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Conan K Wang, Hafiza Abdul Ghani, Anna Bundock, Joachim Weidmann, Peta J Harvey, Ingrid A Edwards, Christina I Schroeder, Joakim E Swedberg, David J Craik
The epidermal growth factor (EGF)-like domain is one of the most abundant disulfide-containing domains in nature and is involved in many cellular processes critical to life. Although many EGF-like domains participate in calcium-dependent functions by responding to the local calcium concentration, little is known about how this responsiveness is programmed at the molecular level. Here, we reveal the structural and environmental determinants underpinning the folding of a synthetic analogue of the EGF-A domain (from the low-density lipoprotein receptor)...
May 1, 2018: ACS Chemical Biology
Conan K Wang, David J Craik
Bioactive peptides have potential as drug leads, but turning them into drugs is a challenge because of their typically poor metabolic stability. Molecular grafting is one approach to stabilizing and constraining peptides and involves melding a bioactive peptide sequence onto a suitable molecular scaffold. This method has the benefit of improving the stability of the bioactive peptide lead and potentially expanding its functionality. Here we step through the molecular grafting process and describe its successes and limitations...
May 2018: Nature Chemical Biology
Davide Mercadante, Frauke Gräter, Csaba Daday
The analysis of contacts is a powerful tool to understand biomolecular function in a series of contexts, from the investigation of dynamical behavior at equilibrium to the study of nonequilibrium dynamics in which the system moves between multiple states. We thus propose a tool called CONtact ANalysis (CONAN) that, from molecular dynamics (MD) trajectories, analyzes interresidue contacts, creates videos of time-resolved contact maps, and performs correlation, principal component, and cluster analysis, revealing how specific contacts relate to functionally relevant states sampled by MD...
March 27, 2018: Biophysical Journal
A O Jenkins, E Gormley, N Gcebe, G T Fosgate, A Conan, C Aagaard, A L Michel, V P M G Rutten
Accurate diagnosis of tuberculosis in cattle may be compromised in areas where there are high rates of exposure to environmental/non-tuberculous mycobacteria (NTM). This cross reaction of immune responses to Mycobacterium bovis antigens shared with NTMs can result in reduced specificity of commonly used diagnostic tests including tuberculin skin tests and the interferon gamma assay (IFN-ɣ). In this study we assessed the cross-reactive immune responses of M. bovis (infected) and NTM exposed animals to M. bovis and M...
April 1, 2018: Preventive Veterinary Medicine
Pedro Mecê, Jessica Jarosz, Jean-Marc Conan, Cyril Petit, Kate Grieve, Michel Paques, Serge Meimon
To evaluate the contribution of fixational eye movements to dynamic aberration, 50 healthy eyes were examined with an original custom-built Shack-Hartmann aberrometer, running at a temporal frequency of 236Hz, with 22 lenslets across a 5mm pupil, synchronized with a 236Hz pupil tracker. A comparison of the dynamic behavior of the first 21 Zernike modes (starting from defocus) with and without digital pupil stabilization, on a 3.4s sequence between blinks, showed that the contribution of fixational eye movements to dynamic aberration is negligible...
February 1, 2018: Biomedical Optics Express
Taryn Klarner, E Paul Zehr
Evidence first described in reduced animal models over 100 years ago led to deductions about the control of locomotion through spinal locomotor central pattern generating (CPG) networks. These discoveries in nature were contemporaneous with another form of deductive reasoning found in popular culture-that of Arthur Conan Doyle's detective "Sherlock Holmes". Since the invasive methods used in reduced non-human animal preparations are not amenable to study in humans, we are left instead with deducing from other measures and observations...
March 14, 2018: Journal of Neurophysiology
S Georgin-Lavialle, V Hentgen, K Stankovic Stojanovic, C Bachmeyer, F Rodrigues, L Savey, S Abbara, P-L Conan, T Fraisse, M Delplanque, A Rouet, N Sbeih, I Koné-Paut, G Grateau
Familial Mediterranean Fever (FMF) is the most frequent monogenic auto-inflammatory disease. FMF is an autosomal recessive disease, which affects populations from Mediterranean origin and is associated with MEFV gene mutations encoding for the protein pyrin. Pyrin activation enhances the secretion of interleukin 1 by myelo-monocytic cells. Main features of the disease are acute attacks of serositis mainly located on the abdomen, less frequently on chest and joints, accompanied by fever and biological inflammatory markers elevation...
