Farm diversity, classification schemes and multifunctionality.

Diversity is not only intrinsic to agriculture; it can be considered also as one of its main assets as it provides a wide range of responses that can help to face uncertain futures. The ongoing encounter between changing spatial and temporal frameworks and a set of diverse farming strategies is leading to the emergence of an ongoing flow of development models that could materialize in a wide range of farming practices, contrasting enterprise models, changing relations between rural households and agricultural holdings, and differentiated patterns that link farming and farming families to the wider context in which they are embedded. The many-sided diversity encountered in agriculture is not only the outcome of the agency and polyvalence of the actors involved; their agency and polyvalence are in turn inspired and strengthened by the material and symbolic diversity, which contributes to a further unfolding of diversity. A proper understanding of the range, dimensions, significance and causes of diversity has been, over the centuries, a main concern--first for what is now known as classical agronomy, and later on in agrarian sciences. Yet the classification schemes, developed and used for such an understanding, have increasingly become an Achilles heel as each of them relies on specific assumptions that will bring out particular features of the overall farm diversity and will result in different perspectives of what agriculture is and how it fits into societal projects. Consequently, they are at the core of many debates and struggles, not only within agrarian sciences but increasingly on a wider societal level. The growing recognition of multifunctionality in agriculture, especially in the context of the changing EU policy, strengthens the relevance and importance of this debate. In this new context, we discuss advantages and limits of different classification principles by comparing two methodologies which have been extensively used in France and The Netherlands.

Molecular mechanisms in clathrin-mediated membrane budding revealed through subcellular proteomics.

Subcellular proteomics is a powerful new approach that combines subcellular fractionation and MS (mass spectrometry) to identify the protein complement of cellular compartments. The approach has been applied to isolated organelles and major suborganellar structures and each study has identified known proteins not previously understood to associate with the compartment and novel proteins that had been described only as predicted open-reading frames from genome sequencing data. We have utilized subcellular proteomics to analyse the protein components of CCVs (clathrin-coated vesicles) isolated from adult brain. Accounting for identified fragmented peptides allows for a quantitative assessment of protein complexes associated with CCVs, and the identification of many of the known components of post-fusion synaptic vesicles demonstrates that a main function for brain CCVs is to recycle synaptic vesicles. In addition, we have identified a number of novel proteins that participate in CCV formation and function at the trans-Golgi network and the plasma membrane. Characterization of two of these proteins, NECAP1 and NECAP2, has led to the identification of a new consensus motif that mediates protein interactions with the clathrin adaptor protein 2. These studies highlight the ability of proteomics to reveal new insights into the mechanisms and functional roles of subcellular compartments.

A multi-centre study of Osseotite implants supporting mandibular restorations: a 3-year report.

This multi-centre study evaluated the performance of the Osseotite implant in the mandibular arch. Osseotite implants (n = 688) were placed in 172 patients; 43.5% were placed in the anterior mandible and 66.5% in the posterior mandible. Fifteen per cent of the implants were placed in soft bone, 56.9% in normal bone and 28.1% in dense bone. During placement, 49.9% of the implants were identified as having a tight fit, 48.6% a firm fit and 1.5% a loose fit. About one-third of the implants (32.4%) were short (10 mm in length or less). After 36 months, only 5 implants had been lost, for a cumulative survival rate of 99.3%. The 3-year results of this study indicate a high degree of predictability with placement of Osseotite implants in the mandibular arch.

The myotubularin family: from genetic disease to phosphoinositide metabolism.

The myotubularin-related genes define a large family of eukaryotic proteins, most of them initially characterized by the presence of a ten-amino acid consensus sequence related to the active sites of tyrosine phosphatases, dual-specificity protein phosphatases and the lipid phosphatase PTEN. Myotubularin (hMTM1), the founder member, is mutated in myotubular myopathy, and a close homolog (hMTMR2) was recently found mutated in a recessive form of Charcot-Marie-Tooth neuropathy. Although myotubularin was thought to be a dual-specificity protein phosphatase, recent results indicate that it is primarily a lipid phosphatase, acting on phosphatidylinositol 3-monophosphate, and might be involved in the regulation of phosphatidylinositol 3-kinase (PI 3-kinase) pathway and membrane trafficking.

The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy.

