaging the viral RNA. Our “two-way” virtual docking screen also provides a framework to prioritize drugs for testing in future emergencies requiring rapidly available clinical drugs and/or treating diseases where a moderate number of targets are known.
Genome wide association study of frost tolerance in wheat
Authors: Soleimani Behnaz , Lehnert Heike , Babben Steve , Keilwagen Jens , Koch Michael , Arana-Ceballos Fernando Alberto , Chesnokov Yuriy , Pshenichnikova Tatyana , Schondelmaier Jörg , Ordon Frank , Börner Andreas , Perovic Dragan
Published: March 2022

Winter wheat growing areas in the Northern hemisphere are regularly exposed to heavy frost. Due to the negative impact on yield, the identification of genetic factors controlling frost tolerance (FroT) and development of tools for breeding is of prime importance. Here, we detected QTL associated with FroT by genome wide association studies (GWAS) using a diverse panel of 276 winter wheat genotypes that was phenotyped at five locations in Germany and Russia in three years. The panel was genotyped using the 90 K iSelect array and SNPs in FroT candidate genes. In total, 17,566 SNPs were used for GWAS resulting in the identification of 53 markers significantly associated (LOD ≥ 4) to FroT, corresponding to 23 QTL regions located on 11 chromosomes (1A, 1B, 2A, 2B, 2D, 3A, 3D, 4A, 5A, 5B and 7D). The strongest QTL effect confirmed the importance of chromosome 5A for FroT. In addition, to our best knowledge, eight FroT QTLs were discovered for the first time in this study comprising one QTL on chromosomes 3A, 3D, 4A, 7D and two on chromosomes 1B and 2D. Identification of novel FroT candidate genes will help to better understand the FroT mechanism in wheat and to develop more effective combating strategies.
Pharmacological differences between beta-blockers and postoperative mortality following colon cancer surgery
Authors: Ekestubbe Lovisa , Bass Gary Alan , Forssten Maximilian Peter , Sjölin Gabriel , Cao Yang , Matthiessen Peter , Ahl Hulme Rebecka , Mohseni Shahin
Published: March 2022

β-blocker therapy has been positively associated with improved survival in patients undergoing oncologic colorectal resection. This study investigates if the type of β-blocker used affects 90-day postoperative mortality following colon cancer surgery. The study was designed as a nationwide retrospective cohort study including all adult (≥ 18 years old) patients with ongoing β-blocker therapy who underwent elective and emergency colon cancer surgery in Sweden between January 1, 2007 and December 31, 2017. Patients were divided into four cohorts: metoprolol, atenolol, bisoprolol, and other beta-blockers. The primary outcome of interest was 90-day postoperative mortality. A Poisson regression model with robust standard errors was used, while adjusting for all clinically relevant variables, to determine the association between different β-blockers and 90-day postoperative mortality. A total of 9254 patients were included in the study. There was no clinically significant difference in crude 90-day postoperative mortality rate [n (%)] when comparing the four beta-blocker cohorts metoprolol, atenolol, bisoprolol and other beta-blockers. [97 (1.8%) vs. 28 (2.0%) vs. 29 (1.7%) vs. 11 (1.2%), p = 0.670]. This remained unchanged when adjusting for relevant covariates in the Poisson regression model. Compared to metoprolol, there was no statistically significant decrease in the risk of 90-day postoperative mortality with atenolol [adj. IRR (95% CI): 1.45 (0.89–2.37), p = 0.132], bisoprolol [adj. IRR (95% CI): 1.45 (0.89–2.37), p = 0.132], or other beta-blockers [adj. IRR (95% CI): 0.92 (0.46–1.85), p = 0.825]. In patients undergoing colon cancer surgery, the risk of 90-day postoperative mortality does not differ between the investigated types of β-adrenergic blocking agents.
Coronary calcification and bone microarchitecture by high-resolution peripheral quantitative computed tomography from the São Paulo Ageing and Health (SPAH) Study
Authors: Guzman Luis Fernando Escobar , Lopes Neuza Helena Moreira , Torres Georgea H. Fernandes , Takayama Liliam , de Sousa Andrade Solange , Lanz-Luces José Ramón , Pereira Rosa Maria R. , Rochitte Carlos Eduardo
Published: March 2022

Epidemiological studies reveal a link between osteoporosis and the risk of ischemic cardiovascular disease. We illustrate an association between coronary calcification and bone microarchitecture in older adults based on the SPAH study. This cross-sectional research comprised 256 individuals subjected to cardiac coronary computed tomography angiography (CCTA) for coronary artery calcification (CAC), high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia and radius with standardized z score parameters, and dual-energy X-ray absorptiometry (DXA) to evaluate bone status. We used Student’s t test and the Mann–Whitney and Chi-squared tests for comparison of basal measurements. Association analysis was performed using the Poisson regression model with adjustment for CAC and sex. Multivariate analysis revealed different bone variables for predicting CAC in DXA and HR-pQCT scenarios. Although most of the bone parameters are related to vascular calcification, only cortical porosity (Ct.Po) remained uniform by HR-pQCT. Results for were as follows: the tibia—women (exp β = 1.12 (95% CI 1.10–1.13, p < 0.001) and men (exp β = 1.44, 95% CI 1.42–1.46, p < 0.001); the radius—women (exp β = 1.07 (95% CI 1.07–1.08, p < 0.001) and men (exp β = 1.33 (95% CI 1.30–1.37, p < 0.001). These findings suggest an inverse relationship between CAC and cortical bone content, as assessed by HR-pQCT, with higher coronary calcification in individuals older than 65 years.
Benchmarking of quantum protocols
Authors: Liao Chin-Te , Bahrani Sima , da Silva Francisco Ferreira , Kashefi Elham
Published: March 2022

