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991.
992.
Elodie Poiroux Christine Cavaro-Ménard Stéphanie Leruez Jean Michel Lemée Isabelle Richard Mickael Dinomais 《PloS one》2015,10(11)
Many of the brain structures involved in performing real movements also have increased activity during imagined movements or during motor observation, and this could be the neural substrate underlying the effects of motor imagery in motor learning or motor rehabilitation. In the absence of any objective physiological method of measurement, it is currently impossible to be sure that the patient is indeed performing the task as instructed. Eye gaze recording during a motor imagery task could be a possible way to “spy” on the activity an individual is really engaged in. The aim of the present study was to compare the pattern of eye movement metrics during motor observation, visual and kinesthetic motor imagery (VI, KI), target fixation, and mental calculation. Twenty-two healthy subjects (16 females and 6 males), were required to perform tests in five conditions using imagery in the Box and Block Test tasks following the procedure described by Liepert et al. Eye movements were analysed by a non-invasive oculometric measure (SMI RED250 system). Two parameters describing gaze pattern were calculated: the index of ocular mobility (saccade duration over saccade + fixation duration) and the number of midline crossings (i.e. the number of times the subjects gaze crossed the midline of the screen when performing the different tasks). Both parameters were significantly different between visual imagery and kinesthesic imagery, visual imagery and mental calculation, and visual imagery and target fixation. For the first time we were able to show that eye movement patterns are different during VI and KI tasks. Our results suggest gaze metric parameters could be used as an objective unobtrusive approach to assess engagement in a motor imagery task. Further studies should define how oculomotor parameters could be used as an indicator of the rehabilitation task a patient is engaged in. 相似文献
993.
Sushmita L. Allam Jean-Marie C. Bouteiller Eric Y. Hu Nicolas Ambert Renaud Greget Serge Bischoff Michel Baudry Theodore W. Berger 《PloS one》2015,10(10)
Glutamatergic synapses are the most prevalent functional elements of information processing in the brain. Changes in pre-synaptic activity and in the function of various post-synaptic elements contribute to generate a large variety of synaptic responses. Previous studies have explored postsynaptic factors responsible for regulating synaptic strength variations, but have given far less importance to synaptic geometry, and more specifically to the subcellular distribution of ionotropic receptors. We analyzed the functional effects resulting from changing the subsynaptic localization of ionotropic receptors by using a hippocampal synaptic computational framework. The present study was performed using the EONS (Elementary Objects of the Nervous System) synaptic modeling platform, which was specifically developed to explore the roles of subsynaptic elements as well as their interactions, and that of synaptic geometry. More specifically, we determined the effects of changing the localization of ionotropic receptors relative to the presynaptic glutamate release site, on synaptic efficacy and its variations following single pulse and paired-pulse stimulation protocols. The results indicate that changes in synaptic geometry do have consequences on synaptic efficacy and its dynamics. 相似文献
994.
Maud Condomines Jon Arnason Reuben Benjamin Gertrude Gunset Jason Plotkin Michel Sadelain 《PloS one》2015,10(6)
Adoptive T cell therapy represents a promising treatment for cancer. Human T cells engineered to express a chimeric antigen receptor (CAR) recognize and kill tumor cells in a MHC-unrestricted manner and persist in vivo when the CAR includes a CD28 costimulatory domain. However, the intensity of the CAR-mediated CD28 activation signal and its regulation by the CTLA-4 checkpoint are unknown. We investigated whether T cells expressing an anti-CD19, CD3 zeta and CD28-based CAR (19-28z) displayed the same proliferation and anti-tumor abilities than T cells expressing a CD3 zeta-based CAR (19z1) costimulated through the CD80/CD28, ligand/receptor pathway. Repeated in vitro antigen-specific stimulations indicated that 19-28z+ T cells secreted higher levels of Th1 cytokines and showed enhanced proliferation compared to those of 19z1+ or 19z1-CD80+ T cells. In an aggressive pre-B cell leukemia model, mice treated with 19-28z+ T cells had 10-fold reduced tumor progression compared to those treated with 19z1+ or 19z1-CD80+ T cells. shRNA-mediated CTLA-4 down-regulation in 19z1-CD80+ T cells significantly increased their in vivo expansion and anti-tumor properties, but had no effect in 19-28z+ T cells. Our results establish that CTLA-4 down-regulation may benefit human adoptive T cell therapy and demonstrate that CAR design can elude negative checkpoints to better sustain T cell function. 相似文献
995.
