bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential regulation of gene expression pathways with dexamethasone and ACTH after early life seizures
Authors: Brabec Jeffrey L. , Ouardouz Mohamed , Mahoney J. Matthew , Scott Rod C. , Hernan Amanda E. 
Published: May 2022

AbstractEarly-life seizures (ELS) are associated with persistent cognitive deficits such as ADHD and memory impairment. These co-morbidities have a dramatic negative impact on the quality of life of patients. Therapies that improve cognitive outcomes have enormous potential to improve patients’ quality of life. Our previous work in a rat flurothyl-induction model showed that administration of adrenocorticotropic hormone (ACTH) at time of seizure induction led to improved learning and memory in the animals despite no effect on seizure latency or duration. Administration of dexamethasone (Dex), a corticosteroid, did not have the same positive effect on learning and memory and has even been shown to exacerbate injury in a rat model of temporal lobe epilepsy. We hypothesized that ACTH exerted positive effects on cognitive outcomes through beneficial changes to gene expression and proposed that administration of ACTH at seizure induction would return gene-expression in the brain towards the normal pattern of expression in the Control animals whereas Dex would not. Twenty-six Sprague-Dawley rats were randomized into vehicle- Control, and ACTH-, Dex-, and vehicle-ELS. Rat pups were subjected to 60 flurothyl seizures from P5 to P15. After seizure induction, brains were removed and the hippocampus and PFC were dissected, RNA was extracted and sequenced, and differential expression analysis was performed using generalized estimating equations. Differential expression analysis showed that ACTH pushes gene expression in the brain back to a more normal state of expression through enrichment of pathways involved in supporting homeostatic balance and down-regulating pathways that might contribute to excitotoxic cell-damage post-ELS.
Comparison of immunogenicity and safety of inactivated, adenovirus-vectored and heterologous adenovirus-vectored/mRNA vaccines in patients with systemic lupus erythematosus and rheumatoid arthritis: a prospective cohort study
Authors: Assawasaksakul Theerada , Lertussavavivat Tanat , Sathitratanacheewin Seelwan , Oudomying Nont , Vichaiwattana Preeyaporn , Wanlapakorn Nasamon , Poovorawan Yong , Avihingsanon Yingyos , Assawasaksakul Nawaporn , Kittanamongkolchai Wonngarm 
Published: May 2022

AbstractBackgroundImpaired immune response to COVID-19 vaccines have been observed in autoimmune rheumatic disease patients. Determining the most effective and safe vaccine regimen is critically needed in such a population. We aim to compare the immunogenicity and safety of three COVID-19 vaccine regimens in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).MethodsSLE and RA patients aged 18-65 years who received inactivated (CoronaVac or COVILO), adenovirus-vectored (AZD1222), or heterogeneous (AZD1222/BNT162b2) vaccines were enrolled. Humoral and cellular immune responses were assessed at day 28 after the second vaccination. This was performed using the serum binding antibody level against receptor-binding domain of the SARS-CoV-2 spike protein (anti-RBD Ig) and IFNy-ELISpot assay (ELISpot) respectively. Reactogenicity was reviewed on day 7 following each vaccination. Disease activity was assessed before and on day 28 after the second vaccination.ResultsThe cohort consisted of 94 patients (64 SLE and 30 RA). Inactivated, AZD1222, and AZD1222/BNT162b2 vaccines were administered to 23, 43, and 28 patients, respectively. Anti-RBD titers were lowest in the inactivated vaccine group (2.84 AU/mL; 95% CI 0.96-8.44), followed by AZD1222 (233.7 AU/mL; 95% CI 99.0 - 505.5) and AZD1222/BNT162b2 (688.6 AU/mL; 95% CI 271 - 1745), p 0<0.0001. After adjusting for relevant factors, the inactivated vaccine was associated with the lowest humoral response, while adenovirus-vectored/mRNA vaccine was the highest. The proportion of positive ELISpot test was also lowest in the inactivated vaccine group (27%), followed by the adenovirus-vectored vaccine (67%), and adenovirus-vectored/mRNA vaccine (73%)(p = 0.03). All types of vaccine were well-tolerated. There was no flare of autoimmune disease post-vaccination.ConclusionAdenovirus-vectored and adenovirus-vectored/mRNA vaccines elicited a stronger humoral and cellular immune response than inactivated vaccines, suggesting that they may be more suitable in SLE and RA patients receiving immunosuppressive therapy.
A protein signature associated with active tuberculosis identified by plasma profiling and network-based analysis
Authors: Mousavian Zaynab , Folkesson Elin , Fröberg Gabrielle , Foroogh Fariba , Correia-Neves Margarida , Bruchfeld Judith , Källenius Gunilla , Sundling Christopher 
Published: May 2022

