Accumulation of Glycogen and Upregulation of LEA-1 in C. elegans daf-2(e1370) Support Stress Resistance, Not Longevity.

DAF-16-dependent activation of a dauer-associated genetic program in the C. elegans insulin/IGF-1 daf-2(e1370) mutant leads to accumulation of large amounts of glycogen with concomitant upregulation of glycogen synthase, GSY-1. Glycogen is a major storage sugar in C. elegans that can be used as a short-term energy source for survival, and possibly as a reservoir for synthesis of a chemical chaperone trehalose. Its role in mitigating anoxia, osmotic and oxidative stress has been demonstrated previously. Furthermore, daf-2 mutants show increased abundance of the group 3 late embryogenesis abundant protein LEA-1, which has been found to act in synergy with trehalose to exert its protective role against desiccation and heat stress in vitro, and to be essential for desiccation tolerance in C. elegans dauer larvae. Here we demonstrate that accumulated glycogen is not required for daf-2 longevity, but specifically protects against hyperosmotic stress, and serves as an important energy source during starvation. Similarly, lea-1 does not act to support daf-2 longevity. Instead, it contributes to increased resistance of daf-2 mutants to heat, osmotic, and UV stress. In summary, our experimental results suggest that longevity and stress resistance can be uncoupled in IIS longevity mutants.

Taurine reduces blue light-induced retinal neuronal cell apoptosis in vitro.

BACKGROUND: The massive uptake of organic compatible osmolytes is a self-protective response to multiple stressors. OBJECTIVE: This study aimed to determine the protective effects of the osmolyte taurine against blue light-induced apoptosis in retinal neuronal cells in vitro. METHODS: Real-time PCR was used to measure osmolyte transport. Radioimmunoassays were performed to measure osmolyte uptake. Cell Counting Kit-8 assays were conducted to measure cellular viability. Flow cytometry analysis was used to measure apoptosis. RESULTS: Compared with normotonic stress, hypertonic stress-induced uptake of osmolytes, including betaine, myoinositol, and taurine, into the retinal neuronal cells. Blue light increased osmolyte transporter mRNA expression together with osmolyte uptake. Furthermore, taurine significantly suppressed blue light-induced retinal neuronal cell apoptosis. CONCLUSION: The compatible osmolyte taurine may have an important role in cell resistance to blue light and cell survival.

Influence of static magnetic fields in phototaxis and osmotic stress in Gymnodinium catenatum (Dinophyceae).

Phototaxis response of the toxic microalgae Gymnodinium catenatum was studied in vitro. The percentage of cells remaining at mid-depth 20 min after stirring increased with solar radio, X-ray and solar flares output. It also increased with geomagnetic activity and temperature, and was dependent on culture time. Increase in the local static magnetic field with a permanent magnet did not influence the positive phototaxis response. However, survival and growth to a provoked hypo-osmotic shock in an altered static magnetic field was dependent on culture time and geomagnetic activity at a threshold below 22 nT. The results from phototaxis and hypo-osmotic shock experiments were in line with the previous hypothesis for the existence of two separate deleterious mechanisms conditioning the natural blooms of G. catenatum: one that is dependent on solar radiation and the other that is related to geomagnetic activity. Variations in electromagnetic fields caused by tectonic activity were also capable of influencing G. catenatum phototaxis and growth response in vitro.

ß-amylase 1 (BAM1) degrades transitory starch to sustain proline biosynthesis during drought stress.

