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41.
In this paper, we present a continuous attractor network model that we hypothesize will give some suggestion of the mechanisms
underlying several neural processes such as velocity tuning to visual stimulus, sensory discrimination, sensorimotor transformations,
motor control, motor imagery, and imitation. All of these processes share the fundamental characteristic of having to deal
with the dynamic integration of motor and sensory variables in order to achieve accurate sensory prediction and/or discrimination.
Such principles have already been described in the literature by other high-level modeling studies (Decety and Sommerville
in Trends Cogn Sci 7:527–533, 2003; Oztop et al. in Neural Netw 19(3):254–271, 2006; Wolpert et al. in Philos Trans R Soc
358:593–602, 2003). With respect to these studies, our work is more concerned with biologically plausible neural dynamics
at a population level. Indeed, we show that a relatively simple extension of the classical neural field models can endow these
networks with additional dynamic properties for updating their internal representation using external commands. Moreover,
an analysis of the interactions between our model and external inputs also shows interesting properties, which we argue are
relevant for a better understanding of the neural processes of the brain. 相似文献
42.
Gertner-Dardenne J Castellano R Mamessier E Garbit S Kochbati E Etienne A Charbonnier A Collette Y Vey N Olive D 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(9):4701-4708
Vγ9Vδ2 T cells are attractive candidates for antileukemic activity. The analysis of Vγ9Vδ2 T cells in newly diagnosed acute myeloid leukemia (AML) patients revealed that their absolute cell numbers were normal in the blood as well as in the bone marrow but showed a striking imbalance in the differentiation subsets, with preponderance of the effector memory population. This unusual phenotype was restored after removal of leukemic cells in patients, which reached complete remission after chemotherapy, suggesting that leukemic cells might be involved in the alteration of γδ T cell development in AML. Accordingly, coculture between AML cells and Vγ9Vδ2 T cells induced selection of effector cells. In accordance with their effector memory status, in vitro proliferation of Vγ9Vδ2 T cells was reduced compared with normal controls. Nevertheless, Vγ9Vδ2 T cells efficiently killed autologous AML blasts via the perforin/granzyme pathway. The ligands for DNAM-1 were expressed by AML cells. We showed that killing of AML blasts was TCR and DNAM-1 dependent. Using a xenotransplantation murine model, we showed that Vγ9Vδ2 T cells homed to the bone marrow in close proximity of engrafted leukemic cells and enhanced survival. These data demonstrate that Vγ9Vδ2 T cells are endowed with the ability to interact with and eradicate AML blasts both in vitro and in a mouse model. Collectively, our data revealed that Vγ9Vδ2 T cells have a potent antileukemic activity provided that optimal activation is achieved, such as with synthetic TCR agonists. This study enhances the interest of these cells for therapeutic purposes such as AML treatment. 相似文献
43.
New molecular resources regarding the so-called “non-standard models” in biology extend the present knowledge and are essential for molecular evolution and diversity studies (especially during the development) and evolutionary inferences about these zoological groups, or more practically for their fruitful management. Sepia officinalis, an economically important cephalopod species, is emerging as a new lophotrochozoan developmental model. We developed a large set of expressed sequence tags (ESTs) from embryonic stages of S. officinalis, yielding 19,780 non-redundant sequences (NRS). Around 75% of these sequences have no homologs in existing available databases. This set is the first developmental ESTs library in cephalopods. By exploring these NRS for tubulin, a generic protein family, and reflectin, a cephalopod specific protein family,we point out for both families a striking molecular diversity in S. officinalis. 相似文献
44.
45.
