bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potent activation of SARM1 by NMN analogue VMN underlies vacor neurotoxicity
Authors: Loreto Andrea , Angeletti Carlo , Gu Weixi , Osborne Andrew , Nieuwenhuis Bart , Gilley Jonathan , Arthur-Farraj Peter , Merlini Elisa , Amici Adolfo , Luo Zhenyao , Hartley-Tassell Lauren , Ve Thomas , Desrochers Laura M. , Wang Qi , Kobe Bostjan , Orsomando Giuseppe , Coleman Michael P. 
Published: September 2020

AbstractAxon loss underlies symptom onset and progression in many neurodegenerative disorders. Axon degeneration in injury and disease is promoted by activation of the nicotinamide adenine dinucleotide (NAD)-consuming enzyme SARM1 (sterile alpha and TIR motif-containing protein 1). Here, we report vacor mononucleotide (VMN), a metabolite of the pesticide and neurotoxin vacor, as the most potent yet SARM1 activator. Removal of SARM1 shows complete rescue from vacor-induced neuron and axon deathin vitroandin vivo. We present the crystal structure of VMN bound to theDrosophilaSARM1 regulatory armadillo-repeat domain, thus facilitating drug development to prevent SARM1 activation in human disease. This study indicates the likely mechanism of action of vacor as a pesticide and lethal neurotoxin in humans, provides important new tools for drug discovery, and further demonstrates that SARM1 removal can permanently block programmed axon death specifically induced by toxicity as well as genetic mutation.
Metagenomic insights into ecosystem function in the microbial mats of Blue Holes, Shark Bay
Authors: Kindler Gareth S , Wong Hon Lun , Larkum Anthony W D , Johnson Michael , MacLeod Fraser I , Burns Brendan P 
Published: September 2020

AbstractMicrobial mat ecosystems vary in complexity and structure depending on the environmental constraints placed by nature. Here, we describe in detail for the first time the community composition and functional potential of the microbial mats found in the supratidal, gypsum-rich, and hypersaline region of Blue Holes, Shark Bay. This was achieved via high throughput sequencing of total mat community DNA on the Illumina NextSeq platform. Mat communities were mainly comprised of Proteobacteria (29%), followed by Bacteroidetes/Chlorobi Group (11%), and Planctomycetes (10%). These mats were found to also harbor a diverse community of potentially novel microorganisms including members from the DPANN and Asgard archaea, Candidate Phyla Radiation (CPR) and other candidate phyla, with highest diversity indices found in the lower regions of the mat. Major metabolic cycles belonging to sulfur, carbon, nitrogen, and fermentation were detected in the mat metagenomes with the assimilatory sulfate reduction pathway being distinctly abundant. Critical microbial interactions were also inferred, and from 117 medium-to-high quality metagenome-assembled genomes (MAGs), viral defense mechanisms (CRISPR, BREX, and DISARM), elemental transport, osmoprotection, heavy metal and UV resistance were also detected in the mats. These analyses have provided a greater understanding of these distinct mat systems in Shark Bay, including key insights into adaptive responses.
Long-term cellulose enrichment selects for highly cellulolytic consortia and competition for public goods
Authors: Lewin Gina R. , Davis Nicole M. , McDonald Bradon R. , Book Adam J. , Chevrette Marc G. , Suh Steven , Boll Ardina , Currie Cameron R. 
Published: September 2020

