484 research outputs found
Disentangling the determinants of symbiotic species richness in native and invasive gammarids (Crustacea, Amphipoda) of the Baltic region
Dispersal of alien species is a global problem threatening native biodiversity. Co-introduction of nonnative parasites and pathogens adds to the severity of this threat, but this indirect impact has received less attention. To shed light on the key factors determining the richness of microorganisms in native and invasive host species, we compared symbiotic (parasitic and epibiotic) communities of gammarids across different habitats and localities along the Baltic coast of Poland. Seven gammarid species, two native and five invasive, were sampled from 16 freshwater and brackish localities. Sixty symbiotic species of microorganisms of nine phyla were identified. This taxonomically diverse species assemblage of symbionts allowed us to assess the effect of host translocation and regional ecological determinants driving assembly richness in the gammarid hosts. Our results revealed that (i) the current assemblages of symbionts of gammarid hosts in the Baltic region are formed by native and co-introduced species; (ii) species richness of the symbiotic community was higher in the native Gammarus pulex than in the invasive hosts, probably reflecting a process of species loss by invasive gammarids in the new area and the distinct habitat conditions occupied by G. pulex and invasive hosts; (iii) both host species and locality were key drivers shaping assembly composition of symbionts, whereas habitat condition (freshwater versus brackish) was a stronger determinant of communities than geographic distance; (iv) the dispersion patterns of the individual species richness of symbiotic communities were best described by Poisson distributions; in the case of an invasive host, the dispersion of the rich species diversity may switch to a right-skewed negative binomial distribution, suggesting a host-mediated regulation process. We believe this is the first analysis of the symbiotic species richness in native and invasive gammarid hosts in European waters based on original field data and a broad range of taxonomic groups including Microsporidia, Choanozoa, Ciliophora, Apicomplexa, Platyhelminthes, Nematoda, Nematomorha, Acanthocephala and Rotifera, to document the patterns of species composition and distributio
Resonant inelastic x-ray scattering (RIXS) spectra of magnesium diboride
Using the tight-binding linear muffin-tin orbitals method, the soft x-ray
fluorescence K-emission spectra of boron in MgB_2, excited close to the
absorption edge, are estimated. In the calculations the angle of incidence
between the direction of the incoming photon and the hexagonal axis of the
specimen is 60 degrees and 75 degrees. Comparison with experiment is possible
in the former case where good agreement is found. Furthermore, another resonant
feature below the Fermi energy is predicted for the larger angle. This feature
can be related to the excitations to the antibonding B pi-band in the
neighbourhood of the L-H line in the Brillouin zone.Comment: 4 pages with 4 figure
Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus.
Detection of cytosolic DNA is a central element of the innate immunity system against viral infection. The Ku heterodimer, a component of the NHEJ pathway of DNA repair in the nucleus, functions as DNA sensor that detects dsDNA of viruses that replicate in the cytoplasm. Vaccinia virus expresses two proteins, C4 and C16, that inactivate DNA sensing and enhance virulence. The structural basis for this is unknown. Here we determine the structure of the C16 - Ku complex using cryoEM. Ku binds dsDNA by a preformed ring but C16 sterically blocks this access route, abrogating binding to a dsDNA end and its insertion into DNA-PK, thereby averting signalling into the downstream innate immunity system. C4 replicates these activities using a domain with 54% identity to C16. Our results reveal how vaccinia virus subverts the capacity of Ku to recognize viral DNA
Evaluation of potential of high Si high C steel nanostructured bainite for wear and fatigue applications
The present study is concerned with the potential of high carbon, high silicon steel grades isothermally transformed to bainite at low temperature (<300 C). The first part gives an overview of the design principles, allowing very high strength and ductility to be achieved while minimising transformation duration. Wear and fatigue properties are then investigated for over 10 variants of such materials, manufactured in the laboratory or industrially. The results are discussed against published data. Tensile strengths above 2 GPa are routinely achieved, with, in one case, an exceptional and unprecedented total elongation of over 20%. Bainite plate thickness and retained austenite content are shown to be important factors in controlling the yield strength, though additional, non-negligible parameters remain to be quantified. Rolling-sliding wear performances are found to be exceptional, with as little as 1% of the specific wear rate of conventional 100Cr6 isothermally transformed to bainite. It is suggested that this results from the decomposition of retained austenite in the worn layer, which considerably increases hardness and presumably introduces compressive residual stresses. Fatigue performance was slightly improved over 100Cr6 for one of the two industrially produced materials but significantly lower otherwise. Factors controlling fatigue resistance require further investigations. © 2013 Institute of Materials, Minerals and Mining Published by Maney on behalf of the Institute.Peer Reviewe
