Resistance to caspase-8 and -9 fragments in a malignant pleural mesothelioma cell line with acquired cisplatin-resistance

Apoptotic cysteine–aspartate proteases (caspases) are essential for the progression and execution of apoptosis, and detection of caspase fragmentation or activity is often used as markers of apoptosis. Cisplatin (cis-diamminedichloroplatinum (II)) is a chemotherapeutic drug that is clinically used for the treatment of solid tumours. We compared a cisplatin-resistant pleural malignant mesothelioma cell line (P31res1.2) with its parental cell line (P31) regarding the consequences of in vitro acquired cisplatin-resistance on basal and cisplatin-induced (equitoxic and equiapoptotic cisplatin concentrations) caspase-3, -8 and -9 fragmentation and proteolytic activity. Acquisition of cisplatin-resistance resulted in basal fragmentation of caspase-8 and -9 without a concomitant increase in proteolytic activity, and there was an increased basal caspase-3/7 activity. Similarly, cisplatin-resistant non-small-cell lung cancer cells, H1299res, had increased caspase-3 and -9 content compared with the parental H1299 cells. In P31 cells, cisplatin exposure resulted in caspase-9-mediated caspase-3/7 activation, but in P31res1.2 cells the cisplatin-induced caspase-3/7 activation occurred before caspase-8 or -9 activation. We therefore concluded that in vitro acquisition of cisplatin-resistance rendered P31res1.2 cells resistant to caspase-8 and caspase-9 fragments and that cisplatin-induced, initiator-caspase independent caspase-3/7 activation was necessary to overcome this resistance. Finally, the results demonstrated that detection of cleaved caspase fragments alone might be insufficient as a marker of caspase activity and ensuing apoptosis induction

Sterilization of hydrogen peroxide resistant bacterial spores with stabilized chlorine dioxide

Bacillus pumilus SAFR-032 spores isolated from a clean room environment are known to exhibit enhanced resistance to peroxide, desiccation, UV radiation and chemical disinfection than other spore-forming bacteria. The survival of B. pumilus SAFR-032 spores to standard clean room sterilization practices requires development of more stringent disinfection agents. Here, we report the effects of a stabilized chlorine dioxide-based biocidal agent against spores of B. pumilus SAFR-032 and Bacillus subtilis ATCC 6051. Viability was determined via CFU measurement after exposure. Chlorine dioxide demonstrated efficacy towards sterilization of spores of B. pumilus SAFR-032 equivalent or better than exposure to hydrogen peroxide. These results indicate efficacy of chlorine dioxide delivered through a stabilized chlorine dioxide product as a means of sterilization of peroxide- and UV-resistant spores.This work is supported by the National Institutes of Health (1R01GM090064-01), a NASA EPSCoR Research Infrastructure Development (RID) grant NN07AL49A, and the University of Oklahoma.Ye

Natural Intelligence and Anthropic Reasoning

This paper aims to justify the concept of natural intelligence in the biosemiotic context. I will argue that the process of life is (i) a cognitive/semiotic process and (ii) that organisms, from bacteria to animals, are cognitive or semiotic agents. To justify these arguments, the neural-type intelligence represented by the form of reasoning known as anthropic reasoning will be compared and contrasted with types of intelligence explicated by four disciplines of biology – relational biology, evolutionary epistemology, biosemiotics and the systems view of life – not biased towards neural intelligence. The comparison will be achieved by asking questions related to the process of observation and the notion of true observers. To answer the questions I will rely on a range of established concepts including SETI (search for extraterrestrial intelligence), Fermi’s paradox, bacterial cognition, versions of the panspermia theory, as well as some newly introduced concepts including biocivilisations, cognitive/semiotic universes, and the cognitive/semiotic multiverse. The key point emerging from the answers is that the process of cognition/semiosis – the essence of natural intelligence – is a biological universal.Brunel University Londo

Structural studies of (N-phenylthioureidoalkyl- and -aryl)phosphonates

The crystal structures of three (N-phenylthioureidoalkyl- and - aryl) phosphonates, i.e. diphenyl [(3-phenylthioureido) phenylpropyl] phosphonate, diphenyl [1-(3-phenylthioureido) benzyl] phosphonate and diphenyl [2,2-dimethyl-1-(3-phenylthioureido) propyl] phosphonate, have been determined by X-ray diffraction. The conformations of the title molecules, the geometry of the thioureide fragments and molecular packing arrangements are analyzed and compared with literature data

Two derivatives of (N-phenylthioureidoalkyl)phosphonates

The structures of diphenyl [3-methyl-1-(3-phenylthioureido)butyl]phosphonate and diphenyl [2-methyl-1-(3-phenylthioureido)butyl]phosphonate, both C24H27N2O3PS, are reported. In both compounds, the thiourea moiety adopts a syn-syn conformation (i.e. the S-C-N-C torsion angles are synperiplanar), which enables N-H...O hydrogen bonds to be formed between centrosymmetrically related molecules. The geometries around the P atoms can be described as distorted tetrahedral. Some of the functional groups in each structure are disordered. The bulk of the different alkyl substituents between the amide and phosphonate groups influences the molecular conformation and crystal packing. Although the structures of these compounds and two related derivatives appear to be similar, they are not isostructural