bluuebunny/crossref_metadata_2025 huggingface dataset:
A substrate binding model for the KEOPS tRNA modifying complex
Authors: Beenstock Jonah , Ona Samara Mishelle , Porat Jennifer , Orlicky Stephen , Wan Leo C. K. , Ceccarelli Derek F. , Maisonneuve Pierre , Szilard Rachel K. , Yin Zhe , Setiaputra Dheva , Mao Daniel Y. L. , Khan Morgan , Raval Shaunak , Schriemer David C. , Bayfield Mark A. , Durocher Daniel , Sicheri Frank
Published: December 2020

The KEOPS complex, which is conserved across archaea and eukaryotes, is composed of four core subunits; Pcc1, Kae1, Bud32 and Cgi121. KEOPS is crucial for the fitness of all organisms examined. In humans, pathogenic mutations in KEOPS genes lead to Galloway–Mowat syndrome, an autosomal-recessive disease causing childhood lethality. Kae1 catalyzes the universal and essential tRNA modification N6-threonylcarbamoyl adenosine, but the precise roles of all other KEOPS subunits remain an enigma. Here we show using structure-guided studies that Cgi121 recruits tRNA to KEOPS by binding to its 3’ CCA tail. A composite model of KEOPS bound to tRNA reveals that all KEOPS subunits form an extended tRNA-binding surface that we have validated in vitro and in vivo to mediate the interaction with the tRNA substrate and its modification. These findings provide a framework for understanding the inner workings of KEOPS and delineate why all KEOPS subunits are essential.
Arabidopsis calcium-dependent protein kinase 3 regulates actin cytoskeleton organization and immunity
Authors: Lu Yi-Ju , Li Pai , Shimono Masaki , Corrion Alex , Higaki Takumi , He Sheng Yang , Day Brad
Published: December 2020

Pattern-triggered immunity and effector-triggered immunity are two primary forms of innate immunity in land plants. The molecular components and connecting nodes of pattern-triggered immunity and effector-triggered immunity are not fully understood. Here, we report that the Arabidopsis calcium-dependent protein kinase CPK3 is a key regulator of both pattern-triggered immunity and effector-triggered immunity. In vitro and in vivo phosphorylation assays, coupled with genetic and cell biology-based analyses, show that actin-depolymerization factor 4 (ADF4) is a physiological substrate of CPK3, and that phosphorylation of ADF4 by CPK3 governs actin cytoskeletal organization associated with pattern-triggered immunity. CPK3 regulates stomatal closure induced by flg22 and is required for resistance to Pst DC3000. Our data further demonstrates that CPK3 is required for resistance to Pst DC3000 carrying the effector AvrPphB. These results suggest that CPK3 is a missing link between cytoskeleton organization, pattern-triggered immunity and effector-triggered immunity.
Early decarbonisation of the European energy system pays off
Authors: Victoria Marta , Zhu Kun , Brown Tom , Andresen Gorm B. , Greiner Martin
Published: December 2020

For a given carbon budget over several decades, different transformation rates for the energy system yield starkly different results. Here we consider a budget of 33 GtCO2 for the cumulative carbon dioxide emissions from the European electricity, heating, and transport sectors between 2020 and 2050, which represents Europe’s contribution to the Paris Agreement. We have found that following an early and steady path in which emissions are strongly reduced in the first decade is more cost-effective than following a late and rapid path in which low initial reduction targets quickly deplete the carbon budget and require a sharp reduction later. We show that solar photovoltaic, onshore and offshore wind can become the cornerstone of a fully decarbonised energy system and that installation rates similar to historical maxima are required to achieve timely decarbonisation. Key to those results is a proper representation of existing balancing strategies through an open, hourly-resolved, networked model of the sector-coupled European energy system.
Revealing the structures of megadalton-scale DNA complexes with nucleotide resolution
Authors: Kube Massimo , Kohler Fabian , Feigl Elija , Nagel-Yüksel Baki , Willner Elena M. , Funke Jonas J. , Gerling Thomas , Stömmer Pierre , Honemann Maximilian N. , Martin Thomas G. , Scheres Sjors H. W. , Dietz Hendrik
Published: December 2020

The methods of DNA nanotechnology enable the rational design of custom shapes that self-assemble in solution from sets of DNA molecules. DNA origami, in which a long template DNA single strand is folded by many short DNA oligonucleotides, can be employed to make objects comprising hundreds of unique DNA strands and thousands of base pairs, thus in principle providing many degrees of freedom for modelling complex objects of defined 3D shapes and sizes. Here, we address the problem of accurate structural validation of DNA objects in solution with cryo-EM based methodologies. By taking into account structural fluctuations, we can determine structures with improved detail compared to previous work. To interpret the experimental cryo-EM maps, we present molecular-dynamics-based methods for building pseudo-atomic models in a semi-automated fashion. Among other features, our data allows discerning details such as helical grooves, single-strand versus double-strand crossovers, backbone phosphate positions, and single-strand breaks. Obtaining this higher level of detail is a step forward that now allows designers to inspect and refine their designs with base-pair level interventions.
XBP1 links the 12-hour clock to NAFLD and regulation of membrane fluidity and lipid homeostasis
Authors: Meng Huan , Gonzales Naomi M. , Lonard David M. , Putluri Nagireddy , Zhu Bokai , Dacso Clifford C. , York Brian , O’Malley Bert W.
Published: December 2020