AbstractObjectivesTuberculosis (TB) is a bacterial infectious disease caused byMycobacterium tuberculosis. Annually, an estimated 10 million people are diagnosed with active TB, and approximately 1.4 million dies of the disease. If left untreated, each person with active TB will infect 10 to 15 new individuals every year. Therefore, interrupting disease transmission by accurate early detection and diagnosis, paired with appropriate treatment is of major importance. In this study, we aimed to identify biomarkers associated with the development of active TB that can then be further developed for clinical testing.MethodsWe assessed the relative plasma concentration of 92 proteins associated with inflammation in individuals with active TB (n=19), latent TB (n=13), or healthy controls (n=10). We then constructed weighted protein co-expression networks to reveal correlations between protein expression profiles in all samples. After clustering the networks into four modules, we assessed their association with active TB.ResultsOne module consisting of 16 proteins was highly associated with active TB. We used multiple independent transcriptomic datasets from studies investigating respiratory infections and non-TB diseases. We then identified and removed genes encoding proteins within the module that were low expressed in active TB or associated with non-TB diseases, resulting in a 12-protein plasma signature associated with active TB.ConclusionWe identified a plasma protein signature that is highly enriched in patients with active TB but not in individuals with latent TB or healthy controls and that also had minimal cross-reactivity with common viral or bacterial lower respiratory tract infections.
Advancing antimicrobial resistance monitoring in surface waters with metagenomic and quasimetagenomic methods
Authors: Ottesen Andrea , Kocurek Brandon , Ramachandran Padmini , Reed Elizabeth , Commichaux Seth , Engelbach Gunnar , Mammel Mark , Fleurant Sanchez Saint , Zhao Shaohua , Kabera Claudine , Merrill Amy , Bonin Nathalie , Worley Hannah , Noyes Noelle , Boucher Christina , McDermott Patrick , Strain Errol 
Published: May 2022

AbstractSurface waters present a unique challenge for the monitoring of critically important antimicrobial resistance. Metagenomic approaches provide unbiased descriptions of taxonomy and antimicrobial resistance genes in many environments, but for surface water, culture independent data is insufficient to describe critically important resistance. To address this challenge and expand resistome reporting capacity of antimicrobial resistance in surface waters, we apply metagenomic and quasimetagenomic (enriched microbiome) data to examine and contrast water from two sites, a creek near a hospital, and a reservoir used for recreation and municipal water. Approximately 30% of the National Antimicrobial Resistance Monitoring System’s critically important resistance gene targets were identified in enriched data contrasted to only 1% in culture independent data. Four different analytical approaches consistently reported substantially more antimicrobial resistance genes in quasimetagenomic data compared to culture independent data across most classes of antimicrobial resistance. Statistically significant differential fold changes (p<0.05) of resistance determinants were used to infer microbiological differences in the waters. Important pathogens associated with critical antimicrobial resistance were described for each water source. While the single time-point for only two sites represents a small pilot project, the successful reporting of critically important resistance determinants is proof of concept that the quasimetagenomic approach is robust and can be expanded to multiple sites and timepoints for national and global monitoring and surveillance of antimicrobial resistance in surface waters.
Loss of the chromatin remodeler, ATRX, promotes aggressive features of osteosarcoma with increased NF-κB signaling and integrin receptor binding
Authors: DeWitt Suzanne Bartholf , Plumlee Sarah Hoskinson , Brighton Hailey E. , Sivaraj Dharshan , Martz E. J. , Zand Maryam , Kumar Vardhman , Sheth Maya U. , Floyd Warren , Spruance Jacob , Hawkey Nathan , Varghese Shyni , Ruan Jianhua , Kirsch David G. , Somarelli Jason A. , Alman Ben , Eward William C. 
Published: May 2022