AbstractThe complexity of microbial communities hinders our understanding of how microbial diversity and microbe-microbe interactions impact community functions. Here, using six independent communities originating from the refuse dumps of leaf-cutter ants and enriched using the plant polymer cellulose as the sole source of carbon, we examine how changes in bacterial diversity and interactions impact plant biomass decomposition. Over up to 60 serial transfers (∼8 months), cellulolytic ability increased then stabilized in four enrichment lines and was variable in two lines. Bacterial community characterization using 16S rRNA gene amplicon sequencing showed community succession differed between the highly cellulolytic and variably cellulolytic enrichment lines. Metagenomic and metatranscriptomic analyses revealed thatCellvibrioand/orCellulomonasdominated each enrichment line and produced the majority of cellulase enzymes, while diverse taxa were retained within these communities over the duration of transfers. Interestingly, the less cellulolytic communities had a higher diversity of organisms competing for the cellulose breakdown product cellobiose, suggesting that cheating slowed cellulose degradation. In addition, we found competitive exclusion as an important factor shaping all the communities, with the mutual exclusion of specific cellulolytic taxa within individual enrichment lines and the high expression of genes associated with the production of antagonistic compounds. Our results provide insights into how microbial diversity and competition affect the stability and function of cellulose-degrading communities.ImportanceMicrobial communities are a key driver of the carbon cycle through the breakdown of complex polysaccharides in diverse environments including soil, marine systems, and the mammalian gut.However, due to the complexity of these communities, the species-species interactions that impact community structure and ultimately shape the rate of decomposition are difficult to define. Here we performed serial enrichment on cellulose using communities inoculated from leaf-cutter ant refuse dumps, a cellulose-rich environment. By concurrently tracking cellulolytic ability and community composition and through metagenomic and metatranscriptomic sequencing, we analyzed the ecological dynamics of the enrichment lines. Our data suggest that antagonism is prevalent in these communities and that competition for soluble sugars may slow degradation and lead to community instability. Together, these results help reveal the relationships between competition and polysaccharide decomposition, with implications in diverse areas ranging from microbial community ecology to cellulosic biofuels production.
An immunodominance hierarchy exists in CD8+T cell responses to HLA-A*02:01-restricted epitopes identified from the non-structural polyprotein 1a of SARS-CoV-2
Authors: Takagi Akira , Matsui Masanori 
Published: September 2020

AbstractCOVID-19 vaccines are being rapidly developed and human trials are underway. Almost all of these vaccines have been designed to induce antibodies targeting spike protein of SARS-CoV-2 in expectation of neutralizing activities. However, non-neutralizing antibodies are at risk of causing antibody-dependent enhancement. Further, the longevity of SARS-CoV-2-specific antibodies is very short. Therefore, in addition to antibody-induced vaccines, novel vaccines on the basis of SARS-CoV-2-specific cytotoxic T lymphocytes (CTLs) should be considered in the vaccine development. Here, we attempted to identify HLA-A*02:01-restricted CTL epitopes derived from the non-structural polyprotein 1a of SARS-CoV-2. Eighty-two peptides were firstly predicted as epitope candidates on bioinformatics. Fifty-four in 82 peptides showed high or medium binding affinities to HLA-A*02:01. HLA-A*02:01 transgenic mice were then immunized with each of the 54 peptides encapsulated into liposomes. The intracellular cytokine staining assay revealed that 18 out of 54 peptides were CTL epitopes because of the induction of IFN-γ-producing CD8+T cells. In the 18 peptides, 10 peptides were chosen for the following analyses because of their high responses. To identify dominant CTL epitopes, mice were immunized with liposomes containing the mixture of the 10 peptides. Some peptides were shown to be statistically predominant over the other peptides. Surprisingly, all mice immunized with the liposomal 10 peptide mixture did not show the same reaction pattern to the 10 peptides. There were three pattern types that varied sequentially, suggesting the existence of an immunodominance hierarchy, which may provide us more variations in the epitope selection for designing CTL-based COVID-19 vaccines.ImportanceFor the development of vaccines based on SARS-CoV-2-specific cytotoxic T lymphocytes (CTLs), we attempted to identify HLA-A*02:01-restricted CTL epitopes derived from the non-structural polyprotein 1a of SARS-CoV-2. Out of 82 peptides predicted on bioinformatics, 54 peptides showed good binding affinities to HLA-A*02:01. Using HLA-A*02:01 transgenic mice, 18 in 54 peptides were found to be CTL epitopes in the intracellular cytokine staining assay. Out of 18 peptides, 10 peptides were chosen for the following analyses because of their high responses. To identify dominant epitopes, mice were immunized with liposomes containing the mixture of the 10 peptides. Some peptides were shown to be statistically predominant. Surprisingly, all immunized mice did not show the same reaction pattern to the 10 peptides. There were three pattern types that varied sequentially, suggesting the existence of an immunodominance hierarchy, which may provide us more variations in the epitope selection for designing CTL-based COVID-19 vaccines.
Rapid transition to distance learning due to COVID-19: Perceptions of postgraduate dental learners and instructors
Authors: Rad Fatemeh Amir , Otaki Farah , Baqain Zaid , Zary Nabil , Al-Halabi Manal 
Published: September 2020

