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1.  Long-term survey of a syringe-dispensing machine needle exchange program: answering public concerns 
Syringe-dispensing machines (SDM) provide syringes at any time even to hard-to-reach injecting drug users (IDUs). They represent an important harm reduction strategy in large populated urban areas such as Paris. We analyzed the performance of one of the world's largest SDM schemes based in Paris over 12 years to understand its efficiency and its limitations, to answer public and stakeholder concerns and optimize its outputs.
Parisian syringe dispensing and exchange machines were monitored as well as their sharp disposals and associated bins over a 12-year period. Moreover, mechanical counting devices were installed on specific syringe-dispensing/exchange machines to record the characteristics of the exchange process.
Distribution and needle exchange have risen steadily by 202% for the distribution and 2,000% for syringe recovery even without a coin counterpart. However, 2 machines out of 34 generate 50% of the total activity of the scheme. It takes 14 s for an IDU to collect a syringe, while the average user takes 3.76 syringes per session 20 min apart. Interestingly, collection time stops early in the evening (19 h) for the entire night.
SDMs had an increasing distribution role during daytime as part of the harm reduction strategy in Paris with efficient recycling capacities of used syringes and a limited number of kits collected by IDU. Using counting devices to monitor Syringe Exchange Programs (SEPs) is a very helpful tool to optimize use and answer public and stakeholder concerns.
PMCID: PMC4037274  PMID: 24885902
2.  Light sheet-based fluorescence microscopy: more dimensions, more photons, and less photodamage 
HFSP Journal  2008;2(5):266-275.
Light-sheet-based fluorescence microscopy (LSFM) is a fluorescence technique that combines optical sectioning, the key capability of confocal and two-photon fluorescence microscopes with multiple-view imaging, which is used in optical tomography. In contrast to conventional wide-field and confocal fluorescence microscopes, a light sheet illuminates only the focal plane of the detection objective lens from the side. Excitation is, thus, restricted to the fluorophores in the volume near the focal plane. This provides optical sectioning and allows the use of regular cameras in the detection process. Compared to confocal fluorescence microscopy, LSFM reduces photo bleaching and photo toxicity by up to three orders of magnitude. In LSFM, the specimen is embedded in a transparent block of hydrogel and positioned relative to the stationary light sheet using precise motorized translation and rotation stages. This feature is used to image any plane in a specimen. Additionally, multiple views obtained along different angles can be combined into a single data set with an improved resolution. LSFMs are very well suited for imaging large live specimens over long periods of time. However, they also perform well with very small specimens such as single yeast cells. This perspective introduces the principles of LSFM, explains the challenges of specimen preparation, and introduces the basics of a microscopy that takes advantage of multiple views.
PMCID: PMC2639947  PMID: 19404438
3.  Transitional forms between the three domains of life and evolutionary implications 
The question as to the origin and relationship between the three domains of life is lodged in a phylogenetic impasse. The dominant paradigm is to see the three domains as separated. However, the recently characterized bacterial species have suggested continuity between the three domains. Here, we review the evidence in support of this hypothesis and evaluate the implications for and against the models of the origin of the three domains of life. The existence of intermediate steps between the three domains discards the need for fusion to explain eukaryogenesis and suggests that the last universal common ancestor was complex. We propose a scenario in which the ancestor of the current bacterial Planctomycetes, Verrucomicrobiae and Chlamydiae superphylum was related to the last archaeal and eukaryotic common ancestor, thus providing a way out of the phylogenetic impasse.
PMCID: PMC3177640  PMID: 21920985
eukaryotic origin; archaea; evolution; transition forms; platypus
4.  Taxonomic colouring of phylogenetic trees of protein sequences 
BMC Bioinformatics  2006;7:79.
Phylogenetic analyses of protein families are used to define the evolutionary relationships between homologous proteins. The interpretation of protein-sequence phylogenetic trees requires the examination of the taxonomic properties of the species associated to those sequences. However, there is no online tool to facilitate this interpretation, for example, by automatically attaching taxonomic information to the nodes of a tree, or by interactively colouring the branches of a tree according to any combination of taxonomic divisions. This is especially problematic if the tree contains on the order of hundreds of sequences, which, given the accelerated increase in the size of the protein sequence databases, is a situation that is becoming common.
