Functional impact of oxygen-saturated zeolite nanoparticles on macrophages in the context of glioblastoma: an in vitro and in vivo study.

In the context of glioblastoma (GBM), hypoxia and inflammation are two main players of the tumor microenvironment. Hypoxia stimulates various features involves in tumor growth and also maintains a specific environment that favors protumor macrophages. Therefore, targeting hypoxia could potentially restore an anti-tumor M1 phenotype in macrophages. Besides, iron demonstrated its capacity to stimulate the polarization of macrophages towards an M1-like phenotype. In this paper we took advantages of microporous nanoparticles to co-deliver both oxygen and iron to bone marrow derived macrophages (BMDM) enabling the investigation of changes in polarization status and proteomic profiles. The nanoparticles were used in two in vivo models of glioblastoma, specifically, in both immunodeficient and immunocompetent settings. Our in vitro findings revealed that iron doped nanoparticles, saturated with oxygen were deemed safe for macrophages but did not demonstrate the capacity to change the M1 or M2 phenotypes. However, these nanoparticles induced some changes in proteomics pathways. The present study reports on in vivo experimentation that revealed the effects of nanoparticles on the hypoxic fraction, tumor volume, and macrophage phenotype in a GBM model. The findings indicated that the presence of nanoparticles led to a reduction in the hypoxic fraction in one of the GBM models, while no significant changes were observed in the tumor volume or macrophage phenotype. The present data showed that nanoparticles possess the capability of delivering both oxygen and iron to macrophages; though, they do not possess the ability to effectively repolarize M2 macrophages. Such strategies could be used in conjunction with other potent molecules to avoid M1 macrophages to inevitably differentiate to M2 macrophages.

Quantifying virtual self-motion sensations induced by galvanic vestibular stimulation.

BACKGROUND: The vestibular system provides a comprehensive estimate of self-motion in 3D space. Widely used to artificially stimulate the vestibular system, binaural-bipolar square-wave Galvanic Vestibular Stimulation (GVS) elicits a virtual sensation of roll rotation. Postural responses to GVS have been clearly delineated, however quantifying the perceived virtual rotation vector has not been fully realised. OBJECTIVE: We aimed to quantify the perceived virtual roll rotation vector elicited by GVS using a psychophysical approach on a 3D turntable. METHODS: Participants were placed supine on the 3D turntable and rotated around the naso-occipital axis while supine and received square-wave binaural-bipolar GVS or sham stimulation. GVS amplitudes and intensities were systematically manipulated. The turntable motion profile consisted of a velocity step of 20°/s2 until the trial velocity between 0-20°/s was reached, followed by a 1°/s ramp until the end of the trial. In a psychophysical adaptive staircase procedure, we systematically varied the roll velocity to identify the exact velocity that cancelled the perceived roll sensation induced by GVS. RESULTS: Participants perceived a virtual roll rotation towards the cathode of approximately 2°/s velocity for 1 mA GVS and 6°/s velocity for 2.5 mA GVS. The observed values were stable across repetitions. CONCLUSIONS: Our results quantify for the first time the perceived virtual roll rotations induced by binaural-bipolar square-wave GVS. Importantly, estimates were based on perceptual judgements, in the absence of motor or postural responses and in a head orientation where the GVS-induced roll sensation did not interact with the perceived direction of gravity. This is an important step towards applications of GVS in different settings, including sensory substitution or Virtual Reality.

Visuo-vestibular conflicts within the roll plane modulate multisensory verticality perception.