AbstractThe outbreak of COVID-19 necessitated abrupt transition from on campus, face-to- face sessions to online, distance learning in higher education institutions. The purpose of this study was to investigate the perceptions of postgraduate dental learners and instructors about the transition to distance learning, including the changes to the learning and teaching and its efficaciousness.A mixed-methods approach to research was utilized. All the instructors and postgraduate learners were invited to participate in the online survey. Quantitative data was analyzed using descriptive and inferential analyses on SPSS for Windows version 25.0, and for the responses to the open-ended questions, multi-staged Thematic Analysis was utilized.Both groups of stakeholders: learners and instructors, were quite satisfied with the rapid transition to distance learning due to COVID-19. Instructors were significantly more satisfied than the learners. The stakeholders adapted well to the change. The perception of the stakeholders regarding the case-based scenarios significantly influenced their level of satisfaction. As perceived by the stakeholders, the transition to distance learning entailed advantages and challenges. Going through the experience equipped the stakeholders with lessons learned and enabled them to develop informed opinions of how best to sustain learning and teaching irrespective of how matters unfold in relation to the pandemic.In conclusion, the worldwide dental education community faced unprecedented challenges due to the onset of COVID-19. Yet, in the grand scheme of things, it is important for decision-makers not to miss-out on the worthwhile opportunities, inherent in the experience, to reinforce curriculums, and maximize the learning and teaching.
A empirical comparison of preservation methods for synthetic DNA data storage
Authors: Organick Lee , Nguyen Bichlien H. , McAmis Rachel , Chen Weida D. , Kohll A. Xavier , Ang Siena Dumas , Grass Robert N. , Ceze Luis , Strauss Karin 
Published: September 2020

ABSTRACTSynthetic DNA has recently risen as a viable alternative for long-term digital data storage. To ensure that information is safely recovered after storage, it is essential to appropriately preserve the physical DNA molecules encoding the data. While preservation of biological DNA has been studied previously, synthetic DNA differs in that it is typically much shorter in length, it has different sequence profiles with fewer, if any, repeats (or homopolymers), and it has different contaminants. In this paper we evaluate nine different methods used to preserve data files encoded in synthetic DNA by accelerated aging of nearly 29,000 DNA sequences. In addition to a molecular count comparison, we also sequence and analyze the DNA after aging. Our findings show that errors and erasures are stochastic and show no practical distribution difference between preservation methods. Finally, we compare the physical density of these methods and provide a stability versus density trade-offs discussion.
Measurement of Kinetics of Hammerhead Ribozyme Cleavage Reactions using Toehold Mediated Strand Displacement
Authors: Kapadia Jay Bhakti , Kharma Nawwaf , Davis Alen Nellikulam , Kamel Nicolas , Perreault Jonathan 
Published: September 2020

ABSTRACTThis paper presents a probe comprising a fluorophore and a quencher, enabling measurement of hammerhead ribozyme cleavage reactions, without labeled RNA molecules, regular sampling or use of polyacrylamide gels. The probe is made of two DNA strands; one strand is labelled with a fluorophore at its 5’-end, while the other strand is labelled with a quencher at its 3’-end. These two DNA strands are perfectly complementary, but with a 3’-overhang of the fluorophore strand. These unpaired nucleotides act as a toehold, which is utilized by a detached cleaved fragment (coming from a self-cleaving hammerhead ribozyme) as the starting point for a strand displacement reaction. This reaction causes the separation of the fluorophore strand from the quencher strand, culminating in fluorescence, detectable in a plate reader. Notably, the emitted fluorescence isproportionalto the amount of detached cleaved-off RNAs, displacing the DNA quencher strand. This method can replace or complement radio-hazardous unstable32P as a method of measurement of the kinetics of ribozyme cleavage reactions; it also eliminates the need for polyacrylamide gels, for the same purpose. Critically, this method allows to distinguish between the total amount of cleaved ribozymes and the amount ofdetachedfragments, resulting from that cleavage reaction.
Towards new models of cancer care in Australia: lessons from Victoria's response to the COVID‐19 pandemic
Authors: Underhill Craig , Parente Phillip , McArthur Grant , Haydon Andrew , McLachlan Sue‐Anne , Wong Zee Wan , Segelov Eva ,   Victorian COVID‐19 Cancer Network
Published: September 2020

