Showing papers by "University of Bordeaux published in 2008"

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Abstract: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms Recent reviews have described the range of assays that have been used for this purpose(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi) Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response

Sudden Cardiac Arrest Associated with Early Repolarization

Abstract: Background: Early repolarization is a common electrocardiographic finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest. Methods: We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of electrocardiographic early repolarization. The latter was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects. Results: Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P<0.001). Among case subjects, those with early repolarization were more likely to be male and to have a history of syncope or sudden cardiac arrest during sleep than those without early repolarization. In eight subjects, the origin of ectopy that initiated ventricular arrhythmias was mapped to sites concordant with the localization of repolarization abnormalities. During a mean (+/-SD) follow-up of 61+/-50 months, defibrillator monitoring showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without such an abnormality (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008). Conclusions: Among patients with a history of idiopathic ventricular fibrillation, there is an increased prevalence of early repolarization.

Lithium deintercalation in LiFePO4 nanoparticles via a domino-cascade model

Abstract: Lithium iron phosphate is one of the most promising positive-electrode materials for the next generation of lithium-ion batteries that will be used in electric and plug-in hybrid vehicles. Lithium deintercalation (intercalation) proceeds through a two-phase reaction between compositions very close to LiFePO(4) and FePO(4). As both endmember phases are very poor ionic and electronic conductors, it is difficult to understand the intercalation mechanism at the microscopic scale. Here, we report a characterization of electrochemically deintercalated nanomaterials by X-ray diffraction and electron microscopy that shows the coexistence of fully intercalated and fully deintercalated individual particles. This result indicates that the growth reaction is considerably faster than its nucleation. The reaction mechanism is described by a 'domino-cascade model' and is explained by the existence of structural constraints occurring just at the reaction interface: the minimization of the elastic energy enhances the deintercalation (intercalation) process that occurs as a wave moving through the entire crystal. This model opens new perspectives in the search for new electrode materials even with poor ionic and electronic conductivities.

Spatial Relational Memory Requires Hippocampal Adult Neurogenesis

Abstract: The dentate gyrus of the hippocampus is one of the few regions of the mammalian brain where new neurons are generated throughout adulthood. This adult neurogenesis has been proposed as a novel mechanism that mediates spatial memory. However, data showing a causal relationship between neurogenesis and spatial memory are controversial. Here, we developed an inducible transgenic strategy allowing specific ablation of adult-born hippocampal neurons. This resulted in an impairment of spatial relational memory, which supports a capacity for flexible, inferential memory expression. In contrast, less complex forms of spatial knowledge were unaltered. These findings demonstrate that adult-born neurons are necessary for complex forms of hippocampus-mediated learning.

Dinuclear Dysprosium(III) Single-Molecule Magnets with a Large Anisotropic Barrier†

Abstract: Due to the large intrinsic magnetic anisotropy of the lanthanide ions, rare-earth metal systems, and in particular dysprosium (Dy) based materials, have sparked increasing interest in the area of molecular magnetism. In a molecular complex, when such a unique property is combined with a high-spin ground state (S), slow relaxation of the magnetization can be obtained as seen for single-molecule magnets (SMMs). Although, a number of mixed transition-metal/ lanthanide SMMs have been reported, pure lanthanide SMMs are relatively scarce. The latter molecules are rare owing to the difficulty in promoting magnetic interactions in these systems. These interactions are attained by the overlap of bridging ligand orbitals with the 4f orbitals of the lanthanide ions. Thus, ligand design is one of the key components for achieving such interactions in pure lanthanide-based systems. To induce significant magnetic interaction between the lanthanide ions and synthesize high-energy-barrier SMMs, we have been investigating the use of (2-hydroxy-3-methoxyphenyl)methylene (isonicotino)hydrazine (H2hmi) as a rigid chelate in lanthanide chemistry. Such a linear ligand provides O,N,O,O-based multichelating sites that are especially favorable for lanthanide ion complex formation. They can form dinuclear systems using the bridging phenoxide oxygen atom, and the pyridine group promotes the formation of extended networks that can control the organization of the SMM units in the three-dimensional structure. Herein we report the use of the H2hmi ligand to design materials based on ferromagnetically coupled dinuclear dysprosium(III) SMMs with large relaxation barriers. [Dy2(hmi)2(NO3)2(MeOH)2] (1) and [Dy2(hmi)2(NO3)2 (MeOH)2]1·MeCN (2·MeCN) were obtained from a suspension of Dy(NO3)3·5H2O / H2hmi in methanol (treated with triethylamine) and in a 3:1 mixture of acetonitrile and methanol (treated with pyridine), respectively. After two days, pale orange single crystals were obtained, which were kept in contact with the mother liquor to prevent deterioration. Complexes 1 (Figure 1) and 2 (Figure 2) crystallize in monoclinic P21/c and orthorhombic Pbca space groups, respectively. Both complexes have similar dinuclear