The integration of visuo-vestibular information is crucial when interacting with the external environment. Under normal circumstances, vision and vestibular signals provide corroborating information, for example regarding the direction and speed of self-motion. However, conflicts in visuo-vestibular signalling, such as optic flow presented to a stationary observer, can change subsequent processing in either modality. While previous studies have demonstrated the impact of sensory conflict on unisensory visual or vestibular percepts, here we investigated whether visuo-vestibular conflicts impact sensitivity to multisensory percepts, specifically verticality. Participants were exposed to a visuo-vestibular conflicting or non-conflicting motion adaptor before completing a Vertical Detection Task. Sensitivity to vertical stimuli was reduced following visuo-vestibular conflict. No significant differences in criterion were found. Our findings suggest that visuo-vestibular conflicts not only modulate processing in unimodal channels, but also broader multisensory percepts, which may have implications for higher-level processing dependent on the integration of visual and vestibular signals.

A gravitational contribution to perceived body weight.

The weightlessness experienced by astronauts has fascinated scientists and the public. On Earth, body weight is given by Newton's laws as mass times gravitational acceleration. That is, an object's weight is determined by the pull of gravity on it. We hypothesised that perceived body weight is - like actual weight - dependent on the strength of gravity. If so, changes in the experienced strength of gravity should alter the experience of one's own body weight. We asked participants to estimate the weight of two body parts, their hand or their head, both in normal terrestrial gravity (1 g) and during exposure to experimentally altered gravitational fields, 0 g and +1.8 g during parabolic flight and +1 g using a short arm human centrifuge. For both body parts, there was an increase in perceived weight during the experience of hypergravity, and a decrease during the experience of microgravity. Our results show that experimental alterations of gravity produce rapid changes in the perceived weight of specific individual body parts. Traditionally, research has focused on the social factors for weight perception, as in the putative role of mass media in eating disorders. Our results, in contrast, emphasize that the perception of body weight is highly malleable, and shaped by immediate sensory signals.

Profiling Autoantibodies against Salivary Proteins in Sicca Conditions.

Salivary gland dysfunction occurs in several autoimmune and immune-related conditions, including Sjögren syndrome (SS); immune checkpoint inhibitor-induced sicca (ICIS) that develops in some cancer patients and is characterized by severe, sudden-onset dry mouth; and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Although subjects with these conditions present with oral dryness and often exhibit inflammatory infiltration of the salivary gland, little is known about the B-cell humoral responses directed against salivary gland protein targets. In this study, autoantibodies were evaluated against Ro52, Ro60, and La, as well as against a panel of 22 proteins derived from the salivary proteome. The tested cohort included healthy volunteers and subjects with SS, ICIS, and APECED without and with sicca. As expected, a high percentage of autoantibody seropositivity was detected against Ro52, Ro60, and La in SS, but only a few ICIS patients were seropositive for these autoantigens. A few APECED subjects also harbored autoantibodies to Ro52 and La, but only Ro60 autoantibodies were weakly associated with a small subset of APECED patients with sicca. Additional testing of the salivary panel failed to detect seropositive autoantibodies against any of the salivary-enriched proteins in the SS and ICIS subjects. However, APECED subjects selectively demonstrated seropositivity against BPI fold containing family A member 1 (BPIFA1), BPI fold containing family A member 2 (BPIFA2)/parotid salivary protein (PSP), and lactoperoxidase, 3 salivary-enriched proteins. Moreover, high levels of serum autoantibodies against BPIFA1 and BPIFA2/PSP occurred in 30% and 67% of the APECED patients with sicca symptoms, respectively, and were associated with an earlier age onset of oral dryness (P = 0.001). These findings highlight the complexity of humoral responses in different sicca diseases and provide new insights and biomarkers for APECED-associated sicca (ClinicalTrials.gov: NCT00001196; NCT00001390; NCT01425892; NCT01386437).

Ineffectiveness of tactile gating shows cortical basis of nociceptive signaling in the Thermal Grill Illusion.

