Influence of Nutrient Availability and Quorum Sensing on the Formation of Metabolically Inactive Microcolonies Within Structurally Heterogeneous Bacterial Biofilms: An Individual-Based 3D Cellular Automata Model

The resistance of bacterial biofilms to antibiotic treatment has been attributed to the emergence of structurally heterogeneous microenvironments containing metabolically inactive cell populations. In this study, we use a three-dimensional individual-based cellular automata model to investigate the influence of nutrient availability and quorum sensing on microbial heterogeneity in growing biofilms. Mature biofilms exhibited at least three structurally distinct strata: a high-volume, homogeneous region sandwiched between two compact sections of high heterogeneity. Cell death occurred preferentially in layers in close proximity to the substratum, resulting in increased heterogeneity in this section of the biofilm; the thickness and heterogeneity of this lowermost layer increased with time, ultimately leading to sloughing. The model predicted the formation of metabolically dormant cellular microniches embedded within faster-growing cell clusters. Biofilms utilizing quorum sensing were more heterogeneous compared to their non-quorum sensing counterparts, and resisted sloughing, featuring a cell-devoid layer of EPS atop the substratum upon which the remainder of the biofilm developed. Overall, our study provides a computational framework to analyze metabolic diversity and heterogeneity of biofilm-associated microorganisms and may pave the way toward gaining further insights into the biophysical mechanisms of antibiotic resistance.     

Short-Term Antiretroviral Treatment Recommendations Based on Sensitivity Analysis of a Mathematical Model for HIV Infection of CD4<Superscript>+</Superscript>T Cells

HIV infection is one of the most difficult infections to control and manage. The most recent recommendations to control this infection vary according to the guidelines used (US, European, WHO) and are not patient-specific. Unfortunately, no two individuals respond to infection and treatment quite the same way. The purpose of this paper is to make use of the uncertainty and sensitivity analysis to investigate possible short-term treatment options that are patient-specific. We are able to identify the most significant parameters that are responsible for ART outcome and to formulate some insights into the ART success.     

Additions to <Emphasis Type="Italic">Lindgomyces</Emphasis> (Lindgomycetaceae,Pleosporales, Dothideomycetes), including two new species occurring on submerged wood from North Carolina,USA, with notes on secondary metabolite profiles

Two new species of freshwater ascomycetes belonging to the genus Lindgomyces (Pleosporales, Dothideomycetes) are described and illustrated from submerged wood in North Carolina, USA. Lindgomyces carolinensis is characterized by immersed to erumpent ascomata, fissitunicate broadly cylindrical to clavate asci, and fusiform ascospores with acute ends surrounded by a large, fusiform gelatinous sheath. Lindgomyces cigarospora morphologically differs from L. carolinensis in that its ascospores are fusiform to cylindrical with rounded ends, without a large fusiform gelatinous sheath. These two new species nest in the family Lindgomycetaceae based on analyses of combined SSU and LSU rDNA sequence data. Phylogenetic analyses using ITS sequence data support the establishment of the new taxa as separate species within Lindgomyces. In addition to the new species, we report new ITS sequence data for L. cinctosporus and L. griseosporus from France, and L. ingoldianus from North Carolina, USA. We report a video exhibiting fissitunicate ascus dehiscence in L. carolinensis showing ascospore discharge and unraveling of the gelatinous sheath in real time. Chemical analysis of the organic extracts of L. carolinensis and L. cigarospora resulted in two known cyclodepsipeptides, Sch 378161 and Sch 217048. The in situ spatial mapping of these secondary metabolites on fungal cultures indicates the presence of both compounds on the surface of mycelia, as well as being exuded into the surrounding agar.     

Upregulated microRNA-224 promotes ovarian cancer cell proliferation by targeting KLLN

Human epithelial ovarian cancer is a complex disease, with low 5-yr survival rate largely due to the terminal stage at diagnosis in most patients. MicroRNAs play critical roles during epithelial ovarian cancer progression in vivo and have also been shown to regulate characteristic of ovarian cancer cell line in vitro. Alterative microRNA-224 (microRNA-224) expression affects human epithelial ovarian cancer cell survival, apoptosis, and metastasis. However, people know little about the effects of microRNA-224 on epithelial ovarian cancer cell proliferation. In the current study, we found that the microRNA-224 expression level of human syngeneic epithelial ovarian cancer cells HO8910 (low metastatic ability) was lower than that of HO8910PM (high metastatic ability). Furthermore, microRNA-224 was confirmed to target KLLN in HO8910 and HO8910PM. The known KLLN downstream target cyclin A was regulated by microRNA-224 in HO8910 and HO8910PM. In addition, overexpression of microRNA-224 enhanced the proliferation abilities of HO8910 and knockdown of microRNA-224 suppressed the proliferation abilities of HO8910PM by KLLN-cyclin A pathway. Our results provide new data about microRNAs and their targets involved in proliferation of epithelial ovarian cancer cells by modulating the downstream signaling.     