Comparison of Bisulfite Pyrosequencing and Methylation-Specific qPCR for Methylation Assessment
Different methodological approaches are available to assess DNA methylation biomarkers. In this study, we evaluated two sodium bisulfite conversion-dependent methods, namely pyrosequencing and methylation-specific qPCR (MS-qPCR), with the aim of measuring the closeness of agreement of methylation values between these two methods and its effect when setting a cut-off. Methylation of tumor suppressor gene p16/INK4A was evaluated in 80 lung cancer patients from which cytological lymph node samples were obtained. Cluster analyses were used to establish methylated and unmethylated groups for each method. Agreement and concordance between pyrosequencing and MS-qPCR was evaluated with Pearson's correlation, Bland-Altman, Cohen's kappa index and ROC curve analyses. Based on these analyses, cut-offs were derived for MS-qPCR. An acceptable correlation (Pearson's R2 = 0.738) was found between pyrosequencing (PYRmean) and MS-qPCR (NMP; normalized methylation percentage), providing similar clinical results when categorizing data as binary using cluster analysis. Compared to pyrosequencing, MS-qPCR tended to underestimate methylation for values between 0 and 15%, while for methylation >30% overestimation was observed. The estimated cut-off for MS-qPCR data based on cluster analysis, kappa-index agreement and ROC curve analysis were much lower than that derived from pyrosequencing. In conclusion, our results indicate that independently of the approach used for estimating the cut-off, the methylation percentage obtained through MS-qPCR is lower than that calculated for pyrosequencing. These differences in data and therefore in the cut-off should be examined when using methylation biomarkers in the clinical practice
Functionalized chitosan derivatives as nonviral vectors: Physicochemical properties of acylated N,N,N-trimethyl chitosan/oligonucleotide nanopolyplexes
Cationic polymers have recently attracted attention due to their proven potential for nonviral gene delivery. In this study, we report novel biocompatible nanocomplexes produced using chemically functionalized N,N,N-trimethyl chitosan (TMC) with different N-acyl chain lengths (C 5 -C 18 ) associated with single-stranded oligonucleotides. The TMC derivatives were synthesized by covalent coupling reactions of quaternized chitosan with n-pentanoic (C 5 ), n-decanoic (C 10 ), and n-octadecanoic (C 18 ) fatty acids, which were extensively characterized by Fourier transform-infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance ( 1 H NMR). These N-acylated TMC derivatives (TMC n ) were used as cationic polymeric matrices for encapsulating anionic 18-base single-stranded thiophosphorylated oligonucleotides (ssONs), leading to the formation of polyplexes further characterized by zeta potential (ZP), dynamic light scattering (DLS), binding affinity, transfection efficiency and in vitro cytotoxicity assays. The results demonstrated that the length of the grafted hydrophobic N-acyl chain and the relative amino:phosphate groups ratio (N/P ratio) between the TMC derivatives and ssON played crucial roles in determining the physicochemical properties of the obtained nanocomplexes. While none of the tested derivatives showed appreciable cytotoxicity, the type of acyl chain had a remarkable influence on the cell transfection capacity of TMC-ssON nanocomplexes with the derivatives based on stearic acid showing the best performance based on the results of in vitro assays using a model cell line expressing luciferase (HeLa/Luc705).We acknowledge the financial support from the following Brazilian agencies: CAPES, FAPEMIG, CNPq, and FINEP. This work was co-financed by Fundação para a Ciência e a Tecnologia (FCT, Portugal) within the projects PTDC/CTM-NAN/NAN/115124/2009 and HMSP-ICT/0020/2010. Additionally, PMDM thanks the European Commission – Marie Curie Actions (PIEF-GA-2011-300485) for the postdoctoral fellowship. VL thanks the FCT fo the fellowship (SFRH/BPD/69110/2010). We are grateful to Dr Sandhra Carvalho (UFMG, Brazil) for the bioimaging analyses. The authors acknowledge the Centro de Materiais daUniversidade do Porto (CEMUP) for SEM and1H NMR analysis
Mitochondrial DNA, anti-tuberculosis drugs-induced hepatotoxicity and Alzheimer's disease
Anemia at hospital admission and its relation to outcomes in patients with heart failure (from the polish cohort of 2 European Society of Cardiology Heart Failure Registries)
