bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergence of universality in the transmission dynamics of COVID-19
Authors: Paul Ayan , Bhattacharjee Jayanta Kumar , Pal Akshay , Chakraborty Sagar 
Published: February 2021

ABSTRACTThe complexities involved in modeling the transmission dynamics of COVID-19 has been a major roadblock in achieving predictability in the spread and containment of the disease. In addition to understanding the modes of transmission, the effectiveness of the mitigation methods also needs to be built into any effective model for making such predictions. We show that such complexities can be circumvented by appealing to scaling principles which lead to the emergence of universality in the transmission dynamics of the disease. The ensuing data collapse renders the transmission dynamics largely independent of geopolitical variations, the effectiveness of various mitigation strategies, population demographics, etc. We propose a simple two-parameter model—the Blue Sky model—and show that one class of transmission dynamics can be explained by a solution that lives at the edge of a blue sky bifurcation. In addition, the data collapse leads to an enhanced degree of predictability in the disease spread for several geographical scales which can also be realized in a model-independent manner as we show using a deep neural network. The methodology adopted in this work can potentially be applied to the transmission of other infectious diseases and new universality classes may be found. The predictability in transmission dynamics and the simplicity of our methodology can help in building policies for exit strategies and mitigation methods during a pandemic.
Impact of personalized-dose vaccination in Covid-19 with a limited vaccine supply in a 100 day period in the U.S.A.
Authors: Hunziker Patrick 
Published: February 2021

AbstractBackgroundWe aimed at minimizing loss of lives in the Covid-19 pandemic in the USA by identifying optimal vaccination strategies during a 100-day period with limited vaccine supplies. While lethality is highest in the elderly, transmission and case numbers are highest in the younger. A strategy of first vaccinating the elderly is widely used, thought to protect the vulnerable, elderly best. Despite lower immunogenicity in the elderly, mRNA vaccines retain high efficacy, implying that in the younger, reduced vaccine doses might suffice, thereby increasing vaccination counts with a given vaccine supply.MethodsUsing published immunogenicity data of the Moderna mRNA-1273 vaccine, we examined the value of personalized-dose vaccination strategies, using a modeling approach incorporating age-related vaccine immunogenicity, social contact patterns, population structure, Covid-19 case and death rates in the USA in late January 2021. An increase if the number of persons that can be vaccinated and a potential reduction of the individual protective efficacy was accounted for.ResultsAge-personalized dosing strategies reduced cases faster, shortening the pandemic, reducing the delay to reaching <100’000 cases/day from 64 to 30 days and avoiding 25’000 deaths within 100 days in the USA. In an “elderly first” vaccination strategy, mortality is higher even in the elderly. Findings were robust with transmission blocking efficacies of reduced dose vaccination between 30% to 90%, and with a vaccine supply from 1 to 3 million full dose vaccinations per day.ConclusionRapid reduction of Covid-19 case and death rate in the USA in 100 days with a limited vaccine supply is best achieved when personalized, age-tailored dosing for highly effective vaccines is used, according to this vaccination strategy model parameterized to U.S. demographics, Covid-19 transmission and vaccine characteristics. Protecting the vulnerable is most effectively achieved by personalized-dose vaccination of all population segments, while an “elderly first” approach costs more lives, even in the elderly.
In vitro inactivation of SARS-CoV-2 with 0.5% povidone iodine nasal spray (Nasodine) at clinically relevant concentrations and timeframes using tissue culture and PCR based assays
Authors: Tucker S.P. , Goodall S. , Julander J. , Mendenhall M. , Friedland P. , Molloy P.L. 
Published: February 2021

