3D nanoscale analysis of bone healing around degrading Mg implants evaluated by X-ray scattering tensor tomography

The nanostructural adaptation of bone is crucial for its biocompatibility with orthopedic implants. The bone nanostructure also determines its mechanical properties and performance. However, the bone\u27s temporal and spatial nanoadaptation around degrading implants remains largely unknown. Here, we present insights into this important bone adaptation by applying scanning electron microscopy, elemental analysis, and small-angle X-ray scattering tensor tomography (SASTT). We extend the novel SASTT reconstruction method and provide a 3D scattering reciprocal space map per voxel of the sample\u27s volume. From this reconstruction, parameters such as the thickness of the bone mineral particles are quantified, which provide additional information on nanostructural adaptation of bone during healing. We selected a rat femoral bone and a degrading ZX10 magnesium implant as model system, and investigated it over the course of 18 months, using a sham as control. We observe that the bone\u27s nanostructural adaptation starts with an initially fast interfacial bone growth close to the implant, which spreads by a re-orientation of the nanostructure in the bone volume around the implant, and is consolidated in the later degradation stages. These observations reveal the complex bulk bone-implant interactions and enable future research on the related biomechanical bone responses. Statement of significance: Traumatic bone injuries are among the most frequent causes of surgical treatment, and often require the placement of an implant. The ideal implant supports and induces bone formation, while being mechanically and chemically adapted to the bone structure, ensuring a gradual load transfer. While magnesium implants fulfill these requirements, the nanostructural changes during bone healing and implant degradation remain not completely elucidated. Here, we unveil these processes in rat femoral bones with ZX10 magnesium implants and show different stages of bone healing in such a model system

Explosive Nucleosynthesis: What we learned and what we still do not understand

This review touches on historical aspects, going back to the early days of nuclear astrophysics, initiated by B$^2$FH and Cameron, discusses (i) the required nuclear input from reaction rates and decay properties up to the nuclear equation of state, continues (ii) with the tools to perform nucleosynthesis calculations and (iii) early parametrized nucleosynthesis studies, before (iv) reliable stellar models became available for the late stages of stellar evolution. It passes then through (v) explosive environments from core-collapse supernovae to explosive events in binary systems (including type Ia supernovae and compact binary mergers), and finally (vi) discusses the role of all these nucleosynthesis production sites in the evolution of galaxies. The focus is put on the comparison of early ideas and present, very recent, understanding.Comment: 11 pages, to appear in Springer Proceedings in Physics (Proc. of Intl. Conf. "Nuclei in the Cosmos XV", LNGS Assergi, Italy, June 2018

Non-thermal emission processes in massive binaries

In this paper, I present a general discussion of several astrophysical processes likely to play a role in the production of non-thermal emission in massive stars, with emphasis on massive binaries. Even though the discussion will start in the radio domain where the non-thermal emission was first detected, the census of physical processes involved in the non-thermal emission from massive stars shows that many spectral domains are concerned, from the radio to the very high energies. First, the theoretical aspects of the non-thermal emission from early-type stars will be addressed. The main topics that will be discussed are respectively the physics of individual stellar winds and their interaction in binary systems, the acceleration of relativistic electrons, the magnetic field of massive stars, and finally the non-thermal emission processes relevant to the case of massive stars. Second, this general qualitative discussion will be followed by a more quantitative one, devoted to the most probable scenario where non-thermal radio emitters are massive binaries. I will show how several stellar, wind and orbital parameters can be combined in order to make some semi-quantitative predictions on the high-energy counterpart to the non-thermal emission detected in the radio domain. These theoretical considerations will be followed by a census of results obtained so far, and related to this topic... (see paper for full abstract)Comment: 47 pages, 5 postscript figures, accepted for publication in Astronomy and Astrophysics Review. Astronomy and Astrophysics Review, in pres

