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A new in-silico method for determination of helical transmembrane domains based on the PepLook scan: application to IL-2Rβ and IL-2Rγc receptor chains
Yan Charlois, Laurence Lins, Robert Brasseur
BMC Structural Biology , 2011, DOI: 10.1186/1472-6807-11-26
Abstract: Using sequences whose NMR-structures are already known (GpA, EphA1 and Erb2-HER2), we first determined that the hydrophobic to hydrophilic accessible surface area ratio (ASAr) was the best criterion for delimiting the TMD sequence. The length of the helical structure and the Impala method further supported the determination of the TMD limits. This method was applied to the IL-2Rβ and IL-2Rγ TMD sequences of Homo sapiens, Rattus norvegicus, Mus musculus and Bos taurus.We succeeded in reducing the variation in the TMD limits to only 2 residues and in gaining structural information.IL-2 and IL-15 are two structurally close hematopoietic cytokines, both presenting a functional redundancy and both involved in immunology and inflammatory diseases. IL-2 was implicated in the first metastatic melanoma immunotherapy [1] and is used in adoptive immunotherapy with tumor infiltrating lymphocytes (TILs). Most treatments require high doses of IL-2 [2,3] and induce a systemic toxicity similar to GM-CSF (Granulocyte Macrophage-Colony Stimulating Factor) treatments [4]. These secondary effects restrict the therapy and have led to investigations into other forms of treatment, such as the promising IL-15 therapy.Transduction receptor chains IL-2Rβ and IL-2Rγc (class I hematopoietic receptors) form an intermediate-affinity complex capable of binding IL-2 and IL-15. Whereas the IL-2Rβ chain is restricted to dimeric receptor for IL-15 and IL-2 [5] or to specific trimeric receptors (IL-2Rβ/IL-2Rγ/IL-2Rα and IL-2Rβ/IL-2Rγ/IL-15Rα), the IL-2Rγc chain is involved in γc-family receptors, that is to say the IL-2, IL-4, IL-7, IL-9, IL-15, IL-21 and GM-CSF receptors[6]. γc-deficit is implicated in immunodeficiency, such as X-linked Severe Combined ImmunoDeficiency (X-SCID)[7].Fluorescence resonance energy transfer (FRET) studies suggest that IL-2Rα, IL-7Rα and IL-15Rα chains are co-localized[8] with IL-2Rβ and γc chains within lipid rafts[9]. IL-2Rα and IL-15Rα chains also appear to co-localize
C-Terminal Mutants of Apolipoprotein L-I Efficiently Kill Both Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense
Laurence Lecordier,Benoit Vanhollebeke,Philippe Poelvoorde,Patricia Tebabi,Fran?oise Paturiaux-Hanocq,Fabienne Andris,Laurence Lins,Etienne Pays
PLOS Pathogens , 2009, DOI: 10.1371/journal.ppat.1000685
Abstract: Apolipoprotein L-I (apoL1) is a human-specific serum protein that kills Trypanosoma brucei through ionic pore formation in endosomal membranes of the parasite. The T. brucei subspecies rhodesiense and gambiense resist this lytic activity and can infect humans, causing sleeping sickness. In the case of T. b. rhodesiense, resistance to lysis involves interaction of the Serum Resistance-Associated (SRA) protein with the C-terminal helix of apoL1. We undertook a mutational and deletional analysis of the C-terminal helix of apoL1 to investigate the linkage between interaction with SRA and lytic potential for different T. brucei subspecies. We confirm that the C-terminal helix is the SRA-interacting domain. Although in E. coli this domain was dispensable for ionic pore-forming activity, its interaction with SRA resulted in inhibition of this activity. Different mutations affecting the C-terminal helix reduced the interaction of apoL1 with SRA. However, mutants in the L370-L392 leucine zipper also lost in vitro trypanolytic activity. Truncating and/or mutating the C-terminal sequence of human apoL1 like that of apoL1-like sequences of Papio anubis resulted in both loss of interaction with SRA and acquired ability to efficiently kill human serum-resistant T. b. rhodesiense parasites, in vitro as well as in transgenic mice. These findings demonstrate that SRA interaction with the C-terminal helix of apoL1 inhibits its pore-forming activity and determines resistance of T. b. rhodesiense to human serum. In addition, they provide a possible explanation for the ability of Papio serum to kill T. b. rhodesiense, and offer a perspective to generate transgenic cattle resistant to both T. b. brucei and T. b. rhodesiense.