Painful burning sensations can be elicited by a spatially-alternating pattern of warm and cold stimuli applied on the skin, the so called "Thermal Grill Illusion" (TGI). Here we investigated whether the TGI percept originates spinally or centrally. Since the inhibition of nociceptive input by concomitant non-nociceptive somatosensory input has a strong spinal component, we reasoned that, if the afferent input underlying the TGI originates at spinal level, then the TGI should be inhibited by a concomitant non-nociceptive somatosensory input. Conversely, if TGI is the result of supraspinal processing, then no effect of touch on TGI would be expected. We elicited TGI sensations in a purely thermal condition without tactile input, and found no evidence that tactile input affected the TGI. These results provide further evidence against a spinal mechanism generating the afferent input producing the TGI, and indicate that the peculiar burning sensation of the TGI results from supraspinal interactions between thermoceptive and nociceptive systems.

Neglect's perspective on the Ponzo illusion.

Visual illusions have been used to explore implicit perception in neglect. Previous studies have highlighted differences between length and surface illusion perception in neglect, but much less is known about depth illusion perception. In the Ponzo illusion (a classic depth illusion), two converging oblique lines modulate the perceived length of two horizontal lines. In the current study, we presented modified versions of the Ponzo illusion in which only one of the converging oblique lines was presented (alternatively the right or the left one). This manipulation allowed us to explore (1) how acute patients with neglect process depth illusions, and (2) whether awareness of both converging lines is necessary for the full effect of the illusion. To examine these questions, we had participants (i.e. healthy controls, patients with neglect and right brain-damaged patients) to make a perceptual judgment regarding the perceived length of the upper versus lower horizontal line within the Ponzo frame in four conditions: (1) the classic Ponzo illusion, (2) a "modified left" Ponzo illusion with a single oblique line on the left, (3) a "modified right" Ponzo illusion with a single oblique line on the right and (4) a control condition with parallel lines. The results indicated that all participants perceived the canonical Ponzo illusion and the modified right illusion. Critically, patients with neglect did not perceive the modified left illusion. In addition, for neglect patients, there was no difference in the strength of the perceived illusion when comparing the canonical illusion with the modified right illusion. Importantly, single case analysis revealed a high degree of variability in the neglect group that seemed to be linked with the amount of damage to occipital areas. Overall our results indicate that: (1) the classic Ponzo illusion might be perceived in neglect patients based solely on perception of the right side of the stimulus configuration, and (2) differences between types of illusions (i.e. depth vs. length), and variability between patients suggest that caution is needed when utilizing these kinds of illusions to assess implicit processing in neglect.

Exploring motor and visual imagery in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease characterized by the progressive atrophy of both the first and the second motor neurons. Although the cognitive profile of ALS patients has already been defined by the occurrence of language dysfunctions and frontal deficit symptoms, it is less clear whether the degeneration of upper and lower motor neurons affects motor imagery abilities. Here, we directly investigated motor imagery in ALS patients by means of an established task that allows to examine the presence of the effects of the biomechanical constraints. Twenty-three ALS patients and 23 neurologically unimpaired participants have been administered with the (1) hand laterality task (HLT) in which participants were asked to judge the laterality of a rotated hand and the (2) mirror letter discrimination task (MLD) in which participants were asked to judge whether a rotated alphanumeric character was in its canonical or mirror-reversed form (i.e. control task). Results show that patients present the same pattern of performance as unimpaired participants at the MLD, while at the HLT, they present only partially with the effects of biomechanical constraints. Taken together, our findings provide evidences that motor imagery abilities, related to the mental simulation of an action, are affected by this progressive disease.

Alkylphenol oxidation with a laccase from a white-rot fungus: effects of culture induction and of ABTS used as a mediator.