ABSTRACTBACKGROUNDThere has been considerable speculation regarding the potential of PVP-I nasal disinfection as an adjunct to other countermeasures during the ongoing SARS-CoV-2 pandemic. Nasodine is a commercial formulation of 0.5% PVP-I that has been evaluated for safety and efficacy in human trials as a treatment for the common cold, including a Phase III trial (ANZCTR: ACTRN12619000764134). This study presents the first report of thein vitroefficacy of this formulation against SARS-CoV-2.METHODSWe conductedin vitroexperiments to determine if the PVP-I formulation inactivated SARS-CoV-2 using two independent assays and virus isolates, and incorporating both PCR-based detection and cell culture methods to assess residual virus after exposure to the formulation.RESULTSBased on cell culture results, the PVP-I formulation was found to rapidly inactivate SARS-CoV-2 isolatesin vitroin short timeframes (15 seconds to 15 minutes) consistent with the minimum and maximum potential residence time in the nose. The Nasodine formula was found to be more effective than 0.5% PVP-I in saline. Importantly, it was found that the formulation inactivated culturable virus but had no effect on PCR-detectable viral RNA.CONCLUSIONSThe PVP-I formulation eliminated the viability of SARS-CoV-2 virus with short exposure times consistent with nasal use. PCR alone may not be adequate for viral quantification in nasal PVP-I studies; future studies should incorporate cell culture to assess viral viability. Nasal disinfection with PVP-I may be a useful intervention for newly-diagnosed COVID-19 patients to reduce transmission risk and disease progression to the lower respiratory tract.
Evolution of the bread wheat D-subgenome and enriching it with diversity fromAegilops tauschii
Authors: Gaurav Kumar , Arora Sanu , Silva Paula , Sánchez-Martín Javier , Horsnell Richard , Gao Liangliang , Brar Gurcharn S. , Widrig Victoria , Raupp Jon , Singh Narinder , Wu Shuangye , Kale Sandip M. , Chinoy Catherine , Nicholson Paul , Quiroz-Chávez Jesús , Simmonds James , Hayta Sadiye , Smedley Mark A. , Harwood Wendy , Pearce Suzi , Gilbert David , Kangara Ngonidzashe , Gardener Catherine , Forner-Martínez Macarena , Liu Jiaqian , Yu Guotai , Boden Scott , Pascucci Attilio , Ghosh Sreya , Hafeez Amber N. , O’Hara Tom , Waites Joshua , Cheema Jitender , Steuernagel Burkhard , Patpour Mehran , Justesen Annemarie Fejer , Liu Shuyu , Rudd Jackie C. , Avni Raz , Sharon Amir , Steiner Barbara , Kirana Rizky Pasthika , Buerstmayr Hermann , Mehrabi Ali A. , Nasyrova Firuza Y. , Chayut Noam , Matny Oadi , Steffenson Brian J. , Sandhu Nitika , Chhuneja Parveen , Lagudah Evans , Elkot Ahmed F. , Tyrrell Simon , Bian Xingdong , Davey Robert P. , Simonsen Martin , Schauser Leif , Tiwari Vijay K. , Kutcher H. Randy , Hucl Pierre , Li Aili , Liu Deng-Cai , Mao Long , Xu Steven , Brown-Guedira Gina , Faris Justin , Dvorak Jan , Luo Ming-Cheng , Krasileva Ksenia , Lux Thomas , Artmeier Susanne , Mayer Klaus F. X. , Uauy Cristobal , Mascher Martin , Bentley Alison R. , Keller Beat , Poland Jesse , Wulff Brande B. H. 
Published: February 2021

AbstractAegilops tauschii,the diploid wild progenitor of the D-subgenome of bread wheat, constitutes a reservoir of genetic diversity for improving bread wheat performance and environmental resilience. To better define and understand this diversity, we sequenced 242Ae. tauschiiaccessions and compared them to the wheat D-subgenome. We characterized a rare, geographically-restricted lineage ofAe. tauschiiand discovered that it contributed to the wheat D-subgenome, thereby elucidating the origin of bread wheat from at least two independent hybridizations. We then usedk-mer-based association mapping to identify discrete genomic regions with candidate genes for disease and pest resistance and demonstrated their functional transfer into wheat by transgenesis and wide crossing, including the generation of a library of ‘synthetic’ hexaploids incorporating diverseAe. tauschiigenomes. This pipeline permits rapid trait discovery in the diploid ancestor through to functional genetic validation in a hexaploid background amenable to breeding.
Regulation of lateral root development by shoot-sensed far-red light via HY5 is nitrate-dependent and involves the NRT2.1 nitrate transporter
Authors: van Gelderen Kasper , Kang Chiakai , Li Peijin , Pierik Ronald 
Published: February 2021