During photosynthesis of higher plants, absorbed light energy is converted into chemical energy that, in part, is accumulated in the form of transitory starch within chloroplasts. In the following night, transitory starch is mobilized to sustain the heterotrophic metabolism of the plant. ß-amylases are glucan hydrolases that cleave α-1,4-glycosidic bonds of starch and release maltose units from the non-reducing end of the polysaccharide chain. In Arabidopsis, nocturnal degradation of transitory starch involves mainly ß-amylase-3 (BAM3). A second ß-amylase isoform, ß-amylase-1 (BAM1), is involved in diurnal starch degradation in guard cells, a process that sustains stomata opening. However, BAM1 also contributes to diurnal starch turnover in mesophyll cells under osmotic stress. With the aim of dissecting the role of ß-amylases in osmotic stress responses in Arabidopsis, mutant plants lacking either BAM1 or BAM3 were subject to a mild (150mM mannitol) and prolonged (up to one week) osmotic stress. We show here that leaves of osmotically-stressed bam1 plants accumulated more starch and fewer soluble sugars than both wild-type and bam3 plants during the day. Moreover, bam1 mutants were impaired in proline accumulation and suffered from stronger lipid peroxidation, compared with both wild-type and bam3 plants. Taken together, these data strongly suggest that carbon skeletons deriving from BAM1 diurnal degradation of transitory starch support the biosynthesis of proline required to face the osmotic stress. We propose the transitory-starch/proline interplay as an interesting trait to be tackled by breeding technologies aimingto improve drought tolerance in relevant crops.

In vitro study of platelet function confirms the contribution of the ultraviolet B (UVB) radiation in the lesions observed in riboflavin/UVB-treated platelet concentrates.

BACKGROUND: Platelet inactivation technologies (PITs) have been shown to increase platelet storage lesions (PSLs). This study investigates amotosalen/ultraviolet (UV)A- and riboflavin/UVB-induced platelet (PLT) lesions in vitro. Particular attention is given to the effect of UVB alone on PLTs. STUDY DESIGN AND METHODS: Buffy coat-derived PLT concentrates (PCs) were treated with amotosalen/UVA, riboflavin/UVB, or UVB alone and compared to untreated PCs throughout storage. In vitro PLT function was assessed by blood gas and metabolite analyses, flow cytometry-based assays (CD62P, JC-1, annexin V, PAC-1), hypotonic shock response, and static adhesion to fibrinogen-coated wells. RESULTS: In our experimental conditions, riboflavin/UVB-treated PCs showed the most pronounced differences compared to untreated and amotosalen/UVA-treated PCs. The riboflavin/UVB treatment led to a significant increase of anaerobic glycolysis rate despite functional mitochondria, a significant increase of CD62P on Day 2, and a decrease of JC-1 aggregates and increase of annexin V on Day 7. The expression of active GPIIbIIIa (PAC-1) and the adhesion to fibrinogen was significantly increased from Day 2 of storage in riboflavin/UVB-treated PCs. Importantly, we showed that these lesions were caused by the UVB radiation alone, independently of the presence of riboflavin. CONCLUSION: The amotosalen/UVA-treated PCs confirmed previously published results with a slight increase of PSLs compared to untreated PCs. Riboflavin/UVB-treated PCs present significant in vitro PSLs compared to untreated PCs. These lesions are caused by the UVB radiation alone and probably involve the generation of reactive oxygen species. The impact of these observations on clinical use must be investigated.

The osmotic resistance, and zeta potential responses of human erythrocytes to transmembrane modification of Ca2+ fluxes in the presence of the imposed low rate radiation field of 90Sr.

PURPOSE: To investigate the effects of the imposed low dose rate ionizing field on membrane stability of human erythrocytes under modulation of transmembrane exchange of Ca(2+). MATERIALS AND METHODS: Osmotic resistance of human erythrocytes was determined by a measure of haemoglobin released from erythrocytes when placed in a medium containing serial dilutions of Krebs isotonic buffer. The zeta potential as indicator of surface membrane potential was calculated from value of the cellular electrophoretic mobility. The irradiation of erythrocyte suspensions carried out by applying suitable aliquots of (90)Sr in incubation media. RESULTS: Irradiation of human erythrocytes by (90)Sr (1.5-15.0 µGy·h(-1)) induced a reversible increase of hyposmotic hemolysis and negative charge value on the outer membrane surface as well as changed responses these parameters to modification of Ca(2+) fluxes with calcimycin and nitrendipine. CONCLUSIONS: Findings indicate that the low dose rate radionuclides ((90)Sr) field modifies both Ca(2+)-mediated, and Ca(2+)-independent cellular signalling regulating mechanical stability of erythrocyte membrane. A direction of that modification presumably depends on the initial structure of membranes, and it is determined by the quality and quantitative parameters of changes in membrane structure caused by concrete operable factors.

