bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of circulating tumor DNA for detection and monitoring of endometrial cancer recurrence and progression
Authors: Moss Esther L. , Gorsia Diviya N. , Collins Anna , Sandhu Pavandeep , Foreman Nalini , Gore Anu , Wood Joey , Kent Christopher , Silcock Lee , Guttery David S. 
Published: March 2020

ABSTRACTDespite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients using targeted next-generation sequencing (tNGS) and personalized ctDNA assays. Using tNGS, at least 1 somatic mutation at a variant allele frequency (VAF) >20% was detected in 69% (9/13) of patient tumors. The four patients with no detectable tumor mutations at >20% VAF were whole exome sequenced, with all four harboring mutations in genes not analyzed by tNGS. Analysis of matched and longitudinal plasma DNA revealed earlier detection of EC recurrence and progression and dynamic kinetics of ctDNA levels reflecting treatment response. We also detected acquired high microsatellite instability (MSI-H) in ctDNA from one patient whose primary tumor was MSI stable. Our study suggests that ctDNA analysis, and in particular MSI analysis in ctDNA could become a useful biomarker for early detection and monitoring of EC recurrence and progression.
Study of the mental health status of medical personnel dealing with new coronavirus pneumonia
Authors: Xing Jun , Sun Ning , Xu Jun , Geng Shuling , Li Yuqian 
Published: March 2020

AbstractObjectiveThis paper studied the relationship between personality traits and mental health conditions of medical personnel to provide a basis and reference for the implementation of targeted education on mental health.MethodsA self-report inventory, the Symptom Checklist-90 (SCL-90), was used to investigate the mental health status of 548 medical personnel dealing with the new coronavirus pneumonia in eight provinces and cities of China.ResultsThe overall mean SCL-90 score and mean values of factors (somatization, obsessive-compulsive, anxiety, phobic anxiety, and psychoticism) of the medical personnel were significantly higher than in the norm group (p < 0.05), while their average interpersonal sensitivity score was significantly lower (p < 0.01). In addition, personal factors affecting the mental health status of medical personnel were identified. ( all p < 0.05).ConclusionThe overall mental health status of medical personnel responding to new coronavirus pneumonia is generally higher than that of the norm group in China. The results of this study should contribute to measures to alleviate the psychological pressures on medical personnel dealing with the new coronavirus epidemic in China.
Projecting the transmission dynamics of SARS-CoV-2 through the post-pandemic period
Authors: Kissler Stephen M. , Tedijanto Christine , Goldstein Edward M. , Grad Yonatan H. , Lipsitch Marc 
Published: March 2020

AbstractThere is an urgent need to project how transmission of the novel betacoronavirus SARS-CoV-2 will unfold in coming years. These dynamics will depend on seasonality, the duration of immunity, and the strength of cross-immunity to/from the other human coronaviruses. Using data from the United States, we measured how these factors affect transmission of human betacoronaviruses HCoV-OC43 and HCoV-HKU1. We then built a mathematical model to simulate transmission of SARS-CoV-2 through the year 2025. We project that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after an initial pandemic wave. We summarize the full range of plausible transmission scenarios and identify key data still needed to distinguish between them, most importantly longitudinal serological studies to determine the duration of immunity to SARS-CoV-2.
The impact of social distancing and epicenter lockdown on the COVID-19 epidemic in mainland China: A data-driven SEIQR model study
Authors: Zhang Yuzhen , Jiang Bin , Yuan Jiamin , Tao Yanyun 
Published: March 2020

AbstractThe outbreak of coronavirus disease 2019 (COVID-19) which originated in Wuhan, China, constitutes a public health emergency of international concern with a very high risk of spread and impact at the global level. We developed data-driven susceptible-exposed-infectious-quarantine-recovered (SEIQR) models to simulate the epidemic with the interventions of social distancing and epicenter lockdown. Population migration data combined with officially reported data were used to estimate model parameters, and then calculated the daily exported infected individuals by estimating the daily infected ratio and daily susceptible population size. As of Jan 01, 2020, the estimated initial number of latently infected individuals was 380.1 (95%-CI: 379.8∼381.0). With 30 days of substantial social distancing, the reproductive number in Wuhan and Hubei was reduced from 2.2 (95%-CI: 1.4∼3.9) to 1.58 (95%-CI: 1.34∼2.07), and in other provinces from 2.56 (95%-CI: 2.43∼2.63) to 1.65 (95%-CI: 1.56∼1.76). We found that earlier intervention of social distancing could significantly limit the epidemic in mainland China. The number of infections could be reduced up to 98.9%, and the number of deaths could be reduced by up to 99.3% as of Feb 23, 2020. However, earlier epicenter lockdown would partially neutralize this favorable effect. Because it would cause in situ deteriorating, which overwhelms the improvement out of the epicenter. To minimize the epidemic size and death, stepwise implementation of social distancing in the epicenter city first, then in the province, and later the whole nation without the epicenter lockdown would be practical and cost-effective.
Natural bacterial assemblages inArabidopsis thalianatissues become more distinguishable and diverse during host development
Authors: Beilsmith Kathleen , Perisin Matthew , Bergelson Joy 
Published: March 2020