AbstractPlants are very effective in responding to environmental changes during competition for light and nutrients. Low Red:Far-Red (low R:FR)-mediated neighbor detection allows plants to compete successfully with other plants for available light. This above-ground signal can also reduce lateral root growth by inhibiting lateral root emergence, a process that might help the plant invest resources in shoot growth. Nitrate is an essential nutrient for plant growth andArabidopsis thalianaresponds to low nitrate conditions by enhancing nutrient uptake and reducing lateral and main root growth. There are indications that low R:FR signaling and low nitrate signaling can affect each other. It is unknown which response is prioritized when low R:FR light- and low nitrate signaling co-occur. We investigated the effect of low nitrate conditions on the low R:FR response of theA. thalianaroot system in agar plate media, combined with the application of supplemental Far-Red (FR) light to the shoot. We observed that under low nitrate conditions main and lateral root growth was reduced, but more importantly, that the response of the root system to low R:FR was suppressed. Consistently, a loss-of-function mutant of a nitrate transporter geneNRT2.1lacked low R:FR-induced lateral root reduction and its root growth was hypersensitive to low nitrate. ELONGATED HYPOCOTYL5 (HY5) plays an important role in the root response to low R:FR and we found that it was less sensitive to low nitrate conditions with regards to lateral root growth. In addition, we found that low R:FR increasesNRT2.1expression and that low nitrate enhancesHY5expression. HY5 also affectsNRT2.1expression, however, it depended on the presence of ammonium in which direction this effect was. Replacing part of the nitrogen source with ammonium also removed the effect of low R:FR on the root system, showing that changes in nitrogen sources can be crucial for root plasticity. Together our results show that nitrate signaling can repress low R:FR responses and that this involves signaling via HY5 and NRT2.1.
Monitoring mitochondrial translation by pulse SILAC
Authors: Imami Koshi , Selbach Matthias , Ishihama Yasushi 
Published: February 2021

AbstractMitochondrial ribosomes are specialized to translate the 13 membrane proteins encoded in the mitochondrial genome, which shapes the oxidative phosphorylation (OXPHOS) complexes essential for cellular energy metabolism. Despite the importance of mitochondrial translation control, it is challenging to identify and quantify the mitochondrial-encoded proteins due to their hydrophobic nature and low abundance. Here, we introduce a mass spectrometry-based proteomic method that combines biochemical isolation of mitochondria with pulse stable isotope labeling by amino acids in cell culture (pSILAC). Our method provides the highest protein identification rate with the shortest measurement time among currently available methods, enabling us to quantify 12 out of the 13 mitochondrial-encoded proteins. We applied this method to uncover the global picture of (post-)translational regulation of both mitochondrial- and nuclear-encoded subunits of OXPHOS complexes. We found that inhibition of mitochondrial translation led to degradation of orphan nuclear-encoded subunits that are considered to form subcomplexes with the mitochondrial-encoded subunits. The results also allowed us to infer the subcomplex members of each OXPHOS complex. This method should be readily applicable to study mitochondrial translation programs in many contexts, including oxidative stress and mitochondrial disease.
Identification of anti-severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) oxysterol derivatives in vitro
Authors: Ohashi Hirofumi , Wang Feng , Stappenbeck Frank , Tsuchimoto Kana , Kobayashi Chisa , Saso Wakana , Kataoka Michiyo , Kuramochi Kouji , Muramatsu Masamichi , Suzuki Tadaki , Sureau Camille , Takeda Makoto , Wakita Takaji , Parhami Farhad , Watashi Koichi 
Published: February 2021

AbstractDevelopment of effective antiviral drugs targeting the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) are urgently needed to combat the coronavirus disease 2019 (COVID-19). Oxysterols, defined as oxidized derivatives of cholesterol, include endogenous (naturally occurring) cholesterol metabolites as well as semi-synthetic oxysterol derivatives. We have previously studied the use of semi-synthetic oxysterol derivatives as drug candidates for inhibition of cancer, fibrosis, and bone regeneration. In this study, we have screened a panel of naturally occurring and semi-synthetic oxysterol derivatives for anti-SARS-CoV-2 activity, using a cell culture infection assay. We show that the natural oxysterols, 7-ketocholesterol, 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, and 27-hydroxycholesterol, substantially inhibited SARS-CoV-2 propagation in cultured cells. Among semi-synthetic oxysterols, Oxy186 displayed antiviral activity comparable to natural oxysterols. In addition, related oxysterol analogues Oxy210 and Oxy232 displayed more robust anti-SARS-CoV-2 activities, reducing viral replication more than 90% at 10 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fall into a therapeutically relevant range (19 μM), based on the dose-dependent curve for antiviral activity in our cell culture infection assay. Mechanistic studies suggest that Oxy210 reduced replication of SARS-CoV-2 with disrupting the formation of double membrane vesicles (DMVs), intracellular membrane compartments associated with viral replication. Oxy210 also inhibited the replication of hepatitis C virus, another RNA virus whose replication is associated with DMVs, but not the replication of the DMV-independent hepatitis D virus. Our study warrants further evaluation of Oxy210 and Oxy232 as a safe and reliable oral medication, which could help protect vulnerable populations with increased risk developing COVID-19.
The secreted peptide IRP functions as a DAMP in rice immunity
Authors: Wang Pingyu , Jia Huimin , Guo Ting , Zhang Yuanyuan , Li Zhengguo , Kawano Yoji 
Published: February 2021