A distinct 12-hour clock exists in addition to the 24-hour circadian clock to coordinate metabolic and stress rhythms. Here, we show that liver-specific ablation of X-box binding protein 1 (XBP1) disrupts the hepatic 12-hour clock and promotes spontaneous non-alcoholic fatty liver disease (NAFLD). We show that hepatic XBP1 predominantly regulates the 12-hour rhythmicity of gene transcription in the mouse liver and demonstrate that perturbation of the 12-hour clock, but not the core circadian clock, is associated with the onset and progression of this NAFLD phenotype. Mechanistically, we provide evidence that the spliced form of XBP1 (XBP1s) binds to the hepatic 12-hour cistrome to directly regulate the 12-hour clock, with a periodicity paralleling the harmonic activation of the 12-hour oscillatory transcription of many rate-limiting metabolic genes known to have perturbations in human metabolic disease. Functionally, we show that Xbp1 ablation significantly reduces cellular membrane fluidity and impairs lipid homeostasis via rate-limiting metabolic processes in fatty acid monounsaturated and phospholipid remodeling pathways. These findings reveal that genetic disruption of the hepatic 12-hour clock links to the onset and progression of NAFLD development via transcriptional regulator XBP1, and demonstrate a role for XBP1 and the 12-hour clock in the modulation of phospholipid composition and the maintenance of lipid homeostasis.
Stabilization of ε-iron carbide as high-temperature catalyst under realistic Fischer–Tropsch synthesis conditions
Authors: Lyu Shuai , Wang Li , Li Zhe , Yin Shukun , Chen Jie , Zhang Yuhua , Li Jinlin , Wang Ye
Published: December 2020

The development of efficient catalysts for Fischer–Tropsch (FT) synthesis, a core reaction in the utilization of non-petroleum carbon resources to supply energy and chemicals, has attracted much recent attention. ε-Iron carbide (ε-Fe2C) was proposed as the most active iron phase for FT synthesis, but this phase is generally unstable under realistic FT reaction conditions (> 523 K). Here, we succeed in stabilizing pure-phase ε-Fe2C nanocrystals by confining them into graphene layers and obtain an iron-time yield of 1258 μmolCOgFe−1s−1under realistic FT synthesis conditions, one order of magnitude higher than that of the conventional carbon-supported Fe catalyst. The ε-Fe2C@graphene catalyst is stable at least for 400 h under high-temperature conditions. Density functional theory (DFT) calculations reveal the feasible formation of ε-Fe2C by carburization of α-Fe precursor through interfacial interactions of ε-Fe2C@graphene. This work provides a promising strategy to design highly active and stable Fe-based FT catalysts.
Integrative modeling of membrane-associated protein assemblies
Authors: Roel-Touris Jorge , Jiménez-García Brian , Bonvin Alexandre M. J. J.
Published: December 2020

Membrane proteins are among the most challenging systems to study with experimental structural biology techniques. The increased number of deposited structures of membrane proteins has opened the route to modeling their complexes by methods such as docking. Here, we present an integrative computational protocol for the modeling of membrane-associated protein assemblies. The information encoded by the membrane is represented by artificial beads, which allow targeting of the docking toward the binding-competent regions. It combines efficient, artificial intelligence-based rigid-body docking by LightDock with a flexible final refinement with HADDOCK to remove potential clashes at the interface. We demonstrate the performance of this protocol on eighteen membrane-associated complexes, whose interface lies between the membrane and either the cytosolic or periplasmic regions. In addition, we provide a comparison to another state-of-the-art docking software, ZDOCK. This protocol should shed light on the still dark fraction of the interactome consisting of membrane proteins.
Coupling of H3K27me3 recognition with transcriptional repression through the BAH-PHD-CPL2 complex in Arabidopsis
Authors: Zhang Yi-Zhe , Yuan Jianlong , Zhang Lingrui , Chen Chunxiang , Wang Yuhua , Zhang Guiping , Peng Li , Xie Si-Si , Jiang Jing , Zhu Jian-Kang , Du Jiamu , Duan Cheng-Guo
Published: December 2020

Histone 3 Lys 27 trimethylation (H3K27me3)-mediated epigenetic silencing plays a critical role in multiple biological processes. However, the H3K27me3 recognition and transcriptional repression mechanisms are only partially understood. Here, we report a mechanism for H3K27me3 recognition and transcriptional repression. Our structural and biochemical data showed that the BAH domain protein AIPP3 and the PHD proteins AIPP2 and PAIPP2 cooperate to read H3K27me3 and unmodified H3K4 histone marks, respectively, in Arabidopsis. The BAH-PHD bivalent histone reader complex silences a substantial subset of H3K27me3-enriched loci, including a number of development and stress response-related genes such as the RNA silencing effector gene ARGONAUTE 5 (AGO5). We found that the BAH-PHD module associates with CPL2, a plant-specific Pol II carboxyl terminal domain (CTD) phosphatase, to form the BAH-PHD-CPL2 complex (BPC) for transcriptional repression. The BPC complex represses transcription through CPL2-mediated CTD dephosphorylation, thereby causing inhibition of Pol II release from the transcriptional start site. Our work reveals a mechanism coupling H3K27me3 recognition with transcriptional repression through the alteration of Pol II phosphorylation states, thereby contributing to our understanding of the mechanism of H3K27me3-dependent silencing.
Evidence of exposure to SARS-CoV-2 in cats and dogs from households in Italy
Authors: Patterson E. I. , Elia G. , Grassi A. , Giordano A. , Desario C. , Medardo M. , Smith S. L. , Anderson E. R. , Prince T. , Patterson G. T. , Lorusso E. , Lucente M. S. , Lanave G. , Lauzi S. , Bonfanti U. , Stranieri A. , Martella V. , Solari Basano F. , Barrs V. R. , Radford A. D. , Agrimi U. , Hughes G. L. , Paltrinieri S. , Decaro N.
Published: December 2020