Isabelle Perrault Fadi?F. Hamdan Marlène Rio José-Mario Capo-Chichi Nathalie Boddaert Jean-Claude Décarie Bruno Maranda Rima Nabbout Michel Sylvain Anne Lortie Philippe?P. Roux Elsa Rossignol Xavier Gérard Giulia Barcia Patrick Berquin Arnold Munnich Guy?A. Rouleau Josseline Kaplan Jean-Michel Rozet Jacques?L. Michaud 《American journal of human genetics》2014,94(6):891-897
Epileptic encephalopathies are increasingly thought to be of genetic origin, although the exact etiology remains uncertain in many cases. We describe here three girls from two nonconsanguineous families affected by a clinical entity characterized by dysmorphic features, early-onset intractable epilepsy, intellectual disability, and cortical blindness. In individuals from each family, brain imaging also showed specific changes, including an abnormally marked pontobulbar sulcus and abnormal signals (T2 hyperintensities) and atrophy in the occipital lobe. Exome sequencing performed in the first family did not reveal any gene with rare homozygous variants shared by both affected siblings. It did, however, show one gene, DOCK7, with two rare heterozygous variants (c.2510delA [p.Asp837Alafs∗48] and c.3709C>T [p.Arg1237∗]) found in both affected sisters. Exome sequencing performed in the proband of the second family also showed the presence of two rare heterozygous variants (c.983C>G [p.Ser328∗] and c.6232G>T [p.Glu2078∗]) in DOCK7. Sanger sequencing confirmed that all three individuals are compound heterozygotes for these truncating mutations in DOCK7. These mutations have not been observed in public SNP databases and are predicted to abolish domains critical for DOCK7 function. DOCK7 codes for a Rac guanine nucleotide exchange factor that has been implicated in the genesis and polarization of newborn pyramidal neurons and in the morphological differentiation of GABAergic interneurons in the developing cortex. All together, these observations suggest that loss of DOCK7 function causes a syndromic form of epileptic encephalopathy by affecting multiple neuronal processes. 相似文献
996.
Dominique Hervé Anne Philippi Reda Belbouab Michel Zerah Stéphane Chabrier Sophie Collardeau-Frachon Francoise Bergametti Aurore Essongue Eliane Berrou Valérie Krivosic Christian Sainte-Rose Emmanuel Houdart Frédéric Adam Kareen Billiemaz Marilyne Lebret Sabine Roman Sandrine Passemard Gwenola Boulday Audrey Delaforge Stéphanie Guey Xavier Dray Hugues Chabriat Peter Brouckaert Maryjke Bryckaert Elisabeth Tournier-Lasserve 《American journal of human genetics》2014,94(3):385-394
Moyamoya is a cerebrovascular condition characterized by a progressive stenosis of the terminal part of the internal carotid arteries (ICAs) and the compensatory development of abnormal “moyamoya” vessels. The pathophysiological mechanisms of this condition, which leads to ischemic and hemorrhagic stroke, remain unknown. It can occur as an isolated cerebral angiopathy (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes). Here, we describe an autosomal-recessive disease leading to severe moyamoya and early-onset achalasia in three unrelated families. This syndrome is associated in all three families with homozygous mutations in GUCY1A3, which encodes the α1 subunit of soluble guanylate cyclase (sGC), the major receptor for nitric oxide (NO). Platelet analysis showed a complete loss of the soluble α1β1 guanylate cyclase and showed an unexpected stimulatory role of sGC within platelets. The NO-sGC-cGMP pathway is a major pathway controlling vascular smooth-muscle relaxation, vascular tone, and vascular remodeling. Our data suggest that alterations of this pathway might lead to an abnormal vascular-remodeling process in sensitive vascular areas such as ICA bifurcations. These data provide treatment options for affected individuals and strongly suggest that investigation of GUCY1A3 and other members of the NO-sGC-cGMP pathway is warranted in both isolated early-onset achalasia and nonsyndromic moyamoya. 相似文献
997.
