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1.
Paulo FP Pimenta Alessandra S Orfano Ana C Bahia Ana PM Duarte Claudia M Ríos-Velásquez Fabrício F Melo Felipe AC Pessoa Giselle A Oliveira Keillen MM Campos Luis Martínez Villegas Nilton Barnabé Rodrigues Rafael Nacif-Pimenta Rejane C Sim?es Wuelton M Monteiro Rogerio Amino Yara M Traub-Cseko José BP Lima Maria GV Barbosa Marcus VG Lacerda Wanderli P Tadei Nágila FC Secundino 《Memórias do Instituto Oswaldo Cruz》2015,110(1):23-47
In the Americas, areas with a high risk of malaria transmission are mainly located in
the Amazon Forest, which extends across nine countries. One keystone step to
understanding the Plasmodium life cycle in Anopheles species from the Amazon Region
is to obtain experimentally infected mosquito vectors. Several attempts to colonise
Ano- pheles species have been conducted, but with only short-lived success or no
success at all. In this review, we review the literature on malaria transmission from
the perspective of its Amazon vectors. Currently, it is possible to develop
experimental Plasmodium vivax infection of the colonised and field-captured vectors
in laboratories located close to Amazonian endemic areas. We are also reviewing
studies related to the immune response to P. vivax infection of Anopheles aquasalis,
a coastal mosquito species. Finally, we discuss the importance of the modulation of
Plasmodium infection by the vector microbiota and also consider the anopheline
genomes. The establishment of experimental mosquito infections with Plasmodium
falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide
interesting models for studying malaria in the Amazonian scenario is important.
Understanding the molecular mechanisms involved in the development of the parasites
in New World vectors is crucial in order to better determine the interaction process
and vectorial competence. 相似文献
2.
Van Goethem S Van der Veken P Dubois V Soroka A Lambeir AM Chen X Haemers A Scharpé S De Meester I Augustyns K 《Bioorganic & medicinal chemistry letters》2008,18(14):4159-4162
To obtain selective and potent inhibitors of dipeptidyl peptidases 8 and 9, we synthesized a series of substituted isoindolines as modified analogs of allo-Ile-isoindoline, the reference DPP8/9 inhibitor. The influence of phenyl substituents and different P2 residues on the inhibitors’ affinity toward other DPPs and more specifically, their potential to discriminate between DPP8 and DPP9 will be discussed. Within this series compound 8j was shown to be a potent and selective inhibitor of DPP8/9 with low activity toward DPP II. 相似文献
3.
Guiet R Van Goethem E Cougoule C Balor S Valette A Al Saati T Lowell CA Le Cabec V Maridonneau-Parini I 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(7):3806-3814
Tumor-associated macrophages are known to amplify the malignant potential of tumors by secreting a variety of cytokines and proteases involved in tumor cell invasion and metastasis, but how these macrophages infiltrate tumors and whether the macrophage migration process facilitates tumor cell invasion remain poorly documented. To address these questions, we used cell spheroids of breast carcinoma SUM159PT cells as an in vitro model of solid tumors. We found that macrophages used both the mesenchymal mode requiring matrix metalloproteinases (MMPs) and the amoeboid migration mode to infiltrate tumor cell spheroids. Whereas individual SUM159PT cells invaded Matrigel using an MMP-dependent mesenchymal mode, when they were grown as spheroids, tumor cells were unable to invade the Matrigel surrounding spheroids. When spheroids were infiltrated or in contact with macrophages, tumor cell invasiveness was restored. It was dependent on the capacity of macrophages to remodel the matrix and migrate in an MMP-independent mesenchymal mode. This effect of macrophages was much reduced when spheroids were infiltrated by Matrigel migration-defective Hck(-/-) macrophages. In the presence of macrophages, SUM159PT migrated into Matrigel in the proximity of macrophages and switched from an MMP-dependent mesenchymal migration to an amoeboid mode resistant to protease inhibitors.Thus, in addition to the well-described paracrine loop between macrophages and tumor cells, macrophages can also contribute to the invasiveness of tumor cells by remodeling the extracellular matrix and by opening the way to exit the tumor and colonize the surrounding tissues in an MMP-dispensable manner. 相似文献
4.