Galactic Effects on Habitability

The galactic environment has been suspected to influence planetary habitability in many ways. Very metal-poor regions of the Galaxy, or those largely devoid of atoms more massive than H and He, are thought to be unable to form habitable planets. Moreover, if such planets do form, the young system is subjected to close stellar passages while it resides in its stellar birth cluster. Various potential hazards remain after clusters disperse. For instance, central galactic regions may present risks to habitability via nearby supernovae, gamma ray bursts (GRBs), and frequent comet showers. In addition, planets residing within very wide binary star systems are affected by the Galaxy, as local gravitational perturbations from the Galaxy can increase the binary's eccentricity until it destabilizes the planets it hosts. Here we review the most recent work on the main galactic influences over planetary habitability. Although there must be some metallicity limit below which rocky planets cannot form, recent exoplanet surveys show that they form around stars with a very large range of metallicities. Once formed, the probability of star clusters destabilizing planetary systems only becomes high for rare, extremely long-lived clusters. Regarding threats to habitability from supernovae, GRBs, and comet showers, many recent studies suggest that their hazards are more limited than originally thought. Finally, denser regions of the Galaxy enhance the threat that very wide binary companions pose to planetary habitability, but the probability that a very wide binary star disrupts habitability will always be substantially below 100% for any environment. While some Milky Way regions must be more hospitable to habitable planets than others, it is difficult to state that habitable planets are confined to any well-defined region of the Galaxy or that any other particular region of the Galaxy is uninhabitable.Comment: Invited review chapter, accepted for publication in the "Handbook of Exoplanets"; 19 pages; 2 figure

Weighted functional linear regression models for gene-based association analysis

<div><p>Functional linear regression models are effectively used in gene-based association analysis of complex traits. These models combine information about individual genetic variants, taking into account their positions and reducing the influence of noise and/or observation errors. To increase the power of methods, where several differently informative components are combined, weights are introduced to give the advantage to more informative components. Allele-specific weights have been introduced to collapsing and kernel-based approaches to gene-based association analysis. Here we have for the first time introduced weights to functional linear regression models adapted for both independent and family samples. Using data simulated on the basis of GAW17 genotypes and weights defined by allele frequencies via the beta distribution, we demonstrated that type I errors correspond to declared values and that increasing the weights of causal variants allows the power of functional linear models to be increased. We applied the new method to real data on blood pressure from the ORCADES sample. Five of the six known genes with <i>P</i> < 0.1 in at least one analysis had lower <i>P</i> values with weighted models. Moreover, we found an association between diastolic blood pressure and the <i>VMP1</i> gene (<i>P</i> = 8.18×10⁻⁶), when we used a weighted functional model. For this gene, the unweighted functional and weighted kernel-based models had <i>P</i> = 0.004 and 0.006, respectively. The new method has been implemented in the program package FREGAT, which is freely available at <a href="https://cran.r-project.org/web/packages/FREGAT/index.html" target="_blank">https://cran.r-project.org/web/packages/FREGAT/index.html</a>.</p></div

Genomic characteristics of cattle copy number variations

<p>Abstract</p> <p>Background</p> <p>Copy number variation (CNV) represents another important source of genetic variation complementary to single nucleotide polymorphism (SNP). High-density SNP array data have been routinely used to detect human CNVs, many of which have significant functional effects on gene expression and human diseases. In the dairy industry, a large quantity of SNP genotyping results are becoming available and can be used for CNV discovery to understand and accelerate genetic improvement for complex traits.</p> <p>Results</p> <p>We performed a systematic analysis of CNV using the Bovine HapMap SNP genotyping data, including 539 animals of 21 modern cattle breeds and 6 outgroups. After correcting genomic waves and considering the pedigree information, we identified 682 candidate CNV regions, which represent 139.8 megabases (~4.60%) of the genome. Selected CNVs were further experimentally validated and we found that copy number "gain" CNVs were predominantly clustered in tandem rather than existing as interspersed duplications. Many CNV regions (~56%) overlap with cattle genes (1,263), which are significantly enriched for immunity, lactation, reproduction and rumination. The overlap of this new dataset and other published CNV studies was less than 40%; however, our discovery of large, high frequency (> 5% of animals surveyed) CNV regions showed 90% agreement with other studies. These results highlight the differences and commonalities between technical platforms.</p> <p>Conclusions</p> <p>We present a comprehensive genomic analysis of cattle CNVs derived from SNP data which will be a valuable genomic variation resource. Combined with SNP detection assays, gene-containing CNV regions may help identify genes undergoing artificial selection in domesticated animals.</p

