Marine algae as attractive source to skin care

As the largest organ in the human body, the skin has multiple functions of which one of the most important is the protection against various harmful stressors. The keratinised stratified epidermis and an underlying thick layer of collagen-rich dermal connective tissues are important components of the skin. The environmental stressors such as ultraviolet radiation (UVR) and pollution increase the levels of reactive oxygen species (ROS), contributing to clinical manifestations such as wrinkle formation and skin aging. Skin aging is related to the reduction of collagen production and decrease of several enzymatic activities including matrix metalloproteinases (MMPs), which degrade collagen structure in the dermis; and tissue inhibitor of metalloproteinases (TIMPs), which inhibit the action of MMPs. In addition to alterations of DNA, signal transduction pathways, immunology, UVR, and pollution activate cell surface receptors of keratinocytes and fibroblasts in the skin. This action leads to a breakdown of collagen in the extracellular matrix and a shutdown of new collagen synthesis. Therefore, an efficient antioxidants strategy is of major importance in dermis and epidermis layers. Marine resources have been recognised for their biologically active substances. Among these, marine algae are rich-sources of metabolites, which can be used to fight against oxidative stress and hence skin aging. These metabolites include, among others, mycosporine-like amino acids (MAAs), polysaccharides, sulphated polysaccharides, glucosyl glycerols, pigments, and polyphenols. This paper reviews the role of oxidative processes in skin damage and the action of the compounds from algae on the physiological processes to maintain skin health.     

Impairment of survival signaling and efferocytosis in TRPC3-deficient macrophages

We have recently shown that in macrophages proper operation of the survival pathways phosphatidylinositol-3-kinase (PI3K)/AKT and nuclear factor kappa B (NFkB) has an obligatory requirement for constitutive, non-regulated Ca²⁺ influx. In the present work we examined if Transient Receptor Potential Canonical 3 (TRPC3), a member of the TRPC family of Ca²⁺-permeable cation channels, contributes to the constitutive Ca²⁺ influx that supports macrophage survival. We used bone marrow-derived macrophages obtained from TRPC3^−/− mice to determine the activation status of survival signaling pathways, apoptosis and their efferocytic properties. Treatment of TRPC3^+/+ macrophages with the pro-apoptotic cytokine TNFα induced time-dependent phosphorylation of IκBα, AKT and BAD, and this was drastically reduced in TRPC3^−/− macrophages. Compared to TRPC3^+/+ cells TRPC3^−/− macrophages exhibited reduced constitutive cation influx, increased apoptosis and impaired efferocytosis. The present findings suggest that macrophage TRPC3, presumably through its constitutive function, contributes to survival signaling and efferocytic properties.     

Electroactivity of phototrophic river biofilms and constitutive cultivable bacteria

Electroactivity is a property of microorganisms assembled in biofilms that has been highlighted in a variety of environments. This characteristic was assessed for phototrophic river biofilms at the community scale and at the bacterial population scale. At the community scale, electroactivity was evaluated on stainless steel and copper alloy coupons used both as biofilm colonization supports and as working electrodes. At the population scale, the ability of environmental bacterial strains to catalyze oxygen reduction was assessed by cyclic voltammetry. Our data demonstrate that phototrophic river biofilm development on the electrodes, measured by dry mass and chlorophyll a content, resulted in significant increases of the recorded potentials, with potentials of up to +120 mV/saturated calomel electrode (SCE) on stainless steel electrodes and +60 mV/SCE on copper electrodes. Thirty-two bacterial strains isolated from natural phototrophic river biofilms were tested by cyclic voltammetry. Twenty-five were able to catalyze oxygen reduction, with shifts of potential ranging from 0.06 to 0.23 V, cathodic peak potentials ranging from -0.36 to -0.76 V/SCE, and peak amplitudes ranging from -9.5 to -19.4 μA. These isolates were diversified phylogenetically (Actinobacteria, Firmicutes, Bacteroidetes, and Alpha-, Beta-, and Gammaproteobacteria) and exhibited various phenotypic properties (Gram stain, oxidase, and catalase characteristics). These data suggest that phototrophic river biofilm communities and/or most of their constitutive bacterial populations present the ability to promote electronic exchange with a metallic electrode, supporting the following possibilities: (i) development of electrochemistry-based sensors allowing in situ phototrophic river biofilm detection and (ii) production of microbial fuel cell inocula under oligotrophic conditions.     