AbstractTo study the spatial and temporal dynamics of bacterial colonization under field conditions, we planted and sampledArabidopsis thalianaduring two years at two Michigan sites and surveyed colonists by sequencing 16S rRNA gene amplicons. Mosaic and dynamic assemblages revealed the plant as a patchwork of tissue habitats that differentiated with age. Although assemblages primarily varied between roots and shoots, amplicon sequence variants (ASVs) also differentiated phyllosphere tissues. Increasing assemblage diversity indicated that variants dispersed more widely over time, decreasing the importance of stochastic variation in early colonization relative to tissue differences. As tissues underwent developmental transitions, the root and phyllosphere assemblages became more distinct. This pattern was driven by common variants rather than those restricted to a particular tissue or transiently present at one developmental stage. Patterns also depended critically on fine phylogenetic resolution: when ASVs were grouped at coarse taxonomic levels, their associations with host tissue and age weakened. Thus, the observed spatial and temporal variation in colonization depended upon bacterial traits that were not broadly shared at the family level. Some colonists were consistently more successful at entering specific tissues, as evidenced by their repeatable spatial prevalence distributions across sites and years. However, these variants did not overtake plant assemblages, which instead became more even over time. Together, these results suggested that the increasing effect of tissue type was related to colonization bottlenecks for specific ASVs rather than to their ability to dominate other colonists once established.ImportanceDeveloping synthetic microbial communities that can increase plant yield or deter pathogens requires basic research on several fronts, including the efficiency with which microbes colonize plant tissues, how plant genes shape the microbiome, and the microbe-microbe interactions involved in community assembly. Findings on each of these fronts depend upon the spatial and temporal scales at which plant microbiomes are surveyed. In our study, phyllosphere tissues housed increasingly distinct microbial assemblages as plants aged, indicating that plants can be considered as collections of tissue habitats in which microbial colonists-- natural or synthetic-- establish with differing success. Relationships between host genes and community diversity might vary depending on when samples are collected, given that assemblages grew more diverse as plants aged. Both spatial and temporal trends weakened when colonists were grouped by family, suggesting that functional rather than taxonomic profiling will be necessary to understand the basis for differences in colonization success.
Metagenomic data reveal diverse fungal and algal communities associated with the lichen symbiosis
Authors: Smith Hayden , Dal Grande Francesco , Muggia Lucia , Keuler Rachel , Divakar Pradeep K. , Grewe Felix , Schmitt Imke , Lumbsch H. Thorsten , Leavitt Steven D. 
Published: March 2020

AbstractLichens have traditionally been considered the symbiotic phenotype from the interactions of a single fungal partner and one or few photosynthetic partners. However, the lichen symbiosis has been shown to be far more complex and may include a wide range of other interacting organisms, including non-photosynthetic bacteria, accessory fungi, and algae. In this study, we analyzed metagenomic shotgun sequences to better characterize lichen mycobiomes. Specifically, we inferred the range of fungi associated within lichen thalli from five groups of lichens – horsehair lichens (mycobiont=Bryoriaspp.), shadow lichens (taxa in Physciaceae), rock posies (Rhizoplacaspp.), rock tripes (Umbilicariaspp.), and green rock shields (Xanthoparmeliaspp.). Metagenomic reads from the multi-copy nuclear ribosomal internal transcribed spacer region, the standard DNA barcode region for fungi, were extracted, clustered, and used to infer taxonomic assignments. Our data revealed diverse lichen-associated mycobiomes, and closely related mycobionts tended to have more similar mycobiomes. Many of the members of the lichen-associated mycobiomes identified here have not previously been found in association with lichens. We found little evidence supporting the ubiquitous presence of Cystobasidiales yeasts in macrolichens, although reads representing this putative symbiotic partner were found in samples of horsehair lichens, albeit in low abundance. Our study further highlights the ecosystem-like features of lichens, with partners and interactions far from being completely understood. Future research is needed to more fully and accurately characterize lichen mycobiomes and how these fungi interact with the major lichen components – the photo- and mycobionts.
A TAL effector-like protein of symbioticMycetohabitansincreases stress tolerance and alters the transcriptome of the fungal hostRhizopus microsporus
Authors: Carter Morgan E. , Carpenter Sara C.D. , Dubrow Zoë E. , Sabol Mark R. , Rinaldi Fabio C. , Lastovestsky Olga A. , Mondo Stephen J. , Pawlowska Teresa E. , Bogdanove Adam J. 
Published: March 2020

