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.     

Polyamines in yellow lupin (<Emphasis Type="Italic">Lupinus luteus</Emphasis> L.) tolerance to soil drought

Polyamines (PAs) are related to many physiological processes, including soil drought stress. Two yellow lupin ‘Morocco 4’ (drought tolerant) and ‘Taper’ (drought sensitive) were exposed to soil drought for 2 weeks. The half of the examined plants were additionally sprayed with a solution of polyamine biosynthesis inhibitor—dl-α-difluoromethylarginine (DFMA). Yellow lupin leaves showed a 19% increase and seeds a 54% decrease in the total PA contents. The seeds contained fourfold less PAs than the leaves under drought conditions. The highest amount of spermidine and lack of agmatine were found in the leaves, while in the seeds the highest content of spermine and the presence of agmatine was confirmed. The use of DFMA under drought conditions decreased the content of spermine in ‘Morocco 4’ and ‘Taper’ (41 and 19%, respectively) and spermidine in ‘Taper’ (by 13%), as well as reduced two out of three of the yield components. More tolerant ‘Morocco 4’, after DFMA treatment was characterized by a higher spermidine and spermine content and a smaller decrease in yield components compared to the less tolerant ‘Taper’. Simultaneously subjecting plants to soil drought and DFMA treatment caused in ‘Morocco 4’ a decline in the number of pods and seeds per plant and seeds dry weight per plant (64, 50 and 54%, respectively), while in ‘Taper’ a reduction of the number of pods per plant and seeds per pod (32 and 27%, respectively) was observed. These results confirm that PAs are involved in yellow lupin tolerance and may play a protective function under soil drought conditions.     

Interpopulation variation in pollinators and floral scent of the lady’s-slipper orchid <Emphasis Type="Italic">Cypripedium calceolus</Emphasis> L.

Floral scent is a key mediator in many plant–pollinator interactions. It is known to vary not only among plant species, but also within species among populations. However, there is a big gap in our knowledge of whether such variability is the result of divergent selective pressures exerted by a variable pollinator climate or alternative scenarios (e.g., genetic drift). Cypripedium calceolus is a Eurasian deceptive lady’s-slipper orchid pollinated by bees. It is found from near sea level to altitudes of 2500 m. We asked whether pollinator climate and floral scents vary in a concerted manner among different altitudes. Floral scents of four populations in the Limestone Alps were collected by dynamic headspace and analyzed by gas chromatography coupled to mass spectrometry (GC/MS). Flower visitors and pollinators (the subset of visitors with pollen loads) were collected and identified. Preliminary coupled gas chromatographic and electroantennographic measurements with floral scents and pollinators revealed biologically active components. More than 70 compounds were detected in the scent samples, mainly aliphatics, terpenoids, and aromatics. Although several compounds were found in all samples, and all samples were dominated by linalool and octyl acetate, scents differed among populations. Similarly, there were strong differences in flower visitor spectra among populations with most abundant flower visitors being bees and syrphid flies at low and high altitudes, respectively. Pollinator climate differed also among populations; however, independent of altitude, most pollinators were bees of Lasioglossum, Andrena, and Nomada. Only few syrphids acted as pollinators and this is the first record of flies as pollinators in C. calceolus. The electrophysiological tests showed that bees and syrphid flies sensed many of the compounds released by the flowers, among them linalool and octyl acetate. Overall, we found that both floral scent and visitor/pollinator climate differ among populations. We discuss whether interpopulation variation in scent is a result of pollinator-mediated selection.