Transit defect of potassium-chloride Co-transporter 3 is a major pathogenic mechanism in hereditary motor and sensory neuropathy with agenesis of the corpus callosum

Missense and protein-truncating mutations of the human potassium-chloride co-transporter 3 gene (KCC3) cause hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), which is a severe neurodegenerative disease characterized by axonal dysfunction and neurodevelopmental defects. We previously reported that KCC3-truncating mutations disrupt brain-type creatine kinase-dependent activation of the co-transporter through the loss of its last 140 amino acids. Here, we report a novel and more distal HMSN/ACC-truncating mutation (3402C → T; R1134X) that eliminates only the last 17 residues of the protein. This small truncation disrupts the interaction with brain-type creatine kinase in mammalian cells but also affects plasma membrane localization of the mutant transporter. Although it is not truncated, the previously reported HMSN/ACC-causing 619C → T (R207C) missense mutation also leads to KCC3 loss of function in Xenopus oocyte flux assay. Immunodetection in Xenopus oocytes and in mammalian cultured cells revealed a decreased amount of R207C at the plasma membrane, with significant retention of the mutant proteins in the endoplasmic reticulum. In mammalian cells, curcumin partially corrected these mutant protein mislocalizations, with more protein reaching the plasma membrane. These findings suggest that mis-trafficking of mutant protein is an important pathophysiological feature of HMSN/ACC causative KCC3 mutations.     

Carbonic anhydrase inhibitors: inhibition of cytosolic isozymes I and II with sulfamide derivatives

A novel class of effective CAIs has been identified, starting from a very weak carbonic anhydrase inhibitor (CAI), sulfamide, whose X-ray crystal structure in the adduct with hCA II has recently been reported. A series of N,N-disubstituted- and N-substituted-sulfamides were prepared from the corresponding amines and N-(tert-butoxycarbonyl)-N-[4-(dimethylazaniumylidene)-1,4-dihydropyridin-1-ylsulfonyl]azanide or the unstable N-(tert-butoxycarbonyl)sulfamoyl chloride. The disubstituted compounds being too bulky, were ineffective as CAIs, whereas mono-substituted derivatives (incorporating aliphatic, cyclic and aromatic moieties) as well as a bis-sulfamide, behaved as micro-nanomolar inhibitors of two cytosolic isozymes, hCA I and hCA II, responsible for critical physiological processes in higher vertebrates. Aryl-sulfamides were more effective than aliphatic derivatives. Low nanomolar inhibitors have been detected, which generally incorporated 4-substituted phenyl moieties in their molecule. This is the first example of CAIs in which low nanomolar inhibitors were generated starting from a very ineffective lead molecule.     

Adherence modifies the regulation of gene expression induced by interleukin-10

Interleukin-10 (IL-10) is a well known anti-inflammatory cytokine. However, we previously showed that it could present pro-inflammatory properties on human monocytes in the absence of adherence. In the present study, using macroarray technology, we analyzed the effects of IL-10 and adherence on the expression of 1050 genes in human monocytes cultured for 3 hours on plastic or Teflon(R) (to avoid adherence). Adherence alone induced specifically the expression of 12 genes and repressed that of 25 genes. In adherent monocytes, IL-10 induced the expression of 21 genes and repressed that of 50 genes. In non-adherent monocytes, IL-10 induced the expression of 45 genes and repressed that of 67. Only 3 common genes were induced while 35 common genes were repressed by IL-10 in the two culture conditions. Interestingly, we showed that IL-10 modulated conversely on Teflon(R) and plastic the expression of 16 genes, of which SOCS molecules, coproporphyrinogen oxidase, matrix metalloproteinases and complement receptor-1 (CD35). This study demonstrates that adherence has profound modulatory effects on the properties and the signaling induced by IL-10. The discovery that IL-10 can inhibit the production of coproporphyrinogen oxidase (an enzyme involved in the synthesis of heme) may shed some lights on the mechanisms of anaemia induced by IL-10. Furthermore, the inhibition of the expression of SOCS1 by IL-10 in the absence of adherence, may explain its priming effects on a subsequent LPS stimulation that we previously described.     

Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex

Neuron-glia interactions are essential for synaptic function, and glial glutamate (re)uptake plays a key role at glutamatergic synapses. In knockout mice, for either glial glutamate transporters, GLAST or GLT-1, a classical metabolic response to synaptic activation (i.e., enhancement of glucose utilization) is decreased at an early functional stage in the somatosensory barrel cortex following activation of whiskers. Investigation in vitro demonstrates that glial glutamate transport represents a critical step for triggering enhanced glucose utilization, but also lactate release from astrocytes through a mechanism involving changes in intracellular Na(+) concentration. These data suggest that a metabolic crosstalk takes place between neurons and astrocytes in the developing cortex, which would be regulated by synaptic activity and mediated by glial glutamate transporters.     

Hypoxia and vitamin D differently contribute to leptin and dickkopf-related protein 2 production in human osteoarthritic subchondral bone osteoblasts

Introduction

Bone remodelling and increased subchondral densification are important in osteoarthritis (OA). Modifications of bone vascularization parameters, which lead to ischemic episodes associated with hypoxic conditions, have been suspected in OA. Among several factors potentially involved, leptin and dickkopf-related protein 2 (DKK2) are good candidates because they are upregulated in OA osteoblasts (Obs). Therefore, in the present study, we investigated the hypothesis that hypoxia may drive the expression of leptin and DKK2 in OA Obs.