Disorganization of the neurofilament network is a prominent feature of several neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), infantile spinal muscular atrophy and axonal Charcot-Marie-Tooth disease. Giant axonal neuropathy (GAN, MIM 256850), a severe, autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system, is characterized by neurofilament accumulation, leading to segmental distension of the axons. GAN corresponds to a generalized disorganization of the cytoskeletal intermediate filaments (IFs), to which neurofilaments belong, as abnormal aggregation of multiple tissue-specific IFs has been reported: vimentin in endothelial cells, Schwann cells and cultured skin fibroblasts, and glial fibrillary acidic protein (GFAP) in astrocytes. Keratin IFs also seem to be alterated, as most patients present characteristic curly or kinky hairs. We report here identification of the gene GAN, which encodes a novel, ubiquitously expressed protein we have named gigaxonin. We found one frameshift, four nonsense and nine missense mutations in GAN of GAN patients. Gigaxonin is composed of an amino-terminal BTB (for Broad-Complex, Tramtrack and Bric a brac) domain followed by a six kelch repeats, which are predicted to adopt a beta-propeller shape. Distantly related proteins sharing a similar domain organization have various functions associated with the cytoskeleton, predicting that gigaxonin is a novel and distinct cytoskeletal protein that may represent a general pathological target for other neurodegenerative disorders with alterations in the neurofilament network.

Stochastic resonance at phase noise in signal transmission

A model is developed for a periodic signal corrupted by an arbitrarily distributed phase noise and transmitted by an arbitrary memoryless system. The model establishes a new form of the phenomenon of stochastic resonance, whereby signal transmission can be enhanced by addition of noise. This is revealed by the standard signal-to-noise ratio of stochastic resonance, which here receives an explicit theoretical expression, and which is shown improvable via noise addition. This model is the first to propose a theory of stochastic resonance with phase noise. It represents a unique framework for further investigations on stochastic resonance and its applications.

Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway.

Myotubular myopathy (MTM1) is an X-linked disease, characterized by severe neonatal hypotonia and generalized muscle weakness, with pathological features suggesting an impairment in maturation of muscle fibres. The MTM1 gene encodes a protein (myotubularin) with a phosphotyrosine phosphatase consensus. It defines a family of at least nine genes in man, including the antiphosphatase hMTMR5/Sbf1 and hMTMR2, recently found mutated in a recessive form of Charcot-Marie-Tooth disease. Myotubularin shows a dual specificity protein phosphatase activity in vitro. We have performed an in vivo test of tyrosine phosphatase activity in Schizosaccharomyces pombe, indicating that myotubularin does not have a broad specificity tyrosine phosphatase activity. Expression of active human myotubularin inhibited growth of S.pombe and induced a vacuolar phenotype similar to that of mutants of the vacuolar protein sorting (VPS) pathway and notably of mutants of VPS34, a phosphatidylinositol 3-kinase (PI3K). In S.pombe cells deleted for the endogenous MTM homologous gene, expression of human myotubularin decreased the level of phosphatidylinositol 3-phosphate (PI3P). We have created a substrate trap mutant which shows relocalization to plasma membrane projections (spikes) in HeLa cells and was inactive in the S.pombe assay. This mutant, but not the wild-type or a phosphatase site mutant, was able to immunoprecipitate a VPS34 kinase activity. Wild-type myotubularin was also able to directly dephosphorylate PI3P and PI4P in vitro. Myotubularin may thus decrease PI3P levels by down-regulating PI3K activity and by directly degrading PI3P.

MTM1 mutations in X-linked myotubular myopathy.

X-linked myotubular myopathy (XLMTM; MIM# 310400) is a severe congenital muscle disorder caused by mutations in the MTM1 gene. This gene encodes a dual-specificity phosphatase named myotubularin, defining a large gene family highly conserved through evolution (which includes the putative anti-phosphatase Sbf1/hMTMR5). We report 29 mutations in novel cases, including 16 mutations not described before. To date, 198 mutations have been identified in unrelated families, accounting for 133 different disease-associated mutations which are widespread throughout the gene. Most point mutations are truncating, but 26% (35/133) are missense mutations affecting residues conserved in the Drosophila ortholog and in the homologous MTMR1 gene. Three recurrent mutations affect 17% of the patients, and a total of 21 different mutations were found in several independent families. The frequency of female carriers appears higher than expected (only 17% are de novo mutations). While most truncating mutations cause the severe and early lethal phenotype, some missense mutations are associated with milder forms and prolonged survival (up to 54 years).

[Physician-patient relations in family medicine]. / La relation médecin-patient en médecine familiale.