We investigated the potential of the laccase from the white-rot fungus Marasmius quercophilus to transform certain alkylphenols (p-nonylphenol, p-octylphenol and p-t-octylphenol). We tested the reactivity of this enzyme under different conditions: in liquid cultures and using the partially purified laccase with and without 2,2'-azino-bis-3-ehtylbenzothiazoline-6-sulfonicacid (ABTS) as a mediator. The percentage of p-t-octylphenol disappearance in liquid cultures was 69.0 ± 1.5% and 81 ± 5% after a 8-d or 15-d incubation, respectively, with p-nonylphenol, these percentages were 62 ± 4% and 91 ± 6% and with p-octylphenol 37 ± 3% and 65 ± 1% after a 15-d and a 21-d incubations, respectively. Induced pre-cultures were also used to inoculate the liquid cultures to enhance p-octylphenol transformation: the percentages of disappearance were 91.0 ± 0.5% and 97 ± 1% after a 8-d and a 15-d incubation, respectively. Mass spectrometry analysis showed that the products of oxidation of p-octylphenol were dimers with a mass of 411 m/z. Furthermore, we identified a purple compound (m/z 476) formed when ABTS was added to the reaction medium with the purified laccase. This result confirms that, in complex environments such as soils or litters where many molecules can interact with the enzyme substrate or the product of oxidation, laccase activities and those of other phenoloxidases should not be measured with ABTS.

A method to quantify transesterification activities of lipases in litters.

Lipases are glycerol ester hydrolases (EC 3.1.1.3) produced by a wide range of microorganisms. They catalyse the hydrolysis of different esters but this reaction is reversible, depending on the water content of the reaction medium, via esterification and transesterification. The synthetic activity of lipases can be of major importance in natural ecosystems since it can be involved in carbon stockage in soils or litters. Here, the detection of transesterification activities of lipases in litter is reported for the first time. We used two different litters: litter of Quercus pubescens (QP) and litter of both Q. pubescens and Q. ilex. Different p-nitrophenyl esters and pentanol were used to test transesterification in a reaction medium with an organic solvent (heptane). We showed that these activities were proportional to the amount of litter, the incubation time and the substrate concentration and that they increased with temperature. Furthermore, the lipases from the litters studied were very thermostable since they were still active after 2 h at 70 degrees C. These activities showed common properties of lipases: the highest activities were obtained with a medium acyl-chain substrate p-nitrophenyl caprylate and transesterification activities were correlated to water activity, a(w). The following parameters are recommended to quantify transesterification activities in litter: 10 mM of p-nitrophenyl caprylate, 1 g of litter, 500 microL of pentanol, q.s.p. 4 mL of heptane incubated at 30 degrees C for 2 h.

A spectrophotometric transesterification-based assay for lipases in organic solvent.

A new method to evaluate lipase activities in nonaqueous conditions using vinyl ester absorbance at ultraviolet (UV) wavelengths is described. The model reaction is the transesterification between vinyl stearate and pentanol in hexane at 30 degrees C or in decane at 50 degrees C. The conversion of vinyl stearate into pentyl stearate is monitored through decreasing UV absorbance at 200 nm. Six commercial lipases were tested with this method, and results were compared with gas chromatography (GC) quantification and a classical spectrophotometric method using p-nitrophenyl palmitate. Results from the new spectrophotometric assay are similar both to results from GC quantification (R(2)=0.999) and to results from p-nitrophenyl palmitate (R(2)=0.989). The proposed method is able to evaluate both high activity from immobilized lipases such as immobilized Candida antarctica B lipase (3060 +/- 350 U g(-1)) and low activity from crude enzymatic extracts such as Carica papaya dried latex (0.1 +/- 0.04 U g(-1)). The method has also been used to measure kinetic parameters of C. antarctica B lipase for vinyl stearate and the correlation between its synthesis activity and its concentration. The method has also proved to be effective in studying the acyl selectivity of a lipase by comparing its activities with increasing chain lengths of vinyl esters.

Effects of pollutants on laccase activities of Marasmius quercophilus, a white-rot fungus isolated from a Mediterranean schlerophyllous litter.

