Beyond sense-specific processing: decoding texture in the brain from touch and sonified movement.

Texture, a fundamental object attribute, is perceived through multisensory information including touch and auditory cues. Coherent perceptions may rely on shared texture representations across different senses in the brain. To test this hypothesis, we delivered haptic textures coupled with a sound synthesizer to generate real-time textural sounds. Participants completed roughness estimation tasks with haptic, auditory, or bimodal cues in an MRI scanner. Somatosensory, auditory, and visual cortices were all activated during haptic and auditory exploration, challenging the traditional view that primary sensory cortices are sense-specific. Furthermore, audio-tactile integration was found in secondary somatosensory (S2) and primary auditory cortices. Multivariate analyses revealed shared spatial activity patterns in primary motor and somatosensory cortices, for discriminating texture across both modalities. This study indicates that primary areas and S2 have a versatile representation of multisensory textures, which has significant implications for how the brain processes multisensory cues to interact more efficiently with our environment.

The impact of movement sonification on haptic perception changes with aging.

Combining multisensory sources is crucial to interact with our environment, especially for older people who are facing sensory declines. Here, we examined the influence of textured sounds on haptic exploration of artificial textures in healthy younger and older adults by combining a tactile device (ultrasonic display) with synthetized textured sounds. Participants had to discriminate simulated textures with their right index while they were distracted by three disturbing, more or less textured sounds. These sounds were presented as a real-time auditory feedback based on finger movement sonification and thus gave the sensation that the sounds were produced by the haptic exploration. Finger movement velocity increased across both groups in presence of textured sounds (Rubbing or Squeaking) compared to a non-textured (Neutral) sound. While young adults had the same discrimination threshold, regardless of the sound added, the older adults were more disturbed by the presence of the textured sounds with respect to the Neutral sound. Overall, these findings suggest that irrelevant auditory information was taken into account by all participants, but was appropriately segregated from tactile information by young adults. Older adults failed to segregate auditory information, supporting the hypothesis of general facilitation of multisensory integration with aging.

First Report of the Nivalenol Chemotype of Fusarium graminearum Causing Head Blight of Wheat in the Grand Duchy of Luxembourg.

Head blight caused by Fusarium graminearum is one of the major diseases of wheat (Triticum aestivum L.) in Luxembourg (2) and there is concern for mycotoxins in diseased grain. Isolates of F. graminearum have been assigned to chemotypes based on the particular toxins produced. Ten wheat fields representing different topoclimatological areas of Luxembourg were surveyed in 2007 and 2008 to determine the frequency and distribution of chemotypes. Partially blighted wheat heads were collected, and diseased grains were plated on Fusarium-selective agar (dichloran-chloramphenicol-peptone) for 12 days at 22 ± 2°C with a 12-h light period. Monoconidial isolates of F. graminearum (79 in 2007 and 85 in 2008) were obtained by conidia dilution on 2% water agar and needle selection under a microscope. F. graminearum isolates showed rapid growth on potato dextrose agar, dense aerial mycelium with red pigment deposits in the plate, macroconidia with five to six defined septa, and a basal cell with the typical foot shape. Microconidia were absent. To confirm species identification, a PCR reaction was carried out using the F. graminearum species-specific primers Fg16F (5'-CTCCGGATATGTTGCGTCAA-3') and Fg16R (5'-GGTAGGTATCCGACATGGCAA-3') according to Demeke et al. (1). Chemotype of each isolate was determined according to Ward et al. (4). In particular, PCR primer 12CON (5' CATGAGCATGGTGATGTC-3') coupled with primer 12NF (5'-TCTCCTCGTTGTATCTGG-3') and primer 3CON (5'-TGGCAAAGACTGGTTCAC-3') coupled with primer 3NA (5'-GTGCACAGAATATACGAGC-3') identified the nivalenol chemotype, primer 12CON coupled with primer 12-15F (5'-TACAGCGGTCGCAACTTC-3') and primer 3CON coupled with primer 3D15A (5'-ACTGACCCAAGCTGCCATC-3') identified the 15-acetylated deoxynivalenol (DON) chemotype, while primer 12CON coupled with primer 12-3F (5'-CTTTGGCAAGCCCGTGCA-3') and primer 3CON coupled with primer 3D3A (5'-CGCATTGGCTAACACATG-3') identified 3-acetylated DON chemotype. Reactions were repeated two times and positive controls (provided by Kerry O'Donnell, NRRL collection, Peoria, IL) and a negative control (water) were used in each reaction. Frequency of the nivalenol chemotype was found to be 2.5% in 2007 and 1% in 2008. Interestingly, the nivalenol chemotype was absent in southern Luxembourg. According to this finding, nivalenol was likely to be present at low levels in grain from Reisdorf and Echternach in 2007 (central Luxembourg) and in 2008 from grain of Troisvierges (northern Luxembourg). The remaining isolates in both years belonged to the 15-acetylated DON chemotype and the 3-acetylated DON chemotype was not detected. Compared with a previous report from the Netherlands (3), the nivalenol chemotype in Luxembourg is less frequent and widespread. To our knowledge, this is the first report of the nivalenol chemotype of F. graminearum causing head blight on wheat in Luxembourg. References:(1) T. Demeke et al. Int. J. Food Microbiol. 103:271, 2005. (2) F. Giraud et al. Plant Dis. 92:1587, 2008. (3) C. Waalwijk et al. Eur. J. Plant Pathol. 109:743, 2003. (4) T. J. Ward et al. Fung. Genet. Biol. 45:473, 2008.