Moore MM Honma M Clements J Awogi T Douglas GR van Goethem F Gollapudi B Kimura A Muster W O'Donovan M Schoeny R Wakuri S 《Mutation research》2011,723(2):84-86
The Mouse Lymphoma Expert Workgroup of the International Workshop for Genotoxicity Tests (IWGT) met in Basel, Switzerland in August of 2009. The Workgroup (WG) was tasked with discussing the appropriate top concentration for non-pharmaceuticals that would be required for the conduct of the mouse lymphoma assay (MLA) when sufficient cytotoxicity [to between 10 and 20% relative total growth (RTG)] has not been attained. The WG approached this task by (1) enumerating the various regulatory decisions/use for MLA data, (2) discussing the appropriate assays to which MLA data and assay performance should be compared and (3) discussing all the proposals put forth concerning the top concentration for non-pharmaceuticals. In addition, one of the members presented a summary of a re-evaluation of the National Toxicology Program MLA data using the IWGT harmonized guidance that was underway as a separate (non IWGT) activity, being conducted by two members of the Expert WG. The WG was asked to vote on each of the various proposals for top concentration for when cytotoxicity is not concentration limiting. While there was general agreement that the top concentration for non-pharmaceuticals should be re-evaluated and likely lowered from the current recommended levels, there was no agreement on a specific new recommendation. 相似文献
5.
Structure based virtual screening of ligands to identify cysteinyl leukotriene receptor 1 antagonist
Srinivas Bandaru Vijaya Kumar Marri Priyadarshani Kasera Purnima Kovuri Amandeep Girdhar Deepti Raj Mittal Sabeen Ikram Ravi GV Anuraj Nayarisseri 《Bioinformation》2014,10(10):652-657
Montelukast and Zafirlukast are known leukotriene receptor antagonists prescribed in asthma treatment. However, these fall short
as mono therapy and are frequently used in combination with inhaled glucocorticosteroids with or without long acting beta 2
agonists. Therefore, it is of interest to apply ligand and structure based virtual screening strategies to identify compounds akin to
lead compounds Montelukast and Zafirlukast. Hence, compounds with structures having 95% similarity to these compounds were
retrieved from NCBI׳s PubChem database. Compounds similar to lead were grouped and docked at the antagonist binding site of
cysteinyl leukotriene receptor 1. This exercise identified compounds UNII 70RV86E50Q (Pub Cid 71587778) and Sure CN 9587085
(Pub Cid 19793614) with higher predicted binding compared to Montelukast and Zafirlukast. It is shown that the compound Sure
CN 9587085 showed appreciable ligand receptor interaction compared to UNII 70RV86E50Q. Thus, the compound Sure CN
9587085 is selected as a potent antagonist to cysteinyl leukotriene receptor 1 for further consideration in vitro and in vivo validation. 相似文献
6.
Evelien Heylen Sebastiaan Van Goethem Thomas Olsson Dirk Hendriks 《Analytical biochemistry》2010,396(1):152-154
To date, several assays for procarboxypeptidase U (proCPU) determination exist, all having their own inherent disadvantages and advantages. A drawback of activity-based assays is the interference of the constitutively active carboxypeptidase N (CPN) in plasma. Recent screening of Bz-Xaa-Arg peptides with modified aromatic amino acids at the P1 position revealed a selective CPU substrate, N-benzoyl-ortho-cyano-phenylalanyl-arginine (Bz-o-cyano-Phe-Arg), which will allow straightforward determination of proCPU in plasma. Our assay shows an excellent linearity in the concentration range of 20-2600 U/L, with within- and between-run precision values of 2.7% and 4.6%, respectively. A good correlation with our high-performance liquid chromatography (HPLC)-assisted proCPU activity assay using hippuryl-l-arginine (HipArg) as substrate was found. Besides the major improvement regarding the selectivity, the assay is much easier to perform and far less time-consuming compared with the proCPU activity assay using HipArg as substrate. 相似文献
7.
