Computational multigene interactions in virus growth and infection spread.

Viruses persist in nature owing to their extreme genetic heterogeneity and large population sizes, which enable them to evade host immune defenses, escape antiviral drugs, and adapt to new hosts. The persistence of viruses is challenging to study because mutations affect multiple virus genes, interactions among genes in their impacts on virus growth are seldom known, and measures of viral fitness are yet to be standardized. To address these challenges, we employed a data-driven computational model of cell infection by a virus.

Astrovirology: how viruses enhance our understanding of life in the Universe.

Viruses are the most numerically abundant biological entities on Earth. As ubiquitous replicators of molecular information and agents of community change, viruses have potent effects on the life on Earth, and may play a critical role in human spaceflight, for life-detection missions to other planetary bodies and planetary protection. However, major knowledge gaps constrain our understanding of the Earth's virosphere: (1) the role viruses play in biogeochemical cycles, (2) the origin(s) of viruses and (3) the involvement of viruses in the evolution, distribution and persistence of life.

Enhancement of Prebiotic Peptide Formation in Cyclic Environments.

The dynamic behaviors of prebiotic reaction networks may be critically important to understanding how larger biopolymers could emerge, despite being unfavorable to form in water. We focus on understanding the dynamics of simple systems, prior to the emergence of replication mechanisms, and what role they may have played in biopolymer formation. We specifically consider the dynamics in cyclic environments using both model and experimental data.

Kinetic Modeling and Parameter Estimation of a Prebiotic Peptide Reaction Network.

Although our understanding of how life emerged on Earth from simple organic precursors is speculative, early precursors likely included amino acids. The polymerization of amino acids into peptides and interactions between peptides are of interest because peptides and proteins participate in complex interaction networks in extant biology. However, peptide reaction networks can be challenging to study because of the potential for multiple species and systems-level interactions between species.

Left Atrial Appendage Occlusion Device Placement Aborted Because of Coronary Artery Bypass Graft.

Left atrial appendage occlusion device (LAAO) implantation among patients who have had coronary artery bypass grafting can be challenging. We report a case of scheduled LAAO device implantation that was aborted due to the anomalous course of a bypass graft that appeared to be adherent to the left atrial appendage. ().

Glycine to Oligoglycine via Sequential Trimetaphosphate Activation Steps in Drying Environments.

Polyphosphate-mediated peptide bond formation is central to protein synthesis in modern organisms, but a simpler form of activation likely preceded the emergence of proteins and RNA. One suggested scenario involves trimetaphosphate (TP), an inorganic phosphate that promotes peptide condensation. Peptide bond formation can also be promoted by high pH and drying, but the interaction of these factors with TP has yet to be characterized kinetically.

Reliance of Host-Encoded Regulators of Retromobility on Ty1 Promoter Activity or Architecture.

The Ty1 retrotransposon family is maintained in a functional but dormant state by its host, . Several hundred and genes encoding co-factors and restrictors of Ty1 retromobility, respectively, have been identified. Well-characterized examples include and , encoding subunits of the Mediator transcriptional co-activator complex; control of retromobility by Med3 and Med15 requires the Ty1 promoter in the U3 region of the long terminal repeat.

Mathematical modeling of the lower urinary tract: A review.

Aims: Understand what progress has been made toward a functionally predictive lower urinary tract (LUT) model, identify knowledge gaps, and develop from them a path forward.

Methods: We surveyed prominent mathematical models of the basic LUT components (bladder, urethra, and their neural control) and categorized the common modeling strategies and theoretical assumptions associated with each component. Given that LUT function emerges from the interaction of these components, we emphasized attempts to model their connections, and highlighted unmodeled aspects of LUT function.

Virus-like Particles: Measures and Biological Functions.

Virus-like particles resemble infectious virus particles in size, shape, and molecular composition; however, they fail to productively infect host cells. Historically, the presence of virus-like particles has been inferred from total particle counts by microscopy, and infectious particle counts or plaque-forming-units (PFUs) by plaque assay; the resulting ratio of particles-to-PFUs is often greater than one, easily 10 or 100, indicating that most particles are non-infectious. Despite their inability to hijack cells for their reproduction, virus-like particles and the defective genomes they carry can exhibit a broad range of behaviors: interference with normal virus growth during co-infections, cell killing, and activation or inhibition of innate immune signaling.

Resolving the Rules of Robustness and Resilience in Biology Across Scales.

Why do some biological systems and communities persist while others fail? Robustness, a system's stability, and resilience, the ability to return to a stable state, are key concepts that span multiple disciplines within and outside the biological sciences. Discovering and applying common rules that govern the robustness and resilience of biological systems is a critical step toward creating solutions for species survival in the face of climate change, as well as the for the ever-increasing need for food, health, and energy for human populations. We propose that network theory provides a framework for universal scalable mathematical models to describe robustness and resilience and the relationship between them, and hypothesize that resilience at lower organization levels contribute to robust systems.

Kinetics of Asian and African Zika virus lineages over single-cycle and multi-cycle growth in culture: Gene expression, cell killing, virus production, and mathematical modeling.

Since 2014, an Asian lineage of Zika virus has caused outbreaks, and it has been associated with neurological disorders in adults and congenital defects in newborns. The resulting threat of the Zika virus to human health has prompted the development of new vaccines, which have yet to be approved for human use. Vaccines based on the attenuated or chemically inactivated virus will require large-scale production of the intact virus to meet potential global demands.

Patterns of virus growth across the diversity of life.