First Report of Wheat Leaf Rust in the Grand Duchy of Luxembourg and the Progress of its Appearance over the 2003-2008 Period.

Wheat leaf rust caused by Puccinia triticina Eriks. was identified for the first time in 2000 in the Grand Duchy of Luxembourg on the basis of orange-to-brown, round-to-ovoid, erumpent uredinia (1 to 1.5 mm in diameter) scattered on the upper and lower leaf surfaces and producing orange-brown urediniospores that are subgloboid, approximately 20 µm in diameter, and with up to eight germ pore scattered in thick, echinulate walls. In a second phase, wheat was monitored weekly (starting from Zadoks growth stage 30, pseudo stem erection) during the 2003-2008 cropping seasons for wheat leaf rust. Disease severity (percentage of leaf area with symptoms) was recorded in four, replicated field experiments located in three villages (Diekirch District: Reuler; and Grevenmacher District: Burmerange and Christnach), which are representative of the different agroclimatological zones of Luxembourg. A significant difference in severity was observed between the sites (P < 0.01) and the years (P < 0.05). Over the 6-year period, Burmerange and Reuler consistently showed the highest and lowest disease severity, respectively. In 2003 and 2007, Burmerange (a southern site with the highest average spring temperatures of 13.6 and 14.0°C, respectively) showed the highest disease severity with 66 and 57%, respectively, whereas the lowest severity (<1% for both years) was observed in the north at Reuler (site with the lowest average spring temperatures of 12.0 and 12.4°C, respectively). Christnach, located midway between Reuler and Burmerange, showed an intermediate disease severity with 7% (2003) and 22% (2007). The disease appeared at growth stages 77 (late milk) and 87 (hard dough) in the period 2003-2005, but at an earlier stage (45, boots swollen) for 2006-2008 (P < 0.001). In 2005, low severity was recorded due to a severe drought during May, June, and July. A reason for this earlier appearance of leaf rust occurrences in the two districts may be related to an increase in the average spring temperature (average March to May temperature for Luxembourg was 8.3°C for the 1971-2000 period, 9.5°C for the 2003-2005 period, 9.9°C for the 2006-2008 period, 2007 was exceptional with 11.9°C, P < 0.01). In the past, cereal disease management strategies were oriented toward the control of predominant and yield-reducing diseases such as that caused by Septoria tritici Desm. Because the succession of mild winters and warm springs during the last 5 years allowed the early occurrence and the fast development of wheat leaf rust in the Grand Duchy of Luxembourg, it is advisable to take this disease into account in fungicide application schemes.

