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Kevin T Du Clos, Ian T Jones, Tyler J Carrier, Damian C Brady, Peter A Jumars
Benthic marine suspension feeders provide an important link between benthic and pelagic ecosystems. The strength of this link is determined by suspension-feeding rates. Many studies have measured suspension-feeding rates using indirect clearance-rate methods, which are based on the depletion of suspended particles. Direct methods that measure the flow of water itself are less common, but they can be more broadly applied because, unlike indirect methods, direct methods are not affected by properties of the cleared particles...
March 27, 2017: Journal of Experimental Biology
Lucie Colineau, Joachim Clos, Kyung-Mee Moon, Leonard J Foster, Neil E Reiner
Protozoa of the genus Leishmania infect macrophages in their mammalian hosts causing a spectrum of diseases known as the leishmaniases. The search for leishmania effectors that support macrophage infection is a focus of significant interest. One such candidate is leishmania chaperonin 10 (CPN10) which is secreted in exosomes and may have immunosuppressive properties. Here, we report for the first time that leishmania CPN10 localizes to the cytosol of infected macrophages. Next, we generated two genetically modified strains of Leishmania donovani (Ld): one strain overexpressing CPN10 (CPN10+++) and the second, a CPN10 single allele knockdown (CPN10+/-), as the null mutant was lethal...
March 11, 2017: Medical Microbiology and Immunology
Lydia Giménez-Llort, Miriam Ratia, Belén Pérez, Pelayo Camps, Diego Muñoz-Torrero, Albert Badia, M Victoria Clos
The current pharmacological approach to Alzheimer's disease (AD) treatment, mostly based on acetylcholinesterase inhibitors (AChEIs), is being revisited, especially in terms of the temporal frames and the potential benefits of their noncanonic actions, raising the question of whether inhibitors of AChE might also act in a disease-modifying manner. Besides, in the last decades, the pharmacophoric moieties of known AChEIs have been covalently linked to other pharmacophores in the pursuit of multitarget hybrid molecules that are expected to induce long-lasting amelioration of impaired neurotransmission and clinical symptoms but also to exert disease-modifying effects...
April 2017: Behavioural Pharmacology
Chiara Borsari, Nuno Santarem, Juan Torrado, Ana Isabel Olías, María Jesús Corral, Catarina Baptista, Sheraz Gul, Markus Wolf, Maria Kuzikov, Bernhard Ellinger, Gesa Witt, Philip Gribbon, Jeanette Reinshagen, Pasquale Linciano, Annalisa Tait, Luca Costantino, Lucio H Freitas-Junior, Carolina B Moraes, Pascoalino Bruno Dos Santos, Laura Maria Alcântara, Caio Haddad Franco, Claudia Danielli Bertolacini, Vanessa Fontana, Paloma Tejera Nevado, Joachim Clos, José María Alunda, Anabela Cordeiro-da-Silva, Stefania Ferrari, Maria Paola Costi
Chalcones display a broad spectrum of pharmacological activities. Herein, a series of 2'-hydroxy methoxylated chalcones was synthesized and evaluated towards Trypanosoma brucei, Trypanosoma cruzi and Leishmania infantum. Among the synthesized library, compounds 1, 3, 4, 7 and 8 were the most potent and selective anti-T. brucei compounds (EC50 = 1.3-4.2 μM, selectivity index >10-fold). Compound 4 showed the best early-tox and antiparasitic profile. The pharmacokinetic studies of compound 4 in BALB/c mice using hydroxypropil-β-cyclodextrins formulation showed a 7...
January 27, 2017: European Journal of Medicinal Chemistry
H L Bateman, G I McCracken, J M Thomason, J S Ellis
INTRODUCTION: Outcome-based programmes provide a framework to support educators and learners in understanding content and end points within taught courses. Management of these outcomes in the Dental Degree at Newcastle University has been a challenge in relation to quality assurance and enhancement, having over 1500 detailed student-level outcomes (SLO). This research aimed to explore the implications of adopting a more superficial "course" level of outcome (CLO), when reviewed against a reference set of external LO requirements...
November 29, 2016: European Journal of Dental Education: Official Journal of the Association for Dental Education in Europe
Govinda Clos, Diego Porras, Ulrich Warring, Tobias Schaetz
We use trapped atomic ions forming a hybrid Coulomb crystal and exploit its phonons to study an isolated quantum system composed of a single spin coupled to an engineered bosonic environment. We increase the complexity of the system by adding ions and controlling coherent couplings and, thereby, we observe the emergence of thermalization: Time averages of spin observables approach microcanonical averages while related fluctuations decay. Our platform features precise control of system size, coupling strength, and isolation from the external world to explore the dynamics of equilibration and thermalization...
