bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critical role of the RpoE stress response pathway in polymyxin resistance of Escherichia coli
Authors: Zeng Ximin , Hinenoya Atsushi , Guan Ziqiang , Xu Fuzhou , Lin Jun 
Published: January 2023

Abstract

Objectives
Polymyxins, including colistin, are the drugs of last resort to treat MDR bacterial infections in humans. In-depth understanding of the molecular basis and regulation of polymyxin resistance would provide new therapeutic opportunities to combat increasing polymyxin resistance. Here we aimed to identify novel targets that are crucial for polymyxin resistance using Escherichia coli BL21(DE3), a unique colistin-resistant model strain.

Methods
BL21(DE3) was subjected to random transposon mutagenesis for screening colistin-susceptible mutants. The insertion sites of desired mutants were mapped; the key genes of interest were also inactivated in different strains to examine functional conservation. Specific genes in the known PmrAB and PhoPQ regulatory network were inactivated to examine crosstalk among different pathways. Lipid A species and membrane phospholipids were analysed by normal phase LC/MS.

Results
Among eight mutants with increased susceptibility to colistin, five mutants contained different mutations in three genes (rseP, degS and surA) that belong to the RpoE stress response pathway. Inactivation of rpoE, pmrB, eptA or pmrD led to significantly increased susceptibility to colistin; however, inactivation of phoQ or eptB did not change colistin MIC. RpoE mutation in different E. coli and Salmonella resistant strains all led to significant reduction in colistin MIC (16–32-fold). Inactivation of rpoE did not change the lipid A profile but significantly altered the phospholipid profile.

Conclusions
Inactivation of the important members of the RpoE regulon in polymyxin-resistant strains led to a drastic reduction in polymyxin MIC and an increase of lysophospholipids with no change in lipid A modifications.
Insect PRXamides: Evolutionary Divergence, Novelty, and Loss in a Conserved Neuropeptide System
Authors: Farris Sarah M 
Published: January 2023

Abstract
The PRXamide neuropeptides have been described in both protostome and deuterostome species, including all major groups of the Panarthropoda. Best studied are the insect PRXamides consisting of three genes: pk/pban, capa, and eth, each encoding multiple short peptides that are cleaved post-translationally. Comparisons of genome and transcriptome sequences reveal that while retaining its fundamental ancestral organization, the products of the pk/pban gene have undergone significant change in the insect Order Diptera. Basal dipteran pk/pban genes are much like those of other holometabolous insects, while more crown species have lost two peptide coding sequences including the otherwise ubiquitous pheromone biosynthesis activating neuropeptide (PBAN). In the genomic model species Drosophila melanogaster, one of the remaining peptides (hugin) plays a potentially novel role in feeding and locomotor regulation tied to circadian rhythms. Comparison of peptide coding sequences of pk/pban across the Diptera pinpoints the acquisition or loss of the hugin and PBAN peptide sequences respectively, and provides clues to associated changes in life history, physiology, and/or behavior. Interestingly, the neural circuitry underlying pk/pban function is highly conserved across the insects regardless of the composition of the pk/pban gene. The rapid evolution and diversification of the Diptera provide many instances of adaptive novelties from genes to behavior that can be placed in the context of emerging selective pressures at key points in their phylogeny; further study of changing functional roles of pk/pban may then be facilitated by the high-resolution genetic tools available in Drosophila melanogaster.
Allosteric autoregulation of DNA binding via a DNA-mimicking protein domain: a biophysical study of ZNF410–DNA interaction using small angle X-ray scattering
Authors: Kaur Gundeep , Ren Ren , Hammel Michal , Horton John R , Yang Jie , Cao Yu , He Chenxi , Lan Fei , Lan Xianjiang , Blobel Gerd A , Blumenthal Robert M , Zhang Xing , Cheng Xiaodong 
Published: January 2023