PROBLEM ADDRESSED: In addition to clinical instruction, residents need "people" skills that will enable them to deal with all sorts of patients in difficult clinical situations. We planned a series of 12 seminars to teach these skills to first-year residents. OBJECTIVES OF PROGRAM: To ask relevant questions typical of the patient-centred approach; with empathy and respect, to encourage patients to express their emotions; to become more aware of one's own emotions and reactions in one's work as a physician; to negotiate with patients, taking into account both the patient's agenda and one's own. MAIN COMPONENTS OF PROGRAM: Clinical problems drawn from a list of situations likely to involve difficult contact with patients were used to achieve program objectives. Various teaching methods (discussion, brief presentation, practical demonstration, role play) were used during the four stages of skills development: information, demonstration, practice, and feedback. Various tools were used to test the program. CONCLUSION: Proper planning requires ongoing exploration of objectives, content, teaching methods, and evaluation. This discussion of the teaching principles applied in planning our seminars might inspire others to develop similar programs.

Genomic organization of the MTM1 gene implicated in X-linked myotubular myopathy.

X-linked recessive myotubular myopathy (XLMTM) is a very severe congenital muscular disease characterised by an impaired maturation of muscle fibres, and caused by defects in the MTM1 gene. This gene defines a new family of putative tyrosine phosphatases conserved through evolution. We have determined intronic flanking sequences for all the 15 exons to facilitate the detection of mutations in patients and genetic counselling. We characterised a new polymorphic marker in the immediate vicinity of the gene, which might prove useful for linkage analysis. Sequencing of the TATA-less predicted promoter provides the basis for transcriptional regulatory studies.

Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human.

X-linked myotubular myopathy (XLMTM) is a severe congenital muscle disorder due to mutations in the MTM1 gene. The corresponding protein, myotubularin, contains the consensus active site of tyrosine phosphatases (PTP) but otherwise shows no homology to other phosphatases. Myotubularin is able to hydrolyze a synthetic analogue of tyrosine phosphate, in a reaction inhibited by orthovanadate, and was recently shown to act on both phosphotyrosine and phosphoserine. This gene is conserved down to yeast and strong homologies were found with human ESTs, thus defining a new dual specificity phosphatase (DSP) family. We report the presence of novel members of the MTM gene family in Schizosaccharomyces pombe, Caenorhabditis elegans, zebrafish, Drosophila, mouse and man. This represents the largest family of DSPs described to date. Eight MTM-related genes were found in the human genome and we determined the chromosomal localization and expression pattern for most of them. A subclass of the myotubularin homologues lacks a functional PTP active site. Missense mutations found in XLMTM patients affect residues conserved in a Drosophila homologue. Comparison of the various genes allowed construction of a phylogenetic tree and reveals conserved residues which may be essential for function. These genes may be good candidates for other genetic diseases.

Transcriptional activity of pannier is regulated negatively by heterodimerization of the GATA DNA-binding domain with a cofactor encoded by the u-shaped gene of Drosophila.

The genes pannier (pnr) and u-shaped (ush) are required for the regulation of achaete-scute during establishment of the bristle pattern in Drosophila. pnr encodes a protein belonging to the GATA family of transcription factors, whereas ush encodes a novel zinc finger protein. Genetic interactions between dominant pnr mutants bearing lesions situated in the amino-terminal zinc finger of the GATA domain and ush mutants have been described. We show here that both wild-type Pannier and the dominant mutant form activate transcription from the heterologous alpha globin promoter when transfected into chicken embryonic fibroblasts. Furthermore, Pnr and Ush are found to heterodimerize through the amino-terminal zinc finger of Pnr and when associated with Ush, the transcriptional activity of Pnr is lost. In contrast, the mutant pnr protein with lesions in this finger associates only poorly with Ush and activates transcription even when cotransfected with Ush. These interactions have been investigated in vivo by overexpression of the mutant and wild-type proteins. The results suggest an antagonistic effect of Ush on Pnr function and reveal a new mode of regulation of GATA factors during development.

Signal transcoding by nonlinear sensory neurons: information-entropy maximization, optimal transfer function, and anti-Hebbian adaptation.