Ser/Thr/Tyr Protein Phosphorylation in the Archaeon Halobacterium salinarum—A Representative of the Third Domain of Life

In the quest for the origin and evolution of protein phosphorylation, the major regulatory post-translational modification in eukaryotes, the members of archaea, the “third domain of life”, play a protagonistic role. A plethora of studies have demonstrated that archaeal proteins are subject to post-translational modification by covalent phosphorylation, but little is known concerning the identities of the proteins affected, the impact on their functionality, the physiological roles of archaeal protein phosphorylation/dephosphorylation, and the protein kinases/phosphatases involved. These limited studies led to the initial hypothesis that archaea, similarly to other prokaryotes, use mainly histidine/aspartate phosphorylation, in their two-component systems representing a paradigm of prokaryotic signal transduction, while eukaryotes mostly use Ser/Thr/Tyr phosphorylation for creating highly sophisticated regulatory networks. In antithesis to the above hypothesis, several studies showed that Ser/Thr/Tyr phosphorylation is also common in the bacterial cell, and here we present the first genome-wide phosphoproteomic analysis of the model organism of archaea, Halobacterium salinarum, proving the existence/conservation of Ser/Thr/Tyr phosphorylation in the “third domain” of life, allowing a better understanding of the origin and evolution of the so-called “Nature's premier” mechanism for regulating the functional properties of proteins

A combined linkage, microarray and exome analysis suggests MAP3K11 as a candidate gene for left ventricular hypertrophy

Background: Electrocardiographic measures of left ventricular hypertrophy (LVH) are used as predictors of cardiovascular risk. We combined linkage and association analyses to discover novel rare genetic variants involved in three such measures and two principal components derived from them. Methods: The study was conducted among participants from the Erasmus Rucphen Family Study (ERF), a Dutch family-based sample from the southwestern Netherlands. Variance components linkage analyses were performed using Merlin. Regions of interest (LOD > 1.9) were fine-mapped using microarray and exome sequence data. Results: We observed one significant LOD score for the second principal component on chromosome 15 (LOD score = 3.01) and 12 suggestive LOD scores. Several loci contained variants identified in GWAS for these traits; however, these did not explain the linkage peaks, nor did other common variants. Exome sequence data identified two associated variants after multiple testing corrections were applied. Conclusions: We did not find common SNPs explaining these linkage signals. Exome sequencing uncovered a relatively rare variant in MAPK3K11 on chromosome 11 (MAF = 0.01) that helped account for the suggestive linkage peak observed for the first principal component. Conditional analysis revealed a drop in LOD from 2.01 to 0.88 for MAP3K11, suggesting that this variant may partially explain the linkage signal at this chromosomal location. MAP3K11 is related to the JNK pathway and is a pro-apoptotic kinase that plays an important role in the induction of cardiomyocyte apoptosis in various pathologies, including LVH

Human genomic regions with exceptionally high levels of population differentiation identified from 911 whole-genome sequences

Data availability: The 1000 Genomes phase I integrated callset used in this study is publicly available at [The 1000 Genomes Project. http://www.1000genomes.org/]. For a list of samples used in this study, refer to Table S1 in Additional file 1. Additional files: Additional file 1: This file contains supplementary Tables ST1 to ST4 (https://static-content.springer.com/esm/art%3A10.1186%2Fgb-2014-15-6-r88/MediaObjects/13059_2014_3364_MOESM1_ESM.xlsx). Additional file 2: This file contains supplementary Figures F1 to F16 (https://static-content.springer.com/esm/art%3A10.1186%2Fgb-2014-15-6-r88/MediaObjects/13059_2014_3364_MOESM2_ESM.pdf). Additional file 3: Full list of participants and institutions in the 1000 Genomes Project (https://static-content.springer.com/esm/art%3A10.1186%2Fgb-2014-15-6-r88/MediaObjects/13059_2014_3364_MOESM3_ESM.pdf).Copyright © 2014 Colonna et al. Background: Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes. Results: We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively. Conclusions: We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research.The Wellcome Trust (098051), an Italian National Research Council (CNR) short-term mobility fellowship from the 2013 program to VC, and an EMBO Short Term Fellowship ASTF 324–2010 to VC