Enhancement of high-density lipoprotein-associated protease inhibitor activity prevents atherosclerosis progression.

Background And Aims: Inflammatory cells within atherosclerotic lesions secrete proteolytic enzymes that contribute to lesion progression and destabilization, increasing the risk for an acute cardiovascular event. Elastase is a serine protease, secreted by macrophages and neutrophils, that may contribute to the development of unstable plaque. We previously reported interaction of endogenous protease-inhibitor proteins with high-density lipoprotein (HDL), including alpha-1-antitrypsin, an inhibitor of elastase.

Focal Neurotoxicity Associated With Topical 5-Fluorouracil.

Topical 5-Fluorouracil (5-FU) is an antineoplastic chemotherapy drug used to treat precancerous and cancerous skin growths, such as actinic keratoses (AKs), squamous cell carcinoma in situ, and superficial basal cell carcinoma. The topical agent may rarely cause neurotoxic adverse effects. Multiple cases of systemic 5-FU and capecitabine chemotherapy-induced neuropathies have been reported.

Coupled environmental and demographic fluctuations shape the evolution of cooperative antimicrobial resistance.

There is a pressing need to better understand how microbial populations respond to antimicrobial drugs, and to find mechanisms to possibly eradicate antimicrobial-resistant cells. The inactivation of antimicrobials by resistant microbes can often be viewed as a cooperative behaviour leading to the coexistence of resistant and sensitive cells in large populations and static environments. This picture is, however, greatly altered by the fluctuations arising in volatile environments, in which microbial communities commonly evolve.

Enhancement of High-Density Lipoprotein-Associated Protease Inhibitor Activity Prevents Atherosclerosis Progression.

Background: Inflammatory cells within atherosclerotic lesions secrete various proteolytic enzymes that contribute to lesion progression and destabilization, increasing the risk for an acute cardiovascular event. The relative contributions of specific proteases to atherogenesis is not well understood. Elastase is a serine protease, secreted by macrophages and neutrophils, that may contribute to the development of unstable plaque.

Dennd5b-Deficient Mice are Resistant to PCSK9-Induced Hypercholesterolemia and Diet-Induced Hepatic Steatosis.

Dennd5b plays a pivotal role in intestinal absorption of dietary lipids in mice and is associated with body mass index in humans. This study examined the impact of whole-body Dennd5b deletion on plasma lipid concentrations, atherosclerosis, and hepatic lipid metabolism in mice. Hypercholesterolemia was induced in Dennd5b mice by infection with an adeno-associated virus expressing the proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) gain-of-function mutation (PCSK9D377Y) and feeding a Western diet for 12 weeks.

Effect of mobility in the rock-paper-scissor dynamics with high mortality.

In the evolutionary dynamics of a rock-paper-scissor model, the effect of natural death plays a major role in determining the fate of the system. Coexistence, being an unstable fixed point of the model, becomes very sensitive toward this parameter. In order to study the effect of mobility in such a system which has explicit dependence on mortality, we perform Monte Carlo simulation on a two-dimensional lattice having three cyclically competing species.

How does homophily shape the topology of a dynamic network?

We consider a dynamic network of individuals that may hold one of two different opinions in a two-party society. As a dynamical model, agents can endlessly create and delete links to satisfy a preferred degree, and the network is shaped by homophily, a form of social interaction. Characterized by the parameter J∈[-1,1], the latter plays a role similar to Ising spins: agents create links to others of the same opinion with probability (1+J)/2 and delete them with probability (1-J)/2.

Exclusion of the fittest predicts microbial community diversity in fluctuating environments.

Microorganisms live in environments that inevitably fluctuate between mild and harsh conditions. As harsh conditions may cause extinctions, the rate at which fluctuations occur can shape microbial communities and their diversity, but we still lack an intuition on how. Here, we build a mathematical model describing two microbial species living in an environment where substrate supplies randomly switch between abundant and scarce.

Population Dynamics in a Changing Environment: Random versus Periodic Switching.

Environmental changes greatly influence the evolution of populations. Here, we study the dynamics of a population of two strains, one growing slightly faster than the other, competing for resources in a time-varying binary environment modeled by a carrying capacity switching either randomly or periodically between states of abundance and scarcity. The population dynamics is characterized by demographic noise (birth and death events) coupled to a varying environment.

Effect of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of a Single Dose of Oral Ivosidenib in Otherwise Healthy Participants.

Ivosidenib, a small-molecule inhibitor of mutant isocitrate dehydrogenase 1, is primarily cleared by hepatic metabolism. This open-label study investigated the impact of hepatic impairment on ivosidenib pharmacokinetics (ClinicalTrials.gov: NCT03282513).

Impact of rainfall properties on the performance of hydrological models for green roofs simulation.

Green roofs (GR) are effective tools for the mitigation of the negative hydrological impact linked to uncontrolled urbanization. Models for runoff response of vegetated covers support planning decisions about the use of this technology in ever-expanding areas, but there is still large uncertainty in this research area. The goal of the present study was to define the accuracy of three selected models for the simulation of the hydrological behavior of a GR, with a particular focus on the precipitation pattern characteristics.

Fixation properties of rock-paper-scissors games in fluctuating populations.