[Arterial and venous thrombosis in lung cancer]. / Thrombose artérielle et veineuse et cancer bronchique.

We report the case of a 61-year old man in whom a deep venous thrombosis was the presenting feature of disseminated lung carcinoma. A few days later, an arterial thrombosis occurred necessitating amputation. Within a few weeks, the lung cancer progressed dramatically and the patient died. While the association between venous thrombosis and cancer is well known, the relationship between cancer and arterial thrombosis has been less explored. This observation allows discussion of the pathophysiological and clinical aspects of this association, as well as the implications for patient care.

First Report of Fusarium Head Blight on Winter Wheat in the Grand Duchy of Luxembourg.

Following a comparatively mild winter (1.9°C above average [2000-2007]), Fusarium head blight (FHB) on winter wheat was observed during the 2007 season in 17 sites representing all three districts of Diekirch, Grevenmacher, and Luxembourg. The cultivars encountered were diverse and included Achat, Akteur, Aron, Bussard, Cubus, Enorm, Exclusiv, Flair, Rosario, Tommi, and Urban. The preceding crops were maize (six sites), rapeseed (three sites), and one site each of pea, triticale, winter barley, and winter wheat. Rainfalls recorded during the flowering period (June 1-23, mean June 12 for GS 65) ranged from 13 to 62 (mean 38) mm. An overall prevalence of FHB (percentage of infected spikes) of 8.9 ± 15.5% (mean ± SD) and a severity (percentage of infected grains per spike) of 21.0 ± 17.8% were recorded. A significant difference in FHB severity was observed between the cantons north and south of Luxembourg City, 13.4 ± 13.1% (range 0.01 to 46.4) and 35.1 ± 18.1% (range 6.2 to 61.9), respectively (Man-Whitney, P = 0.027), indicating the importance to take regional specificities such as topoclimatological aspects into account. Maize as a preceding crop resulted in significant higher prevalence of FHB as opposed to the other crops (5.9 ± 1.6% versus 3.3 ± 2.2%, Man-Whitney, P = 0.022).

[Bronchoscopic treatment of bronchopleural fistula]. / Traitement endoscopique des fistules bronchopleurales.

Bronchopleural fistula is an uncommon complication occurring especially following lung resection (pneumonectomy) and associated with high morbidity and mortality rates. The treatment is surgical but some studies reported bronchoscopic treatment. Localization and size of the fistula may indicate different endoscopic procedures. This overview described the different endoscopic procedures and their benefits.

[IHC, FISH, CISH, NGS in non-small cell lung cancer: What changes in the biomarker era?] / IHC, FISH, CISH, NGS dans les cancers bronchiques non à petites cellules : quelles évolutions dans l'ère des biomarqueurs ?

Lung cancer is the leading cause of cancer deaths in France, with about 30,000 deaths per year. The overwhelming majority (90 %) are tobacco-related. The prognosis is dark but great therapeutic advances have been made with the development of targeted therapies first and then immunotherapy afterwards. These medications are conditioned to the expression of biomarkers that require specific tools in routine to measure them. We will detail in this chapter several techniques of anatomopathology, cytogenetics and molecular biology necessary for the detection of biomarkers in lung cancers, and their applications in thoracic oncology in 2018.

ATP-induced apoptosis of thymocytes is mediated by activation of P2 X 7 receptor and involves de novo ceramide synthesis and mitochondria.