Solutions of negatively charged graphene sheets and ribbons.

Abstract: Negatively charged graphene layers from a graphite intercalation compound spontaneously dissolve in N-methylpyrrolidone, without the need for any sonication, yielding stable, air-sensitive, solutions of laterally extended atom-thick graphene sheets and ribbons with dimensions over tens of micrometers. These can be deposited on a variety of substrates. Height measurements showing single-atom thickness were performed by STM, AFM, multiple beam interferometry, and optical imaging on Sarfus wafers, demonstrating deposits of graphene flakes and ribbons. AFM height measurements on mica give the actual height of graphene (ca. 0.4 nm).

Surface Mobility of Postsynaptic AMPARs Tunes Synaptic Transmission

Abstract: AMPA glutamate receptors (AMPARs) mediate fast excitatory synaptic transmission. Upon fast consecutive synaptic stimulation, transmission can be depressed. Recuperation from fast synaptic depression has been attributed solely to recovery of transmitter release and/or AMPAR desensitization. We show that AMPAR lateral diffusion, observed in both intact hippocampi and cultured neurons, allows fast exchange of desensitized receptors with naive functional ones within or near the postsynaptic density. Recovery from depression in the tens of millisecond time range can be explained in part by this fast receptor exchange. Preventing AMPAR surface movements through cross-linking, endogenous clustering, or calcium rise all slow recovery from depression. Physiological regulation of postsynaptic receptor mobility affects the fidelity of synaptic transmission by shaping the frequency dependence of synaptic responses.

Sonochemical Approach to the Synthesis of Fe3O4@SiO2 Core−Shell Nanoparticles with Tunable Properties

Abstract: In this study, we report a rapid sonochemical synthesis of monodisperse nonaggregated Fe3O4@SiO2 magnetic nanoparticles (NPs). We found that coprecipitation of Fe(II) and Fe(III) in aqueous solutio...

Electron Transfer Mechanisms upon Lithium Deintercalation from LiCoO2 to CoO2 Investigated by XPS

Abstract: Lithium deintercalation of LixCoO2 from x = 1 to x ≈ 0 has been carried out electrochemically. The changes in the electronic structure from LiCoO2 to CoO2 have been investigated by X-ray photoelectron spectroscopy (XPS) to bring some new developments about the electron transfer mechanisms upon lithium deintercalation. All available XPS core peaks (Co 2p, Co 3p, Co 3s, O 1s, F 1s, P 2p, C 1s) and valence spectra have been analyzed. The contributions of the electrode material and of the electrode/electrolyte interface have been clearly distinguished. We show that cobalt and oxygen simultaneously undergo a partial oxidation process and that the sole participation of oxygen atoms to the charge transfer process, as it is sometimes assumed, can be excluded. The surface film consists of organic and inorganic species resulting from degradation of the electrolyte.