[Abstract] Anemia is a commonly observed co-morbidity in heart failure (HF). The aim of the study was to assess prevalence, risk factors for, and effect of anemia on short- and long-term outcomes in HF. The study included 1,394 Caucasian patients hospitalized for HF, with known hemoglobin concentration on hospital admission, participating in 2 HF registries of the European Society of Cardiology (Pilot and Long-Term). Anemia was defined as hemoglobin concentration of <13 g/dl for men and <12 g/dl for women. Primary end points were (1) all-cause death at 1 year and (2) a composite of all-cause death and rehospitalization for HF at 1 year. Secondary end points included inter alia death during index hospitalization. In addition, we investigated the effect of changes in hemoglobin concentration during hospitalization on prognosis. Anemia occurred in 33% of patients. Predictors of anemia included older age, diabetes, greater New York Heart Association class at hospital admission and kidney disease. During 1-year follow-up, 21% of anemic and 13% of nonanemic patients died (p <0.0001). Combined primary end point occurred in 45% of anemic and in 33% of nonanemic patients (p <0.0001). Anemia was strongly predictive of all the prespecified clinical end points in univariate analyses but not in multivariate analyses. Changes in hemoglobin concentration during hospitalization had no effect on 1-year outcomes. In conclusion, anemia was present in 1/3 of patients with HF. Mild-to-moderate anemia seems more a marker of older age, worse clinical condition, and a higher co-morbidity burden, rather than an independent risk factor in HF
Emerging Two-Dimensional Crystallization of Cucurbit[8]uril Complexes: From Supramolecular Polymers to Nanofibers.
The binding of imidazolium salts to cucurbit[8]uril, CB[8], triggers a stepwise self-assembly process with semiflexible polymer chains and crystalline nanostructures as early- and late-stage species, respectively. In such a process, which involves the crystallization of the host-guest complexes, the guest plays a critical role in directing self-assembly toward desirable morphologies. These include platelet-like aggregates and two-dimensional (2D) fibers, which, moreover, exhibit viscoelastic and lyotropic properties. Our observations provide a deeper understanding of the self-assembly of CB[8] complexes, with fundamental implications in the design of functional 2D systems and crystalline materials.EPSRC (reference no. EP/ G060649/1),
ERC Starting Investigator Grant (project no. 240629, ASPiRe)
Next Generation Fellowship from the Walters-Kundert Foundation.
MINE- CO, the FSE and the FEDER for funding through projects RYC-2015-18471 (Ramoń y Cajal program) and CTQ2017- 84087-R.
Royal Society University Research Fellowship UF160152.
EPSRC CDT in Nanoscience and Nanotechnology (NanoDTC), grant number EP/L015978/1
Delivery of Splice Switching Oligonucleotides by Amphiphilic Chitosan-Based Nanoparticles
Splice switching oligonucleotides (SSOs) are a class of single-stranded antisense oligonucleotides (ssONs) being used as gene therapeutics and demonstrating great therapeutic potential. The availability of biodegradable and biocompatible delivery vectors that could improve delivery efficiencies, reduce dosage, and, in parallel, reduce toxicity concerns could be advantageous for clinical translation. In this work we explored the use of quaternized amphiphilic chitosan-based vectors in nanocomplex formation and delivery of splice switching oligonucleotides (SSO) into cells, while providing insights regarding cellular uptake of such complexes. Results show that the chitosan amphiphilic character is important when dealing with SSOs, greatly improving colloidal stability under serum conditions, as analyzed by dynamic light scattering, and enhancing cellular association. Nanocomplexes were found to follow an endolysosomal route with a long lysosome residence time. Conjugation of a hydrophobic moiety, stearic acid, to quaternized chitosan was a necessary condition to achieve transfection, as an unmodified quaternary chitosan was completely ineffective. We thus demonstrate that amphiphilic quaternized chitosan is a biomaterial that holds promise and warrants further development as a platform for SSO delivery strategies.This work was cofinanced by Fundacão para a Ciência e a Tecnologia (FCT, Portugal) within projects HMSP-ICT/0020/2010 and PTDC/CTM-NAN/NAN/115124/2009. Additionally, P.M.D.M.acknowledges the support from the Marie Curie Actions of the European Community’s 7th Framework Program (PIEF-GA-2011-300485); J.C.S. acknowledges the graduate fellowship from Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq, Ministry of Science and Technology, Brazil); C.P.G. and V.L. acknowledge FCT for their scholarships (SFRH/BD/79930/2011 and SFRH/BPD/69110/2010). We thank M. Lázaro from the Bioimaging Center for Biomaterials and Regenerative Therapies (b.IMAGE) for help with confocal microscopy. 1H NMR and Cryo-SEM were performed at the Centro de Materiais daUniversidade do Porto (CEMUP)
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