Methods

Obs from the sclerotic portion of OA tibial plateaus were cultured under either 20% or 2% oxygen tension in the presence or not of 50 nM 1,25-dihydroxyvitamin D₃ (VitD₃). The expression of leptin, osteocalcin, DKK2, hypoxia-inducible factor 1α (Hif-1α) and Hif-2α was measured by real-time polymerase chain reaction and leptin production was measured by enzyme-linked immunosorbent assay (ELISA). The expression of Hif-1α, Hif-2α, leptin and DKK2 was reduced using silencing RNAs (siRNAs). The signalling pathway of hypoxia-induced leptin was investigated by Western blot analysis and with mitogen-activated protein kinase (MAPK) inhibitors.

Results

The expression of leptin and DKK2 in Obs was stimulated 7-fold and 1.8-fold, respectively (P <0.05) under hypoxia. Interestingly, whereas VitD₃ stimulated leptin and DKK2 expression 2- and 4.2-fold, respectively, under normoxia, it stimulated their expression by 28- and 6.2-fold, respectively, under hypoxia (P <0.05). The hypoxia-induced leptin production was confirmed by ELISA, particularly in the presence of VitD₃ (P <0.02). Compared to Obs incubated in the presence of scramble siRNAs, siHif-2α inhibited VitD₃-stimulated leptin mRNA and protein levels by 70% (P =0.004) and 60% (P <0.02), respectively, whereas it failed to significantly alter the expression of DKK2. siHif-1α has no effect on these genes. Immunoblot analysis showed that VitD₃ greatly stabilized Hif-2α under hypoxic conditions. The increase in leptin expression under hypoxia was also regulated, by p38 MAPK (P <0.03) and phosphoinositide 3-kinase (P <0.05). We found that the expression of leptin and DKK2 were not related to each other under hypoxia.

Conclusions

Hypoxic conditions via Hif-2 regulation trigger Obs to produce leptin, particularly under VitD₃ stimulation, whereas DKK2 is regulated mainly by VitD₃ rather than hypoxia.     

DNA Repair Pathways in Trypanosomatids: from DNA Repair to Drug Resistance

SUMMARY

All living organisms are continuously faced with endogenous or exogenous stress conditions affecting genome stability. DNA repair pathways act as a defense mechanism, which is essential to maintain DNA integrity. There is much to learn about the regulation and functions of these mechanisms, not only in human cells but also equally in divergent organisms. In trypanosomatids, DNA repair pathways protect the genome against mutations but also act as an adaptive mechanism to promote drug resistance. In this review, we scrutinize the molecular mechanisms and DNA repair pathways which are conserved in trypanosomatids. The recent advances made by the genome consortiums reveal the complete genomic sequences of several pathogens. Therefore, using bioinformatics and genomic sequences, we analyze the conservation of DNA repair proteins and their key protein motifs in trypanosomatids. We thus present a comprehensive view of DNA repair processes in trypanosomatids at the crossroads of DNA repair and drug resistance.     

Seasonal diving behaviour in lactating subantarctic fur seals on Amsterdam Island

Diving behaviour was investigated in female subantarctic fur seals (Arctocephalus tropicalis) breeding on Amsterdam Island, Indian Ocean. Data were collected using electronic Time Depth Recorders on 19 seals during their first foraging trip after parturition in December, foraging trips later in summer, and during winter. Subantarctic fur seals at Amsterdam Island are nocturnal, shallow divers. Ninety-nine percent of recorded dives occurred at night. The diel dive pattern and changes in dive parameters throughout the night suggest that fur seals follow the nycthemeral migrations of their main prey. Seasonal changes in diving behaviour amounted to the fur seals performing progressively deeper and longer dives from their first foraging trip through winter. Dive depth and dive duration increased from the first trip after parturition (16.6 ± 0.5 m and 62.1 ± 1.6 s respectively, n=1000) to summer (19.0 ± 0.4 m and 65 ± 1 s, respectively, n=2000) through winter (29.0 ± 1.0 m and 91.2 ± 2.2 s, respectively, n=800). In summer, subantarctic fur seals increased the proportion of time spent at the bottom during dives of between 10 and 20 m, apparently searching for prey when descending to these depths, which corresponded to the oceanic mixed layer. In winter, fur seals behaved similarly when diving between 20 and 50 m, suggesting that the most profitable depths for feeding moved down during the study period. Most of the dives did not exceed the physiological limits of individuals. Although dive frequency did not vary (10 dives/h of night), the vertical travel distance and the time spent diving increased throughout the study period, while the post-dive interval decreased, indicating that subantarctic fur seals showed a greater diving effort in winter, compared to earlier seasons. Accepted: 1 August 1999