Structural features of two distinct molecular complexes of copper(II) cationic porphyrin and deoxyribonucleotides

The associations of the water-soluble cationic copper(II)-5,10,15,20-meso-tetrakis(4-N-methylpyridyl) porphyrin (CuP) with d(pT)9 oligothymidylate and its building blocks deoxythymidine (dT) and deoxythymidine 5'-monophosphate (dTMP) were investigated by spectrophotometric titration [absorption, nanosecond transient resonance Raman (ns-RR) and picosecond time-resolved resonance Raman (ps-TR3) spectroscopies] to elucidate the structural requirements for the CuP exciplex formation in molecular complexes with unchained mononucleotides. In the d(pT)9 a factor analysis and global fit of the CuP absorption spectra revealed the formation of a single spectral species attributable to a 1 : 1 CuP. d(pT)9 complex throughout a wide range of d(pT)9/CuP ratios (0-10). Using ps-TR3 spectroscopy, the CuP. d(pT)9 complex was shown to be fully responsible for exciplex formation. In contrast, CuP mixed with dTMP ([dTMP]/[CuP] < 3000) yielded two spectroscopically distinct types of molecular complexes with 1 : 1 (CuP. dTMP) and 1 : 2 (CuP. (dTMP)2) (or even higher for [dTMP]/[CuP] > 3000) stoichiometry, the latter being spectroscopically identical to the CuP. d(pT)9 and providing a microenvironment favorable for exciplex formation to the same extent as the oligothymidylate. On the other hand, the 1 : 1 CuP. dTMP complex (prevailing for [dTMP]/[CuP] < 100) yielded no exciplex features. Similar behavior was observed for the CuP complexed with dT. To explain the difference in the ability of the CuP. dTMP and CuP. (dTMP)2 species to form the exciplex, two types of molecular complexes were suggested and discussed, differing in the orientation of the thymine planes with respect to the porphyrin macrocycle.     

Evaluation of two library-independent microbial source tracking methods to identify sources of fecal contamination in French estuaries

In order to identify the origin of the fecal contamination observed in French estuaries, two library-independent microbial source tracking (MST) methods were selected: (i) Bacteroidales host-specific 16S rRNA gene markers and (ii) F-specific RNA bacteriophage genotyping. The specificity of the Bacteroidales markers was evaluated on human and animal (bovine, pig, sheep, and bird) feces. Two human-specific markers (HF183 and HF134), one ruminant-specific marker (CF193'), and one pig-specific marker (PF163) showed a high level of specificity (>90%). However, the data suggest that the proposed ruminant-specific CF128 marker would be better described as an animal marker, as it was observed in all bovine and sheep feces and 96% of pig feces. F RNA bacteriophages were detected in only 21% of individual fecal samples tested, in 60% of pig slurries, but in all sewage samples. Most detected F RNA bacteriophages were from genotypes II and III in sewage samples and from genotypes I and IV in bovine, pig, and bird feces and from pig slurries. Both MST methods were applied to 28 water samples collected from three watersheds at different times. Classification of water samples as subject to human, animal, or mixed fecal contamination was more frequent when using Bacteroidales markers (82.1% of water samples) than by bacteriophage genotyping (50%). The ability to classify a water sample increased with increasing Escherichia coli or enterococcus concentration. For the samples that could be classified by bacteriophage genotyping, 78% agreed with the classification obtained from Bacteroidales markers.     

The perpetuation and epidemic recurrence of communicable diseases in human populations

Recurrence of communicable diseases is a looming threat for human populations. Factors explaining the recurrences are partially known, involving demographics, biology, and complex relationships with the environment, but no comprehensive theory exists today. Here, we review some recent results obtained in modelling studies with a view to understanding better the mechanisms of perpetuation. Factors intrinsic to the interaction of pathogen and host have regained interest in this respect, especially with multiple pathogen and multiple population interactions. Extrinsic factors, including pure demography and environmental forcing are also strong predictors. With increasingly detailed data available, large-scale integrated models will help sorting out the multiple influences on recurrence.     

Synthesis and biological evaluation of 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors

The synthesis and biological evaluation of a number of differently substituted 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives are reported. From the inhibition results on a selection of disease-relevant protein kinases [IC₅₀ (μM) DYRK1A = 11; CDK5 = 0.41; GSK-3 = 1.5] we have observed that 3,6-diamino-4-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4) constitutes a potential new and simple lead compound in the search of drugs for the treatment of Alzheimer’s disease.     