Marrocco K Criqui MC Zervudacki J Schott G Eisler H Parnet A Dunoyer P Genschik P 《PloS one》2012,7(4):e35173
Background
Selective protein degradation via the ubiquitin-26S proteasome is a major mechanism underlying DNA replication and cell division in all Eukaryotes. In particular, the APC/C (Anaphase Promoting Complex or Cyclosome) is a master ubiquitin protein ligase (E3) that targets regulatory proteins for degradation allowing sister chromatid separation and exit from mitosis. Interestingly, recent work also indicates that the APC/C remains active in differentiated animal and plant cells. However, its role in post-mitotic cells remains elusive and only a few substrates have been characterized.Methodology/Principal Findings
In order to identify novel APC/C substrates, we performed a yeast two-hybrid screen using as the bait Arabidopsis APC10/DOC1, one core subunit of the APC/C, which is required for substrate recruitment. This screen identified DRB4, a double-stranded RNA binding protein involved in the biogenesis of different classes of small RNA (sRNA). This protein interaction was further confirmed in vitro and in plant cells. Moreover, APC10 interacts with DRB4 through the second dsRNA binding motif (dsRBD2) of DRB4, which is also required for its homodimerization and binding to its Dicer partner DCL4. We further showed that DRB4 protein accumulates when the proteasome is inactivated and, most importantly, we found that DRB4 stability depends on APC/C activity. Hence, depletion of Arabidopsis APC/C activity by RNAi leads to a strong accumulation of endogenous DRB4, far beyond its normal level of accumulation. However, we could not detect any defects in sRNA production in lines where DRB4 was overexpressed.Conclusions/Significance
Our work identified a first plant substrate of the APC/C, which is not a regulator of the cell cycle. Though we cannot exclude that APC/C-dependent degradation of DRB4 has some regulatory roles under specific growth conditions, our work rather points to a housekeeping function of APC/C in maintaining precise cellular-protein concentrations and homeostasis of DRB4. 相似文献46.
47.
Background
Visual behavior is known to be atypical in Autism Spectrum Disorders (ASD). Monitor-based eye-tracking studies have measured several of these atypicalities in individuals with Autism. While atypical behaviors are known to be accentuated during natural interactions, few studies have been made on gaze behavior in natural interactions. In this study we focused on i) whether the findings done in laboratory settings are also visible in a naturalistic interaction; ii) whether new atypical elements appear when studying visual behavior across the whole field of view.Methodology/Principal Findings
Ten children with ASD and ten typically developing children participated in a dyadic interaction with an experimenter administering items from the Early Social Communication Scale (ESCS). The children wore a novel head-mounted eye-tracker, measuring gaze direction and presence of faces across the child''s field of view. The analysis of gaze episodes to faces revealed that children with ASD looked significantly less and for shorter lapses of time at the experimenter. The analysis of gaze patterns across the child''s field of view revealed that children with ASD looked downwards and made more extensive use of their lateral field of view when exploring the environment.Conclusions/Significance
The data gathered in naturalistic settings confirm findings previously obtained only in monitor-based studies. Moreover, the study allowed to observe a generalized strategy of lateral gaze in children with ASD when they were looking at the objects in their environment. 相似文献48.
F Ferro A Ouillé TA Tran P Fontanaud P Bois D Babuty F Labarthe JY Le Guennec 《PloS one》2012,7(7):e41686
Background and purpose
In some pathological conditions carnitine concentration is high while in othersitis low.In bothcases,cardiac arrhythmiascan occur and lead to sudden cardiac death. It has been proposed that in ischaemia, acylcarnitine (acyl-CAR), but not carnitine, is involved in arrhythmiasthrough modulation of ionic currents. We studied the effects of acyl-CARs on hERG, KIR2.1 and Kv7.1/minKchannels (channels responsible for IKR, IK1 and IKS respectively).Experimental approach
HEK293 cells stably expressing hERG, KIR2.1 or Kv7.1/minK were studied using the patch clamp technique. Free carnitine (CAR) and acyl-CAR derivatives from medium- (C8 and C10) and long-chain (C16 and C18∶1) fatty acids were applied intra- and extracellularly at different concentrations. Forstudies onhERG, C16 and C18∶1 free fatty acid were also used.Key results
Extracellular long-chain (LCAC), but not medium-chain, acyl-CAR,induced an increase of IhERG amplitude associated with a dose-dependent speeding of deactivation kinetics. They had no effect on KIR2.1 or Kv7.1/minK currents.Computer simulations of these effects wereconsistent with changes in action potential profile.Conclusions and applications
Extracellular LCAC tonically regulates IhERG amplitude and kineticsunder physiological conditions. This modulation maycontribute tothe changes in action potential duration thatprecede cardiac arrhythmias in ischaemia, diabetes and primary systemic carnitine deficiency. 相似文献49.
50.