FAR-RED ELONGATED HYPOCOTYL3 and FAR-RED IMPAIRED RESPONSE1 transcription factors integrate light and abscisic acid signaling in Arabidopsis.

Light and the phytohormone abscisic acid (ABA) regulate overlapping processes in plants, such as seed germination and seedling development. However, the molecular mechanism underlying the interaction between light and ABA signaling is largely unknown. Here, we show that FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and FAR-RED IMPAIRED RESPONSE1 (FAR1), two key positive transcription factors in the phytochrome A pathway, directly bind to the promoter of ABA-Insensitive5 and activate its expression in Arabidopsis (Arabidopsis thaliana). Disruption of FHY3 and/or FAR1 reduces the sensitivity to ABA-mediated inhibition of seed germination, seedling development, and primary root growth. The seed germination of the fhy3 mutant is also less sensitive to salt and osmotic stress than that of the wild type. Constitutive expression of ABA-Insensitive5 restores the seed germination response of fhy3. Furthermore, the expression of several ABA-responsive genes is decreased in the fhy3 and/or far1 mutants during seed imbibition. Consistently, FHY3 and FAR1 transcripts are up-regulated by ABA and abiotic stresses. Moreover, the fhy3 and far1 mutants have wider stomata, lose water faster, and are more sensitive to drought than the wild type. These findings demonstrate that FHY3 and FAR1 are positive regulators of ABA signaling and provide insight into the integration of light and ABA signaling, a process that may allow plants to better adapt to environmental stresses.

The influence of millimeter waves on the physical properties of large and giant unilamellar vesicles.

Exposure of cell membranes to an electromagnetic field (EMF) in the millimeter wave band (30-300 GHz) can produce a variety of responses. Further, many of the vibrational modes in complex biomolecules fall in the 1-100 GHz range. In addition to fundamental scientific interest, this may have applications in the development of diagnostic and therapeutic medical applications. In the present work, lipid vesicles of different size were used to study the effects of exposure to radiation at 52-72 GHz, with incident power densities (IPD) of 0.0035-0.010 mW/cm(2), on the chemical-physical properties of cell membranes. Large unilamellar vesicles (LUVs) were used to study the effect of the radiation on the physical stability of vesicles by dynamic light scattering. An inhibition of the aging processes (Ostwald ripening), which usually occur in these vesicles because of their thermodynamic instability, resulted. Giant unilamellar vesicles (GUVs) were used to study the effect of the radiation on membrane water permeability under osmotic stress by phase contrast microscopy. In this case, a decrease in the water membrane permeability of the irradiated samples was observed. We advance the hypothesis that both the above effects may be explained in terms of a change of the polarization states of water induced by the radiation, which causes a partial dehydration of the membrane and consequently a greater packing density (increased membrane rigidity).

Protective effect of low UVA irradiation against the action of lethal UVA on Pseudomonas aeruginosa: role of the relA gene.

The exposure of Pseudomonas aeruginosa cells to very low UVA fluences induces a growth delay, a phenomenon proposed in Escherichia coli as an adaptive mechanism related to protection against lethal and mutagenic effects of UVA. This paper reports that the treatment with low UVA irradiation fluences protects P. aeruginosa PAO1 strain from a subsequent lethal exposure. This phenomenon depends on the relA gene, coding for the main (p)ppGpp synthetase, and is unrelated to the induction of quorum sensing or catalase activity, two essential factors involved in the response of P. aeruginosa to UVA. Cross-protection between osmotic stress and UVA is observed when a great protective response to lethal UVA is caused by the induction of resistance to osmotic stress. The increase in resistance to osmotic shock observed in the pre-irradiated PAO1 strain but not in its relA derivative, unable to show photo-protection, leads us to hypothesize that the photo-protection could be attributed to an adaptive response to osmotic stress. It is concluded that the exposure of P. aeruginosa to low UVA doses induces a relA-dependent adaptive response that protects against cell death induced by high doses and causes an increase in the resistance to osmotic stress.

Cell quality of apheresis-derived platelets treated with riboflavin-ultraviolet light after resuspension in platelet additive solution.