Quantum network protocols offer new functionalities such as enhanced security to communication and computational systems. Despite the rapid progress in quantum hardware, it has not yet reached a level of maturity that enables execution of many quantum protocols in practical settings. To develop quantum protocols in real world, it is necessary to examine their performance considering the imperfections in their practical implementation using simulation platforms. In this paper, we consider several quantum protocols that enable promising functionalities and services in near-future quantum networks. The protocols are chosen from both areas of quantum communication and quantum computation as follows: quantum money, W-state based anonymous transmission, verifiable blind quantum computation, and quantum digital signature. We use NetSquid simulation platform to evaluate the effect of various sources of noise on the performance of these protocols, considering different figures of merit. We find that to enable quantum money protocol, the decoherence time constant of the quantum memory must be at least three times the storage time of qubits. Furthermore, our simulation results for the w-state based anonymous transmission protocol show that to achieve an average fidelity above 0.8 in this protocol, the storage time of sender’s and receiver’s particles in the quantum memory must be less than half of the decoherence time constant of the quantum memory. We have also investigated the effect of gate imperfections on the performance of verifiable blind quantum computation. We find that with our chosen parameters, if the depolarizing probability of quantum gates is equal to or greater than 0.05, the security of the protocol cannot be guaranteed. Lastly, our simulation results for quantum digital signature protocol show that channel loss has a significant effect on the probability of repudiation.
Mitochondrial phylogeny of the brittle star genus Ophioderma
Authors: Lessios H. A. , Hendler Gordon
Published: March 2022

We reconstructed the mitochondrial phylogeny of the species of the brittle star genus Ophioderma, using sequences of the Cytochrome Oxidase I gene (COI) to address four questions: (i) Are the species of Ophioderma described on morphological evidence reflected in mitochondrial genealogy? (ii) Which species separated from which? (iii) When did speciation events occur? (iv) What is the rate of COI evolution in ophiuroids? We found that most of the 22 described species we sampled coincide with monophyletic clusters of COI sequences, but there are exceptions, most notably in the eastern Pacific, in which three undescribed species were indicated. The COI phylogeny lacks resolution in the deeper nodes, but it does show that there are four species pairs, the members of which are found on either side of the central American Isthmus. Two pairs with a genetic distance of ~ 4% between Atlantic and Pacific members were probably split during the final stages of Isthmus completion roughly 3 million years ago. The rate of divergence provided by these pairs allowed the calibration of a relaxed molecular clock. Estimated dates of divergence indicate that the lineages leading to extant species coalesce at times much older than congeneric species in other classes of echinoderms, suggesting that low extinction rates may be one of the reasons that ophiuroids are species-rich. The mean rate of COI substitution in Ophioderma is three times slower than that of echinoids. Conclusions of previous mitochondrial DNA studies of ophiuroids that relied on echinoid calibrations to determine divergence times need to be revised.
A new intelligent bearing fault diagnosis model based on triplet network and SVM
Authors: Yang Kaisi , Zhao Lianyu , Wang Chenglin
Published: March 2022

Separating sensitive characteristic signals from original vibration data is an important challenge for rolling bearing fault diagnosis. Because it is difficult to obtain large number of damaged bearings, Rolling bearing fault datasets are often small sample datasets. For the classification of small sample rolling bearing fault datasets, we propose a coupling vibration data classification method based on triplet embedding. The method is divided into two steps: feature extraction and fault identification. First, build a triple embedding based on the CNN model to reduce the original vibration signal, and then train the SVM model for classification. Compared with traditional features and autoencoder, triplet network can learn the differences between samples. Make classification training easier and more accurate. We have evaluated the performance of this method through two bearing experiment examples. The experimental results show that this method is superior to stacked autoencoder, stacked denoising autoencoder and CNN.
Extracellular matrix-derived and low-cost proteins to improve polyurethane-based scaffolds for vascular grafts
Authors: Rodrigues Isabella C. P. , Lopes Éder S. N. , Pereira Karina D. , Huber Stephany C. , Jardini André Luiz , Annichino-Bizzacchi Joyce M. , Luchessi Augusto D. , Gabriel Laís P.
Published: March 2022