April 2018: La Revue de Médecine Interne
Karine Leblanc, Bernard Quéguiner, Frédéric Diaz, Véronique Cornet, Mónica Michel-Rodriguez, Xavier Durrieu de Madron, Chris Bowler, Shruti Malviya, Melilotus Thyssen, Gérald Grégori, Mathieu Rembauville, Olivier Grosso, Julie Poulain, Colomban de Vargas, Mireille Pujo-Pay, Pascal Conan
Diatoms are one of the major primary producers in the ocean, responsible annually for ~20% of photosynthetically fixed CO2 on Earth. In oceanic models, they are typically represented as large (>20 µm) microphytoplankton. However, many diatoms belong to the nanophytoplankton (2-20 µm) and a few species even overlap with the picoplanktonic size-class (<2 µm). Due to their minute size and difficulty of detection they are poorly characterized. Here we describe a massive spring bloom of the smallest known diatom (Minidiscus) in the northwestern Mediterranean Sea...
March 5, 2018: Nature Communications
David W Donnelly, Conan Donnelly, Therese Kearney, David Weller, Linda Sharp, Amy Downing, Sarah Wilding, Penny Wright, Paul Kind, James W F Catto, William R Cross, Malcolm D Mason, Eilis McCaughan, Richard Wagland, Eila Watson, Rebecca Mottram, Majorie Allen, Hugh Butcher, Luke Hounsome, Peter Selby, Dyfed Huws, David H Brewster, Emma McNair, Carol Rivas, Johana Nayoan, Mike Horton, Lauren Matheson, Adam W Glaser, Anna Gavin
OBJECTIVES: To provide data on the prevalence of urinary, bowel and sexual dysfunction in Northern Ireland (NI), to act as a baseline for studies of prostate cancer outcomes and to aid service provision within the general population. SUBJECTS AND METHODS: A cross-sectional postal survey of 10 000 men aged ≥40 years in NI was conducted and age-matched to the distribution of men living with prostate cancer. The EuroQoL five Dimensions five Levels (EQ-5D-5L) and 26-item Expanded Prostate Cancer Composite (EPIC-26) instruments were used to enable comparisons with prostate cancer outcome studies...
February 28, 2018: BJU International
C Dussud, A L Meistertzheim, P Conan, M Pujo-Pay, M George, P Fabre, J Coudane, P Higgs, A Elineau, M L Pedrotti, G Gorsky, J F Ghiglione
Plastic pollution is widespread in ocean ecosystems worldwide, but it is unknown if plastic offers a unique habitat for bacteria compared to communities in the water column and attached to naturally-occurring organic particles. The large set of samples taken during the Tara-Mediterranean expedition revealed for the first time a clear niche partitioning between free-living (FL), organic particle-attached (PA) and the recently introduced plastic marine debris (PMD). Bacterial counts in PMD presented higher cell enrichment factors than generally observed for PA fraction, when compared to FL bacteria in the surrounding waters...
May 2018: Environmental Pollution
Mark Dalton, John Harrison, Anitra Malin, Conan Leavey
BACKGROUND: nurses play a crucial role in the early recognition and management of the deteriorating patient. They are responsible for the care they provide to their patients, part of which is the monitoring of vital signs (blood pressure, pulse, respiratory rate and temperature), which are fundamental in the surveillance of deterioration. The aim of this study was to discover what factors influence how nurses assess patient acuity and their response to acute deterioration. METHODS: a generic qualitative approach was used...
February 22, 2018: British Journal of Nursing: BJN
Gurpreet S Sandhu, Charanjit S Rihal
No abstract text is available yet for this article.
February 2018: Circulation. Cardiovascular Interventions
Cle Donacier Mekuimemba, Françoise Conan, Antonio J Mota, Maria A Palacios, Enrique Colacio, Smail Triki
A new dinuclear complex [{Fe(tpc-OBn)(NCS)(μ-NCS)}2 ] (1) based on the tripodal tpc-OBn ligand (tpc-OBn = tris(2-pyridyl)benzyloxymethane), containing bridging μ-κN:κS-SCN and terminal κN-SCN thiocyanate ligands, has been prepared and characterized by single crystal X-ray diffraction, magnetic studies, and DFT theoretical calculations. This complex represents the first example of dinuclear FeII complex with double μ-κN:κS-SCN bridges in a head-to-tail configuration that exhibits ferromagnetic coupling between metal ions (JFeFe = +1...
February 19, 2018: Inorganic Chemistry
Conan K Wang, Joakim E Swedberg, Peta J Harvey, Quentin Kaas, David J Craik
Several cyclic peptides have been reported to have unexpectedly high membrane permeability. Of these, cyclosporin A is perhaps the most well-known example, particularly in light of its relatively high molecular weight. Observations that cyclosporin A changes conformation depending on its solvent environment led to the hypothesis that conformational dynamics is a prerequisite for its permeability; however, this hypothesis has been difficult to validate experimentally. Here, we use molecular dynamics simulations to explicitly determine the conformational behavior of cyclosporin A and other related cyclic peptides as they spontaneously transition between different environments, including through a lipid bilayer...