BACKGROUND: Previously, we evaluated the Mirasol pathogen reduction technology (PRT) system on platelet (PLT) function before resuspension. We now evaluated this system in the presence of PLT additive solution (PAS). STUDY DESIGN AND METHODS: Double-dose PLTs (n = 15) were generated using a commercially available apheresis system (Trima, Version 5.2, CaridianBCT) allowing for the resuspension in SSP+ (MacoPharma) immediately after collection. Paired units (n = 30) were PRT treated (M) or remained untreated (C) and analyzed for metabolism (pH, pO(2) , glucose, lactate, adenosine triphosphate [ATP]), swirl, hypotonic shock response (HSR), turbidometric aggregation, CD62P expression, annexin A5 and lactate dehydrogenase (LDH) release, mitochondrial enzymatic reduction activity (MTS), transmembrane mitochondrial potential (Δψ), and surface coverage (SC) during shear-induced adhesion throughout 8 days of storage. RESULTS: As seen previously, PRT treatment of PLT units, containing a mean of 3.9 × 10(11) ± 0.3 × 10(11) PLTs in 397 ± 10 mL with a 32% to 34% plasma carryover, was associated with significantly (p < 0.001) increased cell activation, acidity, and glycolytic flux. PRT treatment appeared to up regulate both oxidative pathway and adhesional properties as evidenced by significantly higher MTS reduction, oxygen consumption, and shear-induced SC on Day 1 (p ≤ 0.016). While no significant differences were found for LDH release and ATP content (except for Day 8), M units were significantly inferior (p ≤ 0.021) for aggregation (TRAP-6); for Δψ and annexin A5 release (by Day 5); and for swirl, HSR, and MTS reduction (by Day 7). CONCLUSION: PRT treatment in the presence of PAS was comparable to PRT treatment before resuspension preserving ATP content and mitochondrial function.

The cyst-dividing bacterium Ramlibacter tataouinensis TTB310 genome reveals a well-stocked toolbox for adaptation to a desert environment.

Ramlibacter tataouinensis TTB310(T) (strain TTB310), a betaproteobacterium isolated from a semi-arid region of South Tunisia (Tataouine), is characterized by the presence of both spherical and rod-shaped cells in pure culture. Cell division of strain TTB310 occurs by the binary fission of spherical "cyst-like" cells ("cyst-cyst" division). The rod-shaped cells formed at the periphery of a colony (consisting mainly of cysts) are highly motile and colonize a new environment, where they form a new colony by reversion to cyst-like cells. This unique cell cycle of strain TTB310, with desiccation tolerant cyst-like cells capable of division and desiccation sensitive motile rods capable of dissemination, appears to be a novel adaptation for life in a hot and dry desert environment. In order to gain insights into strain TTB310's underlying genetic repertoire and possible mechanisms responsible for its unusual lifestyle, the genome of strain TTB310 was completely sequenced and subsequently annotated. The complete genome consists of a single circular chromosome of 4,070,194 bp with an average G+C content of 70.0%, the highest among the Betaproteobacteria sequenced to date, with total of 3,899 predicted coding sequences covering 92% of the genome. We found that strain TTB310 has developed a highly complex network of two-component systems, which may utilize responses to light and perhaps a rudimentary circadian hourglass to anticipate water availability at the dew time in the middle/end of the desert winter nights and thus direct the growth window to cyclic water availability times. Other interesting features of the strain TTB310 genome that appear to be important for desiccation tolerance, including intermediary metabolism compounds such as trehalose or polyhydroxyalkanoate, and signal transduction pathways, are presented and discussed.

Expression analysis of five maize MAP kinase genes in response to various abiotic stresses and signal molecules.

Mitogen-activated protein kinase (MAPK) cascades are universal signal transduction modules in eukaryotes. Plant MAPK cascades are complicated networks and play vital roles in signal transduction induced by biotic and abiotic stresses. In this paper, expression patterns of MAPKs in maize roots treated with low-temperature, osmotic stresses, wounding, plant hormones and UV-C irradiation were investigated. Semi-quantitative RT-PCR reveals that the expression of MAPKs in maize roots which treated with low-temperature in light or in low light are inducible. The expression patterns of MAPKs in maize roots with treatments of CaCl2, SA, GA and wounding are approximately the same. A detailed time course experiment shows that the expression patterns of ZmSIMK are different with treatments of PEG and NaCl, respectively. These results suggest that the expression patterns of MAPKs are complicated and the signal pathways are interlaced into a network in maize roots.