Distantly related lipocalins share two conserved clusters of hydrophobic residues: use in homology modeling
Benoit Adam, Benoit Charloteaux, Jerome Beaufays, Luc Vanhamme, Edmond Godfroid, Robert Brasseur, Laurence Lins
BMC Structural Biology , 2008, DOI: 10.1186/1472-6807-8-1
Abstract: The pairwise sequence identity is low among this family, often below 30%, despite a well conserved tertiary structure. Under the 30% identity threshold, alignment methods do not correctly assign and align proteins. The only safe way to assign a sequence to that family is by experimental determination. However, these procedures are long and costly and cannot always be applied. A way to circumvent the experimental approach is sequence and structure analyze. To further help in that task, the residues implicated in the stabilisation of the lipocalin fold were determined. This was done by analyzing the conserved interactions for ten lipocalins having a maximum pairwise identity of 28% and various functions.It was determined that two hydrophobic clusters of residues are conserved by analysing the ten lipocalin structures and sequences. One cluster is internal to the barrel, involving all strands and the 310 helix. The other is external, involving four strands and the helix lying parallel to the barrel surface. These clusters are also present in RaHBP2, a unusual "outlier" lipocalin from tick Rhipicephalus appendiculatus. This information was used to assess assignment of LIR2 a protein from Ixodes ricinus and to build a 3D model that helps to predict function. FTIR data support the lipocalin fold for this protein.By sequence and structural analyzes, two conserved clusters of hydrophobic residues in interactions have been identified in lipocalins. Since the residues implicated are not conserved for function, they should provide the minimal subset necessary to confer the lipocalin fold. This information has been used to assign LIR2 to lipocalins and to investigate its structure/function relationship. This study could be applied to other protein families with low pairwise similarity, such as the structurally related fatty acid binding proteins or avidins.Lipocalins are small secreted proteins (160–200 residues), typically structured in a 8 strands up and down β-barrel. A 310
SAHBNET, an Accessible Surface-Based Elastic Network: An Application to Membrane Protein
Nicolas Dony,Jean Marc Crowet,Bernard Joris,Robert Brasseur,Laurence Lins
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms140611510
Abstract: Molecular Dynamics is a method of choice for membrane simulations and the rising of coarse-grained forcefields has opened the way to longer simulations with reduced calculations times. Here, we present an elastic network, SAHBNET (Surface Accessibility Hydrogen-Bonds elastic NETwork), that will maintain the structure of soluble or membrane proteins based on the hydrogen bonds present in the atomistic structure and the proximity between buried residues. This network is applied on the coarse-grained beads defined by the MARTINI model, and was designed to be more physics-based than a simple elastic network. The SAHBNET model is evaluated against atomistic simulations, and compared with ELNEDYN models. The SAHBNET is then used to simulate two membrane proteins inserted in complex lipid bilayers. These bilayers are formed by self-assembly and the use of a modified version of the GROMACS tool genbox (which is accessible through the gcgs.gembloux.ulg.ac.be website). The results show that SAHBNET keeps the structure close to the atomistic one and is successfully used for the simulation of membrane proteins.
Continuous Maps on Digital Simple Closed Curves  [PDF]
Laurence Boxer
Applied Mathematics (AM) , 2010, DOI: 10.4236/am.2010.15050
Abstract: We give digital analogues of classical theorems of topology for continuous functions defined on spheres, for digital simple closed curves. In particular, we show the following. ? A digital simple closed curve of more than 4 points is not contractible, i.e., its identity map is not nullhomotopic in . ? Let and be digital simple closed curves, each symmetric with respect to the origin, such that (where is the number of points in ). Let be a digitally continuous antipodal map. Then is not nullho- motopic in . ? Let be a digital simple closed curve that is symmetric with respect to the origin. Let be a digitally continuous map. Then there is a pair of antipodes such that .
Ixodes ricinus Tick Lipocalins: Identification, Cloning, Phylogenetic Analysis and Biochemical Characterization
Jér?me Beaufays, Beno?t Adam, Yves Decrem, Pierre-Paul Prév?t, Sébastien Santini, Robert Brasseur, Michel Brossard, Laurence Lins, Luc Vanhamme, Edmond Godfroid
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003941
Abstract: Background During their blood meal, ticks secrete a wide variety of proteins that interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. Methodology/Principal Findings Screening a cDNA library in association with RT-PCR and RACE methodologies allowed us to identify 14 new lipocalin genes in the salivary glands of the Ixodes ricinus hard tick. A computational in-depth structural analysis confirmed that LIRs belong to the lipocalin family. These proteins were called LIR for “Lipocalin from I. ricinus” and numbered from 1 to 14 (LIR1 to LIR14). According to their percentage identity/similarity, LIR proteins may be assigned to 6 distinct phylogenetic groups. The mature proteins have calculated pM and pI varying from 21.8 kDa to 37.2 kDa and from 4.45 to 9.57 respectively. In a western blot analysis, all recombinant LIRs appeared as a series of thin bands at 50–70 kDa, suggesting extensive glycosylation, which was experimentally confirmed by treatment with N-glycosidase F. In addition, the in vivo expression analysis of LIRs in I. ricinus, examined by RT-PCR, showed homogeneous expression profiles for certain phylogenetic groups and relatively heterogeneous profiles for other groups. Finally, we demonstrated that LIR6 codes for a protein that specifically binds leukotriene B4. Conclusions/Significance This work confirms that, regarding their biochemical properties, expression profile, and sequence signature, lipocalins in Ixodes hard tick genus, and more specifically in the Ixodes ricinus species, are segregated into distinct phylogenetic groups suggesting potential distinct function. This was particularly demonstrated by the ability of LIR6 to scavenge leukotriene B4. The other LIRs did not bind any of the ligands tested, such as 5-hydroxytryptamine, ADP, norepinephrine, platelet activating factor, prostaglandins D2 and E2, and finally leukotrienes B4 and C4.
