Silver covalently bound to cyanographene overcomes bacterial resistance to silver nanoparticles and antibiotics

The ability of bacteria to develop resistance to antibiotics is threatening one of the pillars of modern medicine. It was recently understood that bacteria can develop resistance even to silver nanoparticles by starting to produce flagellin, a protein which induces their aggregation and deactivation. This study shows that silver covalently bound to cyanographene (GCN/Ag) kills silver-nanoparticle-resistant bacteria at concentrations 30 times lower than silver nanoparticles, a challenge which has been so far unmet. Tested also against multidrug resistant strains, the antibacterial activity of GCN/Ag is systematically found as potent as that of free ionic silver or 10 nm colloidal silver nanoparticles. Owing to the strong and multiple dative bonds between the nitrile groups of cyanographene and silver, as theory and experiments confirm, there is marginal silver ion leaching, even after six months of storage, and thus very high cytocompatibility to human cells. Molecular dynamics simulations suggest strong interaction of GCN/Ag with the bacterial membrane, and as corroborated by experiments, the antibacterial activity does not rely on the release of silver nanoparticles or ions. Endowed with these properties, GCN/Ag shows that rigid supports selectively and densely functionalized with potent silver-binding ligands, such as cyanographene, may open new avenues against microbial resistance.Web of Scienceart. no. 200309

DNA damage-inducible protein: interaction partners and potential role in proteasomal degradation

Ddi1-like proteins (DNA damage-inducible) have been so far best characterized in yeast (Ddi1 protein from Saccharomyces cerevisiae), drosophila and quite recently also in human (Ddi2 protein). Based on their domain architecture they belong to the family of proteasomal shuttle proteins that transport ubiquitinated proteins for proteasomal degradation. They contain ubiquitin-associated domain (UBA) responsible for the interaction with proteasome subunits and ubiquitin-like domains (UBL) required for the interaction with ubiquitinated proteins. However, they also seem to have other functions. The yeast homolog Ddi1 is involved in cell cycle control, plays a role in the degradation of HO endonuclease and probably also functions as a negative regulator of exocytosis. The cellular functions of recently identified human homolog Ddi2 are not yet understood. In order to contribute to the understanding of the physiologic functions of human Ddi2 protein, we decided to identify potential binding partners of this protein. Therefore, we prepared DNA constructs for the expression of Ddi2 in mammalian HEK293 cells fused to two affinity tags, either FLAG or HA or Myc tag, that enable their facile visualisation and purification. Affinity chromatography coupled to mass spectrometry (AP-MS) aided in identifying..

Culture boom: How digital media are invigorating Australia

The Internet and online media have significantly impacted the Australian media and content industry and will continue to do so. They will be the key drivers of growth for the industry, delivering considerable value to consumers. Companies will need to adapt to the new reality to succeed. The amount of internet content that is created and consumed grows by the day in australia and around the world. the internet is an ever more integral part of daily life and a significant generator of economic activity. to better understand the impact of the internet on consumers, artists, and the content sector in australia, Google commissioned the Boston consulting Group to prepare this independent report. the results have been discussed with Google executives, but BcG is responsible for the analysis and conclusions. Paul Zwillenberg

The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties

Motivated by the clinical success of gold(I) metallotherapeutic Auranofin in the effective treatment of both inflammatory and cancer diseases, we decided to prepare, characterize, and further study the [Au(kin)(PPh3)] complex (1), where Hkin = kinetin, 6-furfuryladenine, for its in vitro anti-cancer and anti-inflammatory activities. The results revealed that the complex (1) had significant in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, and THP-1), with IC50 ≈ 1–5 μM, which was even significantly better than that for the conventional platinum-based drug Cisplatin while comparable with Auranofin. Although its ability to inhibit transcription factor NF-κB activity did not exceed the comparative drug Auranofin, it has been found that it is able to positively influence peroxisome-proliferator-activated receptor-gamma (PPARγ), and as a consequence of this to have the impact of moderating/reducing inflammation. The cellular effects of the complex (1) in A2780 cancer cells were also investigated by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential, and shotgun proteomic analysis. Proteomic analysis of R2780 cells treated with complex (1) and starting compounds revealed possible different places of the effect of the studied compounds. Moreover, the time-dependent cellular accumulation of copper was studied by means of the mass spectrometry study with the aim of exploring the possible mechanisms responsible for its biological effects

High spatial resolution geochemistry and textural characteristics of 'microtektite' glass spherules in proximal Cretaceous-Paleogene sections: insights into glass alteration patterns and precursor melt lithologies

Using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), we have conducted spatially resolved trace element analysis on fresh, unaltered microtektite glasses linked to the Cretaceous-Paleogene (K-Pg) boundary Chicxulub crater and on their surrounding alteration phases. This unique approach offers the opportunity to study in situ and at high spatial resolution both the mixing of different target lithologies and the variation of the major and trace element budget during the alteration process. In addition, two-dimensional element distribution maps reveal important geochemical information beyond the capabilities of single spot laser drilling. Glasses from two localities in opposite quadrants from the source crater were studied. At the Beloc locality (Haiti), the glass population is dominated by the presence of yellow high-Ca glass and black andesitic glass formed by admixture of carbonate/dolomite/anhydrite platform lithologies with crystalline basement. These glasses alter according to the well-established hydration-palagonitization model postulated for mafic volcanic glasses. REEs become progressively leached from the glass to below the detection limit for the applied spot size, while immobile Zr, Hf, Nb, and Ta passively accumulate in the process exhibiting both inter-element ratios and absolute concentrations similar to those for the original glass. In contrast, The Arroyo El Mimbral locality (NE Mexico) is characterized by abundant green glass fragments high in Si, Al and alkalis, and low in Mg, Ca, Fe. Low Si black glass is less abundant though similar in composition to the black glass variety at Beloc. The alteration pattern of high-Si, Al green glass at the Mimbral locality is more complex, including numerous competing reaction processes (ion-exchange, hydration, dissolution, and secondary mineral precipitation) generally controlled by the pH and composition of the surrounding fluid. All green, high-Si, Al glasses are hydrated and variably enriched in Sr, Ba, and Cs, indicating preferred adsorption from seawater during hydration. Despite the onset of ion-exchange reactions, which only seem to have affected the alkalis, the trace element composition of the green high-Si, Al glass is still largely representative of the original melt composition. Refining the geochemical signature of (altered) melt lithologies may advance our current understanding of glass stability in the natural environment and provide insight into the origin and emplacement of ejecta material during crater formation

The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties

Motivated by the clinical success of gold(I) metallotherapeutic Auranofin in the effective treatment of both inflammatory and cancer diseases, we decided to prepare, characterize, and further study the [Au(kin)(PPh3)] complex (1), where Hkin = kinetin, 6-furfuryladenine, for its in vitro anti-cancer and anti-inflammatory activities. The results revealed that the complex (1) had significant in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, and THP-1), with IC50 ≈ 1–5 μM, which was even significantly better than that for the conventional platinum-based drug Cisplatin while comparable with Auranofin. Although its ability to inhibit transcription factor NF-κB activity did not exceed the comparative drug Auranofin, it has been found that it is able to positively influence peroxisome-proliferator-activated receptor-gamma (PPARγ), and as a consequence of this to have the impact of moderating/reducing inflammation. The cellular effects of the complex (1) in A2780 cancer cells were also investigated by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential, and shotgun proteomic analysis. Proteomic analysis of R2780 cells treated with complex (1) and starting compounds revealed possible different places of the effect of the studied compounds. Moreover, the time-dependent cellular accumulation of copper was studied by means of the mass spectrometry study with the aim of exploring the possible mechanisms responsible for its biological effects

Condensed clustered iron oxides for ultrahigh photothermal conversion and in vivo multimodal imaging

Magnetic iron oxide nanocrystals (MIONs) are established as potent theranostic nanoplatforms due to their biocompatibility and the multifunctionality of their spin-active atomic framework. Recent insights have also unveiled their attractive near-infrared photothermal properties, which are, however, limited by their low near-infrared absorbance, resulting in noncompetitive photothermal conversion efficiencies (PCEs). Herein, we report on the dramatically improved photothermal conversion of condensed clustered MIONs, reaching an ultrahigh PCE of 71% at 808 nm, surpassing the so-far MION-based photothermal agents and even benchmark near-infrared photothermal nanomaterials. Moreover, their surface passivation is achieved through a simple self-assembly process, securing high colloidal stability and structural integrity in complex biological media. The bifunctional polymeric canopy simultaneously provided binding sites for anchoring additional cargo, such as a strong near-infrared-absorbing and fluorescent dye, enabling in vivo optical and photoacoustic imaging in deep tissues, while the iron oxide core ensures detection by magnetic resonance imaging. In vitro studies also highlighted a synergy-amplified photothermal effect that significantly reduces the viability of A549 cancer cells upon 808 nm laser irradiation. Integration of such-previously elusive-photophysical properties with simple and cost-effective nanoengineering through self-assembly represents a significant step toward sophisticated nanotheranostics, with great potential in the field of nanomedicine.Web of Science1325292562924

The Differential Effect of Carbon Dots on Gene Expression and DNA Methylation of Human Embryonic Lung Fibroblasts as a Function of Surface Charge and Dose

This study presents a toxicological evaluation of two types of carbon dots (CD), similar in size (<10 nm) but differing in surface charge. Whole-genome mRNA and miRNA expression (RNAseq), as well as gene-specific DNA methylation changes, were analyzed in human embryonic lung fibroblasts (HEL 12469) after 4 h and 24 h exposure to concentrations of 10 and 50 µg/mL (for positive charged CD; pCD) or 10 and 100 µg/mL (for negative charged CD, nCD). The results showed a distinct response for the tested nanomaterials (NMs). The exposure to pCD induced the expression of a substantially lower number of mRNAs than those to nCD, with few commonly differentially expressed genes between the two CDs. For both CDs, the number of deregulated mRNAs increased with the dose and exposure time. The pathway analysis revealed a deregulation of processes associated with immune response, tumorigenesis and cell cycle regulation, after exposure to pCD. For nCD treatment, pathways relating to cell proliferation, apoptosis, oxidative stress, gene expression, and cycle regulation were detected. The expression of miRNAs followed a similar pattern: more pronounced changes after nCD exposure and few commonly differentially expressed miRNAs between the two CDs. For both CDs the pathway analysis based on miRNA-mRNA interactions, showed a deregulation of cancer-related pathways, immune processes and processes involved in extracellular matrix interactions. DNA methylation was not affected by exposure to any of the two CDs. In summary, although the tested CDs induced distinct responses on the level of mRNA and miRNA expression, pathway analyses revealed a potential common biological impact of both NMs independent of their surface charge