AbstractIn response to the COVID‐19 pandemic, the Department of Health and Human Services Victoria (DHHS), the Monash Partners Comprehensive Cancer Consortium (MPCCC) and Victorian Comprehensive Cancer Centre (VCCC) pooled their combined infrastructure to establish the Victorian COVID‐19 Cancer Network (VCCN) backed by a Taskforce of expert members. In a few short months, this state‐wide clinical network implemented a number of new models of care including clinics to manage acutely presenting cancer patients away from emergency departments, chemotherapy in the home, telehealth models and addressing sustainability of clinical trials.
Association of optimal blood pressure with mortality in patients taking antihypertensive medications
Authors: Yun Dong‐Ho , Lee Hye‐Sun , Choi Won‐Jun , Chang Hyuk‐Jae , Son Da‐Hye , Lee Ji‐Won 
Published: September 2020

AbstractWe investigated the relationship between blood pressure (BP) and mortality in patients taking antihypertensive medications in the Korean using data from the 2007‐2015 Korean National Health and Nutrition Examination Surveys. A total of 6601 patients aged 30‐74 years were included. Systolic BP (SBP) and diastolic BP (DBP) were both divided into four groups as follows: SBP < 120, 120 ≤ SBP ≤ 129 130 ≤ SBP ≤ 139, and SBP ≥ 140; DBP < 70, 70 ≤ DBP ≤ 79, 80 ≤ DBP ≤ 89, and DBP ≥ 90. The survival rates and hazard ratios were evaluated using Kaplan‐Meier curves and multivariable Cox regression analyses. To evaluate the predictability of all‐cause mortality according to SBP and/or DBP, we calculated Harrell's concordance‐index. The lowest DBP group had a high risk of mortality regardless of the SBP status. The group with DBP < 70 mm Hg and SBP ≥ 140 mm Hg showed the highest mortality. The discriminatory ability calculated using Harrell's C‐indexes was greater for the combination of SBP and DBP compared to DBP or SBP alone. These results suggest that it is more effective to simultaneously evaluate the effect of SBP and DBP to predict mortality; clinicians should manage DBP < 70 mm Hg when treating hypertensive patients.
Neuropilin‐1 is up‐regulated by cancer‐associated fibroblast‐secreted IL‐8 and associated with cell proliferation of gallbladder cancer
Authors: Chen Chen , Zhang Rui , Ma Li , Li Qi , Zhao Ya‐ling , Zhang Guan‐jun , Zhang Dong , Li Wen‐zhi , Cao Sheng , Wang Lin , Geng Zhi‐min 
Published: September 2020

AbstractWe previously demonstrated that cancer‐associated fibroblasts (CAFs) promoted the proliferation of gallbladder cancer (GBC) cells, but the mechanism is not clear. Neuropilin‐1 (NRP‐1) plays an important role in various malignancies as transmembrane glycoprotein. Our goal was to reveal the relationship between CAFs and NRP‐1 and their potential functions in GBC. In this study, we found NRP‐1 was overexpressed in GBC tissue, associated with poor survival and was up‐regulated by CAFs. The cytokine array cluster analysis revealed IL‐8 secreted by CAFs facilitated the up‐regulation of NRP‐1 in tumour cells. NRP‐1 knockdown suppressed tumour growth in vivo. Gene expression microarray analysis showed 581 differentially regulated genes under NRP‐1 knockdown conditions. Ingenuity pathway analysis demonstrated that NRP‐1 knockdown may inhibit tumour progression by affecting cell proliferation. We then confirmed that NRP‐1 knockdown in NOZ and GBC‐SD cells significantly inhibited cell proliferation. Additionally, the IL‐8 mediated MDM2 and CCNA2 expression were affected by NRP‐1 knockdown. Our findings suggested that NRP‐1 was up‐regulated by CAF‐secreted IL‐8, which subsequently promoted GBC cell proliferation, and these molecules may serve as useful prognostic biomarkers and therapeutic targets for GBC.
Characterization of water-based liquid scintillator for Cherenkov and scintillation separation
Authors: Caravaca J. , Land B. J. , Yeh M. , Orebi Gann G. D. 
Published: September 2020