Rock-paper-scissors games metaphorically model cyclic dominance in ecology and microbiology. In a static environment, these models are characterized by fixation probabilities obeying two different "laws" in large and small well-mixed populations. Here, we investigate the evolution of these three-species models subject to a randomly switching carrying capacity modeling the endless change between states of resources scarcity and abundance.

Human health-related properties of chromones: an overview.

Natural compounds occurring throughout the world are scientifically and practically valuable because of their unique and beneficial properties to control a wide range of disorders in the human body. Chromones are attracting increasing attention as novel therapeutic agents due to their effective bioactivities for human health. Accordingly, the present overview article was designed to scan the biological and pharmacological performance of chromones, including their anti-inflammatory, anticancer, anti-oxidant, and anti-microbial activities.

Rewiring cellular metabolism for heterologous biosynthesis of Taxol.

Taxol is one of the anticancer drugs synthesized naturally in the evergreen forest tree belonging to the yew family () growing on the Pacific. There are reportedly evidence for treating ovarian, breast and lung cancers through this drug given its unique structural and functional features. Extraction of this drug from yew trees bark is one of the most common ways of producing this drug, but 3000 trees are needed to obtain a kilogram of Taxol.

Toxic mineral elements in from Sicilian coasts (Southern Italy).

We assessed the relationship between V, Cr, Mn, Hg, As, Cd, Sn, Sb and Pb concentrations in samples from the coasts of Sicily and the expression of . Toxic mineral elements assessment was carried out by A.A.

Effects of (Lam.) Benth. fruits extract on the development and maturation of the reproductive system in immature male rats.

In the present study, we investigated the effects of (Lam.) Benth. fruits ethanolic extract in prepubertal male rats, to evaluate the influence of the extract on the reproductive system and on pubertal development.

Eco-evolutionary dynamics of a population with randomly switching carrying capacity.

Environmental variability greatly influences the eco-evolutionary dynamics of a population, i.e. it affects how its size and composition evolve.

Survival behavior in the cyclic Lotka-Volterra model with a randomly switching reaction rate.

We study the influence of a randomly switching reproduction-predation rate on the survival behavior of the nonspatial cyclic Lotka-Volterra model, also known as the zero-sum rock-paper-scissors game, used to metaphorically describe the cyclic competition between three species. In large and finite populations, demographic fluctuations (internal noise) drive two species to extinction in a finite time, while the species with the smallest reproduction-predation rate is the most likely to be the surviving one (law of the weakest). Here we model environmental (external) noise by assuming that the reproduction-predation rate of the strongest species (the fastest to reproduce and predate) in a given static environment randomly switches between two values corresponding to more and less favorable external conditions.

Evolution of a Fluctuating Population in a Randomly Switching Environment.

Environment plays a fundamental role in the competition for resources, and hence in the evolution of populations. Here, we study a well-mixed, finite population consisting of two strains competing for the limited resources provided by an environment that randomly switches between states of abundance and scarcity. Assuming that one strain grows slightly faster than the other, we consider two scenarios-one of pure resource competition, and one in which one strain provides a public good-and investigate how environmental randomness (external noise) coupled to demographic (internal) noise determines the population's fixation properties and size distribution.

Heterogeneous out-of-equilibrium nonlinear q-voter model with zealotry.

We study the dynamics of the out-of-equilibrium nonlinear q-voter model with two types of susceptible voters and zealots, introduced in Mellor et al. [Europhys. Lett.

Influence of Luddism on innovation diffusion.

We generalize the classical Bass model of innovation diffusion to include a new class of agents-Luddites-that oppose the spread of innovation. Our model also incorporates ignorants, susceptibles, and adopters. When an ignorant and a susceptible meet, the former is converted to a susceptible at a given rate, while a susceptible spontaneously adopts the innovation at a constant rate.

Nonlinear q-voter model with inflexible zealots.

We study the dynamics of the nonlinear q-voter model with inflexible zealots in a finite well-mixed population. In this system, each individual supports one of two parties and is either a susceptible voter or an inflexible zealot. At each time step, a susceptible adopts the opinion of a neighbor if this belongs to a group of q≥2 neighbors all in the same state, whereas inflexible zealots never change their opinion.

Characterization of spiraling patterns in spatial rock-paper-scissors games.

The spatiotemporal arrangement of interacting populations often influences the maintenance of species diversity and is a subject of intense research. Here, we study the spatiotemporal patterns arising from the cyclic competition between three species in two dimensions. Inspired by recent experiments, we consider a generic metapopulation model comprising "rock-paper-scissors" interactions via dominance removal and replacement, reproduction, mutations, pair exchange, and hopping of individuals.

Cyclic dominance in evolutionary games: a review.

Rock is wrapped by paper, paper is cut by scissors and scissors are crushed by rock. This simple game is popular among children and adults to decide on trivial disputes that have no obvious winner, but cyclic dominance is also at the heart of predator-prey interactions, the mating strategy of side-blotched lizards, the overgrowth of marine sessile organisms and competition in microbial populations. Cyclical interactions also emerge spontaneously in evolutionary games entailing volunteering, reward, punishment, and in fact are common when the competing strategies are three or more, regardless of the particularities of the game.