AbstractZNF410 is a highly-conserved transcription factor, remarkable in that it recognizes a 15-base pair DNA element but has just a single responsive target gene in mammalian erythroid cells. ZNF410 includes a tandem array of five zinc-fingers (ZFs), surrounded by uncharacterized N- and C-terminal regions. Unexpectedly, full-length ZNF410 has reduced DNA binding affinity, compared to that of the isolated DNA binding ZF array, both in vitro and in cells. AlphaFold predicts a partially-folded N-terminal subdomain that includes a 30-residue long helix, preceded by a hairpin loop rich in acidic (aspartate/glutamate) and serine/threonine residues. This hairpin loop is predicted by AlphaFold to lie against the DNA binding interface of the ZF array. In solution, ZNF410 is a monomer and binds to DNA with 1:1 stoichiometry. Surprisingly, the single best-fit model for the experimental small angle X-ray scattering profile, in the absence of DNA, is the original AlphaFold model with the N-terminal long-helix and the hairpin loop occupying the ZF DNA binding surface. For DNA binding, the hairpin loop presumably must be displaced. After combining biophysical, biochemical, bioinformatic and artificial intelligence-based AlphaFold analyses, we suggest that the hairpin loop mimics the structure and electrostatics of DNA, and provides an additional mechanism, supplementary to sequence specificity, of regulating ZNF410 DNA binding.
Optimizing the order of actions in a model of contact tracing
Authors: Meister Michela , Kleinberg Jon 
Published: January 2023

AbstractContact tracing is a key tool for managing epidemic diseases like HIV, tuberculosis, COVID-19, and monkeypox. Manual investigations by human-contact tracers remain a dominant way in which this is carried out. This process is limited by the number of contact tracers available, who are often overburdened during an outbreak or epidemic. As a result, a crucial decision in any contact tracing strategy is, given a set of contacts, which person should a tracer trace next? In this work, we develop a formal model that articulates these questions and provides a framework for comparing contact tracing strategies. Through analyzing our model, we give provably optimal prioritization policies via a clean connection to a tool from operations research called a “branching bandit”. Examining these policies gives qualitative insight into trade-offs in contact tracing applications.
The Clinical Evaluation of a Modified Fmp in Infant Auditory Brainstem Response Tests
Authors: Lightfoot Guy , Georga Constantina , Ferm Inga , Beeby Rachel 
Published: January 2023

Objective:
The performance of a modified calculation of F statistic using multiple points (Fmp) in auditory brainstem response (ABR) tests in infants was evaluated.

Design:
Using UK national guidelines, the ABR threshold was established on 50 infant ears at 4 kHz and 41 infant ears at 1 kHz. A specificity-based Fmp criterion for response presence was established from the distribution of no-response values. This criterion was then applied to determine the sensitivity of Fmp in detecting responses.

Results:
A 97.5% true negative rate in no-response waveforms corresponded to an Fmp of 2.2. This criterion detected 85% of 4 kHz and 68% of 1 kHz responses at 10 dB above the ABR threshold but only 51% of 4 kHz and 32% of 1 kHz responses at the ABR threshold.

Conclusions:
Fmp has reasonable clinical utility at stimulus levels above the ABR threshold but is not an adequate replacement for strictly applied conventional waveform interpretation at the ABR threshold. A proposal is offered that should improve Fmp sensitivity.
Modification in Applying Appendix D of 40 CFR Part 61 to Heated Solid Radionuclide Materials With High Melting and Boiling Points
Authors: Smith Linda L. , McCarter William (Bill) L. , Barnett J. Matthew 
Published: January 2023

Abstract
Appendix D of Title 40 Part 61 of the US Code of Federal Regulations (CFR) provides a procedure that US Department of Energy (US DOE) facility owners and operators can use to estimate radionuclide emissions to the atmosphere for dose calculations instead of measuring emissions for minor sources under the 40 CFR Part 61, Subpart H, National Emission Standards for Emissions of Radionuclides Other Than Radon From Department of Energy Facilities, regulation. The procedure assumes that any radioactive material heated above 100 °C is completely vaporized and emitted to the atmosphere. In 1991, the US DOE Oak Ridge Reservation (ORR) requested approval to use different release fractions (RFs) for uranium because of its high melting and boiling points. In response to the request, the US Environmental Protection Agency (US EPA) Region IV approved the use of modified RFs for elemental uranium provided no reaction had taken place to alter its chemical form. In 2015, the ORR requested approval to use different RFs for tungsten, again because of its high melting and boiling points. EPA Region IV approved the use of modified RFs for heated radioactive tungsten metal. In accordance with the two precedents set for heating uranium and radioactive tungsten metals, in 2016, the ORR requested approval to use modified RFs in a similar fashion for other radioactive solid metals and compounds with melting and boiling points above 500 °C that might be heated above 100 °C in future research projects and experiments. EPA Region IV again granted approval to use modified RFs for the list of compounds. This note discusses the proposed modified RFs and their development.
Potentially inappropriate medication in long-term care wards of a veteran hospital in Taiwan: Investigation using a spreadsheet-based rapid assessment tool
Authors: Wang Ying-Mei , Shen Hung-Wei , Chen Tzeng-Ji 
Published: January 2023