Thymocytes were reported to undergo apoptosis in the presence of extracellular ATP through the activation of the purinergic receptors P2 X 1R, P2 X 7R or both. We investigated the identity of the P2 X R and the signaling pathways involved in ATP-mediated apoptosis. Apoptosis elicited by ATP was prevented by inhibition of P2 X 7R, or in thymocytes bearing a mutated P2 X 7R, and reproduced with a P2 X 7R agonist, but not with a P2 X 1R agonist. Stimulation of thymocytes with either ATP or a P2 X 7R agonist was found to stimulate a late de novo ceramide synthesis and mitochondrial alterations. Inhibition of either processes attenuated apoptosis. Interestingly, stimulation with either ATP or a P2 X 1R agonist induced an early ceramide accumulation and a weak caspases-3/7 activation that did not lead to apoptosis. In conclusion, de novo ceramide generation and mitochondrial alterations, both resulting from P2 X 7R activation, were implicated in ATP-induced thymocyte apoptosis.

[Pericarditis: a giant cell arteritis manifestation]. / La péricardite: une manifestation de la maladie de Horton.

INTRODUCTION: Temporal arteritis is a vasculitis in which inflammatory manifestations mainly involve the external carotid artery area but not exclusively. Through a clinical observation and a review of the literature, we suggest that inflammatory pericarditis could represent a manifestation of temporal arteritis. EXEGESIS: A 75-year-old-woman was admitted for progressive physical deterioration which had been evolving for three months, associated with fever, frontotemporal cephalalgia and severe biological inflammatory syndrome. Chest X-ray reveals a cardiomegaly and suggests a pericarditis, which was rapidly confirmed by echocardiogram. Temporal artery biopsy concludes to the diagnosis of a giant cell arteritis. Steroids treatment is prescribed, leading to a rapid regression of the inflammatory state and the pericarditis without relapse after 6 months of follow-up. CONCLUSION: Only prospective studies on systematic echocardiography when faced with the diagnosis of giant cell arteritis, whatever clinical symptoms, will enable to appreciate the prevalence and prognosis value of this manifestation. Moreover, temporal artery analysis seems to be justified when faced with a sub-acute or chronic "idiopathic" inflammatory pericarditis occurring in the elderly patient. Physiopathogeny is unknown but some hypothesis can be proposed: inflammatory cytokines storm, immune complexes deposition, giant cell vasculitis of pericardial arteries or inflammatory interstitial lesion of the pericardium with or without granuloma.

A 3D-QSAR CoMSIA study on 3-azolylmethylindoles as anti-leishmanial agents.

A three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Similarity Indices Analysis (CoMSIA) was conducted on a series of 3-azolylmethylindoles as anti-leishmanial agents. Evaluation of 24 compounds synthesized in our laboratory served to establish the model. A random search was performed on the library of compounds, and molecules of the training set were aligned on common elements of template molecule 13, one of the most active compounds. The best predictions were obtained from multifit procedure with a CoMSIA model combining steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (q2 = 0.594, r2 = 0.897). The model was validated using an external test set of 7 compounds giving a satisfactory predictive r2 value of 0.649. Information obtained from CoMSIA contour maps could be used for further design of more promising inhibitors.

[Computer-assisted positioning of the acetabular cup for total hip arthroplasty based on joint kinematics without prior imaging: preliminary results with computed tomographic assessment]. / Positionnement de la cupule d'une prothèse totale de hanche par navigation sans image basée sur la cinématique articulaire: Premiers résultats avec evaluation tomodensitométrique de l'orientation des implants.