Efficacy of Sunitinib and Sorafenib in Metastatic Papillary and Chromophobe Renal Cell Carcinoma

Abstract: Purpose Sunitinib and sorafenib are novel tyrosine kinase inhibitors (TKIs) that have shown significant clinical activity in metastatic clear cell renal cell carcinoma (RCC). The activity of sunitinib and sorafenib in non–clear cell histologies has not been evaluated. Patients and Methods Clinical features at study entry and treatment outcomes were evaluated in patients with metastatic papillary RCC (PRCC) and chromophobe RCC (ChRCC) who received either sunitinib or sorafenib as their initial TKI treatment in five US and French institutions. Response rate and survival were documented. Fisher's exact test was used for categoric variables, and the Kaplan-Meier method was used to estimate survival. Results Fifty-three patients were included. The number of patients with papillary and chromophobe histologies was 41 (77%) and 12 (23%), respectively. Response rate, progression-free survival (PFS) time, and overall survival time for the entire cohort were 10%, 8.6 months, and 19.6 months, respectively. Three (25%...

The transcription factor VvMYB5b contributes to the regulation of anthocyanin and proanthocyanidin biosynthesis in developing grape berries

Abstract: Among the dramatic changes occurring during grape berry (Vitis vinifera) development, those affecting the flavonoid pathway have provoked a number of investigations in the last 10 years. In addition to producing several compounds involved in the protection of the berry and the dissemination of the seeds, final products of this pathway also play a critical role in berry and wine quality. In this article, we describe the cloning and functional characterization of VvMYB5b, a cDNA isolated from a grape berry (V. vinifera ‘Cabernet Sauvignon’) library. VvMYB5b encodes a protein belonging to the R2R3-MYB family of transcription factors and displays significant similarity with VvMYB5a, another MYB factor recently shown to regulate flavonoid synthesis in grapevine. The ability of VvMYB5a and VvMYB5b to activate the grapevine promoters of several structural genes of the flavonoid pathway was confirmed by transient expression of the corresponding cDNAs in grape cells. Overexpression of VvMYB5b in tobacco (Nicotiana tabacum) leads to an up-regulation of genes encoding enzymes of the flavonoid pathway and results in the accumulation of anthocyanin- and proanthocyanidin-derived compounds. The ability of VvMYB5b to regulate particularly the anthocyanin and the proanthocyanidin pathways is discussed in relation to other recently characterized MYB transcription factors in grapevine. Taken together, data presented in this article give insight into the transcriptional mechanisms associated with the regulation of the flavonoid pathway throughout grape berry development.

Genomic Stability and Tumour Suppression by the APC/C Cofactor Cdh1

Abstract: The anaphase promoting complex or cyclosome (APC/C) is a ubiquitin protein ligase that, together with Cdc20 or Cdh1, targets cell-cycle proteins for degradation. APC/C–Cdh1 specifically promotes protein degradation in late mitosis and G1. Mutant embryos lacking Cdh1 die at E9.5–E10.5 due to defects in the endoreduplication of trophoblast cells and placental malfunction. This lethality is prevented when Cdh1 is expressed in the placenta. Cdh1-deficient cells proliferate inefficiently and accumulate numeric and structural chromosomal aberrations, indicating that Cdh1 contributes to the maintenance of genomic stability. Cdh1 heterozygous animals show increased susceptibility to spontaneous tumours, suggesting that Cdh1 functions as a haploinsufficient tumour suppressor. These heterozygous mice also show several defects in behaviour associated with increased proliferation of stem cells in the nervous system. These results indicate that Cdh1 is required for preventing unscheduled proliferation of specific progenitor cells and protecting mammalian cells from genomic instability.

