A
bstract
Recently, remarkable progress in recovering the Page curve of an evaporating black hole (BH) in Jackiw-Teitelboim gravity has been achieved through use of Quantum Extremal surfaces (QES). ...Multi-boundary Wormhole (MbW) models have been crucial in parallel model building in three dimensions. Motivated by this we here use the latter models to compute the subregion complexity of the Hawking quanta of the evaporating BH in AdS
3
and obtain the Page curve associated with this information theoretic measure. We use three- and
n
-boundary wormhole constructions to elucidate our computations of volumes below the Hubeny-Rangamani-Takayanagi (HRT) surfaces at different times. Time is represented by the growing length of the throat horizons corresponding to smaller exits of the multi-boundary wormhole and the evaporating bigger exit shrinks with evolving time. We track the change in choice of HRT surfaces with time and plot the volume with time. The smooth transition of Page curve is realized by a discontinuous jump at Page time in volume subregion complexity plots and the usual Page transition is realized as a phase transition due to the inclusion of the island in this context. We discuss mathematical intricacies and physical insights regarding the inclusion of the extra volume at Page time. The analysis is backed by calculations and lessons from kinematic space and tensor networks.
Over the past several decades, the incidence of early-onset colorectal cancer (EOCRC; in patients <50 years old) has increased at an alarming rate. Although robust and scientifically rigorous ...epidemiological studies have sifted out environmental elements linked to EOCRC, our knowledge of the causes and mechanisms of this disease is far from complete. Here, we highlight potential risk factors and putative mechanisms that drive EOCRC and suggest likely areas for fruitful research. In addition, we identify inconsistencies in the evidence implicating a strong effect of increased adiposity and suggest that certain behaviours (such as diet and stress) might place nonobese and otherwise healthy people at risk of this disease. Key risk factors are reviewed, including the global westernization of diets (usually involving a high intake of red and processed meats, high-fructose corn syrup and unhealthy cooking methods), stress, antibiotics, synthetic food dyes, monosodium glutamate, titanium dioxide, and physical inactivity and/or sedentary behaviour. The gut microbiota is probably at the crossroads of these risk factors and EOCRC. The time course of the disease and the fact that relevant exposures probably occur in childhood raise important methodological issues that are also discussed.
Over the past several years, numerous studies have demonstrated the feasibility of using engineered nanoparticles as antifungals, especially against those fungal pathogens that produce mycotoxins and ...infect plants, animals, and humans. The high dosage of nanoparticles has been a concern in such antifungal applications due to the potential toxicological and ecotoxicological impacts. To address such concerns, we have recently introduced the idea of inhibiting mycotoxin biosynthesis using low doses of engineered nanoparticles. At such low doses these particles are minimally toxic to humans and the environment. From our studies we realize that for the effective use of nanotechnology to intervene in the biology of fungal pathogens and for an accurate evaluation of the impacts of the increasingly growing nanomaterials in the environment on fungi and their interacting biotic partners, there is a pressing need for a rigorous understanding of nano-fungal interactions, which is currently far from complete. In this minireview, we build on the available evidence from nano-bio interaction research and our recent interaction studies with
Aspergillus
cells and engineered silver nanoparticles to introduce a potential theoretical model for nano-fungal interactions. The aim of the proposed model is to provide an initial insight on how nanoparticle uptake and their transformation inside fungal cells, possibly influence the production of mycotoxins and other secondary metabolites of filamentous fungi .