Crystal structures of different substrates of bacteriorhodopsin's M intermediate at various pH levels.

The hexagonal P622 crystal of bacteriorhodopsin, which is made up of stacked membranes, is stable provided that the precipitant concentration in the soaking solution is higher than a critical value (i.e., 1.5 M ammonium sulfate). Diffraction data showed that the crystal lattice shrank linearly with increasing precipitant concentration, due primarily to narrowing of intermembrane spaces. Although the crystal shrinkage did not affect the rate of formation of the photoreaction M intermediate, its lifetime increased exponentially with the precipitant concentration. It was suggested that the energetic barrier of the M-to-N transition becomes higher when the motional freedom of the EF loop is reduced by crystal lattice force. As a result of this property, the M state accumulated predominantly when the crystal that was soaked at a high precipitant concentration was illuminated at room temperature. Structural data obtained at various pH levels showed that the overall structure of M is not strongly dependent on pH, except that Glu194 and Glu204 in the proton release complex are more separated at pH 7 than at pH 4.4. This result suggests that light-induced disruption of the paired structure of Glu194 and Glu204 is incomplete when external pH is lower than the pK(a) value of the proton release group in the M state.

Reversible control of exo- and endo-budding transitions in a photosensitive lipid membrane.

We have developed a method for the photomanipulation of lipid membrane morphology in which the shape of a vesicle can be switched by light through the use of a synthetic photosensitive amphiphile containing an azobenzene unit (KAON12). We prepared cell-sized liposomes from KAON12 and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and conducted real-time observations of vesicular transformation in the photosensitive liposome by phase-contrast microscopy. Budding transitions-either budding toward the centre of the liposome (endo-bud) or budding out of the liposome (exo-bud)-could be controlled by light. We discuss the mechanism of this transformation in terms of the change in the effective membrane surface area due to photoisomerization of the constituent molecules.

Weak microwave can alleviate water deficit induced by osmotic stress in wheat seedlings.

The aim of the investigation is to determine the effect of microwave pretreatment of wheat seeds on the resistance of seedlings to osmotic stress. Changes in biophysical, physiological and biochemical characters were measured. The results showed: (1) The magnetic field intensity and seeds temperature increased progressively with microwave pretreatments of 5, 10, 15, 20 s and 25 s compared with controls. Although each microwave pretreatment resulted in an increase in alpha-amylase activity and photon emission intensity, the increase of alpha-amylase activity and photon emission intensity was maximal at a microwave pretreatment of 10 s. (2) Osmotic stress induced by PEG treatment enhanced the concentration of malondialdehyde, while decreasing the activities of nitricoxide synthase, catalase, peroxidase, superoxide dismutase and the concentration of nitric oxide, ascorbic acid, glutathione in the seedlings compared with controls. However, compared to osmotic stress alone, in the seedlings treated with microwave irradiation plus osmotic stress the concentration of malondialdehyde decreased, while the activities of nitricoxide synthase, catalase, peroxidase, superoxide dismutase and the concentration of nitric oxide, ascorbic acid and glutathione increased. These results suggest that a suitable dose of microwave radiation can enhance the capability to eliminate free radicals induced by osmotic stress in wheat seedlings resulting in an increase in resistance to osmotic stress.