AbstractThis paper presents measurements of the scintillation light yield and time profile for a number of concentrations of water-based liquid scintillator, formulated from linear alkylbenzene (LAB) and 2,5-diphenyloxazole (PPO). We find that the scintillation light yield is linear with the concentration of liquid scintillator in water between 1 and 10% with a slope of $$127.9\pm 17.0$$

127.9
±
17.0

ph/MeV/concentration and an intercept value of $$108.3\pm 51.0$$

108.3
±
51.0

ph/MeV, the latter being illustrative of non-linearities with concentration at values less than 1%. This is larger than expected from a simple extrapolation of the pure liquid scintillator light yield. The measured time profiles are consistently faster than that of pure liquid scintillator, with rise times less than 250 ps and prompt decay constants in the range of 2.1–2.85 ns. Additionally, the separation between Cherenkov and scintillation light is quantified using cosmic muons in the CHESS experiment for each formulation, demonstrating an improvement in separation at the centimeter scale. Finally, we briefly discuss the prospects for large-scale detectors.
Chemerin enhances the adhesion and migration of human endothelial progenitor cells and increases lipid accumulation in mice with atherosclerosis
Authors: Jia Jue , Yu Fan , Xiong Yuyun , Wei Weiping , Ma Hong , Nisi Fulvio , Song Xu , Yang Ling , Wang Dong , Yuan Guoyue , Zhou Hongwen 
Published: September 2020

Abstract
Background
The role of adipokines in the development of atherosclerosis (AS) has received increasing attention in recent years. This study aimed to explore the effects of chemerin on the functions of human endothelial progenitor cells (EPCs) and to investigate its role in lipid accumulation in ApoE-knockout (ApoE−/−) mice.

Methods
EPCs were cultured and treated with chemerin together with the specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580 in a time- and dose-dependent manner. Changes in migration, adhesion, proliferation and the apoptosis rate of EPCs were detected. ApoE−/− mice with high-fat diet-induced AS were treated with chemerin with or without SB 203580. Weights were recorded, lipid indicators were detected, and tissues sections were stained.

Results
The data showed that chemerin enhanced the adhesion and migration abilities of EPCs, and reduced the apoptosis ratio and that this effect might be mediated through the p38 MAPK pathway. Additionally, chemerin increased the instability of plaques. Compared with the control group and the inhibitor group, ApoE−/− mice treated with chemerin protein had more serious arterial stenosis, higher lipid contents in plaques and decreased collagen. Lipid accumulation in the liver and kidney and inflammation in the hepatic portal area were enhanced by treatment with chemerin, and the size of adipocytes also increased after chemerin treatment. In conclusion, chemerin can enhance the adhesion and migration abilities of human EPCs and reduce the apoptosis ratio. In animals, chemerin can increase lipid accumulation in atherosclerotic plaques and exacerbate plaques instability. At the same time, chemerin can cause abnormal lipid accumulation in the livers and kidneys of model animals. After specifically blocking the p38 MAPK pathway, the effect of chemerin was reduced.

Conclusions
In conclusion, this study showed that chemerin enhances the adhesion and migration abilities of EPCs and increases the instability of plaques and abnormal lipid accumulation in ApoE−/− mice. Furthermore, these effects might be mediated through the p38 MAPK pathway.
Haplotype threading: accurate polyploid phasing from long reads
Authors: Schrinner Sven D. , Mari Rebecca Serra , Ebler Jana , Rautiainen Mikko , Seillier Lancelot , Reimer Julia J. , Usadel Björn , Marschall Tobias , Klau Gunnar W. 
Published: September 2020

AbstractResolving genomes at haplotype level is crucial for understanding the evolutionary history of polyploid species and for designing advanced breeding strategies. Polyploid phasing still presents considerable challenges, especially in regions of collapsing haplotypes.We present WhatsHap polyphase, a novel two-stage approach that addresses these challenges by (i) clustering reads and (ii) threading the haplotypes through the clusters. Our method outperforms the state-of-the-art in terms of phasing quality. Using a real tetraploid potato dataset, we demonstrate how to assemble local genomic regions of interest at the haplotype level. Our algorithm is implemented as part of the widely used open source tool WhatsHap.