March 1, 2018: Journal of Physical Chemistry. B
Conan So, M Minhaj Siddiqui
No abstract text is available yet for this article.
February 1, 2018: New England Journal of Medicine
Martin R Gaudinski, Emily E Coates, Katherine V Houser, Grace L Chen, Galina Yamshchikov, Jamie G Saunders, LaSonji A Holman, Ingelise Gordon, Sarah Plummer, Cynthia S Hendel, Michelle Conan-Cibotti, Margarita Gomez Lorenzo, Sandra Sitar, Kevin Carlton, Carolyn Laurencot, Robert T Bailer, Sandeep Narpala, Adrian B McDermott, Aryan M Namboodiri, Janardan P Pandey, Richard M Schwartz, Zonghui Hu, Richard A Koup, Edmund Capparelli, Barney S Graham, John R Mascola, Julie E Ledgerwood
BACKGROUND: VRC01 is a human broadly neutralizing monoclonal antibody (bnMAb) against the CD4-binding site of the HIV-1 envelope glycoprotein (Env) that is currently being evaluated in a Phase IIb adult HIV-1 prevention efficacy trial. VRC01LS is a modified version of VRC01, designed for extended serum half-life by increased binding affinity to the neonatal Fc receptor. METHODS AND FINDINGS: This Phase I dose-escalation study of VRC01LS in HIV-negative healthy adults was conducted by the Vaccine Research Center (VRC) at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD)...
January 2018: PLoS Medicine
Florent D Lavergne, Corey D Broeckling, Darren M Cockrell, Scott D Haley, Frank B Peairs, Courtney E Jahn, Adam L Heuberger
Wheat ( Triticum aestivum L.) is an important food crop, and biotic and abiotic stresses significantly impact grain yield. Wheat leaf and stem surface waxes are associated with traits of biological importance, including stress resistance. Past studies have characterized the composition of wheat cuticular waxes, however protocols can be relatively low-throughput and narrow in the range of metabolites detected. Here, gas chromatography-mass spectrometry (GC-MS) metabolomics methods were utilized to provide a comprehensive characterization of the chemical composition of cuticular waxes in wheat leaves and stems...
January 23, 2018: International Journal of Molecular Sciences
Lucien Canuet, Nicolas Védrenne, Jean-Marc Conan, Cyril Petit, Geraldine Artaud, Angelique Rissons, Jerome Lacan
In the framework of satellite-to-ground laser downlinks, an analytical model describing the variations of the instantaneous coupled flux into a single-mode fiber after correction of the incoming wavefront by partial adaptive optics (AO) is presented. Expressions for the probability density function and the cumulative distribution function as well as for the average fading duration and fading duration distribution of the corrected coupled flux are given. These results are of prime interest for the computation of metrics related to coded transmissions over correlated channels, and they are confronted by end-to-end wave-optics simulations in the case of a geosynchronous satellite (GEO)-to-ground and a low earth orbit satellite (LEO)-to-ground scenario...
January 1, 2018: Journal of the Optical Society of America. A, Optics, Image Science, and Vision
W Y Rojas, A D Winter, J Grote, S S Kim, R R Naik, A D Williams, C Weiland, E Principe, D A Fischer, S Banerjee, D Prendergast, E M Campo
As the quest toward novel materials proceeds, improved characterization technologies are needed. In particular, the atomic thickness in graphene and other 2D materials renders some conventional technologies obsolete. Characterization technologies at wafer level are needed with enough sensitivity to detect strain in order to inform fabrication. In this work, NEXAFS spectroscopy was combined with simulations to predict lattice parameters of graphene grown on copper and further transferred to a variety of substrates...
January 30, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Nicola Pratt, Anne Conan, Sreekumari Rajeev
Leptospirosis is an important bacterial zoonotic disease that affects humans and many animal species. Knowledge of prevalence of Leptospira in a given geographic region supports the implementation of effective control/prevention programmes and thus reduces the transmission risks. This study provides Leptospira seroprevalence and serovar distribution in dogs and cats on the Caribbean island of Saint Kitts. Convenient serum samples from domestic dogs ( n = 101) and cats ( n = 50) were tested by the microscopic agglutination test (MAT) using 21 Leptospira serovars belonging to 17 serogroups...
2017: Veterinary Medicine International
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