SARS-CoV-2 emerged from animals and is now easily transmitted between people. Sporadic detection of natural cases in animals alongside successful experimental infections of pets, such as cats, ferrets and dogs, raises questions about the susceptibility of animals under natural conditions of pet ownership. Here, we report a large-scale study to assess SARS-CoV-2 infection in 919 companion animals living in northern Italy, sampled at a time of frequent human infection. No animals tested PCR positive. However, 3.3% of dogs and 5.8% of cats had measurable SARS-CoV-2 neutralizing antibody titers, with dogs from COVID-19 positive households being significantly more likely to test positive than those from COVID-19 negative households. Understanding risk factors associated with this and their potential to infect other species requires urgent investigation.
Peroxisomes form intralumenal vesicles with roles in fatty acid catabolism and protein compartmentalization in Arabidopsis
Authors: Wright Zachary J. , Bartel Bonnie
Published: December 2020

Peroxisomes are vital organelles that compartmentalize critical metabolic reactions, such as the breakdown of fats, in eukaryotic cells. Although peroxisomes typically are considered to consist of a single membrane enclosing a protein lumen, more complex peroxisomal membrane structure has occasionally been observed in yeast, mammals, and plants. However, technical challenges have limited the recognition and understanding of this complexity. Here we exploit the unusually large size of Arabidopsis peroxisomes to demonstrate that peroxisomes have extensive internal membranes. These internal vesicles accumulate over time, use ESCRT (endosomal sorting complexes required for transport) machinery for formation, and appear to derive from the outer peroxisomal membrane. Moreover, these vesicles can harbor distinct proteins and do not form normally when fatty acid β-oxidation, a core function of peroxisomes, is impaired. Our findings suggest a mechanism for lipid mobilization that circumvents challenges in processing insoluble metabolites. This revision of the classical view of peroxisomes as single-membrane organelles has implications for all aspects of peroxisome biogenesis and function and may help address fundamental questions in peroxisome evolution.
Prediction of the Curie temperature considering the dependence of the phonon free energy on magnetic states
Authors: Tanaka Tomonori , Gohda Yoshihiro
Published: December 2020

Prediction of the Curie temperature is of significant importance for the design of ferromagnetic materials. One of the most widely used methods to estimate the Curie temperature from first principles relies on a spin Hamiltonian, for example, the Heisenberg Hamiltonian, and exchange coupling parameters obtained by first-principles calculations at zero temperature. Even though there have been attempts to include the effects of magnetism on phonons, the influence of magnetism-dependent phonons on magnetism has been disregarded in the theoretical estimation of the Curie temperature. Here, we propose a first-principles thermodynamic approach to minimise the total free energy considering both the influences of magnetism on phonons and the feedback effect from phonons to magnetism. By applying our scheme to body-centered cubic Fe, we find a significant reduction of the Curie temperature due to the feedback effect. This result indicates the importance of the feedback effect for a quantitative description of finite-temperature magnetism. In addition, we point out that the reduction in the theoretical Curie temperature arises in a wide range of ferromagnetic materials that exhibit phonon softening due to magnetic disordering.
Long-term safety of tiotropium/olodaterol in older patients with moderate-to-very-severe COPD in the TONADO® studies
Authors: Ferguson Gary T. , Maltais François , Karpel Jill , Bothner Ulrich , Kloer Isabel , Trampisch Matthias , Buhl Roland
Published: December 2020

Older patients with chronic obstructive pulmonary disease (COPD) may be at increased risk of adverse events (AEs) due to decreased protective organ function and increased comorbidities. TONADO® 1 + 2 were replicate, randomized, double-blind, parallel-group, 52-week, Phase III trials comparing the efficacy and safety of tiotropium/olodaterol (5/5 µg) versus the monocomponents via the Respimat® inhaler in patients with moderate-to-very-severe COPD. In this prespecified safety analysis, patients were grouped by age. Of 3100 patients, 1585 (51.1%) were aged <65 years, 1198 (38.7%) 65–<75 years, 309 (10.0%) 75–<85 years, and eight (0.3%) ≥85 years. At baseline, 23.4% had a pre-existing cardiac disorder, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diagnosed diabetes. Overall, there was no increase in major adverse cardiac events, other AEs, or serious AEs with tiotropium/olodaterol versus the monocomponents in any age group, supporting the safety of tiotropium/olodaterol in older patients with COPD.
Experimental characterization of the energetics of quantum logic gates
Authors: Cimini V. , Gherardini S. , Barbieri M. , Gianani I. , Sbroscia M. , Buffoni L. , Paternostro M. , Caruso F.
Published: December 2020

