Copper nanowire embedded hypromellose: An antibacterial nanocomposite film

The present work reports a novel antibacterial nanocomposite film comprising of copper nanowire impregnated biocompatible hypromellose using polyethylene glycol as a plasticiser. Detailed physico-chemical characterization using X-ray diffraction, Fourier transform infrared spectroscopy, UV–Visible spectroscopy and electron microscopy shows uniform dispersion of copper nanowire in the polymer matrix without any apparent oxidation. The film is flexible and shows excellent antibacterial activity against both Gram positive and negative bacteria at 4.8 wt% nanowire loading with MIC values of 400 µg/mL and 500 µg/mL for E. coli and S. aureus respectively. Investigation into the antibacterial mechanism of the nanocomposite indicates multiple pathways including cellular membrane damage caused by released copper ions and reactive oxygen species generation in the microbial cell. Interestingly, the film showed good biocompatibility towards normal human dermal fibroblast at minimum bactericidal concentration (MBC). Compared to the copper nanoparticles reported earlier in vitro studies, this low cytotoxicity of copper nanowires is due to the slow dissolution rate of the film and production of lower amount of ROS producing Cu2+ ions. Thus, the study indicates a strong potential for copper nanowire-based composites films in broader biomedical and clinical applications

Artemisinin Inhibits Chloroplast Electron Transport Activity: Mode of Action

Artemisinin, a secondary metabolite produced in Artemisia plant species, besides having antimalarial properties is also phytotoxic. Although, the phytotoxic activity of the compound has been long recognized, no information is available on the mechanism of action of the compound on photosynthetic activity of the plant. In this report, we have evaluated the effect of artemisinin on photoelectron transport activity of chloroplast thylakoid membrane. The inhibitory effect of the compound, under in vitro condition, was pronounced in loosely and fully coupled thylakoids; being strong in the former. The extent of inhibition was drastically reduced in the presence of uncouplers like ammonium chloride or gramicidin; a characteristic feature described for energy transfer inhibitors. The compound, on the other hand, when applied to plants (in vivo), behaved as a potent inhibitor of photosynthetic electron transport. The major site of its action was identified to be the QB; the secondary quinone moiety of photosystemII complex. Analysis of photoreduction kinetics of para-benzoquinone and duroquinone suggest that the inhibition leads to formation of low pool of plastoquinol, which becomes limiting for electron flow through photosystemI. Further it was ascertained that the in vivo inhibitory effect appeared as a consequence of the formation of an unidentified artemisinin-metabolite rather than by the interaction of the compound per se. The putative metabolite of artemisinin is highly reactive in instituting the inhibition of photosynthetic electron flow eventually reducing the plant growth

Soil fungal networks maintain local dominance of ectomycorrhizal trees

The mechanisms regulating community composition and local dominance of trees in species-rich forests are poorly resolved, but the importance of interactions with soil microbes is increasingly acknowledged. Here, we show that tree seedlings that interact via root-associated fungal hyphae with soils beneath neighbouring adult trees grow faster and have greater survival than seedlings that are isolated from external fungal mycelia, but these effects are observed for species possessing ectomycorrhizas (ECM) and not arbuscular mycorrhizal (AM) fungi. Moreover, survival of naturally-regenerating AM seedlings over ten years is negatively related to the density of surrounding conspecific plants, while survival of ECM tree seedlings displays positive density dependence over this interval, and AM seedling roots contain greater abundance of pathogenic fungi than roots of ECM seedlings. Our findings show that neighbourhood interactions mediated by beneficial and pathogenic soil fungi regulate plant demography and community structure in hyperdiverse forests

Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs)

Selective progesterone receptor modulators (SPRMs) represent a new class of progesterone receptor ligands that exert clinically relevant tissue-selective progesterone agonist, antagonist, partial, or mixed agonist/antagonist effects on various progesterone target tissues in an in vivo situation depending on the biological action studied. The SPRM asoprisnil is being studied in women with symptomatic uterine leiomyomata and endometriosis. Asoprisnil shows a high degree of uterine selectivity as compared to effects on ovulation or ovarian hormone secretion in humans. It induces amenorrhea and decreases leiomyoma volume in a dose-dependent manner in the presence of follicular phase estrogen concentrations. It also has endometrial antiproliferative effects. In pregnant animals, the myometrial, i.e. labor-inducing, effects of asoprisnil are blunted or absent. Studies in non-human primates played a key role during the preclinical development of selective progesterone receptor modulators. These studies provided the first evidence of uterus-selective effects of asoprisnil and structurally related compounds, and the rationale for clinical development of asoprisnil

Mifepristone Increases the Cytotoxicity of Uterine Natural Killer Cells by Acting as a Glucocorticoid Antagonist via ERK Activation