ABSTRACTSmall signaling peptides play important roles in various plant processes, but information regarding their involvement in plant immunity is limited. We previously identified a novel small secreted protein in rice, named immune response peptide (IRP) by the integrated multi-omics analyses. Here, we studied IRP functions in rice immunity. Rice plants overexpressingIRPenhanced resistance to the blast fungus. Application of the IRP peptide to rice suspension cells triggered the expression ofIRPitself and defense genePAL1. RNA-seq results revealed that 84% of genes upregulated by IRP peptide were also induced by chitin, including 13OsWRKYtranscription factors, indicating that IRP and chitin share the similar signaling pathway. Co-treatment with chitin and IRP elevated the expression level ofPAL1andOsWRKYs in an additive manner. When results ofIRPandPAL1expression and MAPK activation by IRP were compared with those by chitin, IRP had a stronger effect on MAPK activation rather thanIRPandPAL1expression. Collectively, our findings indicate that IRP functions as a damage-associated molecular pattern (DAMP) in rice immunity, regulating MAPKs andOsWRKYs to amplify chitin signaling, and provide new insights into how PAMPs and DAMPs cooperatively regulate rice immunity.
Non-essential ribosomal proteins in bacteria and archaea identified using COGs
Authors: Galperin Michael Y. , Wolf Yuri I. , Garushyants Sofya K. , Alvarez Roberto Vera , Koonin Eugene V. 
Published: February 2021

ABSTRACTRibosomal proteins (RPs) are highly conserved across the bacterial and archaeal domains. Although many RPs are essential for survival, genome analysis demonstrates the absence of some RP genes in many bacterial and archaeal genomes. Furthermore, global transposon mutagenesis and/or targeted deletion showed that elimination of some RP genes had only a moderate effect on the bacterial growth rate. Here, we systematically analyze the evolutionary conservation of RPs in prokaryotes by compiling the list of the ribosomal genes that are missing from the one or more genomes in the recently updated version of the Clusters of Orthologous Genes (COG) database. Some of these absences occurred because the respective genes carried frameshifts, presumably, resulting from sequencing errors, while others were overlooked and not translated during genome annotation. Apart from these annotation errors, we identified multiple genuine losses of RP genes in a variety of bacteria and archaea. Some of these losses are clade-specific, whereas others occur in symbionts and parasites with dramatically reduced genomes. The lists of computationally and experimentally defined non-essential ribosomal genes show a substantial overlap, revealing a common trend in prokaryote ribosome evolution that could be linked to the architecture and assembly of the ribosomes. Thus, RPs that are located at the surface of the ribosome and/or are incorporated at a late stage of ribosome assembly are more likely to be non-essential and to be lost during microbial evolution, particularly, in the course of genome compaction.IMPORTANCEIn many prokaryote genomes, one or more ribosomal protein (RP) genes are missing. Analysis of 1,309 prokaryote genomes included in the COG database shows that only about half of the RPs are universally conserved in bacteria and archaea. In contrast, up to 21 other RPs are missing in some genomes, primarily, tiny (<1 Mb) genomes of host-associated bacteria and archaea. Ten universal and nine archaea-specific ribosomal proteins show clear patterns of lineage-specific gene loss. Most of the RPs that are frequently lost from bacterial genomes are located on the ribosome periphery and are non-essential inEscherichia coliandBacillus subtilis. These results reveal general trends and common constraints in the architecture and evolution of ribosomes in prokaryotes.
Half-life of biodegradable plastics in the marine environment depends on material, habitat, and climate zone
Authors: Lott Christian , Eich Andreas , Makarow Dorothée , Unger Boris , Eekert Miriam van , Schuman Els , Reinach Marco Segre , Lasut Markus T. , Weber Miriam 
Published: February 2021