AbstractOsteosarcoma (OS) is a lethal disease with few known targeted therapies. Here we show that decreased ATRX expression is associated with more aggressive tumor cell phenotypes, including increased growth, migration, invasion, and metastasis. These phenotypic changes correspond with activation of NF-κB signaling, extracellular matrix remodeling, increased integrin αvβ3 expression, and ETS family transcription factor binding. Here we characterize these changes in vitro, in vivo, and in a dataset of human OS patients. This increased aggression substantially sensitizes ATRX-deficient OS cells to integrin signaling inhibition. Thus, ATRX plays an important tumor suppression role in OS, and loss of function of this gene may underlie new therapeutic vulnerabilities. The relationship between ATRX expression and integrin binding, NF-κB activation, and ETS family transcription factor binding has not been described in previous studies and may impact the pathophysiology of other diseases with ATRX loss, including other cancers and the ATR-X alpha thalassemia mental retardation syndrome.
Honey bee functional genomics using symbiont-mediated RNAi
Authors: Lariviere Patrick J. , Leonard Sean P. , Horak Richard D. , Powell J. Elijah , Barrick Jeffrey E. 
Published: May 2022

AbstractBees are indispensable pollinators and model organisms for studying social behavior, development, and cognition. However, their eusociality makes it difficult to use standard forward genetic approaches to study gene function. To fill this gap, we engineered the bee gut bacteriumSnodgrassella alvito induce a host RNA interference response that reduces expression of a targeted gene. To employ this FUGUES (FUnctionalGenomicsUsingEngineeredSymbionts) procedure, a double-stranded RNA expression plasmid is cloned inEscherichia coliusing Golden Gate assembly and then transferred toS. alvi. Adult worker bees are then colonized with engineeredS. alvi. Finally, gene knockdown is verified through qRT-PCR, and bee phenotypes of interest can be further assessed. Expression of targeted genes is reduced by as much as 50-75% throughout the entire bee body by five days after colonization. This protocol can be accomplished in four weeks by bee researchers with microbiology and molecular cloning skills.
Engineered sensor bacteria evolve master-level gameplay through accelerated adaptation
Authors: Prakash Satya , Racovita Adrian , Varela Clenira , Walsh Mark , Galizi Roberto , Isalan Mark , Jaramillo Alfonso 
Published: May 2022

AbstractGene circuits enable cells to make decisions by controlling the expression of genes in reaction to specific environmental factors1. These circuits can be designed to encode logical operations2–7, but implementation of more complex algorithms has proved more challenging. Directed evolution optimizes gene circuits8without the need for design knowledge9, but adjusting multiple genes and conditions10in genotype searches poses challenges11. Here we show a multicellular sensor system, AdaptoCells, in Escherichia coli, that can evolve complex behavior through an accelerated adaptation to chemical environments. AdaptoCells recognize chemical patterns and act as a decision-making system. Using an iterative improvement method, we demonstrate that the AdaptoCells can evolve to achieve mastery in the game of tic-tac-toe, demonstrating an unprecedented level of complexity for engineered living cells. We provide an effective and straightforward way to encode complexity in gene circuits, allowing for fast adaptation in response to dynamic environments and leading to optimal decisions.
Individual prediction tendencies facilitate cortical speech tracking
Authors: Schubert Juliane , Schmidt Fabian , Gehmacher Quirin , Bresgen Annika , Weisz Nathan 
Published: May 2022

