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Creators/Authors contains: "Reyes, Jorge"

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  1. Abstract This report investigates a stabilization method for first order hyperbolic differential equations applied to DNA transcription modeling. It is known that the usual unstabilized finite element method contains spurious oscillations for nonsmooth solutions. To stabilize the finite element method the authors consider adding to the first order hyperbolic differential system a stabilization term in space and time filtering. Numerical analysis of the stabilized finite element algorithms and computations describing a few biological settings are studied herein. 
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  2. Abstract Unknown factors regulate mitochondrial U-insertion/deletion (U-indel) RNA editing in procyclic-form (PCF) and bloodstream-form (BSF) T. brucei. This editing, directed by anti-sense gRNAs, creates canonical protein-encoding mRNAs and may developmentally control respiration. Canonical editing by gRNAs that specify protein-encoding mRNA sequences occurs amid massive non-canonical editing of unclear sources and biological significance. We found PCF-specific repression at a major early checkpoint in mRNA ND7, involving helicase KREH2-dependent opposite modulation of canonical and non-canonical ‘terminator’ gRNA utilization. Terminator-programmed editing derails canonical editing and installs proposed repressive structure in 30% of the ND7 transcriptome. BSF-to-PCF differentiation in vitro recreated this negative control. Remarkably, KREH2-RNAi knockdown relieved repression and increased editing progression by reverting canonical/terminator gRNA utilization. ND7 transcripts lacking early terminator-directed editing in PCF exhibited similar negative editing control along the mRNA sequence, suggesting global modulation of gRNA utilization fidelity. The terminator is a ‘moonlighting’ gRNA also associated with mRNA COX3 canonical editing, so the gRNA transcriptome seems multifunctional. Thus, KREH2 is the first identified repressor in developmental editing control. This and our prior work support a model whereby KREH2 activates or represses editing in a stage and substrate-specific manner. KREH2’s novel dual role tunes mitochondrial gene expression in either direction during development. 
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  3. Abstract U-insertion/deletion (U-indel) RNA editing in trypanosome mitochondria is directed by guide RNAs (gRNAs). This editing may developmentally control respiration in bloodstream forms (BSF) and insect procyclic forms (PCF). Holo-editosomes include the accessory RNA Editing Substrate Binding Complex (RESC) and RNA Editing Helicase 2 Complex (REH2C), but the specific proteins controlling differential editing remain unknown. Also, RNA editing appears highly error prone because most U-indels do not match the canonical pattern. However, despite extensive non-canonical editing of unknown functions, accurate canonical editing is required for normal cell growth. In PCF, REH2C controls editing fidelity in RESC-bound mRNAs. Here, we report that KREH2, a REH2C-associated helicase, developmentally controls programmed non-canonical editing, including an abundant 3′ element in ATPase subunit 6 (A6) mRNA. The 3′ element sequence is directed by a proposed novel regulatory gRNA. In PCF, KREH2 RNAi-knockdown up-regulates the 3′ element, which establishes a stable structure hindering element removal by canonical initiator-gRNA-directed editing. In BSF, KREH2-knockdown does not up-regulate the 3′ element but reduces its high abundance. Thus, KREH2 differentially controls extensive non-canonical editing and associated RNA structure via a novel regulatory gRNA, potentially hijacking factors as a ‘molecular sponge’. Furthermore, this gRNA is bifunctional, serving in canonical CR4 mRNA editing whilst installing a structural element in A6 mRNA. 
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  4. null (Ed.)
    The PK-4 system is a micro-gravity dusty plasma experiment currently in operation on-board the International Space Station. The experiment utilizes a long DC discharge in neon or argon gases. We apply our 2D particle-in-cell with Monte Carlo collisions discharge simulation to compute local plasma parameters that serve as input data for future dust dynamics models. The simulation includes electrons, Ne+ ions, and Nem metastable atoms in neon gas and their collisions at solid surfaces including secondary electron emission and glass wall charging. On the time scale of the on-board optical imaging, the positive column appears stable and homogeneous. On the other hand, our simulations show that on microsecond time scales the positive column is highly inhomogeneous: ionization waves with phase velocities in the range between 500 m s−1 and 1200 m s−1 dominate the structure. In these waves, the electric field and charged particle densities can reach amplitudes up to 10 times of their average value. Our experiments on ground-based PK-4 replica systems fully support the numerical findings. In the experiment, the direction of the DC current can be alternated, which has been found to favor dust particle chain formation. We discuss possible mechanisms for how the highly oscillatory plasma environment contributes to the dust particle chain formation. 
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  5. null (Ed.)
  6. Calderaro, Adriana (Ed.)
    The World Health Organization (WHO) declared coronavirus disease-2019 (COVID-19) a global pandemic on 11 March 2020. In Ecuador, the first case of COVID-19 was recorded on 29 February 2020. Despite efforts to control its spread, SARS-CoV-2 overran the Ecuadorian public health system, which became one of the most affected in Latin America on 24 April 2020. The Hospital General del Sur de Quito (HGSQ) had to transition from a general to a specific COVID-19 health center in a short period of time to fulfill the health demand from patients with respiratory afflictions. Here, we summarized the implementations applied in the HGSQ to become a COVID-19 exclusive hospital, including the rearrangement of hospital rooms and a triage strategy based on a severity score calculated through an artificial intelligence (AI)-assisted chest computed tomography (CT). Moreover, we present clinical, epidemiological, and laboratory data from 75 laboratory tested COVID-19 patients, which represent the first outbreak of Quito city. The majority of patients were male with a median age of 50 years. We found differences in laboratory parameters between intensive care unit (ICU) and non-ICU cases considering C-reactive protein, lactate dehydrogenase, and lymphocytes. Sensitivity and specificity of the AI-assisted chest CT were 21.4% and 66.7%, respectively, when considering a score >70%; regardless, this system became a cornerstone of hospital triage due to the lack of RT-PCR testing and timely results. If health workers act as vectors of SARS-CoV-2 at their domiciles, they can seed outbreaks that might put 1,879,047 people at risk of infection within 15 km around the hospital. Despite our limited sample size, the information presented can be used as a local example that might aid future responses in low and middle-income countries facing respiratory transmitted epidemics. 
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  7. Multi-zinc finger proteins are an emerging class of cofactors in DEAH-RHA RNA helicases across highly divergent eukaryotic lineages. DEAH-RHA helicase•zinc finger cofactor partnerships predate the split of kinetoplastid protozoa, which include several human pathogens, from other eukaryotic lineages 100-400 Ma. Despite a long evolutionary history, the prototypical DEAH-RHA domains remain highly conserved. This short review focuses on a recently identified DEAH-RHA helicase•zinc finger cofactor system in kinetoplastid RNA editing, and its potential functional parallels with analogous systems in embryogenesis control in nematodes and antivirus protection in humans. 
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