Reto Niedermann Eva Wyss Simon Annaheim Agnes Psikuta Sarah Davey René Michel Rossi 《International journal of biometeorology》2014,58(1):7-15
The measurement of core body temperature is an efficient method for monitoring heat stress amongst workers in hot conditions. However, invasive measurement of core body temperature (e.g. rectal, intestinal, oesophageal temperature) is impractical for such applications. Therefore, the aim of this study was to define relevant non-invasive measures to predict core body temperature under various conditions. We conducted two human subject studies with different experimental protocols, different environmental temperatures (10 °C, 30 °C) and different subjects. In both studies the same non-invasive measurement methods (skin temperature, skin heat flux, heart rate) were applied. A principle component analysis was conducted to extract independent factors, which were then used in a linear regression model. We identified six parameters (three skin temperatures, two skin heat fluxes and heart rate), which were included for the calculation of two factors. The predictive value of these factors for core body temperature was evaluated by a multiple regression analysis. The calculated root mean square deviation (rmsd) was in the range from 0.28 °C to 0.34 °C for all environmental conditions. These errors are similar to previous models using non-invasive measures to predict core body temperature. The results from this study illustrate that multiple physiological parameters (e.g. skin temperature and skin heat fluxes) are needed to predict core body temperature. In addition, the physiological measurements chosen in this study and the algorithm defined in this work are potentially applicable as real-time core body temperature monitoring to assess health risk in broad range of working conditions. 相似文献
998.
Alex?J. Crick Michel Theron Teresa Tiffert Virgilio?L. Lew Pietro Cicuta Julian?C. Rayner 《Biophysical journal》2014,107(4):846-853
Erythrocyte invasion by Plasmodium falciparum merozoites is an essential step for parasite survival and hence the pathogenesis of malaria. Invasion has been studied intensively, but our cellular understanding has been limited by the fact that it occurs very rapidly: invasion is generally complete within 1 min, and shortly thereafter the merozoites, at least in in vitro culture, lose their invasive capacity. The rapid nature of the process, and hence the narrow time window in which measurements can be taken, have limited the tools available to quantitate invasion. Here we employ optical tweezers to study individual invasion events for what we believe is the first time, showing that newly released P. falciparum merozoites, delivered via optical tweezers to a target erythrocyte, retain their ability to invade. Even spent merozoites, which had lost the ability to invade, retain the ability to adhere to erythrocytes, and furthermore can still induce transient local membrane deformations in the erythrocyte membrane. We use this technology to measure the strength of the adhesive force between merozoites and erythrocytes, and to probe the cellular mode of action of known invasion inhibitory treatments. These data add to our understanding of the erythrocyte-merozoite interactions that occur during invasion, and demonstrate the power of optical tweezers technologies in unraveling the blood-stage biology of malaria. 相似文献
999.
1000.
Michael Garratt Robert C Brooks Jean‐François Lemaître Jean‐Michel Gaillard 《Evolution; international journal of organic evolution》2014,68(4):1207-1215
Conflicts between family members are expected to influence the duration and intensity of parental care. In mammals, the majority of this care occurs as resource transfer from mothers to offspring during gestation and lactation. Mating systems can have a strong influence on the severity of familial conflict—where female promiscuity is prevalent, conflict is expected to be higher between family members, causing offspring to demand more resources. If offspring are capable of manipulating their mothers and receive resources in proportion to their demands, resource transfer should increase with elevated promiscuity. We tested this prediction, unexplored across mammals, using a comparative approach. The total durations of gestation and lactation were not related to testes mass, a reliable proxy of female promiscuity across taxa. Offspring growth during gestation, however, and weaning mass, were positively correlated with testes mass, suggesting that offspring gain resources from their mothers at faster rates when familial conflict is greater. During gestation, the relationship between offspring growth and testes mass was also related to placenta morphology, with a stronger relationship between testes mass and growth observed in species with a less invasive placenta. Familial conflict could have a pervasive influence on patterns of parental care in mammals. 相似文献