October 21, 2016: Physical Review Letters
Naoji Yubuki, Sam S C Huang, Brian S Leander
The Fornicata (Excavata) is a group of microbial eukaryotes consisting of both free-living lineages (e.g., Carpediemonas) and parasitic lineages (e.g. Giardia and Retortamonas) that share several molecular and ultrastructural traits. Carpediemonas-like organisms (CLOs) are free-living lineages that diverged early within the Fornicata, making them important for inferring the early evolutionary history of the group. Molecular phylogenetic analyses of free-living fornicates, including sequences from environmental PCR surveys, have demonstrated that CLOs form six different lineages...
December 2016: Protist
K Hokynar, E J Vesterinen, T M Lilley, A T Pulliainen, S J Korhonen, J Paavonen, M Puolakkainen
Chlamydia-like organisms (CLOs) are recently identified members of the Chlamydiales order. CLOs share intracellular lifestyles and biphasic developmental cycles, and they have been detected in environmental samples as well as in various hosts such as amoebae and arthropods. In this study, we screened bat feces for the presence of CLOs by molecular analysis. Using pan-Chlamydiales PCR targeting the 16S rRNA gene, Chlamydiales DNA was detected in 54% of the specimens. PCR amplification, sequencing, and phylogenetic analysis of the 16S rRNA and 23S rRNA genes were used to classify positive specimens and infer their phylogenetic relationships...
January 15, 2017: Applied and Environmental Microbiology
P Martinkevich, O Rahbek, M Stilling, L K Pedersen, M Gottliebsen, K Søballe, B Møller-Madsen
AIMS: To compare the structural durability of hydroxyapatite-tricalcium phosphate (HATCP) to autologous iliac crest bone graft in calcaneal lengthening osteotomy (CLO) for pes planovalgus in childhood. PATIENTS AND METHODS: We present the interim results of ten patients (HATCP, n = 6 and autograft, n = 5) with a mean age of 11.5 years (8.2 to 14.2) from a randomised controlled non-inferiority trial with six months follow-up. The primary outcome was the stability of the osteotomy as measured by radiostereometric analysis...
November 2016: Bone & Joint Journal
Francesc Font-Clos, Nicholas R Moloney
We calculate the distribution of the size of the percolating cluster on a tree in the subcritical, critical, and supercritical phase. We do this by exploiting a mapping between continuum trees and Brownian excursions, and arrive at a diffusion equation with suitable boundary conditions. The exact solution to this equation can be conveniently represented as a characteristic function, from which the following distributions are clearly visible: Gaussian (subcritical), Kolmogorov-Smirnov (critical), and exponential (supercritical)...
September 2016: Physical Review. E
Kati Hokynar, Jani J Sormunen, Eero J Vesterinen, Esa K Partio, Thomas Lilley, Veera Timonen, Jaana Panelius, Annamari Ranki, Mirja Puolakkainen
Ticks carry several human pathogenic microbes including Borreliae and Flavivirus causing tick-born encephalitis. Ticks can also carry DNA of Chlamydia-like organisms (CLOs). The purpose of this study was to investigate the occurrence of CLOs in ticks and skin biopsies taken from individuals with suspected tick bite. DNA from CLOs was detected by pan-Chlamydiales-PCR in 40% of adult ticks from southwestern Finland. The estimated minimal infection rate for nymphs and larvae (studied in pools) was 6% and 2%, respectively...
August 18, 2016: Microorganisms
Irene Sola, Albert Artigas, Martin C Taylor, F Javier Pérez-Areales, Elisabet Viayna, M Victòria Clos, Belén Pérez, Colin W Wright, John M Kelly, Diego Muñoz-Torrero
Current drugs against human African trypanosomiasis (HAT) suffer from several serious drawbacks. The search for novel, effective, brain permeable, safe, and inexpensive antitrypanosomal compounds is therefore an urgent need. We have recently reported that the 4-aminoquinoline derivative huprine Y, developed in our group as an anticholinesterasic agent, exhibits a submicromolar potency against Trypanosoma brucei and that its homo- and hetero-dimerization can result in to up to three-fold increased potency and selectivity...
November 1, 2016: Bioorganic & Medicinal Chemistry
Álvaro Corral, Rosalba Garcia-Millan, Francesc Font-Clos
The theory of finite-size scaling explains how the singular behavior of thermodynamic quantities in the critical point of a phase transition emerges when the size of the system becomes infinite. Usually, this theory is presented in a phenomenological way. Here, we exactly demonstrate the existence of a finite-size scaling law for the Galton-Watson branching processes when the number of offsprings of each individual follows either a geometric distribution or a generalized geometric distribution. We also derive the corrections to scaling and the limits of validity of the finite-size scaling law away the critical point...
2016: PloS One
Javier Echeverría, Hermann M Niemeyer
The chemical composition of the essential oil of Kurzamra pulchella (Lamiaceae) was determined. Twelve compounds were identified, with isomenthone (60.6%) and pulegone (37.1%) predominating. Chemotaxonomical considerations were discussed.