Influence of microalgae cell wall characteristics on protein extractability and determination of nitrogen-to-protein conversion factors

Additional evidence about the influence of the cell wall physical and chemical characteristics on protein extractability was determined by calculating the conversion factors of five different microalgae known to have different cell wall composition, and their protein extracts. The conversion factors obtained for crude rigid cell walled Chlorella vulgaris, Nannochloropsis oculata and Haematococcus pluvialis were 6.35, 6.28 and 6.25, respectively, but for their protein extracts the values were lower with 5.96, 5.86 and 5.63. On the other hand, conversion factor obtained for fragile cell walled microalgae Porphyridium cruentum and Athrospira platensis was 6.35 for the former and 6.27 for the latter, with no significant difference for their protein extract with 6.34 for the former and 6.21 for the latter. In addition, the highest hydro-soluble protein percentage recovered from total protein was for P. cruentum 80.3 % and A. platensis 69.5 % but lower for C. vulgaris with 43.3 %, N. oculata with 33.3 % and H. pluvialis with 27.5 %. The study spotted the light on the influence of the cell wall on evaluating the conversion factor and protein extractability. In addition, it showed the necessity of finding the conversion factor every time accurate protein quantification is required, and proved that there is not a universal conversion factor that can be recommended.     

New insights into skeletal muscle development and growth in teleost fishes

Recent research has significantly broadened our understanding of how the teleost somite is patterned to achieve embryonic and postembryonic myogenesis. Medial (adaxial) cells and posterior cells of the early epithelial somite generate embryonic superficial slow and deep fast muscle fibers, respectively, whereas anterior somitic cells move laterally to form an external cell layer of undifferentiated Pax7-positive myogenic precursors surrounding the embryonic myotome. In late embryo and in larvae, some of the cells contained in the external cell layer incorporate into the myotome and differentiate into new muscle fibers, thus contributing to medio-lateral expansion of the myotome. This supports the suggestion that the teleost external cell layer is homologous to the amniote dermomyotome. Some of the signalling molecules that promote lateral movement or regulate the myogenic differentiation of external cell precursors have been identified and include stromal cell-derived factor 1 (Sdf1), hedgehog proteins, and fibroblast growth factor 8 (Fgf8). Recent studies have shed light on gene activations that underlie the differentiation and maturation of slow and fast muscle fibers, pointing out that both adaxially derived embryonic slow fibers and slow fibers formed during the myotome expansion of larvae initially and transiently bear features of the fast fiber phenotype.     

An Ecological Risk Assessment of Hexachlorobutadiene

Hexachlorobutadiene (HCBD) has never been commercially produced in Canada and was imported in the past for use as a solvent. Anthropogenic activity is linked with the entry of this substance into the environment. While current Canadian sources of HCBD involve low-level releases, potentially they can be numerous. Until recently, the most significant point source of HCBD in Canada appeared to be the Cole Drain, which discharges into the St. Clair River at Sarnia, Ontario, and includes outfalls from an industrial landfill and a few industrial companies. HCBD has been detected in Canadian surface waters, sediments, aquatic organisms and, occasionally, air. Considering the properties of the substance, including its persistence and bioaccumulation characteristics, the environmental risk assessment of HCBD was focused on the aquatic environment. The results of a conservative assessment suggest that there is a risk of harmful effects for benthic organisms exposed to sediments contaminated by HCBD in the most contaminated part of the St. Clair River.     

A Tissue-Level Electromechanical Model of the Left Ventricle: Application to the Analysis of Intraventricular Pressure

The ventricular pressure profile is characteristic of the cardiac contraction progress and is useful to evaluate the cardiac performance. In this contribution, a tissue-level electromechanical model of the left ventricle is proposed, to assist the interpretation of left ventricular pressure waveforms. The left ventricle has been modeled as an ellipsoid composed of twelve mechano-hydraulic sub-systems. The asynchronous contraction of these twelve myocardial segments has been represented in order to reproduce a realistic pressure profiles. To take into account the different energy domains involved, the tissue-level scale and to facilitate the building of a modular model, multiple formalisms have been used: Bond Graph formalism for the mechano-hydraulic aspects and cellular automata for the electrical activation. An experimental protocol has been defined to acquire ventricular pressure signals from three pigs, with different afterload conditions. Evolutionary Algorithms have been used to identify the model parameters in order to minimize the error between experimental and simulated ventricular pressure signals. Simulation results show that the model is able to reproduce experimental ventricular pressure. In addition, electro-mechanical activation times have been determined in the identification process. For example, the maximum electrical activation time is reached, respectively, 96.5, 139.3 and 131.5 ms for the first, second, and third pigs. These preliminary results are encouraging for the application of the model on non-invasive data like ECG, arterial pressure or myocardial strain.