Combination of laccase and catalase in construction of H(2)O(2)-O(2) based biocathode for applications in glucose biofuel cells

In this study, we propose a new strategy to boost the power density of glucose biofuel cells (GBFCs) biocathodes. By combining laccase with catalase enzymes electrophoretically deposited by means of AC electric fields on multiple walled carbon nanotubes modified platinum black and, then stabilized by an outer layer of polypyrrole in the construction of GC/MWCNTs/Ptb/LAc-CAt/PPy biocathode, we can take advantage of the H(2)O(2) present in the solution or body tissue to increase the level of the dissolved O(2). The results from cyclic voltammetry, amperometry and electrochemical impedance spectroscopy demonstrate that the deposited enzymes laccase and catalase by means of AC-EPD did not inhibit each other and carry out ～90% of the catalytic reduction process of O(2)-H(2)O(2). The power density of the non-compartmentalized GBFC constructed from GC/MWCNTs/Ptb/LAc-CAt/PPy biocathode and GC/MWCNTs/GOx/PPy bioanode in phosphate buffer containing 10mM glucose and equal amounts of dissolved O(2) and H(2)O(2) (0.3mM) is almost doubled because of the presence of catalase enzyme in the constructed biocathode. The latter might be of great interest for in vivo studies of GBFCs where the concentration of dissolved O(2) in the body tissues or biological fluids is very low compared to in vitro conditions (buffers under air).     

Synthesis of 12-oxa, 12-aza and 12-thia cholanetriols

An efficient synthesis of 12-hetero steroids was achieved via a Baeyer-Villiger oxidation and a photolysis as the key steps. We set out to describe in this paper the first synthesis of 12-aza steroids. The characteristic ¹H and ¹³C NMR spectroscopic features of the synthesized compounds are reported.     

Structural requirement of arylindolylpropenones as anti-bladder carcinoma cells agents

Chalcones have been identified as interesting compounds with cytotoxicity, anti-inflammatory and antioxidant properties. In the present study, we report the synthesis and evaluation of new 1-(N-methylindolyl)-3-phenylpropenones as anti-cancer agents acting on bladder carcinoma cell line. Among the 15 investigated molecules, three of them inhibit the growth of bladder cancer cells with IC(50) values less than 4 μM after 48 h of treatment. To investigate their mode of action, cell cycle analyses were performed. The most active compounds induce high accumulation at the G2+M phase as assessed by flow cytometry. The structure-activity relationship drawn from the present study highlights the importance of the substitution pattern of the phenyl ring and provides valuable information for further development of this class of compounds as novel anti-cancer chemotherapeutic agents.     

Time course of vascular arginase expression and activity in spontaneously hypertensive rats

There is growing evidence that vascular arginase plays a role in pathophysiology of vascular diseases. We recently reported high arginase activity/expression in young adult hypertensive spontaneously hypertensive rats (SHR). The aim of the present study was to characterize the time course of arginase pathway abnormalities in SHR and to explore the contributing role of hemodynamics and inflammation. Experiments were conducted on 5, 10, 19 and 26-week-old SHR and their age-matched control Wistar Kyoto (WKY) rats. Arginase activity as well as expression of arginase I, arginase II, endothelial and inducible NOS were determined in aortic tissue extracts. Levels of L-arginine, NO catabolites and IL-6 (a marker of inflammation) were measured in plasma. Arginase activity/expression was also measured in 10-week-old SHR previously treated with hydralazine (20 mg/kg/day, per os, for 5 weeks). As compared to WKY, SHR exhibited high vascular arginase I and II expression from prehypertensive to established stages of hypertension. However, a mismatch between expression and activity was observed at the prehypertensive stage. Arginase expression was not related either to plasma IL-6 levels or to expression of NOS. Prevention of hypertension by hydralazine significantly blunted arginase upregulation and restored arginase activity. Importantly, arginase activity and blood pressure (BP) correlated in SHR. In conclusion, our results demonstrate that arginase upregulation precedes blood pressure rising and identify elevated blood pressure as a contributing factor of arginase dysregulation in genetic hypertension. They also demonstrated a close relationship between arginase activity and BP, thus making arginase a promising target for antihypertensive therapy.     

Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause autosomal recessive Charcot-Marie-Tooth type 4H

Charcot-Marie-Tooth (CMT) disorders are a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies characterized by muscle weakness and wasting, foot and hand deformities, and electrophysiological changes. The CMT4H subtype is an autosomal recessive demyelinating form of CMT that was recently mapped to a 15.8-Mb region at chromosome 12p11.21-q13.11, in two consanguineous families of Mediterranean origin, by homozygosity mapping. We report here the identification of mutations in FGD4, encoding FGD4 or FRABIN (FGD1-related F-actin binding protein), in both families. FRABIN is a GDP/GTP nucleotide exchange factor (GEF), specific to Cdc42, a member of the Rho family of small guanosine triphosphate (GTP)-binding proteins (Rho GTPases). Rho GTPases play a key role in regulating signal-transduction pathways in eukaryotes. In particular, they have a pivotal role in mediating actin cytoskeleton changes during cell migration, morphogenesis, polarization, and division. Consistent with these reported functions, expression of truncated FRABIN mutants in rat primary motoneurons and rat Schwann cells induced significantly fewer microspikes than expression of wild-type FRABIN. To our knowledge, this is the first report of mutations in a Rho GEF protein being involved in CMT.     

Evaluation of cocksfoot (Dactylis glomerata L.) population for drought survival and behavior

Climate change models predict frequent and intense droughts in the world. Development of drought-tolerant species and cultivars is necessary to cope with such changes. Forage grass species are affected, especially in the Mediterranean region. The aim of the present study was to investigate the diversity for drought survival, summer dormancy, and productivity within a cocksfoot population.The study was conducted in Morocco, under field conditions from 2011 to 2013. 283 genotypes of cocksfoot and parents were tested, characterized for dry matter yield, heading date, plant height, senescence, summer dormancy, and drought survival. Results exhibited a large variability between traits. 79% of the population had survived after severe drought summer while 57% yielded more than both parents. Also, 63% of the progeny had an intermediate score of summer dormancy estimated by senescence score. Large variability was also noticed for heading date and plant height. Several accessions combined a high yield and persistence under severe summer drought. Which explain the significant correlation (r = 0.18, P < 0.005) founded between total dry matter accumulated in 2013 and plant survival. Accordingly, our results showed that we can rise persistent and resilient genotypes among population with a good level of biomass.     

The Stringent Response Modulates 4-Hydroxy-2-Alkylquinoline Biosynthesis and Quorum-Sensing Hierarchy in Pseudomonas aeruginosa

As a ubiquitous environmental organism and an important human pathogen, Pseudomonas aeruginosa readily adapts and responds to a wide range of conditions and habitats. The intricate regulatory networks that link quorum sensing and other global regulators allow P. aeruginosa to coordinate its gene expression and cell signaling in response to different growth conditions and stressors. Upon nutrient transitions and starvation, as well as other environmental stresses, the stringent response is activated, mediated by the signal (p)ppGpp. P. aeruginosa produces a family of molecules called HAQ (4-hydroxy-2-alkylquinolines), some of which exhibit antibacterial and quorum-sensing signaling functions and regulate virulence genes. In this study, we report that (p)ppGpp negatively regulates HAQ biosynthesis: in a (p)ppGpp-null (ΔSR) mutant, HHQ (4-hydroxyl-2-heptylquinoline) and PQS (3,4-dihydroxy-2-heptylquinoline) levels are increased due to upregulated pqsA and pqsR expression and reduced repression by the rhl system. We also found that (p)ppGpp is required for full expression of both rhl and las AHL (acyl-homoserine lactone) quorum-sensing systems, since the ΔSR mutant has reduced rhlI, rhlR, lasI, and lasR expression, butanoyl-homoserine lactone (C₄-HSL) and 3-oxo-dodecanoyl-homoserine lactone (3-oxo-C₁₂-HSL) levels, and rhamnolipid and elastase production. Furthermore, (p)ppGpp significantly modulates the AHL and PQS quorum-sensing hierarchy, as the las system no longer has a dominant effect on HAQ biosynthesis when the stringent response is inactivated.     

The Alveolin IMC1h Is Required for Normal Ookinete and Sporozoite Motility Behaviour and Host Colonisation in Plasmodium berghei

Alveolins, or inner membrane complex (IMC) proteins, are components of the subpellicular network that forms a structural part of the pellicle of malaria parasites. In Plasmodium berghei, deletions of three alveolins, IMC1a, b, and h, each resulted in reduced mechanical strength and gliding velocity of ookinetes or sporozoites. Using time lapse imaging, we show here that deletion of IMC1h (PBANKA_143660) also has an impact on the directionality and motility behaviour of both ookinetes and sporozoites. Despite their marked motility defects, sporozoites lacking IMC1h were able to invade mosquito salivary glands, allowing us to investigate the role of IMC1h in colonisation of the mammalian host. We show that IMC1h is essential for sporozoites to progress through the dermis in vivo but does not play a significant role in hepatoma cell transmigration and invasion in vitro. Colocalisation of IMC1h with the residual IMC in liver stages was detected up to 30 hours after infection and parasites lacking IMC1h showed developmental defects in vitro and a delayed onset of blood stage infection in vivo. Together, these results suggest that IMC1h is involved in maintaining the cellular architecture which supports normal motility behaviour, access of the sporozoites to the blood stream, and further colonisation of the mammalian host.