A principle of information-entropy maximization is introduced in order to characterize the optimal representation of an arbitrarily varying quantity by a neural output confined to a finite interval. We then study the conditions under which a neuron can effectively fulfil the requirements imposed by this information-theoretic optimal principle. We show that this can be achieved with the natural properties available to the neuron. Specifically, we first deduce that neural (monotonically increasing and saturating) nonlinearities are potentially efficient for achieving the entropy maximization, for any given input signal. Secondly, we derive simple laws which adaptively adjust modifiable parameters of a neuron toward maximum entropy. Remarkably, the adaptation laws that realize entropy maximization are found to belong to the class of anti-Hebbian laws (a class having experimental groundings), with a special, yet simple, nonlinear form. The present results highlight the usefulness of general information-theoretic principles in contributing to the understanding of neural systems and their remarkable performances for information processing.

Synapse models for neural networks: from ion channel kinetics to multiplicative coefficient wij.

This paper relates different levels at which the modeling of synaptic transmission can be grounded in neural networks: the level of ion channel kinetics, the level of synaptic conductance dynamics, and the level of a scalar synaptic coefficient. The important assumptions to reduce a synapse model from one level to the next are explicitly exhibited. This coherent progression provides control on what is discarded and what is retained in the modeling process, and is useful to appreciate the significance and limitations of the resulting neural networks. This methodic simplification terminates with a scalar synaptic efficacy as it is very often used in neural networks, but here its conditions of validity are explicitly displayed. This scalar synapse also comes with an expression that directly relates it to basic quantities of synaptic functioning, and it can be endowed with meaningful physical units and realistic numerical values. In addition, it is shown that the scalar synapse does not receive the same expression in neural networks operating with spikes or with firing rates. These coherent modeling elements can help to improve, adjust, and refine the investigation of neural systems and their remarkable collective properties for information processing.

Information processing in neural networks by means of controlled dynamic regimes.

This paper is concerned with the modeling of neural systems regarded as information processing entities. I investigate the various dynamic regimes that are accessible in neural networks considered as nonlinear adaptive dynamic systems. The possibilities of obtaining steady, oscillatory or chaotic regimes are illustrated with different neural network models. Some aspects of the dependence of the dynamic regimes upon the synaptic couplings are examined. I emphasize the role that the various regimes may play to support information processing abilities. I present an example where controlled transient evolutions in a neural network, are used to model the regulation of motor activities by the cerebellar cortex.

Actions of isoproterenol in frog proximal tubules.

In the present work, we compared biochemical and electrophysiological actions of isoproterenol on frog proximal tubular cells by using tubule suspensions and giant entities obtained by cell fusion. Isoproterenol (ISO) dose-dependently stimulated cAMP production in tubule suspension and depolarized the "giant cell" membrane. Both effects were triggered by beta receptor occupancy, but strongly differed in their concentration-dependency, since depolarization occurred with an ISO concentration as low as 10(-12) mol/l whereas cAMP accumulation could be seen only with more than 10(-8) mol/l ISO. ISO-induced membrane depolarization was mimicked by forskolin which directly stimulated the catalytic subunit of adenylyl cyclase. In both isoproterenol- and forskolin-stimulated giant cells, membrane depolarization was accompanied by a decrease in membrane conductance, and both effects were inhibited by tetraethylammonium (TEA) and 4-aminopyridine (4-AP). On the other hand, ISO- and forskolin-induced cAMP production were not affected by TEA. The present data thus show that isoproterenol produces two independent effects in frog proximal tubule: it depolarizes the cell membrane by blocking a K+ conductance and activates adenylyl cyclase.

[Paresthesia: incidence following the extraction of 455 mandibular impacted third molars]. / Paresthésie: résultat suite à l'extraction de 455 3e molaires incluses mandibulaires.

The incidence of paresthesia following the extraction of 455 mandibular impacted wisdom teeth is evaluated. No permanent paresthesia to the third branch of the trigeminal nerve is noted and no lingual paresthesia. A temporary dyesthesia of the inferior dental nerve is noted for three patients, with a complete return of integrity after six weeks. We have noted an incidence of temporary paresthesia of 3/455 (0.66 per cent) per tooth.

[Evaluation of maxillofacial injuries in a Quebec hospital]. / Evaluation de la traumatologie maxillo-faciale dans un hôpital de Québec.

This article describes a study done on patients with maxillofacial traumas at the Hôpital Christ-Roi in Quebec City. The patients were selected from those treated during the first three years after the Oral and Maxillofacial Surgery Department was set up. The hospital has 200 beds. In this study, the different epidemiological data and traumatic type are examined. Patient treatment is also discussed. The data analysis is supported by existing literature on the subject.