Background:
Multimorbidity and polypharmacy increase in the aging population and are accompanied by the use of potentially inappropriate medications (PIMs) and adverse drug events (ADEs). This study developed a rapid assessment tool to investigate PIM use among patients in long-term care wards.

Methods:
We retrospectively collected the data of patients in long-term care wards of a veteran hospital in Taiwan between July 2019 and June 2020. The patients with chronic diseases and medications were selected. The data, including gender, age, diagnosis, and medications, were deidentified. Nonchronic disease diagnosis and short-term and topical use medications were excluded. We used Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA) and the 2019 version of the Beers Criteria to establish a rapid assessment tool. The correlations between the prevalence of PIM use and age, the number of diagnoses, and the number of medications were analyzed using SPSS version 23.

Results:
A total of 176 patients were included in this study, of which 76.7% (n = 135) were male and 23.3% (n = 41) were female. The average age of men was 82.1 years and that of women was 83.4 years. The average number of diagnoses for men was 5.5, and that for women was 7.3. The average number of medications for men was 5.8, and that for women was 6.5. The prevalence of PIM use was 59.1% (n = 104). Logistic regression revealed that the prevalence of PIM use may be associated with the number of medications (p < 0.001; odds ratio = 1.378). Decision tree analysis revealed that patients who simultaneously used more than four medications exhibited a higher risk of PIM.

Conclusion:
PIM use is a key factor causing ADEs among older adults. Therefore, comprehensive assessment of PIM use is necessary. This study designed a rapid assessment tool to simultaneously integrate and evaluate medications. Future studies may investigate the effectiveness of the proposed assessment tool.
Examination of 2D frontal and sagittal markerless motion capture: Implications for 2D and 3D markerless applications
Authors: Wade Logan , Needham Laurie , Evans Murray , McGuigan Polly , Colyer Steffi , Cosker Darren , Bilzon James 
Published: January 2023

ABSTRACTThis study examined if occluded joint locations from markerless motion capture produced 2D joint angles with reduced accuracy compared to visible joints, and if 2D frontal plane joint angles were usable for practical applications. Fifteen healthy participants performed over-ground walking whilst recorded by fifteen marker-based cameras and two machine vision cameras (frontal and sagittal plane). Repeated measures Bland-Altman analysis illustrated that markerless standard deviation of bias (random differences) for the occluded-side hip and knee joint angles in the sagittal plane were double that of the camera-side (visible) hip and knee. Camera-side sagittal plane knee and hip angles were near or within marker-based error values previously observed. While frontal plane random differences accounted for 35-46% of total range of motion at the hip and knee, systematic and random differences (−4.6-1.6 ± 3.7-4.2°) were actually similar to previously reported marker-based error values. This was not true for the ankle, where random difference (±12°) was still too high for practical applications. Our results add to previous literature, highlighting shortcomings of current pose estimation algorithms and labelled datasets. As such, this paper finishes by reviewing marker-based methods for creating anatomically accurate markerless training data.
Accounting for unobserved spatial variation in step selection analyses of animal movement via spatial random effects
Authors: Guillen Rafael Arce , Lindgren Finn , Muff Stefanie , Glass Thomas W. , Breed Greg A. , Schlägel Ulrike E. 
Published: January 2023

