Naturallyoccurring differences in cenh3 affect chromosome segregation in zygotic mitosis of hybrids

The point of attachment of spindle microtubules to metaphase chromosomes is known as the centromere. Plant and animal centromeres are epigenetically specified by a centromere-specific variant of Histone H3, CENH3 (a.k.a. CENP-A). Unlike canonical histones that are invariant, CENH3 proteins are accumulating substitutions at an accelerated rate. This diversification of CENH3 is a conundrum since its role as the key determinant of centromere identity remains a constant across species. Here, we ask whether naturally occurring divergence in CENH3 has functional consequences. We performed functional complementation assays on cenh3-1, a null mutation in Arabidopsis thaliana, using untagged CENH3s from increasingly distant relatives. Contrary to previous results using GFP-tagged CENH3, we find that the essential functions of CENH3 are conserved across a broad evolutionary landscape. CENH3 from a species as distant as the monocot Zea mays can functionally replace A. thaliana CENH3. Plants expressing variant CENH3s that are fertile when selfed show dramatic segregation errors when crossed to a wild-type individual. The progeny of this cross include hybrid diploids, aneuploids with novel genetic rearrangements and haploids that inherit only the genome of the wild-type parent. Importantly, it is always chromosomes from the plant expressing the divergent CENH3 that missegregate. Using chimeras, we show that it is divergence in the fast-evolving N-terminal tail of CENH3 that is causing segregation errors and genome elimination. Furthermore, we analyzed N-terminal tail sequences from plant CENH3s and discovered a modular pattern of sequence conservation. From this we hypothesize that while the essential functions of CENH3 are largely conserved, the N-terminal tail is evolving to adapt to lineage-specific centromeric constraints. Our results demonstrate that this lineage-specific evolution of CENH3 causes inviability and sterility of progeny in crosses, at the same time producing karyotypic variation. Thus, CENH3 evolution can contribute to postzygotic reproductive barriers

New Insights into the Structure of Nanoporous Carbons from NMR, Raman, and Pair Distribution Function Analysis

The structural characterization of nanoporous carbons is a challenging task as they generally lack long-range order and can exhibit diverse local structures. Such characterization represents an important step toward understanding and improving the properties and functionality of porous carbons, yet few experimental techniques have been developed for this purpose. Here we demonstrate the application of nuclear magnetic resonance (NMR) spectroscopy and pair distribution function (PDF) analysis as new tools to probe the local structures of porous carbons, alongside more conventional Raman spectroscopy. Together, the PDFs and the Raman spectra allow the local chemical bonding to be probed, with the bonding becoming more ordered for carbide-derived carbons (CDCs) synthesized at higher temperatures. The ring currents induced in the NMR experiment (and thus the observed NMR chemical shifts for adsorbed species) are strongly dependent on the size of the aromatic carbon domains. We exploit this property and use computer simulations to show that the carbon domain size increases with the temperature used in the carbon synthesis. The techniques developed here are applicable to a wide range of porous carbons and offer new insights into the structures of CDCs (conventional and vacuum-annealed) and coconut shell-derived activated carbons.A.C.F., J.M.G., C.M., P.K.A, E.K.H., and C.P.G. acknowledge the Sims Scholarship (A.C.F.), EPSRC (via the Supergen consortium, J.M.G.), and the EU ERC (via an Advanced Fellowship to C.P.G.) for funding. C.M. and P.K.A. acknowledge the School of the Physical Sciences of the University of Cambridge for funding through an Oppenheimer Research Fellowship. P.K.A. acknowledges a Junior Research Fellowship from Gonville and Caius College, Cambridge. A.C.F. and J.M.G. thank the NanoDTC Cambridge for travel funding. M.A., M.Z., and V.P. acknowledge funding from the German Federal Ministry for Research and Education (BMBF) in support of the nanoEES3D project (Award Number 03EK3013) as part of the strategic funding initiative energy storage framework and kindly thank Prof. Arzt (INM) for his continuing support. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. We thank Daan Frenkel for his contributions to this work and Boris Dyatkin for comments on the manuscript.This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/acs.chemmater.5b0321

SFG Study of the Potential-Dependent Adsorption of the p-Toluenesulfonate Anion at an Activated Carbon/Propylene Carbonate Interface

Sum frequency generation spectroscopy has been used to characterize the potential-dependent adsorption of the p-toluenesulfonate anion at the activated carbon/propylene carbonate interface of the commercial carbon YP50F. Spectra recorded from the interface between YP50F and a 1 M tetraethylammonium p-toluenesulfonate in propylene carbonate solution showed no ordered anion adsorption without an applied potential. In contrast, there is clear evidence of increasingly ordered anion adsorption with applied potential. Furthermore, there is evidence of hysteresis such that the anion remains adsorbed when the applied potential was decreased back to 0 V. Significant reversal of polarity was required before the anion signal was lost. Changes to the propylene carbonate solvent peaks during the electrochemical cycle were also observed. The data indicate that the positive electrode charges either via a counterion adsorption mechanism or via an ion-exchange mechanism.E.K.H. acknowledges the European Research Council ERC Grant ERC-2009-AdG-247411 for funding

Interrupting seasonal transmission of Schistosoma haematobium and control of soil-transmitted helminthiasis in northern and central Côte d’Ivoire: a SCORE study protocol

© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Molecular characterization and distribution of Schistosoma cercariae collected from naturally infected bulinid snails in northern and central Côte d’Ivoire

Accurate identification of schistosome species infecting intermediate host snails is important for understanding parasite transmission, schistosomiasis control and elimination. Cercariae emerging from infected snails cannot be precisely identified morphologically to the species level. We used molecular tools to clarify the distribution of the Schistosoma haematobium group species infecting bulinid snails in a large part of Côte d’Ivoire and confirmed the presence of interspecific hybrid schistosomes. Methods Between June 2016 and March 2017, Bulinus snails were sampled in 164 human-water contact sites from 22 villages of the northern and central parts of Côte d’Ivoire. Multi-locus genetic analysis (mitochondrial cox1 and nuclear ITS) was performed on individual schistosome cercariae shed from snails, in the morning and in the afternoon, for species and hybrid identification. Results Overall, 1923 Bulinus truncatus, 255 Bulinus globosus and 1424 Bulinus forskalii were obtained. Among 2417 Bulinus screened, 25 specimens (18 B. truncatus and seven B. globosus) shed schistosomes, with up to 14% infection prevalence per site and time point. Globally, infection rates per time point ranged between 0.6 and 4%. Schistosoma bovis, S. haematobium and S. bovis × S. haematobium hybrids infected 0.5%, 0.2% and 0.4% of the snails screened, respectively. Schistosoma bovis and hybrids were more prevalent in B. truncatus, whereas S. haematobium and hybrid infections were more prevalent in B. globosus. Schistosoma bovis-infected Bulinus were predominantly found in northern sites, while S. haematobium and hybrid infected snails were mainly found in central parts of Côte d’Ivoire. Conclusions The data highlight the necessity of using molecular tools to identify and understand which schistosome species are transmitted by specific intermediate host snails. The study deepens our understanding of the epidemiology and transmission dynamics of S. haematobium and S. bovis in Côte d’Ivoire and provides the first conclusive evidence for the transmission of S. haematobium × S. bovis hybrids in this West African country. Trial registration ISRCTN, ISRCTN10926858. Registered 21 December 2016; retrospectively registered (see: http://www.isrctn.com/ISRCTN10926858)Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published pdf

Novel composite implant in craniofacial bone reconstruction

Bioactive glass (BAG) and polymethyl methacrylate (PMMA) have been used in clinical applications. Antimicrobial BAG has the ability to attach chemically to surrounding bone, but it is not possible to bend, drill or shape BAG during the operation. PMMA has advantages in terms of shaping during the operation, but it does not attach chemically to the bone and is an exothermic material. To increase the usefulness of BAG and PMMA in skull bone defect reconstructions, a new composite implant containing BAG and PMMA in craniofacial reconstructions is presented. Three patients had pre-existing large defects in the calvarial and one in the midface area. An additive manufacturing (AM) model was used preoperatively for treatment planning and custom-made implant production. The trunk of the PMMA implant was coated with BAG granules. Clinical and radiological follow-up was performed postoperatively at 1 week, and 3, 6 and 12 months, and thereafter annually up to 5 years. Computer tomography (CT) and positron emission tomography (PET-CT) were performed at 12 and 24 months postoperatively. Uneventful clinical recovery with good esthetic and functional outcome was seen. CT and PET-CT findings supported good clinical outcome. The BAG–PMMA implant seems to be a promising craniofacial reconstruction alternative. However, more clinical experience is needed

Adjuvant radiation therapy in metastatic lymph nodes from melanoma

<p>Abstract</p> <p>Purpose</p> <p>To analyze the outcome after adjuvant radiation therapy with standard fractionation regimen in metastatic lymph nodes (LN) from cutaneous melanoma.</p> <p>Patients and methods</p> <p>86 successive patients (57 men) were treated for locally advanced melanoma in our institution. 60 patients (69%) underwent LN dissection followed by radiation therapy (RT), while 26 patients (31%) had no radiotherapy.</p> <p>Results</p> <p>The median number of resected LN was 12 (1 to 36) with 2 metastases (1 to 28). Median survival after the first relapse was 31.8 months. Extracapsular extension was a significant prognostic factor for regional control (p = 0.019). Median total dose was 50 Gy (30 to 70 Gy). A standard fractionation regimen was used (2 Gy/fraction). Median number of fractions was 25 (10 to 44 fractions). Patients were treated with five fractions/week. Patients with extracapsular extension treated with surgery followed by RT (total dose ≥50 Gy) had a better regional control than patients treated by surgery followed by RT with a total dose <50 Gy (80% vs. 35% at 5-year follow-up; p = 0.004).</p> <p>Conclusion</p> <p>Adjuvant radiotherapy was able to increase regional control in targeted sub-population (LN with extracapsular extension).</p

Genome-Wide Population-Based Association Study of Extremely Overweight Young Adults – The GOYA Study

Background: Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ~1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations. Methodology/Principal Findings: From two large Danish cohorts we selected all extremely overweight young men and women (n = 2,633), and equal numbers of population-based controls (n = 2,740, drawn randomly from the same populations as the extremes, representing ~212,000 individuals). We followed up novel (at the time of the study) association signals (