Vascular graft surgeries are often conducted in trauma cases, which has increased the demand for scaffolds with good biocompatibility profiles. Biodegradable scaffolds resembling the extracellular matrix (ECM) of blood vessels are promising vascular graft materials. In the present study, polyurethane (PU) was blended with ECM proteins collagen and elastin (Col-El) and gelatin (Gel) to produce fibrous scaffolds by using the rotary jet spinning (RJS) technique, and their effects on in vitro properties were evaluated. Morphological and structural characterization of the scaffolds was performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Micrometric fibers with nanometric rugosity were obtained. Col-El and Gel reduced the mechanical strength and increased the hydrophilicity and degradation rates of PU. No platelet adhesion or activation was observed. The addition of proteins to the PU blend increased the viability, adhesion, and proliferation of human umbilical vein endothelial cells (HUVECs). Therefore, PU-Col-El and PU-Gel scaffolds are promising biomaterials for vascular graft applications.
Aquatic birds have middle ears adapted to amphibious lifestyles
Authors: Zeyl Jeffrey N. , Snelling Edward P. , Connan Maelle , Basille Mathieu , Clay Thomas A. , Joo Rocío , Patrick Samantha C. , Phillips Richard A. , Pistorius Pierre A. , Ryan Peter G. , Snyman Albert , Clusella-Trullas Susana
Published: March 2022

Birds exhibit wide variation in their use of aquatic environments, on a spectrum from entirely terrestrial, through amphibious, to highly aquatic. Although there are limited empirical data on hearing sensitivity of birds underwater, mounting evidence indicates that diving birds detect and respond to sound underwater, suggesting that some modifications of the ear may assist foraging or other behaviors below the surface. In air, the tympanic middle ear acts as an impedance matcher that increases sound pressure and decreases sound vibration velocity between the outside air and the inner ear. Underwater, the impedance-matching task is reversed and the ear is exposed to high hydrostatic pressures. Using micro- and nano-CT (computerized tomography) scans of bird ears in 127 species across 26 taxonomic orders, we measured a suite of morphological traits of importance to aerial and aquatic hearing to test predictions relating to impedance-matching in birds with distinct aquatic lifestyles, while accounting for allometry and phylogeny. Birds that engage in underwater pursuit and deep diving showed the greatest differences in ear structure relative to terrestrial species. In these heavily modified ears, the size of the input areas of both the tympanic membrane and the columella footplate of the middle ear were reduced. Underwater pursuit and diving birds also typically had a shorter extrastapedius, a reduced cranial air volume and connectivity and several modifications in line with reversals of low-to-high impedance-matching. The results confirm adaptations of the middle ear to aquatic lifestyles in multiple independent bird lineages, likely facilitating hearing underwater and baroprotection, while potentially constraining the sensitivity of aerial hearing.
DNA barcoding and phylogeography of the Hoplias malabaricus species complex
Authors: Guimarães Karen Larissa Auzier , Lima Marcos Prado , Santana Diego José , de Souza Mendelsohn Fujiie Belém , Barbosa Rômulo Sarmento , Rodrigues Luís Reginaldo Ribeiro
Published: March 2022

Hoplias malabaricus (Bloch, 1794) is a carnivorous fish species widely distributed from northern to southern South America. This taxon is believed to be a good model for the investigation of biogeographic events that shape the ichthyofauna evolution in the Neotropical freshwater systems. However, many studies have revealed that H. malabaricus hides a species complex that hampers its taxonomic identity and limit its practical value for evolutionary and biogeographic studies. In this paper, we used the mitochondrial gene cytochrome c oxidase subunit I (COI) to delimit cryptic species and explore the phylogeography of H. malabaricus sensu stricto. We found genetic evidence for putative new species in the genus Hoplias and showed that H. malabaricus (Bloch, 1794) is a major clade assigned to barcode index number (BIN) BOLD:ABZ3047. This species is structured in six subpopulations differentiated by high Fst values and restricts gene flow. The subpopulations of the São Francisco/East Atlantic/Eastern Northeast Atlantic/Parnaíba/Itapecuru River basins and Tapajós River Basin were the most differentiated and showed demographic fluctuations. The present distributional pattern is most likely explained through a scenario from the Pleistocene.
Neural spatio-temporal patterns of information processing related to cognitive conflict and correct or false recognitions
Authors: Janik Romuald A. , Podolak Igor T. , Struski Łukasz , Ceglarek Anna , Lewandowska Koryna , Sikora-Wachowicz Barbara , Marek Tadeusz , Fafrowicz Magdalena
Published: March 2022

Using a visual short-term memory task and employing a new methodological approach, we analyzed neural responses from the perspective of the conflict level and correctness/erroneous over a longer time window. Sixty-five participants performed the short-term memory task in the fMRI scanner. We explore neural spatio-temporal patterns of information processing in the context of correct or erroneous response and high or low level of cognitive conflict using classical fMRI analysis, surface-based cortical data, temporal analysis of interpolated mean activations, and machine learning classifiers. Our results provide evidence that information processing dynamics during the retrieval process vary depending on the correct or false recognition—for stimuli inducing a high level of cognitive conflict and erroneous response, information processing is prolonged. The observed phenomenon may be interpreted as the manifestation of the brain’s preparation for future goal-directed action.