Background: Mifepristone (RU486), a potent antagonist of progesterone and glucocorticoids, is involved in immune regulation. Our previous studies demonstrated that mifepristone directly augments the cytotoxicity of human uterine natural killer (uNK) cells. However, the mechanism responsible for this increase in cytotoxicity is not known. Here, we explored whether the increased cytotoxicity in uNK cells produced by mifepristone is due to either anti-progesterone or anti-glucocorticoid activity, and also investigated relevant changes in the mitogen-activated protein kinase (MAPK) pathway. Methodology/Principal Findings: Uterine NK cells were isolated from decidual samples and incubated with different concentrations of progesterone, cortisol, or mifepristone. The cytotoxicity and perforin expression of uNK cells were detected by mitochondrial lactate dehydrogenase-based MTS staining and flow cytometry assays, respectively. Phosphorylation of components of the MAPK signaling pathway was detected by Western blot. Cortisol attenuated uNK cell-mediated cytotoxicity in a concentration-dependent manner whereas progesterone had no effect. Mifepristone alone increased the cytotoxicity and perforin expression of uNK cells; these effects were blocked by cortisol. Furthermore, mifepristone increased the phosphorylation of ERK1/2 in a cortisol-reversible manner. Specific ERK1/2 inhibitor PD98059 or U0126 blocked cortisol- and mifepristone-induced responses in uNK cells

The Bactofilin Cytoskeleton Protein BacM of Myxococcus xanthus Forms an Extended β-Sheet Structure Likely Mediated by Hydrophobic Interactions

Bactofilins are novel cytoskeleton proteins that are widespread in Gram-negative bacteria. Myxococcus xanthus, an important predatory soil bacterium, possesses four bactofilins of which one, BacM (Mxan_7475) plays an important role in cell shape maintenance. Electron and fluorescence light microscopy, as well as studies using over-expressed, purified BacM, indicate that this protein polymerizes in vivo and in vitro into ~3 nm wide filaments that further associate into higher ordered fibers of about 10 nm. Here we use a multipronged approach combining secondary structure determination, molecular modeling, biochemistry, and genetics to identify and characterize critical molecular elements that enable BacM to polymerize. Our results indicate that the bactofilin-determining domain DUF583 folds into an extended β-sheet structure, and we hypothesize a left-handed β-helix with polymerization into 3 nm filaments primarily via patches of hydrophobic amino acid residues. These patches form the interface allowing head-to-tail polymerization during filament formation. Biochemical analyses of these processes show that folding and polymerization occur across a wide variety of conditions and even in the presence of chaotropic agents such as one molar urea. Together, these data suggest that bactofilins are comprised of a structure unique to cytoskeleton proteins, which enables robust polymerization

p73: A Multifunctional Protein in Neurobiology

p73, a transcription factor of the p53 family, plays a key role in many biological processes including neuronal development. Indeed, mice deficient for both TAp73 and ΔNp73 isoforms display neuronal pathologies, including hydrocephalus and hippocampal dysgenesis, with defects in the CA1-CA3 pyramidal cell layers and the dentate gyrus. TAp73 expression increases in parallel with neuronal differentiation and its ectopic expression induces neurite outgrowth and expression of neuronal markers in neuroblastoma cell lines and neural stem cells, suggesting that it has a pro-differentiation role. In contrast, ΔNp73 shows a survival function in mature cortical neurons as selective ΔNp73 null mice have reduced cortical thickness. Recent evidence has also suggested that p73 isoforms are deregulated in neurodegenerative pathologies such as Alzheimer’s disease, with abnormal tau phosphorylation. Thus, in addition to its increasingly accepted contribution to tumorigenesis, the p73 subfamily also plays a role in neuronal development and neurodegeneration

To eat or not to eat? The diet of the endangered iberian wolf (Canis lupus signatus) in a human- dominated landscape in central Portugal

Livestock predation by large carnivores and their persecution by local communities are major conservation concerns. In order to prevent speculations and reduce conflicts, it is crucial to get detailed and accurate data on predators’ dietary ecology, which is particularly important in human dominated landscapes where livestock densities are high. This is the case of the endangered Iberian wolf in Portugal, an endemic subspecies of the Iberian Peninsula, which has seen its population distribution and abundance decline throughout the 20th century. Accordingly, the diet of the Iberian wolf was analyzed, using scat analysis, in a humanized landscape in central Portugal. From 2011 to 2014, a total of 295 wolf scats were collected from transects distributed throughout the study area, prospected on a monthly basis. Scat analysis indicated a high dependence of Iberian wolf on livestock. Domestic goat predominated the diet (62% of the scats), followed by cow (20%) and sheep (13%); the only wild ungulate present in the scat analysis was the wild boar (4% of the scats). Our results show that even though livestock constitute most part of wolves diet, different livestock species may represent different predation opportunities. We conclude that the high levels of livestock consumption may be a result of low diversity and density of wild ungulates that settles livestock as the only abundant prey for wolves. Our findings help on the understanding of the Iberian wolf feeding ecology and have implications for conflict management strategies. Finally, management implications are discussed and solutions are recommended