AbstractSymbioses of bacteria with fungi have only recently been described and are poorly understood. In the symbiosis ofMycetohabitans(formerlyBurkholderia)rhizoxinicawith the fungusRhizopus microsporus, bacterial type III (T3) secretion is known to be essential. Proteins resembling T3-secreted transcription activator-like (TAL) effectors of plant pathogenic bacteria are encoded in the three sequencedMycetohabitans spp.genomes. TAL effectors nuclear localize in plants, where they bind and activate genes important in disease. The Burkholderia TAL-like (Btl) proteins bind DNA but lack the N- and C-terminal regions in which TAL effectors harbor their T3 and nuclear localization signals, and activation domain. We characterized a Btl protein, Btl19-13, and found that, despite the structural differences, it can be T3-secreted and can nuclear localize. Abtl19-13gene knockout did not prevent the bacterium from infecting the fungus, but the fungus became less tolerant to cell membrane stress. Btl19-13 did not alter transcription in a plant-based reporter assay, but 15R. microsporusgenes were differentially expressed in comparisons both of the fungus infected with the wildtype bacterium vs the mutant and with the mutant vs. a complemented strain. Southern blotting revealedbtlgenes in 14 diverseMycetohabitansisolates. However, banding patterns and available sequences suggest variation, and thebtl19-13phenotype could not be rescued by abtlgene from a different strain. Our findings support the conclusion that Btl proteins are effectors that act on host DNA and play important but varied or possibly host-genotype-specific roles in theM. rhizoxinica-R. microsporussymbiosis.
Disentangling latent representations of single cell RNA-seq experiments
Authors: Kimmel Jacob C. 
Published: March 2020

AbstractSingle cell RNA sequencing (scRNA-seq) enables transcriptional profiling at the resolution of individual cells. These experiments measure features at the level of transcripts, but biological processes of interest often involve the complex coordination of many individual transcripts. It can therefore be difficult to extract interpretable insights directly from transcript-level cell profiles. Latent representations which capture biological variation in a smaller number of dimensions are therefore useful in interpreting many experiments. Variational autoencoders (VAEs) have emerged as a tool for scRNA-seq denoising and data harmonization, but the correspondence between latent dimensions in these models and generative factors remains unexplored. Here, we explore training VAEs with modifications to the objective function (i.e.β-VAE) to encourage disentanglement and make latent representations of single cell RNA-seq data more interpretable. Using simulated data, we find that VAE latent dimensions correspond more directly to data generative factors when using these modified objective functions. Applied to experimental data of stimulated peripheral blood mononuclear cells, we find better correspondence of latent dimensions to experimental factors and cell identity programs, but impaired performance on cell type clustering.Publication StatusThis pre-print represents the final output of a preliminary research direction and will not be updated or published in an archival journal. We are happy to discuss future directions we believe to be promising with any interested researchers.
Visual Biochemistry: modular microfluidics enables kinetic insight from time-resolved cryo-EM
Authors: Mäeots Märt-Erik , Lee Byungjin , Nans Andrea , Jeong Seung-Geun , Esfahani Mohammad M. N. , Smith Daniel J. , Lee Chang-Soo , Lee Sung Sik , Peter Matthias , Enchev Radoslav I. 
Published: March 2020

AbstractMechanistic understanding of biochemical reactions requires structural and kinetic characterization of the underlying chemical processes. However, no single experimental technique can provide this information in a broadly applicable manner and thus structural studies of static macromolecules are often complemented by biophysical analysis. Moreover, the common strategy of utilizing mutants or crosslinking probes to stabilize otherwise short-lived reaction intermediates is prone to trapping off-pathway artefacts and precludes determining the order of molecular events. To overcome these limitations and allow visualisation of biochemical processes at near-atomic spatial resolution and millisecond time scales, we developed a time-resolved sample preparation method for cryo-electron microscopy (trEM). We integrated a modular microfluidic device, featuring a 3D-mixing unit and a delay line of variable length, with a gas-assisted nozzle and motorised plunge-freeze set-up that enables automated, fast, and blot-free sample vitrification. This sample preparation not only preserves high-resolution structural detail but also substantially improves protein distribution across the vitreous ice. We validated the method by examining the formation of RecA filaments on single-stranded DNA. We could reliably visualise reaction intermediates of early filament growth across three orders of magnitude on sub-second timescales. Quantification of the trEM data allowed us to characterize the kinetics of RecA filament growth. The trEM method reported here is versatile, easy to reproduce and thus readily adaptable to a broad spectrum of fundamental questions in biology.
CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate and Protein Engineering
Authors: Bracco Paula , Wijma Hein J. , Nicolai Bastian , Rodriguez Buitrago Jhon Alexander , Klünemann Thomas , Vila Agustina , Schrepfer Patrick , Blankenfeldt Wulf , Janssen Dick B. , Schallmey Anett 
Published: March 2020