Although viruses in their natural habitats add up to less than 10% of the biomass, they contribute more than 90% of the genome sequences [1]. These viral sequences or 'viromes' encode viruses that populate the Earth's oceans [2, 3] and terrestrial environments [4, 5], where their infections impact life across diverse ecological niches and scales [6, 7], including humans [8-10]. Most viruses have yet to be isolated and cultured [11-13], and surprisingly few efforts have explored what analysis of available data might reveal about their nature.

Toward Molecular Cooperation by De Novo Peptides.

Theoretical models of the chemical origins of life depend on self-replication or autocatalysis, processes that arise from molecular interactions, recruitment, and cooperation. Such models often lack details about the molecules and reactions involved, giving little guidance to those seeking to detect signs of interaction, recruitment, or cooperation in the laboratory. Here, we develop minimal mathematical models of reactions involving specific chemical entities: amino acids and their condensation reactions to form de novo peptides.

Immunogenetic effects of low dose (CEM43 30) magnetic nanoparticle hyperthermia and radiation in melanoma cells.

In this in vitro study we have used an RNA quantification technique, nanoString, and a conventional protein analysis technique (Western Blot) to assess the genetic and protein expression of B16 murine melanoma cells following a modest magnetic nanoparticle hyperthermia (mNPH) dose equivalent to 30 minutes @ 43°C (CEM43 30) and/or a clinically relevant 8 Gy radiation dose. Melanoma cells with mNPs(2.5 μg Fe/106 cells) were pelleted and exposed to an alternating magnetic field (AMF) to generate the targeted thermal dose.

Phylogenomics of 10,575 genomes reveals evolutionary proximity between domains Bacteria and Archaea.

Rapid growth of genome data provides opportunities for updating microbial evolutionary relationships, but this is challenged by the discordant evolution of individual genes. Here we build a reference phylogeny of 10,575 evenly-sampled bacterial and archaeal genomes, based on a comprehensive set of 381 markers, using multiple strategies. Our trees indicate remarkably closer evolutionary proximity between Archaea and Bacteria than previous estimates that were limited to fewer "core" genes, such as the ribosomal proteins.

ASTRAL-MP: scaling ASTRAL to very large datasets using randomization and parallelization.

Motivation: Evolutionary histories can change from one part of the genome to another. The potential for discordance between the gene trees has motivated the development of summary methods that reconstruct a species tree from an input collection of gene trees. ASTRAL is a widely used summary method and has been able to scale to relatively large datasets.

Trimetaphosphate Activates Prebiotic Peptide Synthesis across a Wide Range of Temperature and pH.

The biochemical activation of amino acids by adenosine triphosphate (ATP) drives the synthesis of proteins that are essential for all life. On the early Earth, before the emergence of cellular life, the chemical condensation of amino acids to form prebiotic peptides or proteins may have been activated by inorganic polyphosphates, such as tri metaphosphate (TP). Plausible volcanic and other potential sources of TP are known, and TP readily activates amino acids for peptide synthesis.

Kinetic Modeling of Virus Growth in Cells.

When a virus infects a host cell, it hijacks the biosynthetic capacity of the cell to produce virus progeny, a process that may take less than an hour or more than a week. The overall time required for a virus to reproduce depends collectively on the rates of multiple steps in the infection process, including initial binding of the virus particle to the surface of the cell, virus internalization and release of the viral genome within the cell, decoding of the genome to make viral proteins, replication of the genome, assembly of progeny virus particles, and release of these particles into the extracellular environment. For a large number of virus types, much has been learned about the molecular mechanisms and rates of the various steps.

Effects of Trimetaphosphate on Abiotic Formation and Hydrolysis of Peptides.

The primordial Earth probably had most of the factors needed for the emergence and development of life. It is believed that it had not only water, but also simple inorganic and organic materials. While studies since the 1950s on the origins of organic matter have established key roles for amino acids, conditions that would have promoted their condensation to make polymers, such as peptides or proteins, have yet to be fully defined.

Inhibition of infection spread by co-transmitted defective interfering particles.

Although virus release from host cells and tissues propels the spread of many infectious diseases, most virus particles are not infectious; many are defective, lacking essential genetic information needed for replication. When defective and viable particles enter the same cell, the defective particles can multiply while interfering with viable particle production. Defective interfering particles (DIPs) occur in nature, but their role in disease pathogenesis and spread is not known.

Quantitative profiling of innate immune activation by viral infection in single cells.

Cells infected by viruses can exhibit diverse patterns of viral and cellular gene expression. The patterns arise in part from the stochastic or noisy reaction kinetics associated with the small number of genomes, enzymes, and other molecules that typically initiate virus replication and activate cellular anti-viral defenses. It is not known what features, if any, of the early viral or cellular gene expression correlate with later processes of viral replication or cell survival.

Differential Disruption of Nucleocytoplasmic Trafficking Pathways by Rhinovirus 2A Proteases.

The RNA rhinoviruses (RV) encode 2A proteases (2A) that contribute essential polyprotein processing and host cell shutoff functions during infection, including the cleavage of Phe/Gly-containing nucleoporin proteins (Nups) within nuclear pore complexes (NPC). Within the 3 RV species, multiple divergent genotypes encode diverse 2A sequences that act differentially on specific Nups. Since only subsets of Phe/Gly motifs, particularly those within Nup62, Nup98, and Nup153, are recognized by transport receptors (karyopherins) when trafficking large molecular cargos through the NPC, the processing preferences of individual 2A predict RV genotype-specific targeting of NPC pathways and cargos.

Evolvix BEST Names for semantic reproducibility across code2brain interfaces.

Names in programming are vital for understanding the meaning of code and big data. We define code2brain (C2B) interfaces as maps in compilers and brains between meaning and naming syntax, which help to understand executable code. While working toward an Evolvix syntax for general-purpose programming that makes accurate modeling easy for biologists, we observed how names affect C2B quality.