We characterize the energetic footprint of a two-qubit quantum gate from the perspective of non-equilibrium quantum thermodynamics. We experimentally reconstruct the statistics of energy and entropy fluctuations following the implementation of a controlled-unitary gate, linking them to the performance of the gate itself and the phenomenology of Landauer’s principle at the single-quantum level. Our work thus addresses the energetic cost of operating quantum circuits, a problem that is crucial for the grounding of the upcoming quantum technologies.
Personalized estimates of morphometric similarity in bipolar disorder and schizophrenia
Authors: Doucet Gaelle E. , Lin Dongdong , Du Yuhui , Fu Zening , Glahn David C. , Calhoun Vincent D. , Turner Jessica , Frangou Sophia
Published: December 2020

Bipolar disorder and schizophrenia are associated with brain morphometry alterations. This study investigates inter-individual variability in brain structural profiles, both within diagnostic groups and between patients and healthy individuals. Brain morphometric measures from three independent samples of patients with schizophrenia (n = 168), bipolar disorder (n = 122), and healthy individuals (n = 180) were modeled as single vectors to generated individualized profiles of subcortical volumes and regional cortical thickness. These profiles were then used to compute a person-based similarity index (PBSI) for subcortical volumes and for regional cortical thickness, to quantify the within-group similarity of the morphometric profile of each individual to that of the other participants in the same diagnostic group. There was no effect of diagnosis on the PBSI for subcortical volumes. In contrast, compared to healthy individuals, the PBSI for cortical thickness was lower in patients with schizophrenia (effect size = 0.4, p ≤ 0.0002), but not in patients with bipolar disorder. The results were robust and reproducible across samples. We conclude that disease mechanisms for these disorders produce modest inter-individual variations in brain morphometry that should be considered in future studies attempting to cluster patients in subgroups.
Increased expression of LCN2 formed a positive feedback loop with activation of the ERK pathway in human kidney cells during kidney stone formation
Authors: Hui Zhang , Jiang Zhu , Qiao Du , Bo Zhao , Qiyuan Kang , Shaohua Bian , Wenbing Yuan , Wei Liu , Cheng Luo , Shuangning Liu , Zhengyi Li , Yingyi Li
Published: December 2020

Kidney stones are a common threat to the health of elderly patients with a high incidence of disease. However, the specific molecular mechanism of the formation of kidney stones has not been elucidated. Here, we combined signalling molecules with signalling pathways in a double positive circulation regulation model. In addition, we found that LCN2 plays a role in promoting kidney stones through regulation of the ERK signalling pathway and expression of other kidney stone-related genes. LCN2 expression was upregulated upon oxalate stimulation. P-ERK1/2 inhibition by U0126 in kidney epithelial cells resulted in decreased expression of LCN2. Furthermore, the upregulation of LCN2 not only depended on the activation of the ERK signalling pathway but also regulated the activation of the ERK signalling pathway. Importantly, upregulation of LCN2 not only caused kidney epithelial cell damage but also promoted the expression of other kidney stone-related genes. Our findings improved the understanding of LCN2 and might lead to the development of new therapeutic and prognostic markers for kidney stones.
Predicted climate change will increase the truffle cultivation potential in central Europe
Authors: Čejka Tomáš , Trnka Miroslav , Krusic Paul J. , Stobbe Ulrich , Oliach Daniel , Václavík Tomáš , Tegel Willy , Büntgen Ulf
Published: December 2020

Climate change affects the distribution of many species, including Burgundy and Périgord truffles in central and southern Europe, respectively. The cultivation potential of these high-prized cash crops under future warming, however, remains highly uncertain. Here we perform a literature review to define the ecological requirements for the growth of both truffle species. This information is used to develop niche models, and to estimate their cultivation potential in the Czech Republic under current (2020) and future (2050) climate conditions. The Burgundy truffle is already highly suitable for cultivation on ~ 14% of agricultural land in the Czech Republic (8486 km2), whereas only ~ 8% of the warmest part of southern Moravia are currently characterised by a low suitability for Périgord truffles (6418 km2). Though rising temperatures under RCP8.5 will reduce the highly suitable cultivation areas by 7%, the 250 km2 (3%) expansion under low-emission scenarios will stimulate Burgundy truffles to benefit from future warming. Doubling the moderate and expanding the highly suitable land by 352 km2 in 2050, the overall cultivation potential for Périgord truffles will rise substantially. Our findings suggest that Burgundy and Périgord truffles could become important high-value crops for many regions in central Europe with alkaline soils. Although associated with uncertainty, long-term investments in truffle cultivation could generate a wide range of ecological and economic benefits.
Metabolomics revealed the influence of breast cancer on lymphatic endothelial cell metabolism, metabolic crosstalk, and lymphangiogenic signaling in co-culture
Authors: Acevedo-Acevedo Suehelay , Millar Douglas C. , Simmons Aaron D. , Favreau Peter , Cobra Paulo F. , Skala Melissa , Palecek Sean P.
Published: December 2020

Breast cancer metastasis occurs via blood and lymphatic vessels. Breast cancer cells ‘educate’ lymphatic endothelial cells (LECs) to support tumor vascularization and growth. However, despite known metabolic alterations in breast cancer, it remains unclear how lymphatic endothelial cell metabolism is altered in the tumor microenvironment and its effect in lymphangiogenic signaling in LECs. We analyzed metabolites inside LECs in co-culture with MCF-7, MDA-MB-231, and SK-BR-3 breast cancer cell lines using $$^1\hbox {H}$$