AbstractStep selection analysis (SSA) is a common framework for understanding animal movement and resource selection using telemetry data. Such data are, however, inherently autocorrelated in space, a complication that could impact SSA-based inference if left unaddressed. Accounting for spatial correlation is standard statistical practice when analyzing spatial data, and its importance is increasingly recognized in ecological models (e.g., species distribution models). Nonetheless, no framework yet exists to account for such correlation when analyzing animal movement using SSA.Here, we extend the popular methodIntegrated Step Selection Analysis(iSSA) by including aGaussian Field(GF) in the linear predictor to account for spatial correlation. For this, we use the Bayesian frameworkR-INLAand theStochastic Partial Differential Equations(SPDE) technique.We show through a simulation study that our method provides unbiased fixed effects estimates, quantifies their uncertainty well and improves the predictions. In addition, we demonstrate the practical utility of our method by applying it to three wolverine (Gulo gulo) tracks.Our method solves the problems of assuming spatially independent locations in the SSA framework. In addition, it offers new possibilities for making long-term predictions of habitat usage.
Effect of oncolytic virotherapy on immune microenvironment in immune subtypes identified in gastric cancer and hepatocellular carcinoma
Authors: Wang Ziyi , Peng Shuguang , Chen Xi , Xie Zhen , Li Shao 
Published: January 2023

AbstractTumor occurrence and progression are significantly influenced by immunity, and the immune infiltration and immune-related gene expression in solid tumors are closely correlated to the response of patients to immunotherapy. In this study, the level of tumor infiltrating immune cells in gastric cancer and hepatocellular carcinoma samples from the TCGA database were assessed using ssGSEA, and the tumor samples were divided into two subtypes (Imm_H and Imm_L) with different immune cell infiltration level. The differences in immune cell percentage and immune checkpoint gene expression between the two subtypes indicated that the Imm_H group had higher levels of immune infiltration, but also more infiltrated immunosuppressive cells and higher mRNA levels of immune checkpoint genes. Then the immune subtype-specific gene network was built and the main modules representing the genes and functions that differ between the two immune subtypes were identified. To explore the effect of oncolytic virus on tumor immune microenvironment, we constructed the previously developed synthetic adenovirus containing the synthetic sensory switch gene circuit, assessed the antitumor effect in mouse models, and measured the proportion of different cell types by single-cell RNA sequencing. The results showed that synthetic oncolytic virus inhibited tumor development and altered the proportion of infiltrating immune cells, suggesting that synthetic oncolytic virus may have different mechanism on the two immune subtypes.Graphical abstract
Metacommunity Structure Preserves Genome Diversity in the Presence of Gene-specific Selective Sweeps
Authors: Pompei Simone , Bella Edoardo , Weitz Joshua S. , Grilli Jacopo , Lagomarsino Marco Cosentino 
Published: January 2023

AbstractThe horizontal transfer of genes is fundamental for the eco-evolutionary dynamics of microbial communities, such as oceanic plankton, soil, and the human microbiome. In the case of an acquired beneficial gene, classic population genetics would predict a genome-wide selective sweep, whereby the genome spreads clonally with the gene, removing genome diversity. Instead, several sources of metagenomic data show the existence of “gene-specific sweeps”, whereby a beneficial gene spreads across a bacterial community, maintaining genome diversity. Several hypotheses have been proposed to explain this process, including the decreasing gene flow between ecologically distant populations, frequency-dependent selection from linked deleterious allelles, and very high rates of horizontal gene transfer. Here, we propose an additional possible scenario grounded in eco-evolutionary principles. Specifically, we show by a mathematical model and simulations that a metacommunity where species can occupy multiple patches helps maintain genome diversity. Assuming a scenario of patches dominated by single species, our model predicts that diversity only decreases moderately upon the arrival of a new beneficial gene, and that losses in diversity can be quickly restored. We explore the generic behavior of diversity as a function of three key parameters, frequency of insertion of new beneficial genes, migration rates and horizontal transfer rates.Our results provides a testable explanation for how diversity can be maintained given gene-specific sweeps even in the absence of high horizontal gene transfer rates.
Inducible TRAP RNA profiling reveals host genes expressed in Arabidopsis cells haustoriated by downy mildew
Authors: Asai Shuta , Cevik Volkan , Jones Jonathan D.G. , Shirasu Ken 
Published: January 2023