PURPOSE OF THE STUDY: Most navigation systems for computer-assisted total hip arthroplasty (THA) require prior computed tomography (CT) or acquisition of multiple bone landmarks on the pelvis. In order to avoid these problems, we developed a computer-assisted navigation system without CT based on a kinematic approach to the hip joint. The principle is to orient the cup in relation to the cone describing the hip joint range of motion. The purpose of this work was to analyze preliminary results. MATERIAL AND METHODS: Eighteen primary THA were implanted with the system (16 women, two men, mean age 68 +/- 7.8 years, age range 54-83 years, 18 degenerative hip disease). Two optoelectronic captors were fixed percutaneously on the pelvis and the distal femur. The acetabulum was prepared first followed by the femur using reamers and broaches of increasing size. The last broach placed in the femur was equipped with a large head adapted to the newly prepared acetabulum. The range of hip motion was recorded to determine the maximal range of motion cone. The acetabular cup was thus positioned in order the prosthesis range of motion included entirely the maximal range of motion of the hip joint. RESULTS: One patient fell three weeks after implantation causing posterior dislocation; there was no recurrence. The Postel-Merle-d'Aubligné score improved from 8 +/- 2.9 (range 3-12) preoperatively to 17 +/- 0.8 (range 16-18) at last follow-up. None of the patients complained about the captor insertion and there were no cases of hematoma or fracture. Operative time was 35-40 minutes longer for the first four cases and was progressively reduced 15-20 minutes for the last four cases. Mean leg length discrepancy was 5.6 +/- 7.5 mm (range 0-25) before implantation and 0.6 +/- 3 mm (range -5 to 10 mm) at last follow-up. CT-scan measurements revealed a mean anteversion of the femoral implant of 18.2 +/- 8.5 degrees (range 0-31). Anatomic anteversion of the cup (measured from the pelvis landmark and thus independently of the position of the pelvis) was 24.7 +/- 8.8 degrees (range 12-40). The sum of the femoral and anatomic acetabular anteversions was 43 +/- 13.1 degrees (range 22-71). Anteversions were 16 degrees for the cup and 16 degrees for the stem for the one case of dislocation. CONCLUSION: This method can be used in routine without lengthening operative time significantly. It safely controls leg length and helps position the cup. This study demonstrated that there is no ideal position for the cup which can be used for all patients. Because of the wide range of inclination and anteversion figures, half of the cases were outside the safety zone recommended by Lewinnek.

Perspectives on heterococcolith geochemical proxies based on high-resolution X-ray fluorescence mapping.

Heterococcoliths are micron-scale calcite platelets produced by coccolithophores. They have been the most abundant and continuous fossil record over the last 215 million years (Myr), offering great potential for geochemical studies, although the heterococcolith fossil record remains underutilised in this domain. We have mapped heterococcoliths' composition using X-ray fluorescence (XRF) with a 100-nm resolution beam to decipher element distributions in heterococcoliths and to investigate the potential development of geochemical proxies for palaeoceanography. The study presents two Middle Jurassic Watznaueria britannica heterococcoliths from Cabo Mondego, Portugal. XRF analysis was performed with a 17 keV incident energy beam at the European Synchrotron Radiation Facility ID22NI beamline to study elements from Sr down to S. Ca, Sr and Mn are distributed following the heterococcolith crystalline arrangement. Cl, Br and S display an homogeneous distribution, whereas K, Fe, Cu, Zn and Rb are concentrated at the edges and in the central area of the heterococcoliths. Distributions of K, Fe, Ti, Fe, Cu, Zn, Rb and to a lesser extent V and Cr are highly influenced by clay contamination and peripheral diagenetic overgrowth. Mn is related to diagenetic Mn-rich CaCO3 overgrowth on top of or between heterococcoliths shields. Cl and Br are likely to be present in heterococcoliths inside interstitial nano-domains. We assume that the cytoplasm [Cl(-) ] and [Br(-) ] are mediated and constant during heterococcolithogenesis. Assuming a linear correlation between cytoplasm [Cl(-) ] and sea water [Cl(-) ], heterococcolith Cl may have potential as a salinity proxy. As S is incorporated into heterococcoliths by sulphated polysaccharides, our study suggests a role for such polysaccharides in heterococcolithogenesis for at least 170 Myr. The low Sr/Ca in the W. britannica specimens studied here may either highlight an unusual cellular physiology of Mesozoic coccolithophores or result from low growth rates in oligotrophic environments.

Alterations in human erythrocyte shape and the state of spectrin and phospholipid phosphorylation induced by cholesterol depletion.

Cholesterol depletion of erythrocytes, obtained after incubation with phosphatidylcholine vesicles, induces in most of the experiments: (1) a discocytestomatocyte transformation as observed by scanning electron microscopy; (2) a specific decrease in spectrin phosphorylation of intact erythrocytes; (3) an increase in lipid phosphorylation. It is concluded that the effect of cholesterol on erythrocyte shape is probably mediated through its action on the activity o of membrane-bound enzymes, proteases or kinases.