1

H

nuclear magnetic resonance (NMR) metabolomics, Seahorse, and the spatial distribution of metabolic co-enzymes using optical redox ratio imaging to describe breast cancer-LEC metabolic crosstalk. LECs co-cultured with breast cancer cells exhibited cell-line dependent altered metabolic profiles, including significant changes in lactate concentration in breast cancer co-culture. Cell metabolic phenotype analysis using Seahorse showed LECs in co-culture exhibited reduced mitochondrial respiration, increased reliance on glycolysis and reduced metabolic flexibility. Optical redox ratio measurements revealed reduced NAD(P)H levels in LECs potentially due to increased NAD(P)H utilization to maintain redox homeostasis. $$^{13}\hbox {C}$$

13

C

-labeled glucose experiments did not reveal lactate shuttling into LECs from breast cancer cells, yet showed other $$^{13}\hbox {C}$$

13

C

signals in LECs suggesting internalized metabolites and metabolic exchange between the two cell types. We also determined that breast cancer co-culture stimulated lymphangiogenic signaling in LECs, yet activation was not stimulated by lactate alone. Increased lymphangiogenic signaling suggests paracrine signaling between LECs and breast cancer cells which could have a pro-metastatic role.
Integrative genomic analysis implicates ERCC6 and its interaction with ERCC8 in susceptibility to breast cancer
Authors: Moslehi Roxana , Tsao Hui-Shien , Zeinomar Nur , Stagnar Cristy , Fitzpatrick Sean , Dzutsev Amiran
Published: December 2020

Up to 30% of all breast cancer cases may be inherited and up to 85% of those may be due to segregation of susceptibility genes with low and moderate risk [odds ratios (OR) ≤ 3] for (mostly peri- and post-menopausal) breast cancer. The majority of low/moderate-risk genes, particularly those with minor allele frequencies (MAF) of < 30%, have not been identified and/or validated due to limitations of conventional association testing approaches, which include the agnostic nature of Genome Wide Association Studies (GWAS). To overcome these limitations, we used a hypothesis-driven integrative genomics approach to test the association of breast cancer with candidate genes by analyzing multi-omics data. Our candidate-gene association analyses of GWAS datasets suggested an increased risk of breast cancer with ERCC6 (main effect: 1.29 ≤ OR ≤ 2.91, 0.005 ≤ p ≤ 0.04, 11.8 ≤ MAF ≤ 40.9%), and implicated its interaction with ERCC8 (joint effect: 3.03 ≤ OR ≤ 5.31, 0.01 ≤ pinteraction ≤ 0.03). We found significant upregulation of ERCC6 (p = 7.95 × 10–6) and ERCC8 (p = 4.67 × 10–6) in breast cancer and similar frequencies of ERCC6 (1.8%) and ERCC8 (0.3%) mutations in breast tumors to known breast cancer susceptibility genes such as BLM (1.9%) and LSP1 (0.3%). Our integrative genomics approach suggests that ERCC6 may be a previously unreported low- to moderate-risk breast cancer susceptibility gene, which may also interact with ERCC8.
Author Correction: Variational Hilbert Quantitative Phase Imaging
Authors: Trusiak Maciej , Cywińska Maria , Micó Vicente , Picazo-Bueno José Ángel , Zuo Chao , Zdańkowski Piotr , Patorski Krzysztof
Published: December 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Management strategies in a SEIR-type model of COVID 19 community spread
Authors: Rǎdulescu Anca , Williams Cassandra , Cavanagh Kieran
Published: December 2020

The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international focus. Significant gaps persist in our knowledge of COVID 19 epidemiology, transmission dynamics, investigation tools and management, despite (or possibly because of) the fact that the outbreak is an unprecedented global threat. On the positive side, enough is currently known about the epidemic process to permit the construction of mathematical predictive models. In our work, we adapt a traditional SEIR epidemic model to the specific dynamic compartments and epidemic parameters of COVID 19, as it spreads in an age-heterogeneous community. We analyze management strategies of the epidemic course (as they were implemented through lockdown and reopening procedures in many of the US states and countries worldwide); however, to more clearly illustrate ideas, we focus on the example of a small scale college town community, with the timeline of control measures introduced in the state of New York. We generate predictions, and assess the efficiency of these control measures (closures, mobility restrictions, social distancing), in a sustainability context.
Efficacy of low dose pirfenidone in idiopathic pulmonary fibrosis: real world experience from a tertiary university hospital
Authors: Song Myung Jin , Moon Sung Woo , Choi Ji Soo , Lee Sang Hoon , Lee Su Hwan , Chung Kyung Soo , Jung Ji Ye , Kang Young Ae , Park Moo Suk , Kim Young Sam , Chang Joon , Kim Song Yee
Published: December 2020

Pirfenidone is an antifibrotic agent that has been proven to slow down the progression of idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the efficacy of low-dose pirfenidone (that is, less than 1200 mg/day). We retrospectively reviewed the medical records of patients with IPF. The patients were divided into the following three groups, those who were not treated with pirfenidone (control) and those who were treated with pirfenidone at doses < 1200 mg/day (low-dose group) and ≥ 1200 mg/day (high-dose group). The adjusted mean changes in forced vital capacity (FVC) in 1 year were − 200.7, − 88.4, and − 94.7 mL in the control, low-dose, and high-dose groups (p = 0.021). The FVC declined more significantly in the control group than in the low-dose and high-dose groups. No significant difference in FVC change was observed between the low-dose and high-dose groups. Dyspepsia, anorexia, and nausea were significantly more frequent in the low-dose than in the high-dose group, suggesting that dose reduction is attributed to gastrointestinal tract-related adverse events. Dose reduction may help patients to better control gastrointestinal tract-related adverse events; continuing taking the medication at low doses is also expected to be effective in reducing the FVC decline.
Stoichiometry of irreversible ligand binding to a one-dimensional lattice
Authors: Tsvetkov Philipp O.
Published: December 2020