Marasmius quercophilus is a white-rot fungus involved in carbon recycling in Mediterranean ecosystems because of its laccase production. Here we described the effect of metal ions and halide salts, on laccase activity in order to point out the action of such environmental pollutants on this enzyme of major importance. Furthermore we tested organic solvent effects on laccase reaction since reaction mixture including solvent can be used in the transformation of xenobiotics. In the case of metal ions, we found that chloride ions were responsible for inhibition while CuSO(4) and MnSO(4) enhanced laccase activity. When halides were tested, we showed the following degree of inhibition: F(-)>Cl(-)>Br(-). Furthermore we found that I(-) was oxidized by laccase with I(2) as the product of the reaction. With ABTS, 50% of the laccase activity remains for solvent concentration ranging from 40% to 60% depending on the solvent used while with syringaldazine solvent concentration ranged from 50% to 70%. The organic solvent effects observed were probably a result of enzyme denaturation and of both enhancement of oxidised product solubilisation and of substrate solubilisation (for syringaldazine). These results show that laccase from M. quercophilus is not rapidly inhibited by certain environmental pollutants which sustains its role in carbon turnover under pertubation. However the strong effect of chloride ion on laccase activity should be further investigated with in situ studies since this could drastically influence carbon recycling in litters from Mediterranean littoral locations.

Massive intraperitoneal stromal tumour: two-year follow-up.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are rare. Few cases of such tumours are reported in the literature. Until recently, they were only treated surgically but, nowadays, for high grade tumours, we can consider wide excision, not only as a palliative measure, but also to enable subsequent treatment with Imatinib mesylate. METHODS: We describe the case of a patient with a high-grade GIST, who, two years after undergoing surgery and medical treatment, is still in remission. Computerised axial tomography (CT) of the abdomen detected the presence of multiple heterogeneous solid masses of various sizes but no localised retroperitoneal adenopathies. MAIN FINDINGS: Median laparotomy was performed and revealed multiple intraperitoneal tumours. The larger masses were excised and the smaller residual implants are currently being treated with Imatinib mesylate. The patient had visceral, parietal and peritoneal dissemination. One of them, located in the supramesocolic area, had a maximal diameter of 20cm. Another one, at the level of the retro-gastric space, had a diameter of 22cm. The other tumours were smaller and spread over the parietal and visceral peritoneum, mainly between the loops of the small intestine and pelvis. Two years after cytoreduction surgery, the patient is well and free of obvious disease and has shown a good tolerance to pharmacological treatment. CONCLUSIONS: Imatinib mesylate has revolutionised the treatment of GIST and offers good palliation and prolongation of overall survival.

Diagnóstico y tratamiento de una malformación vascular yeyunal, mediante laparoscopia / Diagnosis and treatment of a vascular malformation in the jejunum by laparoscopy

No disponible

Quercus suber cork extract displays a tensor and smoothing effect on human skin: an in vivo study.

Recently, it has become indispensable for anti-aging active ingredients to provide a visible and immediate smoothing antiwrinkle effect. In Quercus suber, suberin is the most important structural component of cork cell walls. Studies have shown that suberin is made up mostly of hydroxycarboxylic acids and that it is endowed with many special mechanical and chemical properties that evoke a possible smoothing effect on the surface of the skin. Therefore, we were interested in investigating the effect of this cork extract on the skin's surface in a double-blind clinical study. The study was conducted in 15 healthy volunteers, aged 22 to 52 years. The volunteers applied a gel formula with 3% of cork extract, or placebo gel, on each forearm. Skin surface roughness was evaluated visually by pictures and by silicone replicas 1 and 2 h after application, followed by statistical analysis using the matched-pairs McNemar statistical test. McNemar analysis of the pictures revealed that application of cork extract on the skin resulted in a highly significant reduction of roughness 1 h after application. This effect was observed in 73.3% of volunteers. Two hours after cork extract application, a highly significant improvement of skin roughness was found in 78.6% of volunteers. Moreover, silicone replica treatment confirmed significant improvement in average of roughness at 2 h. These results demonstrate that cork extract provides a remarkable and highly significant tensor and smoothing effect on the skin, which could be of great use in anti-aging skin care products.