Stimulation of polyphosphoinositide turnover upon activation of protein kinases in human erythrocytes.

Activation of protein kinase C in erythrocytes by 4-beta-phorbol 12-myristate 13-acetate (PMA) resulted in a parallel stimulation (time course and dose response) of the phosphorylation of both membrane proteins (heterodimers of 107 kDa and 97 kDa, protein 4.1 and 4.9, respectively) and of phosphatidylinositol 4-phosphate (PIP) and, to a lesser extent, of phosphatidylinositol 4,5-bisphosphate (PIP2). Evidence that the effect on lipid was mediated by protein kinase C activation and not by a direct action of PMA was provided by (1) the lack of effect of a phorbol ester that did not activate protein kinase C or of PMA addition on isolated membranes from control erythrocytes, (2) the reversal of the effect in the presence of protein kinase C inhibitors (alpha-cobrotoxin, H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine) or trifluoperazine). PMA treatment did not change the specific activity of ATP or the content of PIP2, but increased the content of PIP and decreased that of PI, indicating that the phosphorylation or dephosphorylation reactions linking PI and PIP were the target for the action of PMA. PMA treatment had no effect on the Ca2+-dependent PIP/PIP2 phospholipase C activity measured in isolated membranes. Mezerein, another protein kinase activator, had similar effects on both protein and lipid phosphorylation, when added with alpha-cobrotoxin. Activation of protein kinase A by cAMP also produced increases in phosphorylation, although quantitatively different from those induced by protein kinase C, in proteins and PIP. Simultaneous addition of PMA and cAMP at maximal doses resulted in only a partially additive effect on PIP labelling. These results show that inositol lipid turnover can be modulated by a protein kinase C and protein kinase A-dependent process involving the phosphorylation of a common protein. This could be PI kinase or PIP phosphatase or another protein regulating the activity of these enzymes.

Cholesterol depletion affects the Ca2+ influx but not the Ca2+ pump in human erythrocytes.

Control and cholesterol-depleted human erythrocytes were loaded with permeant Ca2+ chelators (Benz2-AM or Quin2-AM) in order to increase their exchangeable Ca2+ pool and to measure both Ca2+ fluxes and [Ca]i (free cytoplasmic calcium concentration). The fluxes were independent of the concentration and of the nature of the intracellular chelator. The ATP content was not decreased by more than 50% under our experimental conditions. Cholesterol depletion (up to 28%) induced a decrease in both Ca2+ fluxes and [Ca]i which was proportional to the extent of the depletion. It is shown that cholesterol depletion primarily altered the properties of the system responsible for Ca2+ entry causing a diminution of the [Ca]i. This, in turn, induced a diminution of the activity of the Ca2+ pump without affecting the properties of this pump.

The measurement in vivo of the rate of unesterified cholesterol exchange between rat plasma and erythrocytes.

In order to investigate the rate of unesterified cholesterol exchange between plasma and erythrocytes in vivo, cholesterol labelling in rats was achieved in one of the following ways: intravenous injection of cholesterol-labelled erythrocytes, subcutaneous injection of labelled acetate, feeding of labelled cholesterol. The specific activity of the unesterified cholesterol was measured at intervals up to 24 h and a kinetic analysis of the data was performed. It assumes that both the cholesterol in the erythrocytes and the unesterified cholesterol in the plasma were homogeneous pools. The rate constants obtained for the movements of unesterified cholesterol from erythrocytes to plasma and from plasma to erythrocytes were not significantly different in the three labelling conditions (mean values: 0.26 and 1.5 h-1, respectively).