In this paper we investigate the problem of irreversible binding of a ligand that covers several identical binding sites on a macromolecule with a one-dimensional lattice. Due to steric constraints, irreversible binding or binding with slow kinetics results in partial saturation of the binding sites thus impacting the stoichiometry of the interaction. Here we present a recursive formula to calculate the exact fraction of the occupied binding sites for a ligand and macromolecule of arbitrary lengths. We also provide an analytical result for the exact fraction of the occupied sites in case of an infinitely long lattice. We conclude with a simplified empirical formula for the exact fraction of the occupied sites in case of an infinitely long lattice.
Frequency spectrum recurrence analysis
Authors: Ladeira Guênia , Marwan Norbert , Destro-Filho João-Batista , Davi Ramos Camila , Lima Gabriela
Published: December 2020

In this paper, we present the new frequency spectrum recurrence analysis technique by means of electro-encephalon signals (EES) analyses. The technique is suitable for time series analysis with noise and disturbances. EES were collected, and alpha waves of the occipital region were analysed by comparing the signals from participants in two states, eyes open and eyes closed. Firstly, EES were characterized and analysed by means of techniques already known to compare with the results of the innovative technique that we present here. We verified that, standard recurrence quantification analysis by means of EES time series cannot statistically distinguish the two states. However, the new frequency spectrum recurrence quantification exhibit quantitatively whether the participants have their eyes open or closed. In sequence, new quantifiers are created for analysing the recurrence concentration on frequency bands. These analyses show that EES with similar frequency spectrum have different recurrence levels revealing different behaviours of the nervous system. The technique can be used to deepen the study on depression, stress, concentration level and other neurological issues and also can be used in any complex system.
Estimating the short-time rate of change in the trend of the Keeling curve
Authors: Nordebo Sven , Naeem Muhammad Farhan , Tans Pieter
Published: December 2020

What exactly is the short-time rate of change (growth rate) in the trend of $$\text {CO}_2$$

CO
2

data such as the Keeling curve? The answer to this question will obviously depend very much on the duration in time over which the trend has been defined, as well as the smoothing technique that has been used. As an estimate of the short-time rate of change we propose to employ a very simple and robust definition of the trend based on a centered 1-year sliding data window for averaging and a corresponding centered 1-year difference (2-year data window) to estimate its rate of change. In this paper, we show that this simple strategy applied to weekly data of the Keeling curve (1974–2020) gives an estimated rate of change which is perfectly consistent with a more sophisticated regression analysis technique based on Taylor and Fourier series expansions. From a statistical analysis of the regression model and by using the Cramér–Rao lower bound, it is demonstrated that the relative error in the estimated rate of change is less than 5 $$\%$$
%
. As an illustration, the estimates are finally compared to some other publicly available data regarding anthropogenic $$\text {CO}_2$$

CO
2

emissions and natural phenomena such as the El Niño.
A diagnostic LAMP assay for the destructive grapevine insect pest, phylloxera (Daktulosphaira vitifoliae)
Authors: Agarwal Arati , Cunningham J. Paul , Valenzuela Isabel , Blacket Mark J.
Published: December 2020

Grape phylloxera (Daktulosphaira vitifoliae) is a destructive insect pest of grapevines that is highly invasive worldwide, despite strict biosecurity containment measures in place at farm and regional levels. Current phylloxera identification by visual inspection and laboratory-based molecular methods is time-consuming and costly. More rapid and cost-effective methods for identification of this pest would benefit industry, growers, and biosecurity services. Loop mediated isothermal amplification (LAMP) is a new portable technology available for rapid and accurate in-field molecular diagnostics. This study outlines the development of a new LAMP assay to enable the identification of phylloxera specimens. New LAMP primers were developed to specifically amplify phylloxera mitochondrial DNA (5′-COI), which we have shown is effective as a DNA barcode for identification of phylloxera, using LAMP technology. Positive LAMP reactions, containing phylloxera DNA, amplified in less than twelve minutes with an anneal derivative temperature of approximately 79 °C to 80 °C compared to a newly designed synthetic DNA (gBlock) fragment which had an anneal derivative temperature of 82 °C. No LAMP amplification was detected in any of the non-target species tested, i.e. no false-positive identification resulted for these species. We also successfully optimised a non-destructive DNA extraction procedure, HotSHOT “HS6”, for use in the field on phylloxera adults, nymphs and eggs, to retain physical specimens. DNA extracted using this method was also suitable for species and genotype molecular identification methods, such as DNA barcoding, qPCR and microsatellite genotyping. The new LAMP assay provides a novel visual molecular tool for accurate diagnostics of phylloxera in the laboratory and field.
Voltage and pH difference across the membrane control the S4 voltage-sensor motion of the Hv1 proton channel
Authors: Schladt T. Moritz , Berger Thomas K.
Published: December 2020