AbstractCYP154C5 fromNocardia farcinicais a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein and substrate engineering based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation could be achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternate binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that water entrance to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure-function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation.
Superabsorbent crosslinked bacterial cellulose biomaterials for chronic wound dressings
Authors: Ciecholewska-Juśko Daria , Żywicka Anna , Junka Adam , Drozd Radosław , Sobolewski Peter , Migdał Paweł , Kowalska Urszula , Toporkiewicz Monika , Fijałkowski Karol 
Published: March 2020

AbstractIn this work, we present novelex situmodification of bacterial cellulose (BC) polymer, that significantly improves its ability to absorb water after drying. The method involves a single inexpensive and easy-to-perform process of BC crosslinking, using citric acid along with catalysts, such as disodium phosphate, sodium bicarbonate, ammonium bicarbonate or their mixtures. In particular, the mixture of disodium phosphate and sodium bicarbonate was the most promising, yielding significantly greater water capacity (over 5 times higher as compared to the unmodified BC) and slower water release (over 6 times as compared to the unmodified BC). Further, our optimized crosslinked BC had over 1.5x higher water capacity than modern commercial dressings dedicated to highly exuding wounds, while exhibiting no cytotoxic effects against fibroblast cell line L929in vitro. Therefore, our novel BC biomaterial may find application in super-absorbent dressings, designed for chronic wounds with imbalanced moisture level.
The neuroplasticity of division of labor: worker polymorphism, compound eye structure and brain organization in the leafcutter ant Atta cephalotes
Authors: Arganda Sara , Hoadley Andrew P. , Razdan Evan S. , Muratore Isabella B. , Traniello James F. A. 
Published: March 2020

AbstractOur understanding of how the design of peripheral sensory structures is coupled with neural processing capacity to adaptively support division of labor is limited. Workers of the remarkably polymorphic fungus-growing ant Atta cephalotes are behaviorally specialized by size: the smallest workers (minims) tend fungi in dark subterranean chambers while larger workers perform tasks mainly outside the nest. These strong differences in worksite light conditions are predicted to influence sensory and processing requirements for vision. We found that eye structure and visual neuropils have been be selected to maximize task performance according to light availability. Minim eyes had few ommatidia, large interommatidial angles and eye parameter values, suggesting selection for visual sensitivity over acuity. Large workers had larger eyes with disproportionally more and larger ommatidia, and smaller interommatidial angles and eye parameter values, reflecting peripheral sensory adaptation to ambient rainforest light. Additionally, optic lobe and mushroom body collar volumes were disproportionately small in minims, and within the optic lobe, lamina and lobula relative volumes increased with worker size whereas the medulla decreased. Visual system phenotypes thus correspond to task specializations in dark or light environments and reflect a functional neuroplasticity underpinning division of labor in this socially complex agricultural ant.
Aerobic scope does matter in temperature-size rule, but only under optimal conditions
Authors: Walczyńska Aleksandra , Labecka Anna Maria , Sobczyk Mateusz 
Published: March 2020

AbstractWe united the theoretical predictions on the factors responsible for the occurrence and evolutionary significance of the temperature-size rule. We tested the causal connection among them assuming that (i) the temperature-size rule is the response to temperature-dependent oxygenic conditions, (ii) body size decrease is a consequence of cell shrinkage in response to exposure to hypoxia, (iii) this response enables to keep the wide scope for aerobic performance, and (iv) it prevents the decrease in fitness. We conducted our tests on three clones of the rotiferLecane inermiswith different thermal preferences. These clones were exposed to three experimental regimes: mild hypoxia, severe hypoxia driven by a too high temperature, and severe hypoxia driven by an inadequate oxygen concentration. The results showed that our causative reasoning was generally correct, but only under mildly hypoxic conditions. In more stressful environments, rotifers had clone- and condition-specific responses, which in fact were equally successful in terms of the levels of fitness. Our results join for the first time all factors connecting the cause and effect in the temperature-size rule. They indicate the importance of the conditions under which it should be tested. The most important messages from this study were that (i) a decrease in the body size was one of but not the only option for preventing fitness reduction under hypoxia, and (ii) such a response to higher temperature enabled the maintenance of wide aerobic scope in clone-specific, thermally optimal conditions.