AbstractThe downy mildew oomyceteHyaloperonospora arabidopsidis, an obligate filamentous pathogen, infects Arabidopsis by forming feeding structures called haustoria inside host cells. Previous transcriptome analyses revealed host genes are specifically induced during infection; however, RNA profiling from infected tissues may fail to capture key transcriptional events occurring exclusively in haustoriated host cells where the pathogen injects virulence effectors to modulate host immunity. To determine interactions between Arabidopsis andH. arabidopsidisat the cellular level, we devised a new translating ribosome affinity purification system applicable to inducible, including pathogen-responsive, promoters thus enabling haustoriated cell-specific RNA profiling. Among the host genes specifically expressed inH. arabidopsidis-haustoriated cells, we found genes that promote either susceptibility or resistance to the pathogen, providing new insights into the Arabidopsis/downy mildew interaction. We propose that our novel protocol for profiling cell-specific transcripts will be applicable to several stimulus-specific contexts and other plant-pathogen interactions.
Predicting Protein-encoding Gene Content inEscherichia coliGenomes
Authors: Nguyen Marcus , Elmore Zachary , Ihle Clay , Moen Francesco S. , Slater Adam D. , Turner Benjamin N. , Parrello Bruce , Best Aaron A. , Davis James J. 
Published: January 2023

AbstractIn this study, we built machine learning classifiers for predicting the presence or absence of the variable genes occurring in 10-90% of all publicly available high-qualityEscherichia coligenomes. The BV-BRC genus-specific protein families were used to define orthologs across the set of genomes, and a single binary classifier was built for predicting the presence or absence of each family in each genome. Each model was built using the nucleotide k-mers from a set of 100 conserved genes as features. The resulting set of 3,259 XGBoost classifiers had a per-genome average macro F1 score of 0.944 [0.943-0.945, 95% CI]. We show that the F1 scores are stable across MLSTs, and that the trend can be recapitulated through sampling with a smaller number of core genes or diverse input genomes. Surprisingly, the presence or absence of poorly annotated proteins, including “hypothetical proteins”, were easily predicted (F1 = 0.902 [0.898-0.906, 95% CI]). Models for proteins with horizontal gene transfer-related functions, including transposition- (F1 = 0.895 [0.882-0.907, 95% CI]), phage- (F1 = 0.872 [0.868-0.876, 95% CI]), and plasmid-related (F1 = 0.824 [0.814-0.834, 95% CI]) functions had slightly lower F1 scores, but were still accurate. Finally, we applied the models to a holdout set of 419 diverseE. coligenomes that were isolated from freshwater environmental sources and observed an average per-genome F1 score of 0.880 [0.876-0.883, 95% CI], demonstrating the extensibility of the models. Overall, this study provides a framework for predicting variable gene content using a limited amount of input sequence data.ImportanceHaving the ability to predict the protein-encoding gene content of a genome is important for a variety of bioinformatic tasks, including assessing genome quality, binning genomes from shotgun metagenomic assemblies, and assessing risk due to the presence of antimicrobial resistance (AMR) and other virulence genes. In this study, we built a series of binary classifiers for predicting the presence or absence of variable genes occurring in 10-90% of all publicly availableE. coligenomes. Overall, the results show that a large portion of theE. colivariable gene content can be predicted with high accuracy, including genes with functions relating to horizontal gene transfer.
Convex representation of metabolic networks with Michaelis-Menten kinetics
Authors: Taylor Josh A. , Rapaport Alain , Dochain Denis 
Published: January 2023

AbstractPolyhedral models of metabolic networks are computationally tractable and can predict some cellular functions. A longstanding challenge is incorporating metabolites without losing tractability. In this paper, we do so using a new second-order cone representation of the Michaelis-Menten kinetics. The resulting model consists of linear stoichiometric constraints alongside second-order cone constraints that couple the reaction fluxes to metabolite concentrations.We formulate several new problems around this model: conic flux balance analysis, which augments flux balance analysis with metabolite concentrations; dynamic conic flux balance analysis; and finding minimal cut sets of networks with both reactions and metabolites. Solving these problems yields information about both fluxes and metabolite concentrations. They are second-order cone or mixed-integer second-order cone programs, which, while not as tractable as their linear counterparts, can nonetheless be solved at practical scales using existing software.