Contrast Enhanced Magnetic Resonance Imaging of Amyloid-β Plaques in a Murine Alzheimer's Disease Model

Background: Early detection of amyloid-β (Aβ) aggregates is a critical step to improve the treatment of Alzheimer’s disease (AD) because neuronal damage by the Aβ aggregates occurs before clinical symptoms are apparent. We have previously shown that luminescent conjugated oligothiophenes (LCOs), which are highly specific towards protein aggregates of Aβ, can be used to fluorescently label amyloid plaque in living rodents. Objective: We hypothesize that the LCO can be used to target gadolinium to the amyloid plaque and hence make the plaque detectable by T1-weighted magnetic resonance imaging (MRI). Methods: A novel LCO-gadolinium construct was synthesized to selectively bind to Aβ plaques and give contrast in conventional T1-weighted MR images after intravenous injection in Tg-APPSwe mice. Results: We found that mice with high plaque-burden could be identified using the LCO-Gd constructs by conventional MRI. Conclusion: Our study shows that MR imaging of amyloid plaques is challenging but feasible, and hence contrast-mediated MR imaging could be a valuable tool for early AD detection.publishedVersio

Cone-setting in spruce is regulated by conserved elements of the age-dependent flowering pathway

Reproductive phase change is well characterized in angiosperm model species, but less studied in gymnosperms. We utilize the early cone-setting acrocona mutant to study reproductive phase change in the conifer Picea abies (Norway spruce), a gymnosperm. The acrocona mutant frequently initiates cone-like structures, called transition shoots, in positions where wild-type P. abies always produces vegetative shoots. We collect acrocona and wild-type samples, and RNA-sequence their messenger RNA (mRNA) and microRNA (miRNA) fractions. We establish gene expression patterns and then use allele-specific transcript assembly to identify mutations in acrocona. We genotype a segregating population of inbred acrocona trees. A member of the SQUAMOSA BINDING PROTEIN-LIKE (SPL) gene family, PaSPL1, is active in reproductive meristems, whereas two putative negative regulators of PaSPL1, miRNA156 and the conifer specific miRNA529, are upregulated in vegetative and transition shoot meristems. We identify a mutation in a putative miRNA156/529 binding site of the acrocona PaSPL1 allele and show that the mutation renders the acrocona allele tolerant to these miRNAs. We show co-segregation between the early cone-setting phenotype and trees homozygous for the acrocona mutation. In conclusion, we demonstrate evolutionary conservation of the age-dependent flowering pathway and involvement of this pathway in regulating reproductive phase change in the conifer P. abies

Improved Limit on Direct α Decay of the Hoyle State

The current evaluation of the triple-α reaction rate assumes that the α decay of the 7.65 MeV, 0+ state in 12C, commonly known as the Hoyle state, proceeds sequentially via the ground state of 8Be. This assumption is challenged by the recent identification of two direct α-decay branches with a combined branching ratio of 17(5)%. If correct, this would imply a corresponding reduction in the triple-α reaction rate with important astrophysical consequences. We have used the 11B(3He,d) reaction to populate the Hoyle state and measured the decay to three α particles in complete kinematics. We find no evidence for direct α-decay branches, and hence our data do not support a revision of the triple-α reaction rate. We obtain an upper limit of 5×10-3 on the direct α decay of the Hoyle state at 95% C.L., which is 1 order of magnitude better than a previous upper limit

Study of the unbound nucleus N-11 by elastic resonance scattering

4 pages, 4 figures, 2 tables.-- PACS nrs.: 21.10.Pc, 25.40.Ny, 27.20.+n.Resonances in the unbound nucleus N-11 have been studied, using the resonance scattering reaction C-10+p. The data give evidence for three states above the C-10+p threshold with energies 1.30, 2.04, and 3.72 MeV. These states can be interpreted, in a potential-model analysis, as the ground state and the first two excited states with spin-parity 1/2(+), 1/2(-), and 5/2(+) arising from the shell-model orbitals 1s(1/2), Op(1/2), and Od(5/2). A narrow state superposed on a broad structure found at higher energy could be interpreted as the mirror state of the 3/2(-) in Be-11 shifted down in energy. This shift would suggest a large radius of the potential.We acknowledge financial support from the European Community under Contract No. CHGE-CT94-0056 (Human Capital and Mobility, Access to the GANIL large scale facility) and from the Russian Foundation RFFI.Peer reviewe

On hyperbolic fixed points in ultrametric dynamics

Let K be a complete ultrametric field. We give lower and upper bounds for the size of linearization discs for power series over K near hyperbolic fixed points. These estimates are maximal in the sense that there exist examples where these estimates give the exact size of the corresponding linearization disc. In particular, at repelling fixed points, the linearization disc is equal to the maximal disc on which the power series is injective.Comment: http://www.springerlink.com/content/?k=doi%3a%2810.1134%2fS2070046610030052%2