Extensive use of engineered nanoparticles has led to their eventual release in the environment. The present work aims to study the removal of Polyvinylpyrrolidone-coated silver nanoparticles ...(PVP-Ag-NPs) using
Aspergillus niger
and depict the role of exopolysaccharides in the removal process. Our results show that the majority of PVP-Ag-NPs were attached to fungal pellets. About 74% and 88% of the PVP-Ag-NPs were removed when incubated with
A. niger
pellets and exopolysaccharide-induced
A. niger
pellets, respectively. Ionized Ag decreased by 553 and 1290-fold under the same conditions as compared to stock PVP-Ag-NP. PVP-Ag-PVP resulted in an increase in reactive oxygen species (ROS) in 24 h. Results show an increase in PVP-Ag-NPs size from 28.4 to 115.9 nm for
A. niger
pellets and 160.3 nm after removal by stress-induced
A. niger
pellets and further increased to 650.1 nm for in vitro EPS removal. The obtained findings show that EPS can be used for nanoparticle removal, by increasing the net size of nanoparticles in aqueous media. This will, in turn, facilitate its removal through conventional filtration techniques commonly used at wastewater treatment plants.
Great progress has been made in understanding the regulation of expression of genes involved in secondary metabolism. Less is known about the mechanisms that govern the spatial distribution of the ...enzymes, cofactors, and substrates that mediate catalysis of secondary metabolites within the cell. Filamentous fungi in the genus
Aspergillus synthesize an array of secondary metabolites and provide useful systems to analyze the mechanisms that mediate the temporal and spatial regulation of secondary metabolism in eukaryotes. For example, aflatoxin biosynthesis in
Aspergillus parasiticus has been studied intensively because this mycotoxin is highly toxic, mutagenic, and carcinogenic in humans and animals. Using aflatoxin synthesis to illustrate key concepts, this review focuses on the mechanisms by which sub-cellular compartmentalization and intra-cellular molecular traffic contribute to the initiation and completion of secondary metabolism within the cell. We discuss the recent discovery of aflatoxisomes, specialized trafficking vesicles that participate in the compartmentalization of aflatoxin synthesis and export of the toxin to the cell exterior; this work provides a new and clearer understanding of how cells integrate secondary metabolism into basic cellular metabolism via the intra-cellular trafficking machinery.
key role for vesicles in fungal secondary metabolism Chanda, Anindya; Roze, Ludmila V; Kang, Suil ...
Proceedings of the National Academy of Sciences - PNAS,
11/2009, Letnik:
106, Številka:
46
Journal Article
Recenzirano
Odprti dostop
Eukaryotes have evolved highly conserved vesicle transport machinery to deliver proteins to the vacuole. In this study we show that the filamentous fungus Aspergillus parasiticus employs this ...delivery system to perform new cellular functions, the synthesis, compartmentalization, and export of aflatoxin; this secondary metabolite is one of the most potent naturally occurring carcinogens known. Here we show that a highly pure vesicle-vacuole fraction isolated from A. parasiticus under aflatoxin-inducing conditions converts sterigmatocystin, a late intermediate in aflatoxin synthesis, to aflatoxin B₁; these organelles also compartmentalize aflatoxin. The role of vesicles in aflatoxin biosynthesis and export was confirmed by blocking vesicle-vacuole fusion using 2 independent approaches. Disruption of A. parasiticus vb1 (encodes a protein homolog of AvaA, a small GTPase known to regulate vesicle fusion in A. nidulans) or treatment with Sortin3 (blocks Vps16 function, one protein in the class C tethering complex) increased aflatoxin synthesis and export but did not affect aflatoxin gene expression, demonstrating that vesicles and not vacuoles are primarily involved in toxin synthesis and export. We also observed that development of aflatoxigenic vesicles (aflatoxisomes) is strongly enhanced under aflatoxin-inducing growth conditions. Coordination of aflatoxisome development with aflatoxin gene expression is at least in part mediated by Velvet (VeA), a global regulator of Aspergillus secondary metabolism. We propose a unique 2-branch model to illustrate the proposed role for VeA in regulation of aflatoxisome development and aflatoxin gene expression.