Optimización de la deshidratación osmótica con pulso de vacío de láminas de sardina / Optimization of vacuum pulse osmotic dehydration of sardine sheets

El objetivo principal de este estudio fue optimizar la transferencia de masa ocurrida durante la deshidratación osmótica con pulso de vacío de láminas de sardina mediante los métodos gráfico y función deseada. Las sardinas se cortaron en láminas y se sumergieron simultáneamente en una salmuera de concentración y temperatura dada según un diseño compuesto central de 3 bloques. Las condiciones experimentales fueron concentraciones de 17, 19, 22, 25, 27 y 28,6 por ciento de NaCl, temperaturas de 28,6; 30; 32; 34 y 35,4°C y tiempos de 113; 140; 180; 220 y 247 min. A cada lámina se le determinó el peso, contenido de humedad y NaCl, se calculó la pérdida de agua, pérdida de peso y ganancia de sal. Los datos se analizaron mediante un ANOVA y regresión lineal múltiple para obtener los modelos de las variables estudiadas, luego se determinó la zona óptima de la deshidratación osmótica utilizando los métodos gráfico y la función deseada. Por el método gráfico se obtuvo una zona óptima correspondiente a una concentración entre 23,9 y 24,6 por ciento de NaCl, un tiempo entre 204 y 207 min y una temperatura de 32,2°C para tener una pérdida agua de 0,23 g agua/g, una ganancia de sal de 0,07 g NaCl/g y una pérdida de peso de 0,17 g/g. Por el método de la función deseada, las condiciones óptimas correspondieron a 23,9 por ciento NaCl, 207 min y 32,2°C.

The aim of this study was to optimize the mass transfer occurred during the vacuum pulse osmotic dehydration of sardine sheets by surface response and desired function methodologies. Sardines were cut into sheets and simultaneously immersed into a brine at given concentration and temperature according to a composite central rotatable design with 3 blocks. The experimental condition were 17; 19; 22; 25; 27 and 28.6% NaCl, 28.6; 30; 32; 34 and 35.4°C and 113; 140; 180; 220 y 247 min. Each sheet was weighed and moisture and salt contents were determined, then water and mass loss, and salt uptake were calculated. Data were analyzed by ANOVA and multiple lineal regressions to obtaining the models for studied variables, and then optimum zone for osmotic dehydration was found by response surface and desired function methodologies. By response surface, an optimum zone of concentration from 23.9 to 24.6% of NaCl, time from 204 to 208 min and temperature of 32.2°C was attained related to a water loss of 0.23 g water/g, uptake salt of 0.07 g NaCl/g and mass loss of 0.17 g/g. The optimum conditions of 23.9% NaCl, 207 min and 32.2°C were attained by desired function.

Adaptation and impairment of DNA repair function in pollen of Betula verrucosa and seeds of Oenothera biennis from differently radionuclide-contaminated sites of Chernobyl.

BACKGROUND AND AIMS: The plants that have remained in the contaminated areas around Chernobyl since 1986 encapsulate the effects of radiation. Such plants are chronically exposed to radionuclides that they have accumulated internally as well as to alpha-, beta- and gamma-emitting radionuclides from external sources and from the soil. This radiation leads to genetic damage that can be countered by DNA repair systems. The objective of this study is to follow DNA repair and adaptation in haploid cells (birch pollen) and diploid cells (seed embryos of the evening primrose) from plants that have been growing in situ in different radionuclide fall-out sites in monitored regions surrounding the Chernobyl explosion of 1986. METHODS: Radionuclide levels in soil were detected using gamma-spectroscopy and radiochemistry. DNA repair assays included measurement of unscheduled DNA synthesis, electrophoretic determination of single-strand DNA breaks and image analysis of rDNA repeats after repair intervals. Nucleosome levels were established using an ELISA kit. KEY RESULTS: Birch pollen collected in 1987 failed to perform unscheduled DNA synthesis, but pollen at gamma/beta-emitter sites has now recovered this ability. At a site with high levels of combined alpha- and gamma/beta-emitters, pollen still exhibits hidden damage, as shown by reduced unscheduled DNA synthesis and failure to repair lesions in rDNA repeats properly. Evening primrose seed embryos generated on plants at the same gamma/beta-emitter sites now show an improved DNA repair capacity and ability to germinate under abiotic stresses (salinity and accelerated ageing). Again those from combined alpha- and gamma/beta-contaminated site do not show this improvement. CONCLUSIONS: Chronic irradiation at gamma/beta-emitter sites has provided opportunities for plant cells (both pollen and embryo cells) to adapt to ionizing irradiation and other environmental stresses. This may be explained by facilitation of DNA repair function.