The influence of simulated microgravity on proliferation and apoptosis in U251 glioma cells

Several studies have indicated that microgravity can influence cellular progression, proliferation, and apoptosis in tumor cell lines. In this study, we observed that simulated microgravity inhibited proliferation and induced apoptosis in U251 malignant glioma (U251MG) cells. Furthermore, expression of the apoptosis-associated proteins, p21 and insulin-like growth factor binding protein-2 (IGFBP-2), was upregulated and downregulated, respectively, following exposure to simulated microgravity. These findings indicate that simulated microgravity inhibits proliferation while inducing apoptosis of U251MG cells. The associated effects appear to be mediated by inhibition of IGFBP-2 expression and stimulation of p21 expression. This suggests that simulated microgravity might represent a promising method to discover new targets for glioma therapeutic strategy.     

Exogenous spermidine alleviates fruit granulation in a <Emphasis Type="Italic">Citrus</Emphasis> cultivar (<Emphasis Type="Italic">Huangguogan</Emphasis>) through the antioxidant pathway

The role of exogenous spermidine (Spd) in alleviating fruit granulation in the grafted seedlings of a Citrus cultivar (Huangguogan) was investigated. Granulation resulted in increased electrical conductivity, cell membrane permeability, and total pectin, soluble pectin, cellulose, and lignin contents. However, it decreased the activities of superoxide dismutase, peroxidase, and catalase, as well as the (Spd + Spm):Put ratio. The application of exogenous Spd onto Huangguogan seedlings significantly increased proline and ascorbate contents, but decreased the H₂O₂ and O ₂ ^?· levels, which suggested that exogenous Spd provided some protection from oxidative damage. In addition, exogenous Spd decreased cell membrane permeability and MDA content, and increased the (Spd + Spm):Put ratio. The activities of antioxidant enzymes, such as catalase, peroxidase, and superoxide dismutase, were increased in Spd-treated seedlings affected by fruit granulation, resulting in a decrease in oxidative stress levels. The protective effects of Spd were reflected by a decrease in superoxide levels through osmoregulation, increased proline and ascorbate contents, and increased antioxidant activities. Our observations reveal the importance of exogenous Spd in alleviating citrus fruit granulation.     

Glutathione and citric acid modulates lead- and arsenic-induced phytotoxicity and genotoxicity responses in two cultivars of <Emphasis Type="Italic">Solanum lycopersicum</Emphasis> L.

This study was conducted through the pot experiments to understand the mechanism of lead (Pb) and arsenic (As)-induced phytotoxicity and their possible alleviation by glutathione (GSH) and citric acid (CA) in two cultivars of Solanum lycopersicum L., i.e., Pusa ruby (PR) and Arka vikas (S22). Therefore, tomato seedlings were germinated in soil-rite supplemented with seven treatments, i.e., control, 10 µM Pb, 10 µM As, 10 µM Pb + 250 µM GSH, 10 µM As + 250 µM GSH, 10 µM Pb + 250 µM CA and 10 µM As + 250 µM CA for 7 days and examined for growth parameters, lipid peroxidation, photosynthetic pigments and antioxidative mechanism. Results of our study showed that Pb and As alone decrease seed germination, growth parameter, chlorophylls and increase anthocyanins and lipid peroxidation in both the cultivars. Pb- and As-induced oxidative stress resulted into significant changes in the plant responses that attributed by increased activity of antioxidative enzymes and non-enzymatic antioxidants. GSH and CA showed potential to alleviate Pb- or As-induced phytotoxicity and strengthen the plant antioxidative machinery and structural integrity. Cultivar PR showed better response than cv. S22. Pb and As treatment caused significant damages to the DNA molecules and structural integrity of the cv. PR roots. These findings can be useful for understanding the Pb- and As-induced phytotoxic biomarkers along with GSH- and CA-mediated alleviation mechanisms, which will provide new insight in developing better system for phytoremediation technology.     

Salicylic acid accumulation as a result of Cu,Zn, Cd and Pb interactions in common reed (<Emphasis Type="Italic">Phragmites australis</Emphasis>) growing in natural ecosystems

Common reed (Phragmites australis (Cav.) Trin. ex Steud.) plants were harvested from four natural water ecosystems of the Bogdanka river catchment (Poznań, Poland) four times throughout the 2014 vegetative season. Over the year, average metal contents followed different decreasing trends according to the analyzed tissue: Zn > Cu ≈ Pb > Cd (rhizomes) and Zn > Pb > Cu > Cd (leaves), and mean translocation ratios (leaves/rhizomes) were found as follows: 0.93, 0.70, 0.65, 0.40 for Zn, Pb, Cd and Cu, respectively. Metal content increased gradually during the growing season, and in the case of Cu, Cd and Pb exceeded the upper limit of average concentration detected in plants from natural ecosystems. However, the content of salicylic acid did not follow the increase of metal accumulation. In rhizomes, the highest production of the metabolite was observed in May and reached 324 ng g^?1 fresh weight (FW) (mean value). Afterwards, a significant drop to 50 ng g^?1 FW was observed. Simultaneously, the highest values of total salicylic acid in P. australis leaves were observed in July and accompanied the intensive development of the aboveground biomass of the plant (11.3 µg g^?1 FW–mean value). Subsequently, its content in leaves showed a significant decrease down to 2.1 µg g^?1 FW in November. Multivariate regression analysis revealed significant interactions between analyzed metals influencing the plant response to metal-derived stress. Cu and Zn showed antagonistic properties considering their uptake and the induction of salicylic acid biosynthesis, whereas non-essential metals (Pb and Cd) acted similarly and stimulated the formation of salicylic acid glucoside.