Selenium (Se) is an essential dietary micronutrient that has been examined for protection against different types of cancers including colon cancer. Despite an established inverse association between ...Se and chronic inflammation induced colon cancer (CICC), the mechanistic understanding of Se's protective effects requires additional in-vivo studies using preclinical animal models of CICC. Adiponectin (APN) is an adipocytokine that is protective against CICC as well. However, its role in the anti-mutagenic effects of the Se-diet remains unknown. To address this knowledge gap, here we examine the ability of dietary Se in reducing CICC in APN knockout mice (KO) and its wild-type C57BL/6. CICC was induced with the colon cancer agent 1,2 dimethyl hydrazine (DMH) along with dextran sodium sulfate (DSS). Se-enhanced diet increased selenoproteins, Gpx-1 and Gpx-2, in the colon tissues, thereby reducing oxidative stress. Se-mediated reduction of CICC was evident from the histopathological studies in both mouse models. In both mice, reduction in inflammation and tumorigenesis associated well with reduced p65 phosphorylation and elevated 53 phosphorylation. Finally, we show that in both models Se-administration promotes goblet cell differentiation with a concomitant increase in the levels of associated proteins, Muc-2 and Math-1. Our findings suggest that Se's protection against CICC involves both colonic epithelial protection and anti-tumor effects that are independent of APN.
Aflatoxins, a family of fungal secondary metabolites, are toxic and carcinogenic compounds that pose an enormous threat to global food safety and agricultural sustainability. Specifically ...agricultural products in African, Southeast Asian and hot and humid regions of American countries suffer most damage from aflatoxin producing molds due to the ideal climate conditions promoting their growth. Our recent studies suggest that
Vibrio gazogenes
(Vg), an estuarine bacterium non-pathogenic to plants and humans, can significantly inhibit aflatoxin biosynthesis in the producers. In this study, we investigated the mechanism underlying Vg-dependent aflatoxin inhibition using the prominent aflatoxin producer,
Aspergillus flavus
. We show that aflatoxin inhibition upon Vg treatment was associated with fungal uptake of Vg-prodigiosin, a red pigment, which was consistently visible inside fungal hyphae during treatment. The association of prodigiosin with aflatoxin inhibition was further evident as
Serratia marcescens
, another prodigiosin producer, significantly inhibited aflatoxin, while non-producers like
Escherichia coli, Staphylococcus aureus
,
Vibrio harveyi
, and
Vibrio fischeri
did not. Also, pure prodigiosin significantly inhibited aflatoxin biosynthesis. Endocytosis inhibitors, filipin and natamycin, reduced the Vg-prodigiosin uptake by the fungus leading to a significant increase in aflatoxin production, suggesting that uptake is endocytosis-dependent. The Vg treatment also reduced hyphal fusion (>98% inhibition) and branching, which are both endosome-dependent processes. Our results, therefore, collectively support our theory that Vg-associated aflatoxin inhibition is mediated by an endocytosis-dependent uptake of Vg-prodigiosin, which possibly leads to a disruption of normal endosomal functions.
Colony expansion is an essential feature of fungal infections. Although mechanisms that regulate hyphal forces on the substrate during expansion have been reported previously, there is a critical ...need of a methodology that can compute the pressure profiles exerted by fungi on substrates during expansion; this will facilitate the validation of therapeutic efficacy of novel antifungals. Here, we introduce an analytical decoding method based on Biot's incremental stress model, which was used to map the pressure distribution from an expanding mycelium of a popular plant pathogen, Aspergillus parasiticus. Using our recently developed Quantitative acoustic contrast tomography (Q-ACT) we detected that the mycelial growth on the solid agar created multiple surface and subsurface wrinkles with varying wavelengths across the depth of substrate that were computable with acousto-ultrasonic waves between 50 MHz-175 MHz. We derive here the fundamental correlation between these wrinkle wavelengths and the pressure distribution on the colony subsurface. Using our correlation we show that A. parasiticus can exert pressure as high as 300 KPa on the surface of a standard agar growth medium. The study provides a novel mathematical foundation for quantifying fungal pressures on substrate during hyphal invasions under normal and pathophysiological growth conditions.
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