Influence of age, sex, and education on the Visual Object and Space Perception Battery (VOSP) in a healthy normal elderly population.

The assessment of visual perception and cognition forms an important part of any general cognitive evaluation. We have studied the possible influence of age, sex, and education on a normal elderly Spanish population (90 healthy subjects) in performance in visual perception tasks. To evaluate visual perception and cognition, we have used the subjects performance with The Visual Object and Space Perception Battery (VOSP). The test consists of 8 subtests: 4 measure visual object perception (Incomplete Letters, Silhouettes, Object Decision, and Progressive Silhouettes) while the other 4 measure visual space perception (Dot Counting, Position Discrimination, Number Location, and Cube Analysis). The statistical procedures employed were either simple or multiple linear regression analyses (subtests with normal distribution) and Mann-Whitney tests, followed by ANOVA with Scheffe correction (subtests without normal distribution). Age and sex were found to be significant modifying factors in the Silhouettes, Object Decision, Progressive Silhouettes, Position Discrimination, and Cube Analysis subtests. Educational level was found to be a significant predictor of function for the Silhouettes and Object Decision subtests. The results of the sample were adjusted in line with the differences observed. Our study also offers preliminary normative data for the administration of the VOSP to an elderly Spanish population. The results are discussed and compared with similar studies performed in different cultural backgrounds.

Variations of lignocellulosic activities in dual cultures of Pleurotus ostreatus and Trichoderma longibrachiatum on unsterilized wheat straw.

Trichoderma spp., soil filamentous fungi, are antagonists that can cause great losses in mushroom production. We have investigated the influence of T. longibrachiatum on the production of lignocellulolytic enzymes by Pleurotus ostreatus during its vegetative growth on a straw-based cultivation substrate that either had been sterilized, pasteurized or not heat treated. The variations in the lignocellulolytic activities and the electrophoretic patterns in single and dual cultures were used as a tool for perturbation assessment. The various heat treatments of the wheat straw before inoculation affected both the bacterial populations and the abilities of T. longibrachiatum and P. ostreatus to colonize the substrate and to produce extracellar lignocellulolytic enzymes. Interactions between T. longibrachiatum and the microflora of the substrate led to a great decrease of hydrolytic activities due to reduced colonization of the substrate. Pleurotus ostreatus also was affected but it was less sensitive than T. longibrachiatum. As a consequence, in dual cultures with P. ostreatus, the competitive ability of T. longibrachiatum was reduced by bacteria in the substrates. The presence of total microflora or thermotolerant microflora increased the production of phenoloxidase activities by P. ostreatus, despite reduced colonization of the substrate. This contributed to the improvement of the competitive ability of P. ostreatus in the pasteurized substrate. Furthermore, a direct effect of bacteria on T. longibrachiatum also was observed. In sterilized substrate, both laccase and Mn-peroxydase activities were increased dramatically in dual cultures due to a faster production of a laccase isoform, which was stimulated by T. longibrachiatum.

Purification of a new isoform of laccase from a Marasmius quercophilus strain isolated from a cork oak litter (Quercus suber L).

A new isoform of laccase from Marasmius quercophilus is described in this study. The strain of this white-rot fungus was isolated for the first time on a cork oak litter. This isoform exhibited certain common properties of laccases (a molecular weight of 65 Kda, an optimum pH of 6.2 with syringaldazine). But this laccase has also particularly novel features: the best activity measured was observed at high temperatures (80 C) and this isoform was not inhibited with EDTA. Furthermore, this induced laccase was able to transform most of the aromatic compounds tested without the addition of mediators to the reaction mixture, and the transformation of certain chlorophenols (2-chlorophenol and 2,4-dichlorophenol) by a laccase isoform from M. quercophilus is reported here for the first time. We also demonstrate the importance of 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) (ABTS) as a mediator since it allowed veratryl alcohol and p-hydroxybenzoic acid transformation. Moreover, new products of transformation were observed using the combination of ABTS with this isoform of laccase.