We have developed PhyloView, a web based tool for colouring phylogenetic trees upon arbitrary taxonomic properties of the species represented in a protein sequence phylogenetic tree. Provided that the tree contains SwissProt, SpTrembl, or GenBank protein identifiers, the tool retrieves the taxonomic information from the corresponding database. A colour picker displays a summary of the findings and allows the user to associate colours to the leaves of the tree according to any number of taxonomic partitions. Then, the colours are propagated to the branches of the tree.
PhyloView can be used at . A tutorial, the software with documentation, and GPL licensed source code, can be accessed at the same web address.
PMCID: PMC1386715  PMID: 16503967
5.  Human Lsg1 defines a family of essential GTPases that correlates with the evolution of compartmentalization 
BMC Biology  2005;3:21.
Compartmentalization is a key feature of eukaryotic cells, but its evolution remains poorly understood. GTPases are the oldest enzymes that use nucleotides as substrates and they participate in a wide range of cellular processes. Therefore, they are ideal tools for comparative genomic studies aimed at understanding how aspects of biological complexity such as cellular compartmentalization evolved.
We describe the identification and characterization of a unique family of circularly permuted GTPases represented by the human orthologue of yeast Lsg1p. We placed the members of this family in the phylogenetic context of the YlqF Related GTPase (YRG) family, which are present in Eukarya, Bacteria and Archea and include the stem cell regulator Nucleostemin. To extend the computational analysis, we showed that hLsg1 is an essential GTPase predominantly located in the endoplasmic reticulum and, in some cells, in Cajal bodies in the nucleus. Comparison of localization and siRNA datasets suggests that all members of the family are essential GTPases that have increased in number as the compartmentalization of the eukaryotic cell and the ribosome biogenesis pathway have evolved.
We propose a scenario, consistent with our data, for the evolution of this family: cytoplasmic components were first acquired, followed by nuclear components, and finally the mitochondrial and chloroplast elements were derived from different bacterial species, in parallel with the formation of the nucleolus and the specialization of nuclear components.
PMCID: PMC1262696  PMID: 16209721
6.  p57Kip2 Stabilizes the MyoD Protein by Inhibiting Cyclin E-Cdk2 Kinase Activity in Growing Myoblasts 
Molecular and Cellular Biology  1999;19(11):7621-7629.
We show that expression of p57Kip2, a potent tight-binding inhibitor of several G1 cyclin–cyclin-dependent kinase (Cdk) complexes, increases markedly during C2C12 myoblast differentiation. We examined the effect of p57Kip2 on the activity of the transcription factor MyoD. In transient transfection assays, transcriptional transactivation of the mouse muscle creatine kinase promoter by MyoD was enhanced by the Cdk inhibitors. In addition, p57Kip2, p21Cip1, and p27Kip1 but not p16Ink4a induced an increased level of MyoD protein, and we show that MyoD, an unstable nuclear protein, was stabilized by p57Kip2. Forced expression of p57Kip2 correlated with hypophosphorylation of MyoD in C2C12 myoblasts. A dominant-negative Cdk2 mutant arrested cells at the G1 phase transition and induced hypophosphorylation of MyoD. Furthermore, phosphorylation of MyoD by purified cyclin E-Cdk2 complexes was inhibited by p57Kip2. In addition, the NH2 domain of p57Kip2 necessary for inhibition of cyclin E-Cdk2 activity was sufficient to inhibit MyoD phosphorylation and to stabilize it, leading to its accumulation in proliferative myoblasts. Taken together, our data suggest that repression of cyclin E-Cdk2-mediated phosphorylation of MyoD by p57Kip2 could play an important role in the accumulation of MyoD at the onset of myoblast differentiation.
PMCID: PMC84790  PMID: 10523650

Results 1-6 (6)