AbstractThe performance of the biodegradable plastic materials polyhydroxyalkanoate (PHA), polybutylene sebacate (PBSe) and polybutylene sebacate co-terephthalate (PBSeT), and of polyethylene (LDPE) was assessed under marine environmental conditions in a three-tier approach. Biodegradation lab tests (20 °C) were complemented by mesocosm tests (20 °C) with natural sand and seawater and by field tests in the warm-temperate Mediterranean Sea (12 – 30 °C) and in tropical Southeast Asia (29 °C) in three typical coastal scenarios. Plastic film samples were exposed in the eulittoral beach, the pelagic open water and the benthic seafloor and their disintegration monitored over time. We used statistical modelling to predict the half-life for each of the materials under the different environmental conditions to render the experimental results numerically comparable across all experimental conditions applied. The biodegradation performance of the materials differed by orders of magnitude depending on climate, habitat and material and revealed the inaccuracy to generically term a material ‘marine biodegradable’. The half-lifet0.5of a film of PHA with 85 μm thickness ranged from 54 d on the seafloor in SE Asia to 1247 d in mesocosm pelagic tests.t0.5for PBSe (25 μm) ranged from 99 d in benthic SE Asia to 2614 d in mesocosm benthic tests, and for PBSeTt0.5ranged from 147 d in the mesocosm eulittoral to 797 d in Mediterranean benthic field tests. For LDPE no biodegradation could be observed. These data can now be used to estimate the persistence of plastic objects should they end up in the marine environments considered here and will help to inform the life cycle (impact) assessment of plastics in the open environment.
DRDOCK: A Drug Repurposing platform integrating automated docking, simulations and a log-odds-based drug ranking scheme
Authors: Tsai Kun-Lin , Chang Sui-Yuan , Yang Lee-Wei 
Published: February 2021

AbstractMotivationDrug repurposing, where drugs originally approved to treat a disease are reused to treat other diseases, has received escalating attention especially in pandemic years. Structure-based drug design, integrating small molecular docking, molecular dynamic (MD) simulations and AI, has demonstrated its evidenced importance in streamlining new drug development as well as drug repurposing. To perform a sophisticated and fully automated drug screening using all the FDA drugs, intricate programming, accurate drug ranking methods and friendly user interface are very much needed.ResultsHere we introduce a new web server, DRDOCK,DrugRepurposingDOcking withConformation-sampling and pose re-ranKing - refined by MD and statistical models, which integrates small molecular docking and molecular dynamic (MD) simulations for automatic drug screening of 2016 FDA-approved drugs over a user-submitted single-chained target protein. The drugs are ranked by a novel drug-ranking scheme using log-odds (LOD) scores, derived from feature distributions of true binders and decoys. Users can submit a selection of LOD-ranked poses for further MD-based binding affinity evaluation. We demonstrated that our platform can indeed recover one of the substrates for nsp16, a cap ribose 2′-O methyltransferase, and recommends that fluralaner, tegaserod and fenoterol could be repurposed for the COVID19 treatment with the latter two being confirmed in SARS-CoV2 suppression experiments. All the sampled docking poses and trajectories can be 3D-viewed and played via our web interface. This platform shall be easy-to-use for general scientists and medicinal researchers to carry out drug repurposing within a couple of days which should add value to our timely responses to, particularly, emergent disease outbreaks.Availability and implementationDRDOCK can be freely accessed fromhttps://dyn.life.nthu.edu.tw/drdock/. (Due to the hardware upgrade, the service is NOT available before 7/18, 2021)
Learning and attention increase visual response selectivity through distinct mechanisms
Authors: Poort Jasper , Wilmes Katharina A. , Blot Antonin , Chadwick Angus , Sahani Maneesh , Clopath Claudia , Mrsic-Flogel Thomas D. , Hofer Sonja B. , Khan Adil G. 
Published: February 2021

SummarySelectivity of cortical neurons for sensory stimuli can increase across days as animals learn their behavioral relevance, and across seconds when animals switch attention. While both phenomena are expressed in the same cortical circuit, it is unknown whether they rely on similar mechanisms. We imaged activity of the same neuronal populations in primary visual cortex as mice learned a visual discrimination task and subsequently performed an attention switching task. Selectivity changes due to learning and attention were uncorrelated in individual neurons. Selectivity increases after learning mainly arose from selective suppression of responses to one of the task relevant stimuli but from selective enhancement and suppression during attention. Learning and attention differentially affected interactions between excitatory and PV, SOM and VIP inhibitory cell classes. Circuit modelling revealed that cell class-specific top-down inputs best explained attentional modulation, while the reorganization of local functional connectivity accounted for learning related changes. Thus, distinct mechanisms underlie increased discriminability of relevant sensory stimuli across longer and shorter time scales.