ABSTRACTListening can be conceptualized as a process of active inference, in which the brain forms internal models to predict and integrate auditory information in a complex interaction of bottom-up and top-down processes. Whether inter-individual “prediction tendencies” shape listening experiences of real-world stimuli such as speech is, however, unknown. In the current study, we used a passive paradigm presenting tone sequences of varying entropy level, to independently quantify auditory prediction tendency (as the tendency to anticipate low-level acoustic features according to their contextual probability) for each individual. This measure was then used to predict the magnitude of cortical speech (envelope) tracking in a multi speaker listening task, where participants listened to audiobooks narrated by a target speaker in isolation or interfered by 1 or 2 distractors. Furthermore, rare semantic violations were introduced into the story, enabling us to also examine effects of word surprisal during continuous speech processing. Our results show that individual prediction tendency facilitates cortical speech tracking. Furthermore, we find interactions between individual prediction tendency and background noise as well as word surprisal in disparate brain regions. In sum, our findings suggest that individual prediction tendencies are generalizable across different listening situations and may serve as a valuable element to explain interindividual differences in natural listening experience.
Identification of Transient Intermediates During Spliceosome Activation by Single Molecule Fluorescence Microscopy
Authors: Fu Xingyang , Kaur Harpreet , Rodgers Margaret L. , Montemayor Eric J. , Butcher Samuel E. , Hoskins Aaron A. 
Published: May 2022

SummarySpliceosome activation is the process of creating the catalytic site for RNA splicing and occurs de novo on each intron following spliceosome assembly. Dozens of factors bind to or are released from the activating spliceosome including the Lsm2-8 heteroheptameric ring that binds the U6 small nuclear RNA (snRNA) 3’-end. Lsm2-8 must be released to permit active site stabilization by the Prp19-containing complex (NineTeen Complex, NTC); however, little is known about the temporal order of events and dynamic interactions that lead up to and follow Lsm2-8 release. We have used colocalization single molecule spectroscopy (CoSMoS) to visualize Lsm2-8 dynamics during activation of yeast spliceosomes. Lsm2-8 is recruited as a component of the tri-snRNP and is released after integration of the Prp19-containing complex (NineTeen Complex, NTC). Despite Lsm2-8 and the NTC being mutually exclusive in existing cryo-EM structures of yeast B complex spliceosomes, we identify a transient intermediate containing both and provide a kinetic framework for its formation and transformation during activation. Prior to assembly, the NTC rapidly and reversibly samples the spliceosome suggesting a mechanism for preventing NTC sequestration by defective spliceosomes that fail to properly activate. In complementary ensemble assays, we show that a base-pairing dependent ternary complex can form between Lsm2-8 and U2 and U6 helix II RNAs. Together our data suggest a Hfq-like function for Lsm2-8 in maintaining U2/U6 helix II integrity before it can be transferred to the NTC by transient formation of the spliceosome.Significance StatementThe spliceosome active site is created de novo during activation and involves numerous conformational and compositional changes. Here, we define a kinetic pathway for yeast spliceosome activation using single molecule fluorescence that includes transient intermediates not previously identified. Real-time measurements allow us to uncover rapid, reversible sampling interactions of the NineTeen Complex (NTC) that may prevent its accumulation on defective spliceosomes. By analogy with bacterial Hfq, we propose that the homologous Lsm2-8 proteins stabilize U2/U6 helix II during activation before the helix is transferred to the NTC in a short-lived spliceosome containing both Lsm2-8 and the NTC. Our data demonstrate how single molecule studies of activation can reveal kinetically-competent intermediates and complement cryo-EM studies of stalled or inhibited complexes.
Toward Interpretable Digital Biomarkers of Walking and Reaching in Parkinson’s Disease
Authors: Ryu Jihye , Torres Elizabeth 
Published: May 2022

AbstractMultimodal digital data registered with wearable biosensors has emerged as highly complementary of clinical pencil-and-paper criteria, offering new insights in ways to detect and diagnose various aspects of Parkinson’s disease. A pressing question is how to combine both the clinical knowledge of PD and the new technology to create interpretable digital biomarkers easily obtainable with off-the-shelf technology. Several challenges concerning disparity in biophysical units, anatomical differences across participants, sensor positioning, and sampling resolution are addressed in this work, along with identification of optimal parameters to automatically differentiate patients with PD from controls. We combine data from a multitude of biosensors registering signals from the central (EEG) and peripheral (magnetometry, kinematics) nervous systems, inclusive of the autonomic nervous system (EKG), as the participants perform natural tasks requiring different levels of intentional planning and automatic control. We find that magnetometer data during walking, across a variety of amplitude and timing signals provide optimal separation of PD from neurotypical controls. We conclude that considering multimodal signals, while differentiating across levels of intent in natural actions can be revealing of important features of PD that otherwise escape the naked eye. Further we add that clinical criteria combined with such optimal digital parameter spaces offer a far more complete picture of PD than using either one of these pieces of data alone.
Comparison of dry and wet electrodes for detecting gastrointestinal activity patterns from body surface electrical recordings
Authors: Erickson Jonathan C. , Hassid Emily , Stepanyan Elen 
Published: May 2022