January 2017: Natural Product Research
Chiara Borsari, Rosaria Luciani, Cecilia Pozzi, Ina Poehner, Stefan Henrich, Matteo Trande, Anabela Cordeiro-da-Silva, Nuno Santarem, Catarina Baptista, Annalisa Tait, Flavio Di Pisa, Lucia Dello Iacono, Giacomo Landi, Sheraz Gul, Markus Wolf, Maria Kuzikov, Bernhard Ellinger, Jeanette Reinshagen, Gesa Witt, Philip Gribbon, Manfred Kohler, Oliver Keminer, Birte Behrens, Luca Costantino, Paloma Tejera Nevado, Eugenia Bifeld, Julia Eick, Joachim Clos, Juan Torrado, María D Jiménez-Antón, María J Corral, José Ma Alunda, Federica Pellati, Rebecca C Wade, Stefania Ferrari, Stefano Mangani, Maria Paola Costi
Flavonoids represent a potential source of new antitrypanosomatidic leads. Starting from a library of natural products, we combined target-based screening on pteridine reductase 1 with phenotypic screening on Trypanosoma brucei for hit identification. Flavonols were identified as hits, and a library of 16 derivatives was synthesized. Twelve compounds showed EC50 values against T. brucei below 10 μM. Four X-ray crystal structures and docking studies explained the observed structure-activity relationships. Compound 2 (3,6-dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one) was selected for pharmacokinetic studies...
August 25, 2016: Journal of Medicinal Chemistry
Paloma Tejera Nevado, Eugenia Bifeld, Katharina Höhn, Joachim Clos
The mechanisms underlying the drug resistance of Leishmania spp. are manifold and not completely identified. Apart from the highly conserved multidrug resistance gene family known from higher eukaryotes, Leishmania spp. also possess genus-specific resistance marker genes. One of them, ARM58, was first identified in Leishmania braziliensis using a functional cloning approach, and its domain structure was characterized in L. infantum Here we report that L. infantum ARM58 is part of a gene cluster at the telomeric end of chromosome 34 also comprising the neighboring genes ARM56 and HSP23...
September 2016: Antimicrobial Agents and Chemotherapy
Eugenia Bifeld, Paloma Tejera Nevado, Janika Bartsch, Julia Eick, Joachim Clos
The majority of PCR-based detection systems for Leishmania spp. and Trypanosoma cruzi aim at high sensitivity and specificity, rather than an accurate parasite load quantification required for experimental infections in basic research and drug development. Here, we describe the use of a dual-labelled probe qPCR to detect and quantify intracellular Old World Leishmania spp. and T. cruzi amastigotes after in vitro and in vivo infection experiments. We show that quantification of parasite actin gene DNA relative to the host cell actin gene DNA accurately reflects the parasite load relative to the host cells and that qPCR quantification is highly sensible to drug-induced cell death...
October 2016: Medical Microbiology and Immunology
Yau Wai-Lok, Ulrike Lambertz, Lucie Colineau, Pascale Pescher, Andrea MacDonald, Dorothea Zander, Silke Retzlaff, Julia Eick, Neil E Reiner, Joachim Clos, Gerald F Späth
Protozoan parasites of the genus Leishmania adapt to their arthropod and vertebrate hosts through the development of defined life cycle stages. Stage differentiation is triggered by environmental stress factors and has been linked to parasite chaperone activities. Using a null mutant approach we previously revealed important, non-redundant functions of the co-chaperone cyclophilin 40 in L. donovani-infected macrophages. Here we characterized in more detail the virulence defect of cyp40-/- null mutants. In vitro viability assays, infection tests using macrophages, and mixed infection experiments ruled out a defect of cyp40-/- parasites in resistance to oxidative and hydrolytic stresses encountered inside the host cell phagolysosome...
May 24, 2016: Journal of Eukaryotic Microbiology
Ariadna Clos, Alba Hernández, María Del Carmen Sánchez, Montserrat Tenesa, Joan Francesc Julián, Carolina Armengol, Margarita Sala
No abstract text is available yet for this article.
April 2017: Gastroenterología y Hepatología
Gerald F Späth, Joachim Clos
Reverse genetics in Leishmania spp has gained importance beyond basic research as efforts increase to discover and validate new drug targets. Often, the most promising targets are essential for viability of the parasites, defying a genetic analysis by current gene replacement strategies. Duncan et al. demonstrate the applicability of DiCre recombination in Leishmania for induced replacement of the kinase CRK3 gene in promastigotes. DiCre gene replacement leads to the rapid loss of the gene and allows monitoring the phenotypic effects of the loss of function, eliminating the need for prolonged cultivation and selection...
June 2016: Molecular Microbiology
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