Sterols and membrane dynamics

Abstract: The effect of sterols from mammals, plants, fungi, and bacteria on model and natural membrane dynamics are reviewed, in the frame of ordering-disordering properties of membranes. It is shown that all sterols share a common property: the ability to regulate dynamics in order to maintain membranes in a microfluid state where it can convey important biological processes. Depending on the sterol class, this property is modulated by molecular modifications that have occurred during evolution. The role of sterols in rafts, antibiotic complexes, and in protecting membranes from the destructive action of amphipathic toxins is also discussed.

Spatial cooperativity in soft glassy flows

Abstract: Amorphous glassy materials of diverse nature-concentrated emulsions, granular materials, pastes, molecular glasses-display complex flow properties, intermediate between solid and liquid, which are at the root of their use in many applications. A general feature of such systems, well documented yet not really understood, is the strongly nonlinear nature of the flow rule relating stresses and strain rates. Here we use a microfluidic velocimetry technique to characterize the flow of thin layers of concentrated emulsions, confined in gaps of different thicknesses by surfaces of different roughnesses. We find evidence for finite-size effects in the flow behaviour and the absence of an intrinsic local flow rule. In contrast to the classical nonlinearities of the rheological behaviour of amorphous materials, we show that a rather simple non-local flow rule can account for all the velocity profiles. This non-locality of the dynamics is quantified by a length, characteristic of cooperativity within the flow at these scales, that is unobservable in the liquid state (lower emulsion concentrations) and that increases with concentration in the jammed state. Beyond its practical importance for applications involving thin layers (for example, coatings), these non-locality and cooperativity effects have parallels in the behaviour of other glassy, jammed and granular systems, suggesting a possible fundamental universality.

Large time existence for 3D water-waves and asymptotics

Abstract: We rigorously justify in $3D$ the main asymptotic models used in coastal oceanography, including: shallow-water equations, Boussinesq systems, Kadomtsev-Petviashvili (KP) approximation, Green-Naghdi equations, Serre approximation and full-dispersion model. We first introduce a ``variable'' nondimensionalized version of the water-waves equations which vary from shallow to deep water, and which involves four dimensionless parameters. Using a nonlocal energy adapted to the equations, we can prove a well-posedness theorem, uniformly with respect to all the parameters. Its validity ranges therefore from shallow to deep-water, from small to large surface and bottom variations, and from fully to weakly transverse waves. The physical regimes corresponding to the aforementioned models can therefore be studied as particular cases; it turns out that the existence time and the energy bounds given by the theorem are always those needed to justify the asymptotic models. We can therefore derive and justify them in a systematic way.

Characterization and Biological Function of the ISOCHORISMATE SYNTHASE2 Gene of Arabidopsis

Abstract: Salicylic acid (SA) is an important mediator of plant defense response. In Arabidopsis (Arabidopsis thaliana), this compound was proposed to derive mainly from isochorismate, itself produced from chorismate through the activity of ISOCHORISMATE SYNTHASE1 (ICS1). Null ics1 mutants still accumulate some SA, suggesting the existence of an enzymatic activity redundant with ICS1 or of an alternative ICS-independent SA biosynthetic route. Here, we studied the role of ICS2, a second ICS gene of the Arabidopsis genome, in the production of SA. We have shown that ICS2 encodes a functional ICS enzyme and that, similar to ICS1, ICS2 is targeted to the plastids. Comparison of SA accumulation in the ics1, ics2, and ics1 ics2 mutants indicates that ICS2 participates in the synthesis of SA, but in limited amounts that become clearly detectable only when ICS1 is lacking. This unequal redundancy relationship was also observed for phylloquinone, another isochorismate-derived end product. Furthermore, detection of SA in the double ics1 ics2 double mutant that is completely devoid of phylloquinone provides genetic evidence of the existence of an ICS-independent SA biosynthetic pathway in Arabidopsis.