Immediate Risk for Cardiovascular Events and Suicide Following a Prostate Cancer Diagnosis: Prospective Cohort Study

Katja Fall and Fang Fang and colleagues find that men newly diagnosed with prostate cancer are at increased risk of cardiovascular events and suicide

Outreach initiatives operated by universities for increasing interest in science and technology

This is an Accepted Manuscript of an article published by Taylor & Francis in European Journal of Engineering Edutaion on 2016, available online: http://www.tandfonline.com/10.1080/03043797.2015.1121468Since the 1990s, the low number of students choosing to study science and technology in higher education has been on the societal agenda and many initiatives have been launched to promote awareness regarding career options. The initiatives particularly focus on increasing enrolment in the engineering programmes. This article describes and compares eight European initiatives that have been established and operated by universities (and in some cases through collaboration with other actors in society). Each initiative is summarised in a short essay that discusses motivation, organisation, pedagogical approach, and activities. The initiatives are characterised by comparing the driving forces behind their creation, how the initiative activities relate to the activities at the university, size based on the number of participants and cost per participant and pedagogical framework. There seem to be two main tracks for building outreach activities, one where outreach activities are based on the university’s normal activities, and one where outreach activities are designed specifically for the visiting students.Gumaelius, L.; Almqvistb, M.; Arnadottir, A.; Axelsson, A.; Conejero, JA.; García Sabater, JP.; Klitgaard, L.... (2016). Outreach initiatives operated by universities for increasing interest in science and technology. European Journal of Engineering Education. 41(6):589-622. https://doi.org/10.1080/03043797.2015.1121468S58962241

A model-independent approach to infer hierarchical codon substitution dynamics

<p>Abstract</p> <p>Background</p> <p>Codon substitution constitutes a fundamental process in molecular biology that has been studied extensively. However, prior studies rely on various assumptions, e.g. regarding the relevance of specific biochemical properties, or on conservation criteria for defining substitution groups. Ideally, one would instead like to analyze the substitution process in terms of raw dynamics, independently of underlying system specifics. In this paper we propose a method for doing this by identifying groups of codons and amino acids such that these groups imply closed dynamics. The approach relies on recently developed spectral and agglomerative techniques for identifying hierarchical organization in dynamical systems.</p> <p>Results</p> <p>We have applied the techniques on an empirically derived Markov model of the codon substitution process that is provided in the literature. Without system specific knowledge of the substitution process, the techniques manage to "blindly" identify multiple levels of dynamics; from amino acid substitutions (via the standard genetic code) to higher order dynamics on the level of amino acid groups. We hypothesize that the acquired groups reflect earlier versions of the genetic code.</p> <p>Conclusions</p> <p>The results demonstrate the applicability of the techniques. Due to their generality, we believe that they can be used to coarse grain and identify hierarchical organization in a broad range of other biological systems and processes, such as protein interaction networks, genetic regulatory networks and food webs.</p

Epitaxial growth of perovskite oxide films facilitated by oxygen vacancies

The authors would like to thank P. Yudin for valuable discussions, N. Nepomniashchaia for VASE studies, and S. Cichon for XPS analysis. The authors acknowledge support from the Czech Science Foundation (Grant No. 19-09671S), the European Structural and Investment Funds and the Ministry of Education, Youth and Sports of the Czech Republic through Programme ‘‘Research, Development and Education’’ (Project No. SOLID21 CZ.02.1.01/0.0/0.0/16-019/0000760), and ERA NET project Sun2Chem (E. K. and L. R.). Calculations have been done on the LASC Cluster in the ISSP UL.Single-crystal epitaxial films of technologically important and scientifically intriguing multifunctional ABO3 perovskite-type metal oxides are essential for advanced applications and understanding of these materials. In such films, a film-substrate misfit strain enables unprecedented crystal phases and unique properties that are not available in their bulk counterparts. However, the prerequisite growth of strained epitaxial films is fundamentally restricted by misfit relaxation. Here we demonstrate that introduction of a small oxygen deficiency concurrently stabilizes epitaxy and increases lattice strain in thin films of archetypal perovskite oxide SrTiO3. By combining experimental and theoretical methods, we found that lattice distortions around oxygen vacancies lead to anisotropic local stresses, which interact with the misfit strain in epitaxial films. Consequently, specific crystallographic alignments of the stresses are energetically favorable and can facilitate epitaxial growth of strained films. Because anisotropic oxygen-vacancy stresses are inherent to perovskite-type and many other oxides, we anticipate that the disclosed phenomenon of epitaxial stabilization by oxygen vacancies is relevant for a very broad range of functional oxides.This work is licensed under CC BY, CC BY-NC licenses.Czech Science Foundation (Grant No. 19-09671S); European Structural and Investment Funds and the Ministry of Education, Youth and Sports of the Czech Republic through Programme ‘‘Research, Development and Education’’ (Project No. SOLID21 CZ.02.1.01/0.0/0.0/16-019/0000760), and ERA NET project Sun2Chem; Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART²