Aggregation-induced emission behavior of a pincer platinum(II) complex bearing a poly(ethylene oxide) chain in aqueous solution

An amphiphilic pincer platinum(II) complex with a poly(ethylene oxide) (PEO) chain exhibited aggregation-induced emission (AIE) because of micelle formation in water. The AIE activity was enhanced by the addition of 1,3,5-benzenetricarboxylic acid, which induced micelle formation through hydrogen-bonding interactions with the PEO chain

Cost-benefit analysis of climate change – A methodological overview of recent studies

Global warming16 has already begun. Climate change has become a self-propelling and self-reinforcing process as a result of the externality associated with greenhouse- gas (GHG) emissions. Although it is an externality related to humankind, according to a number of unique features we should distinguish it from other externalities. Climate change is a global phenomenon in its causes and consequences. The long-term and persistent impacts of climate change will likely continue over centuries without further anthropogenic mechanism. The preindustrial (equilibrium) level of GHG concentration in the atmosphere cannot be restored since it is irreversible, but if we do not stabilise the actual level of atmospheric concentration, the situation will become much worse than it is now. Assessing the impacts of climate change requires careful considerations because of the pervasive uncertainties and risks associated with it

Oncogenic Gain of Function in Glioblastoma Is Linked to Mutant p53 Amyloid Oligomers.

Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of a p53 mutant within amyloid-like p53 oligomers in glioblastoma-derived cells presenting a chemoresistant gain-of-function phenotype. Statistical analysis from fluorescence fluctuation spectroscopy, pressure-induced measurements, and thioflavin T kinetics demonstrates the distribution of oligomers larger than the active tetrameric form of p53 in the nuclei of living cells and the destabilization of native-drifted p53 species that become amyloid. Collectively, these results provide insights into the role of amyloid-like mutant p53 oligomers in the chemoresistance phenotype of malignant and invasive brain tumors and shed light on therapeutic options to avert cancer

Linking NAMEA and Input output for 'consumption vs. production perspective' analyses.

We integrate input output and NAMEA tables for Spain and Italy in 1995, 2000 and 2005, in order to address the hot policy issue of sustainable consumption and production. A comparison of a production and consumption perspective may have relevant policy implications. We deal with the domestic technology assumption and primarily the aggregation bias that may result when calculating indirect emission using different sector aggregation in the analyses (e.g. 16, 32, 50). Extended Input output analysis provides analyses of the emissions embodied in domestic consumption and domestic production by considering the structure of intermediate inputs and environmental efficiency in each production sector. Our empirical findings show that different sectoral aggregation significantly biases the amount of emissions both for the consumption and the production perspective, though differently in the two countries. Italy surprisingly show consumption/production ratios around or lower than one, but in line with some major work at EU level. Our results thus suggest that special attention must be paid when interpreting the EE-IOA of country estimated amounts of embodied emissions, both in domestic final demand and those directly associated with the production sectors when the sectoral aggregation level has a low definition as considered in some recent similar studies.NAMEA, extended input output, sustainable consumption and production, aggregation bias, final demand

Study of Hydrophobic Domains in Humic Acids

Fyzikálně-chemická povaha hydrofobních domén huminových kyselin byla studována z několika hledisek. K objasnění významu fluorescenčních spekter byly vzorky podrobeny sekvenční frakcionaci, která pomohla k částečnému objasnění vlivu vodorozpustných složek, volných a vázaných lipidů na optické vlastnosti huminových kyselin. Výsledky naznačily, že fluorescenční píky tradičně přiřazované superpozici jednotlivých struktur jsou spíše důsledkem agregačních vlastností huminových molekul tvořících vlivem hydrofobního efektu zdánlivě vysoce aromatické struktury. Dále pak bylo zjištěno, že na optických vlastnostech huminových kyselin mají podíl i molekuly, které nemají primárně fluoroforní nebo chromoforní vlastnosti. Tento pohled je v souladu s teorií supramolekulárního uspořádání huminových kyselin. Dále byly studovány agregace, konformační chování a termodynamická stabilita huminových kyselin pomocí metody vysoce rozlišovací ultrazvukové spektroskopie. Bylo prokázáno, že huminové kyseliny mají schopnost agregovat už od velmi nízkých koncentrací (The nature of hydrophobic domains in humic acids was studied from different points of view. To shed light on the meaning of fluorescent spectra, the measured samples underwent the sequential extraction which partially revealed the role of water-soluble components, free and bond lipids in optical properties of humic acids. The results indicated that the fluorescence peaks traditionally attributed to the superposition of individual chemical structures are rather a result of aggregation properties of humic molecules and hydrophobic effect driving aromatic molecules together forming aggregates apparently large molecular weight. Further, it seems that there is a significant influence of non-fluorophores and non-chromophores on the optical properties of humic acids. Results are consistent with the theory on supramolecular structure of humic acids. Next, the aggregation, conformational behaviour and thermodynamic stability of humic acids were studied by high resolution ultrasonic spectroscopy. It was demonstrated that humic molecules are able to interact and form aggregates at very low concentration (