The genome sequence of the model ascomycete fungus Podospora anserina

Abstract: Background: The dung-inhabiting ascomycete fungus Podospora anserina is a model used to study various aspects of eukaryotic and fungal biology, such as ageing, prions and sexual development. Results: We present a 10X draft sequence of P. anserina genome, linked to the sequences of a large expressed sequence tag collection. Similar to higher eukaryotes, the P. anserina transcription/ splicing machinery generates numerous non-conventional tran scripts. Comparison of the P. anserina genome and orthologous gene set with the one of its close relatives, Neurospora crassa, shows that synteny is poorly conserved, the main result of evolution being gene shuffling in the same chromosome. The P. anserina genome contains fewer repeated sequences and has evolved

Polycyclic aromatic hydrocarbons in dense cloud chemistry

Abstract: Virtually all detailed gas-phase models of the chemistry of dense interstellar clouds exclude polycyclic aromatic hydrocarbons (PAHs). This omission is unfortunate because from the few studies that have been done on the subject, it is known that the inclusion of PAHs can affect the gas-phase chemistry strongly. We have added PAHs to our network to determine the role they play in the chemistry of cold dense cores. Initially, only the chemistry of neutral and negatively charged PAH species was considered, since it was assumed that positively charged PAHs are of little importance. Subsequently, this assumption was checked and confirmed. In the models presented here, we include radiative attachment to form PAH−, mutual neutralization between PAH anions and small positively charged ions, and photodetachment. We also test the sensitivity of our results to changes in the size and abundance of the PAHs. Our results confirm that the inclusion of PAHs changes many of the calculated abundances of smaller species considerably. In TMC-1, the general agreement with observations is significantly improved, unlike in L134N. This may indicate a difference in PAH properties between the two regions. With the inclusion of PAHs in dense cloud chemistry, high-metal elemental abundances give a satisfactory agreement with observations. As a result, we do not need to decrease the observed elemental abundances of all metals, and we do not need to vary the elemental C/O ratio in order to produce large abundances of carbon species in TMC-1 (CP).

The role of noradrenaline in tuning and dopamine in switching between signals in the CNS

Abstract: Introduction- Thesis: Neuronal catecholaminergic activity modulates central nervous (CNS) function. - Specifically - Noradrenaline (NA) can exert a tuning or biassing function, whereby the signal-to-noise ratio is altered. Dopamine (DA) activity may promote switching between inputs and outputs of information to specific brain regions. Background: It has been ten years since evidence for a tuning function was advanced for NA (Segal & Bloom, 1976 a, b), and in the last five years the switching hypothesis for DA has been tentatively put forward (Cools, 1980). Review: Recent studies are reviewed to show that while catecholamine activity contributes to neural interactions in separate brain regions, that give rise to the organization of different functions, their working principles may be common between species and independent of the nucleus of origin. Behavioral examples are discussed and an attempt is made to integrate this with evidence from intracellular recording studies. It is suggested that the tuning principle in NA systems is particularly important for the formation of associations and neural plasticity (interference control), and that the switching principle of DA systems modulates the timing, time-sharing and initiation of responses (program-control).

Forests of the past: a window to future changes.

Abstract: The study of past forest change provides a necessary historical context for evaluating the outcome of human-induced climate change and biological invasions. Retrospective analyses based on fossil and genetic data greatly advance our understanding of tree colonization, adaptation, and extinction in response to past climatic change. For instance, these analyses reveal cryptic refugia near or north of continental ice sheets, leading to reevaluation of postglacial tree migration rates. Species extinctions appear to have occurred primarily during periods of high climatic variability. Transoceanic dispersal and colonization in the tropics were widespread at geological time scales, inconsistent with the idea that tropical forests are particularly resistant to biological invasions.

Solid-stabilized emulsions

Abstract: The comprehension of bulk properties of solid-stabilized emulsions (stability, compressibility, elasticity) in relation with interfacial properties has progressed. The association of oil, water and particles allows a large set of materials to be obtained, where emulsions are used either as intermediate or end products. The efficiency of some stimulus-responsive particles to stabilize or destabilize emulsions "on demand" has been experimentally evidenced.