The osmolyte taurine protects against ultraviolet B radiation-induced immunosuppression.

Organic osmolytes, such as taurine, are involved in cell volume homeostasis and cell protection. Epidermal keratinocytes possess an osmolyte strategy, i.e., they take up taurine upon hyperosmotic stress and express the corresponding transporter TAUT. UVB irradiation also triggers taurine uptake and TAUT expression in this cell type. We therefore asked whether taurine plays a role in photoprotection. By using a TAUT-deficient mouse model, lack of taurine in the skin was found to cause a significantly higher sensitivity to UVB-induced immunosuppression. This was not due to an increased generation or decreased repair of UVB-induced DNA photoproducts in the skin of these animals. Instead, decreased skin taurine levels were associated with an increased formation of the soluble immunosuppressive molecule platelet-activating factor (PAF) from the membranes of UVB-irradiated epidermal cells. Blocking PAF activity in taut-deficient mice with a PAF receptor antagonist abrogated their increased sensitivity to UVB-induced immunosuppression. Moreover, taut -/- mice were more sensitive to PAF-mediated immunosuppression than taut +/+ mice. These data suggest that taurine uptake by epidermal cells prevents undue PAF formation, and thereby photoimmunosuppression. Thus, similar to nucleotide excision repair, taurine uptake is critically involved in photoprotection of the skin.

Thalidomide radiosensitizes tumors through early changes in the tumor microenvironment.

PURPOSE: The aim of this work was to study changes in the tumor microenvironment early after an antiangiogenic treatment using thalidomide (a promising angiogenesis inhibitor in a variety of cancers), with special focus on a possible "normalization" of the tumor vasculature that could be exploited to improve radiotherapy. EXPERIMENTAL DESIGN: Tumor oxygenation, perfusion, permeability, interstitial fluid pressure (IFP), and radiation sensitivity were studied in an FSAII tumor model. Mice were treated by daily i.p. injection of thalidomide at a dose of 200 mg/kg. Measurements of the partial pressure of oxygen (pO(2)) were carried out using electron paramagnetic resonance oximetry. Three complementary techniques were used to assess the blood flow inside the tumor: dynamic contrast-enhanced magnetic resonance imaging, Patent Blue staining, and laser Doppler imaging. IFP was measured by a "wick-in-needle" technique. RESULTS: Our results show that thalidomide induces tumor reoxygenation within 2 days. This reoxygenation is correlated with a reduction in IFP and an increase in perfusion. These changes can be attributed to extensive vascular remodeling that we observed using CD31 labeling. CONCLUSIONS: In summary, the microenvironmental changes induced by thalidomide were sufficient to radiosensitize tumors. The fact that thalidomide radiosensitization was not observed in vitro, and that in vivo radiosensitization occurred in a narrow time window, lead us to believe that initial vascular normalization by thalidomide accounts for tumor radiosensitization.

Osmotically induced membrane tension facilitates the triggering of living cell electropermeabilization.

Very little is known about the molecular mechanisms supporting living cell membrane electropermeabilization. This concept is based on the local membrane permeability induced by cell exposure to brief and intense external electric field pulses. During the electric field application, an electro-induced membrane electric potential difference is created that is locally associated with the dielectric properties of the plasma membrane. When the new membrane electric potential difference locally reaches a critical value, a local alteration of the membrane structure is induced and leads to reversible permeabilization. In our study, we attempted to determine whether mechanical tension could modulate the triggering of membrane electropermeabilization. Change in lateral tension of Chinese Hamster Ovary cell membrane has been osmotically induced. Cell electropermeabilization was performed in the minute time range after the osmotic stress, i.e., before the regulatory volume decrease being activated by the cell. Living cell electropermeabilization was analyzed on cell population using flow cytometry. We observed that electropermeabilization triggering was significantly facilitated when the lateral membrane tension was increased. The main conclusion is that the critical value of transmembrane potential needed to trigger membrane electropermeabilization, is smaller when the membrane is under lateral mechanical constraint. This supports the hypothesis that both mechanical and electrical constraints play a key role in transient membrane destabilization.