Modelling Visible Foliar Injury Effects on Canopy Photosynthesis and Potential Crop Yield Losses Resulting from Fluoride Exposure  [PDF]
David Doley, Laurence Rossato
Journal of Environmental Protection (JEP) , 2012, DOI: 10.4236/jep.2012.39113
Abstract: Crop production models are highly developed to account for different nitrogen, light, temperature and water availability conditions and, in some species, disease or air pollutant effects. There is very limited knowledge on responses of many tropical crops, such as oil palm (Elaeis guineensis), to air pollutants although predictions of these effects are essential for industrial planning in several countries. In the absence of limitations due to water supply, the effects of leaf area loss due to necrosis and chlorosis are much more important to canopy photosynthesis than are changes in the physiological attributes that influence the efficiency of light use. Therefore, potential losses of crop production due to air pollutants such as fluoride can be inferred usefully from the extent of visible injury to foliage that may be associated with different levels of pollutant exposure.
The Cross-Sectional Risk Premium of Decomposed Market Volatility in UK Stock Market  [PDF]
Yan Yang, Laurence Copeland
Open Journal of Social Sciences (JSS) , 2014, DOI: 10.4236/jss.2014.27006
Abstract:

We decompose UK market volatility into short- and long-run components using EGARCH component model and examine the cross-sectional prices of the two components. Our empirical results suggest that these two components are significantly priced in the cross-section and the negative risk premia are consistent with the existing literature. The Fama-French three-factor model is improved by the inclusion of the two volatility components. However, our ICAPM model using market excess return and the decomposed volatility components as state variables compares inferiorly to the traditional three-factor model.

Mangue's school ou por uma pedagogia rizomática
Lins, Daniel;
Educa??o & Sociedade , 2005, DOI: 10.1590/S0101-73302005000400008
Abstract: a rizomatic pedagogy whose main axiom is a nomadic or itinerant science and could act as a counterpoint to the royal science is embedded into the ethics and aesthetics of existence, into immanence. as life, thus. it rises out as pure resistance, as pure becoming. here is one of the axes of a school following a rizomatic dynamic: resisting, contaminating, and vitalizing what has become established. in a nomadic pedagogy knowledge turns to be flavors because it allows intelligence to access another world. knowledge as flavor does not change the finite reality of human beings, but attributes to the inexplicable an artistic and creative reality.
Um passaporte húngaro, de Sandra Kogut: cinema polí-tico e intimidade
Consuelo Lins
Galáxia , 2008,
Abstract: Um passaporte húngaro, da cineasta e videoartista brasileira Sandra Kogut, é um filme que utiliza diferentes tecnologias para construir uma narrativa em que a diretora está fortemente presente. Trata-se de um filme em que a esfera da vida privada está em primeiro plano, indo ao encontro de uma realidade midiática que esvazia cada vez mais a esfera pública em favor da intimidade. Contudo, diferentemente do que assistimos na televis o, o filme articula de maneira singular experiências pessoais com a história e a memória coletivas, imprimindo deslocamentos importantes tanto em rela o í produ o midiática quanto ao documentário clássico polí-tico e aos filmes autobiográficos mais correntes. Palavras-chave cinema, documentário, intimidade, memória, polí-tico Abstract A Hungarian Passport, a film by Sandra Kogut, a Brazilian film-maker and video artist, makes use of different technologies in order to construct a narrative in which the director is strongly present. The private life circle is quite evident in the film, conforming to a media reality that progressively does without a public context in favour of the intimate. However, different from what we see on television, this film, in such special manner, articulates personal experiences with collective history and memory, imprinting important displacements both in relation to the mediatic production and the classical political documentary as well as the more common autobiographical films. Key words cinema, documentary, intimacy, memory, politics
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