Ramona Marasco Jean-Baptiste Ramond Marc W. Van Goethem Federico Rossi Daniele Daffonchio 《Microbial biotechnology》2023,16(8):1603-1610
Our planet teeters on the brink of massive ecosystem collapses, and arid regions experience manifold environmental and climatic challenges that increase the magnitude of selective pressures on already stressed ecosystems. Ultimately, this leads to their aridification and desertification, that is, to simplified and barren ecosystems (with proportionally less microbial load and diversity) with altered functions and food webs and modification of microbial community network. Thus, preserving and restoring soil health in such a fragile biome could help buffer climate change's effects. We argue that microorganisms and the protection of their functional properties and networks are key to fight desertification. Specifically, we claim that it is rational, possible and certainly practical to rely on native dryland edaphic microorganisms and microbial communities as well as dryland plants and their associated microbiota to conserve and restore soil health and mitigate soil depletion in newly aridified lands. Furthermore, this will meet the objective of protecting/stabilizing (and even enhancing) soil biodiversity globally. Without urgent conservation and restoration actions that take into account microbial diversity, we will ultimately, and simply, not have anything to protect anymore. 相似文献
8.
Moore MM Honma M Clements J Bolcsfoldi G Burlinson B Cifone M Clarke J Clay P Doppalapudi R Fellows M Gollapudi B Hou S Jenkinson P Muster W Pant K Kidd DA Lorge E Lloyd M Myhr B O'Donovan M Riach C Stankowski LF Thakur AK Van Goethem F;Mouse Lymphoma Assay Workgroup IWGT 《Mutation research》2007,627(1):36-40
The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity Testing (IWGT), comprised of experts from Japan, Europe and the United States, met on September 9, 2005, in San Francisco, CA, USA. This meeting of the MLA Workgroup was devoted to reaching a consensus on issues involved with 24-h treatment. Recommendations were made concerning the acceptable values for the negative/solvent control (mutant frequency, cloning efficiency and suspension growth) and the criteria to define an acceptable positive control response. Consensus was also reached concerning the use of the global evaluation factor (GEF) and appropriate statistical trend analysis to define positive and negative responses for the 24-h treatment. The Workgroup agreed to continue their support of the International Committee on Harmonization (ICH) recommendation that the MLA assay should include a 24-h treatment (without S-9) in those situations where the short treatment (3-4 h) gives negative results. 相似文献
9.
Apoptosis, a genetically programmed cell death, allows for homeostasis and tissue remodelling during development of all multi-cellular organisms. Phagocytes swiftly recognize, engulf and digest apoptotic cells. Yet, to date the molecular mechanisms underlying this phagocytic process are still poorly understood. To delineate the molecular mechanisms of apoptotic cell clearance in Drosophila, we have carried out a deficiency screen and have identified three overlapping phagocytosis-defective mutants, which all delete the fly homologue of the ced-12 gene, known as Dmel\ced12. As anticipated, we have found that Dmel\ced-12 is required for apoptotic cell clearance, as for its C. elegans and mammalian homologues, ced-12 and elmo, respectively. However, the loss of Dmel\ced-12 did not solely account for the phenotypes of all three deficiencies, as zygotic mutations and germ line clones of Dmel\ced-12 exhibited weaker phenotypes. Using a nearby genetically interacting deficiency, we have found that the polycystic kidney disease 2 gene, pkd2, which encodes a member of the TRPP channel family, is also required for phagocytosis of apoptotic cells, thereby demonstrating a novel role for PKD2 in this process. We have also observed genetic interactions between pkd2, simu, drpr, rya-r44F, and retinophilin (rtp), also known as undertaker (uta), a gene encoding a MORN-repeat containing molecule, which we have recently found to be implicated in calcium homeostasis during phagocytosis. However, we have not found any genetic interaction between Dmel\ced-12 and simu. Based on these genetic interactions and recent reports demonstrating a role for the mammalian pkd-2 gene product in ER calcium release during store-operated calcium entry, we propose that PKD2 functions in the DRPR/RTP pathway to regulate calcium homeostasis during this process. Similarly to its C. elegans homologue, Dmel\Ced-12 appears to function in a genetically distinct pathway. 相似文献
10.
Van der Veken P De Meester I Dubois V Soroka A Van Goethem S Maes MB Brandt I Lambeir AM Chen X Haemers A Scharpé S Augustyns K 《Bioorganic & medicinal chemistry letters》2008,18(14):4154-4158
Dipeptide derivatives bearing various P2 residues and pyrrolidine derivatives as P1 mimics were evaluated in order to identify lead structures for the development of DPP8 and DPP9 inhibitors. Structure–activity-relationship data obtained in this way led to the preparation of a series of α-aminoacyl ((2S, 4S)-4-azido-2-cyanopyrrolidines). These compounds were shown to be nanomolar DPP8/9 inhibitors with modest overall selectivity toward DPP IV and DPP II. 相似文献