The voltage-gated proton channel Hv1 is expressed in a variety of cells, including macrophages, sperm, and lung epithelial cells. Hv1 is gated by both the membrane potential and the difference between the intra- and extracellular pH (ΔpH). The coupling of voltage- and ∆pH-sensing is such that Hv1 opens only when the electrochemical proton gradient is outwardly directed. However, the molecular mechanism of this coupling is not known. Here, we investigate the coupling between voltage- and ΔpH-sensing of Ciona intestinalis proton channel (ciHv1) using patch-clamp fluorometry (PCF) and proton uncaging. We show that changes in ΔpH can induce conformational changes of the S4 voltage sensor. Our results are consistent with the idea that S4 can detect both voltage and ΔpH.
Transcriptome analysis reveals that exogenous ethylene activates immune and defense responses in a high late blight resistant potato genotype
Authors: Yang Xiaohui , Chen Li , Yang Yu , Guo Xiao , Chen Guangxia , Xiong Xingyao , Dong Daofeng , Li Guangcun
Published: December 2020

Ethylene (ET) is one of the many important signaling hormones that functions in regulating defense responses in plants. Gene expression profiling was conducted under exogenous ET application in the high late blight resistant potato genotype SD20 and the specific transcriptional responses to exogenous ET in SD20 were revealed. Analysis of differentially expressed genes (DEGs) generated a total of 1226 ET-specific DEGs, among which transcription factors, kinases, defense enzymes and disease resistance-related genes were significantly differentially expressed. GO enrichment and KEGG metabolic pathway analysis also revealed that numerous defense regulation-related genes and defense pathways were significantly enriched. These results were consistent with the interaction of SD20 and Phytophthora infestans in our previous study, indicating that exogenous ET stimulated the defense response and initiated a similar defense pathway compared to pathogen infection in SD20. Moreover, multiple signaling pathways including ET, salicylic acid, jasmonic acid, abscisic acid, auxin, cytokinin and gibberellin were involved in the response to exogenous ET, which indicates that many plant hormones work together to form a complex network to resist external stimuli in SD20. ET-induced gene expression profiling provides insights into the ET signaling transduction pathway and its potential mechanisms in disease defense systems in potato.
Bacterial diversity and functional analysis of severe early childhood caries and recurrence in India
Authors: Kalpana Balakrishnan , Prabhu Puniethaa , Bhat Ashaq Hussain , Senthilkumar Arunsaikiran , Arun Raj Pranap , Asokan Sharath , Gunthe Sachin S. , Verma Rama S.
Published: December 2020

Dental caries is the most prevalent oral disease affecting nearly 70% of children in India and elsewhere. Micro-ecological niche based acidification due to dysbiosis in oral microbiome are crucial for caries onset and progression. Here we report the tooth bacteriome diversity compared in Indian children with caries free (CF), severe early childhood caries (SC) and recurrent caries (RC). High quality V3–V4 amplicon sequencing revealed that SC exhibited high bacterial diversity with unique combination and interrelationship. Gracillibacteria_GN02 and TM7 were unique in CF and SC respectively, while Bacteroidetes, Fusobacteria were significantly high in RC. Interestingly, we found Streptococcus oralis subsp. tigurinus clade 071 in all groups with significant abundance in SC and RC. Positive correlation between low and high abundant bacteria as well as with TCS, PTS and ABC transporters were seen from co-occurrence network analysis. This could lead to persistence of SC niche resulting in RC. Comparative in vitro assessment of biofilm formation showed that the standard culture of S. oralis and its phylogenetically similar clinical isolates showed profound biofilm formation and augmented the growth and enhanced biofilm formation in S. mutans in both dual and multispecies cultures.
Crustal deformation, active tectonics and seismic potential in the Sicily Channel (Central Mediterranean), along the Nubia–Eurasia plate boundary
Authors: Palano Mimmo , Ursino Andrea , Spampinato Salvatore , Sparacino Federica , Polonia Alina , Gasperini Luca
Published: December 2020

Based on multidisciplinary data, including seismological and geodetic observations, as well as seismic reflection profiles and gravity maps, we analysed the pattern of crustal deformation and active tectonics in the Sicily Channel, a key observation point to unravel the complex interaction between two major plates, Nubia and Eurasia, in the Mediterranean Sea. Our data highlight the presence of an active ~ 220-km-long complex lithospheric fault system (here named the Lampedusa-Sciacca Shear Zone), approximately oriented N–S, crossing the study area with left-lateral strike-slip deformations, active volcanism and high heat flow. We suggest that this shear zone represents the most active tectonic domain in the area, while the NW–SE elongated rifting pattern, considered the first order tectonic feature, appears currently inactive and sealed by undeformed recent (Lower Pleistocene?) deposits. Estimates of seismological and geodetic moment-rates, 6.58 × 1015Nm/year and 7.24 × 1017Nm/year, respectively, suggests that seismicity accounts only for ~ 0.9% of crustal deformation, while the anomalous thermal state and the low thickness of the crust would significantly inhibit frictional sliding in favour of creeping and aseismic deformation. We therefore conclude that a significant amount of the estimated crustal deformation-rate occurs aseismically, opening new scenarios for seismic risk assessments in the region.
High yield synthesis of graphene quantum dots from biomass waste as a highly selective probe for Fe3+ sensing
Authors: Abbas Aumber , Tabish Tanveer A. , Bull Steve J. , Lim Tuti Mariana , Phan Anh N.
Published: December 2020