Folding mechanisms steer the amyloid fibril formation propensity of highly homologous proteins

Significant advances in the understanding of the molecular determinants of fibrillogenesis can be expected from comparative studies of the aggregation propensities of proteins with highly homologous structures but different folding pathways. Here, we fully characterize, by means of stopped-flow, T-jump, CD and DSC experiments, the unfolding mechanisms of three highly homologous proteins, zinc binding Ros87 and Ml153-149 and zinc-lacking Ml452-151. The results indicate that the three proteins significantly differ in terms of stability and (un)folding mechanisms. Particularly, Ros87 and Ml153-149 appear to be much more stable to guanidine denaturation and are characterized by folding mechanisms including the presence of an intermediate. On the other hand, metal lacking Ml452-151 folds according to a classic two-state model. Successively, we have monitored the capabilities of Ros87, Ml452-151 and Ml153-149 to form amyloid fibrils under native conditions. Particularly, we show, by CD, fluorescence, DLS, TEM and SEM experiments, that after 168 hours, amyloid formation of Ros87 has started, while Ml153-149 has formed only amorphous aggregates and Ml452-151 is still monomeric in solution. This study shows how metal binding can influence protein folding pathways and thereby control conformational accessibility to aggregation-prone states, which in turn changes aggregation kinetics, shedding light on the role of metal ions in the development of protein deposition diseases

Translational and rotational motions of albumin sensed by a non-covalent associated porphyrin under physiological and acidic conditions: a fluorescence correlation spectroscopy and time resolved anisotropy study.

The interaction between a free-base, anionic water-soluble porphyrin, TSPP, and the drug carrier protein, bovine serum albumin (BSA) has been studied by time-resolved fluorescence anisotropy (TRFA) and fluorescence correlation spectroscopy (FCS) at two different pH-values. Both rotational correlation times and translational diffusion times of the fluorescent species indicate that TSPP binding to albumin induces very little conformational changes in the protein under physiological conditions. By contrast, at low pH, a bi-exponential decay is obtained where a short rotational correlation time (¿ int¿=¿1.2 ns) is obtained, which is likely associated to wobbling movement of the porphyrin in the protein binding site. These physical changes are corroborated by circular dichroism (CD) data which show a 37% loss in the protein helicity upon acidification of the medium. In the presence of excess porphyrin formation of porphyrin J-aggregates is induced, which can be detected by time-resolved fluorescence with short characteristic times. This is also reflected in FCS data by an increase in molecular brightness together with a decrease in the number of fluorescent molecules passing through the detection volume of the sampl

Cost-benefit analysis of climate change – A methodological overview of recent studies

Global warming16 has already begun. Climate change has become a self-propelling and self-reinforcing process as a result of the externality associated with greenhouse- gas (GHG) emissions. Although it is an externality related to humankind, according to a number of unique features we should distinguish it from other externalities. Climate change is a global phenomenon in its causes and consequences. The long-term and persistent impacts of climate change will likely continue over centuries without further anthropogenic mechanism. The preindustrial (equilibrium) level of GHG concentration in the atmosphere cannot be restored since it is irreversible, but if we do not stabilise the actual level of atmospheric concentration, the situation will become much worse than it is now. Assessing the impacts of climate change requires careful considerations because of the pervasive uncertainties and risks associated with it

Myricetin, the main flavonoid in Syzygium cumini leaf, is a novel inhibitor of platelet thiol isomerases PDI and ERp5

Background: Flavonoids have been characterized as a prominent class of compounds to treat thrombotic diseases through the inhibition of thiol isomerases. Syzygium cumini is a flavonoid-rich medicinal plant that contains myricetin and gallic acid. Little is known about the potential anti-platelet properties of S. cumini and its constituent flavonoids. Objective To evaluate the anti-platelet effects and mechanism of action of a polyphenol-rich extract (PESc) from S. cumini leaf and its most prevalent polyphenols, myricetin and gallic acid. Methods PESc, myricetin and gallic acid were incubated with platelet-rich plasma and washed platelets to assess platelet aggregation and activation. In vitro platelet adhesion and thrombus formation as well as in vivo bleeding time were performed. Finally, myricetin was incubated with recombinant thiol isomerases to assess its potential to bind and inhibit these, whilst molecular docking studies predicted possible binding sites. Results: PESc decreased platelet activation and aggregation induced by different agonists. Myricetin exerted potent anti-platelet effects, whereas gallic acid did not. Myricetin reduced the ability of platelets to spread on collagen, form thrombi in vitro without affecting haemostasis in vivo. Fluorescence quenching studies suggested myricetin binds to different thiol isomerases with similar affinity, despite inhibiting only protein disulphide isomerase (PDI) and ERp5 reductase activities (IC50~3.5 μM). Finally, molecular docking studies suggested myricetin formed non-covalent bonds with PDI and ERp5. Conclusions: PESc and its most abundant flavonoid myricetin strongly inhibit platelet function. Additionally, myricetin is a novel inhibitor of ERp5 and PDI, unveiling a new therapeutic perspective for the treatment of thrombotic disorders