The effects of membrane lipid order and cholesterol on the internal and external cationic sites of the Na+-K+ pump in erythrocytes.

cholesterol depletion alters the apparent affinity of the internal cationic sites and the maximal translocation rate but not the affinity of the external cationic sites of the Na+-K+ pump in human erythrocytes. To test whether these effects were mediated by a direct cholesterol-internal site interaction or by a change in membrane lipid order, the effects of five fluidizing amphiphiles (chlorpromazine, imipramine, benzyl alcohol, sodium oleate and sodium benzenesulphonate) on the kinetic parameters of the Na+-K+ pump were determined. The cholesterol removal and all the agents used induced dose-response decreases in membrane lipid order as measured by fluorescence polarization or ESR. Positive and neutral amphiphiles mimicked the effects of cholesterol removal on the affinity of the internal sites of the pump and to a lesser extent on the maximal translocation rate. Anionic amphiphiles had no effect on internal sites, probably because they distributed preferentially within the outer leaflet on the membrane. These results indicate that cholesterol controls the affinity of the internal sites of the Na+-K+ pump by altering the membrane lipid order. In contrast, neither cholesterol depletion nor the agents used altered the affinity of the external sites of the Na+-K+ pump. This difference in sensitivity to membrane lipids order suggests that internal and external cationic sites, although borne by the same protein, are in different lipid environments.

Alpha-adrenergically mediated changes in membrane lipid fluidity and Ca2/ binding in isolated rat liver plasma membranes.

Noradrenaline (0.1-5 microM, in the presence of 5 microM propranolol to block beta-receptors), ATP (100 microM) and angiotensin II (0.1 microM), which are thought to increase cytosolic Ca2+ concentration by mobilizing Ca2+ from internal stores, increased the lipid fluidity as measured by diphenylhexatriene fluorescence polarization in plasma membranes isolated from rat liver. The effect of noradrenaline was dose-dependent and blocked by the alpha-antagonists phenoxybenzamine (50 microM) and phentolamine (1 microM). The response to a maximal dose of noradrenaline (5 microM) and that to ATP (100 microM) were not cumulative, suggesting that both agents use a common mechanism to alter the membrane lipid fluidity. In contrast, the addition of noradrenaline (5 microM) along with the foreign amphiphile Na+-oleate (1-30 microM) resulted in an increase in membrane lipid fluidity which was equivalent to the sum of individual responses to the two agents. In the absence of Mg2+, reducing free Ca2+ concentration by adding EGTA increased membrane lipid fluidity and abolished the effect of noradrenaline, suggesting that Ca2+ is involved in the mechanism by which the hormone exerts its effect on plasma membranes. Noradrenaline (5 microM) and angiotensin II (0.1 microM) also promoted a small release of 45Ca2+ (16 pmol/mg membrane proteins) from prelabelled plasma membranes. The effect of noradrenaline was suppressed by the alpha-antagonist phentolamine (5 microM). It is proposed that noradrenaline, via alpha-adrenergic receptors and other Ca2+ -mobilizing hormones, increases membrane lipid fluidity by displacing a small pool of Ca2+ bound to phospholipids, removing thus the mechanical constraints brought about by this ion.

The involvement of the Ca-dependent K channel and of the KCl co-transport in sickle cell dehydration during cyclic deoxygenation.

We have investigated the mechanisms involved in sickle cell dehydration upon continuous or cyclic deoxygenation: the Ca(2+)-activated K+ channel and the KCl co-transport system. Short-term continuous deoxygenation (1 h) of sickle cells in a Ca(2+)-containing medium promoted a stimulation of the efflux of K+ and cell dehydration. This latter was reduced by the replacement of Ca2+ in the medium by EGTA, but not by addition of [(dihydro-indenyl) oxy] alkanoic acid (DIOA), an inhibitor of the KCl co-transport. During cycles of deoxygenation-reoxygenation, cell dehydration was partly prevented by EGTA and significantly reduced by DIOA only in the presence of Ca2+. The present data support the view that sickle cell dehydration during deoxygenation arises from the stimulation of the Ca(2+)-dependent K+ permeability leading to water loss, whereas during reoxygenation periods, subsequent activation of the KCl co-transport also contributes to cell dehydration.