AbstractObjectiveGastrointestinal motility patterns can be mapped via electrical signals measured non-invasively on the body surface. However, long-term monitoring (≥ 24 hr) may be hindered by skin-irritation inherent with traditional Ag/AgCl pre-gelled (“wet”) electrodes. Therefore, the aim of this work was to investigate the practical utility of using dry electrodes for GI body-surface electrical measurements.ApproachTo directly compare dry versus wet electrodes, we simultaneously recorded electrical signals from both types arranged in a 9 electrode (3 × 3) array during an ≈ 2.5 hr colonic meal-response study. Wavelet-based analyses were used to identify the signature post-meal colonic cyclic motor patterns. Signal quality was assessed for each electrode type through quantitative comparison of the dominant frequency, amplitude, signal-to-noise ratio (SNR), and signal energy vs time in the colonic frequency band. Blinded comparison of signal quality was carried out by four expert manual reviewers in order to assess the practical utility of each electrode type for identifying GI activity patterns.Main resultsDry electrodes recorded high-quality GI signals comparable to that of wet electrodes, with dominant frequency in the range 2.85 - 3.25 cpm; peak-peak amplitudes of 120 ± 40µV, and SNR in the range 7.5 - 11 dB. The CWT colonic frequency band energy versus time correlation coefficient value was ≥ 0.71 for the majority of studies (6 out of 7) indicating very good agreement between dry and wet electrode signals overall. Whereas wet electrodes were rated by expert reviewers as having slightly better signal quality for identifying GI activity patterns, dry electrodes caused no skin irritation and were thus better-tolerated by all subjects.SignificanceDry electrodes are a viable option for long-term GI monitoring studies, offering a potentially more comfortable alternative to conventional wet electrode systems.
Genome-wide translocation events drive the evolution ofCandida africana
Authors: Nnadi Nnaemeka Emmanuel , Giosa Domenico , Izam Yocy , Ubani Amaka , Ngene Anayochukwu , Ayanbimpe Grace Mebi , Enweani-Nwokelo Ifeoma Bessie , Aguiyi John Chinyere 
Published: May 2022

ABSTRACTCandida africanais emerging as an organism of interest. It is evolutionarily divergent fromCandida albicansbut has reduced virulence with a restricted ecological niche. This study aimed at comparing in silico the genome level to detect variations in the two species. Raw Illumina Hiseq data were downloaded from the European Nucleotide Archive (https://www.ebi.ac.uk/ena) with the accession numberSRR6669859and assembled using shovill (v. 1.0.9) the resulting genome was mapped against the haploid referenceCandida albicansSC5314_A22 strain using the D-GENIES webtool and contigs were reordered based on the reference, then gap-filled using GapFiller (v1-10), and annotated using MAKER-P. Synima and progressive Mauve were used to compare the annotated genomes ofCandida africanaandCandida albicansfor synteny. OrthoVenn2 webserver was used for the identification and comparison of orthologous clusters. Microsynteny variations within the genomes were determined using the GEvo. The study revealed the presence of insertions, deletions, and hypervariable regions within the genome ofCandidia africana, showing a high level of synteny withCandida albicans. The genome ofCandida africanais 14.04Mbp with a BUSCO score of 99.66%. The two species form a total of 5146 orthologous protein clusters and shared a total of 5124 protein,C. africanahas a unique cluster protein cluster whileC. albicanshave 18 unique Protein clusters. The genome ofC. africanahas lots of structural variations and the presence of gene losses and gains. These genetic variations possibly play a role in the reduced virulence potential observed inC. africana.