Graphene quantum dots (GQDs), a novel type of zero-dimensional fluorescent materials, have gained considerable attention owing to their unique optical properties, size and quantum confinement. However, their high cost and low yield remain open challenges for practical applications. In this work, a low cost, green and renewable biomass resource is utilised for the high yield synthesis of GQDs via microwave treatment. The synthesis approach involves oxidative cutting of short range ordered carbon derived from pyrolysis of biomass waste. The GQDs are successfully synthesised with a high yield of over 84%, the highest value reported to date for biomass derived GQDs. As prepared GQDs are highly hydrophilic and exhibit unique excitation independent photoluminescence emission, attributed to their single-emission fluorescence centre. As prepared GQDs are further modified by simple hydrothermal treatment and exhibit pronounced optical properties with a high quantum yield of 0.23. These modified GQDs are used for the highly selective and sensitive sensing of ferric ions (Fe3+). A sensitive sensor is prepared for the selective detection of Fe3+ ions with a detection limit of as low as 2.5 × 10–6 M. The utilisation of renewable resource along with facile microwave treatment paves the way to sustainable, high yield and cost-effective synthesis of GQDs for practical applications.
Risk prediction model of gestational diabetes mellitus based on nomogram in a Chinese population cohort study
Authors: Zhang Xiaomei , Zhao Xin , Huo Lili , Yuan Ning , Sun Jianbin , Du Jing , Nan Min , Ji Linong
Published: December 2020

To build a risk prediction model of gestational diabetes mellitus using nomogram to provide a simple-to-use clinical basis for the early prediction of gestational diabetes mellitus (GDM). This study is a prospective cohort study including 1385 pregnant women. (1) It is showed that the risk of GDM in women aged ≥ 35 years was 5.5 times higher than that in women aged < 25 years (95% CI: 1.27–23.73,p < 0.05). In the first trimester, the risk of GDM in women with abnormal triglyceride who were in their first trimester was 2.1 times higher than that of lipid normal women (95% CI: 1.12–3.91,p < 0.05). The area under the ROC curve of the nomogram of was 0.728 (95% CI: 0.683–0.772), the sensitivity and specificity of the model were 0.716 and 0.652, respectively. This study provides a simple and economic nomogram for the early prediction of GDM risk in the first trimester, and it has certain accuracy.
Transcriptomic analysis of Procambarus clarkii affected by “Black May” disease
Authors: Shen Guoqing , Zhang Xiao , Gong Jie , Wang Yang , Huang Pengdan , Shui Yan , Xu Zenghong , Shen Huaishun
Published: December 2020

Each year from April to May, high mortality rates are reported in red swamp crayfish (Procambarus clarkii) cultured in Jiangsu and other regions, in China, and this phenomenon has come to be known as “Black May” disease (BMD). Therefore, in order to investigate the possible causes of this disease, this study gathered BMD-affected P. clarkii samples and performed transcriptome analysis on hepatopancreas, gill, and muscle tissues. A total of 19,995,164, 149,212,804, and 222,053,848 clean reads were respectively obtained from the gills, muscle, and hepatopancreas of BMD-affected P. clarkii, and 114,024 unigenes were identified. The number of differentially expressed genes (DEGs) in gill, muscle, and hepatopancreas was 1703, 964, and 476, respectively. GO and KEGG enrichment analyses of the DEGs were then conducted. Based on KEGG pathway enrichment analysis, the most significantly differentially expressed pathways were mainly those involved with metabolism, human disease, and cellular processes. Further analysis of the significantly DEGs revealed that they were mainly related to the mitochondrial-mediated apoptosis pathway and that the expression of these DEGs was mostly down-regulated. Moreover, the expression of genes related to immune and metabolism-related pathways was also significantly down-regulated, and these significantly-inhibited pathways were the likely causes of P. clarkii death. Therefore, our results provide a basis for the identification of BMD causes.
Clinical and molecular analysis in a cohort of Chinese children with Cornelia de Lange syndrome
Authors: Li Qun , Chang Guoying , Yin Lei , Li Juan , Huang Xiaodong , Shen Yongnian , Li Guoqiang , Xu Yufei , Wang Jian , Wang Xiumin
Published: December 2020

Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder, which causes a range of physical, cognitive, and medical challenges. To retrospectively analyze the clinical characteristics and genetic variations of Chinese patients, and to provide experience for further diagnosis and treatment of CdLS in Chinese children, we identified 15 unrelated Chinese children who presented with unusual facial features, short stature, developmental delay, limb abnormalities, and a wide range of health conditions. In this study, targeted-next generation sequencing was used to screen for causal variants and the clinically relevant variants were subsequently verified using Sanger sequencing. DNA sequencing identified 15 genetic variations, including 11 NIPBL gene variants, two SMC1A gene variants, one RAD21 gene variant, and one HDAC8 variant. The phenotype of these patients was summarized and differences between this cohort and another four groups were compared. The clinical manifestations of the patients in this cohort were mostly consistent with other ethnicities, but several clinical features in our cohort had different frequencies compared with other groups. We identified 15 deleterious variants of which 11 were novel. Variants in the NIPBL gene were the most common cause in our cohort. Our study not only expands upon the spectrum of genetic variations in CdLS, but also broadens our understanding of the clinical features of CdLS.