Reply to comment on Couzi et al. (2018): a phenomenological model for structural phase transitions in incommensurate alkane/urea inclusion compounds.

In a recent paper (Couzi et al. 2018 R. Soc. open sci. 5, 180058. (doi:10.1098/rsos.180058)), we proposed a new phenomenological model to account for the I↔II↔"III" phase sequence in incommensurate n-alkane/urea inclusion compounds, which represents an alternative interpretation to that proposed in work of Toudic et al. In a Comment (Toudic et al. 2019 R. Soc. open sci. 6, 182073. (doi:10.1098/rsos.182073)), Toudic et al. have questioned our assignment of the superspace group of phase II of n-nonadecane/urea, which they have previously assigned, based on a (3 + 2)-dimensional superspace, as C2221(00γ)(10δ). In this Reply, we present new results from a comprehensive synchrotron single-crystal X-ray diffraction study of n-nonadecane/urea, involving measurements as a detailed function of temperature across the I↔II↔"III" phase transition sequence. Our results demonstrate conclusively that "main reflections" (h, k, l, 0) with h+k odd are observed in phase II of n-nonadecane/urea (including temperatures in phase II that are just below the transition from phase I to phase II), in full support of our assignment of the (3+1)-dimensional superspace group P212121(00γ) to phase II. As our phenomenological model is based on phase II and phase "III" of this incommensurate material having the same (3+1)-dimensional superspace group P212121(00γ), it follows that the new X-ray diffraction results are in full support of our phenomenological model.

A phenomenological model for structural phase transitions in incommensurate alkane/urea inclusion compounds.

n-Alkane/urea inclusion compounds are crystalline materials in which n-alkane 'guest' molecules are located within parallel one-dimensional 'host' tunnels formed by a helical hydrogen-bonded arrangement of urea molecules. The periodic repeat distance of the guest molecules along the host tunnels is incommensurate with the periodic repeat distance of the host substructure. The structural properties of the high-temperature phase of these materials (phase I), which exist at ambient temperature, are described by a (3 + 1)-dimensional superspace. Recent publications have suggested that, in the prototypical incommensurate composite systems, n-nonadecane/urea and n-hexadecane/urea, two low-temperature phases II and 'III' exist and that one or both of these phases are described by a (3 + 2)-dimensional superspace. We present a phenomenological model based on symmetry considerations and developed in the frame of a pseudo-spin-phonon coupling mechanism, which accounts for the mechanisms responsible for the I ↔ II ↔ 'III' phase sequence. With reference to published experimental data, we demonstrate that, in all phases of these incommensurate materials, the structural properties are described by (3 + 1)-dimensional superspace groups. Around the temperature of the II ↔ 'III' transition, the macroscopic properties of the material are not actually associated with a phase transition, but instead represent a 'crossover' between two regimes involving different couplings between relevant order parameters.

Bovine and murine models highlight novel roles for SLC25A46 in mitochondrial dynamics and metabolism, with implications for human and animal health.

Neuropathies are neurodegenerative diseases affecting humans and other mammals. Many genetic causes have been identified so far, including mutations of genes encoding proteins involved in mitochondrial dynamics. Recently, the "Turning calves syndrome", a novel sensorimotor polyneuropathy was described in the French Rouge-des-Prés cattle breed. In the present study, we determined that this hereditary disease resulted from a single nucleotide substitution in SLC25A46, a gene encoding a protein of the mitochondrial carrier family. This mutation caused an apparent damaging amino-acid substitution. To better understand the function of this protein, we knocked out the Slc25a46 gene in a mouse model. This alteration affected not only the nervous system but also altered general metabolism, resulting in premature mortality. Based on optic microscopy examination, electron microscopy and on biochemical, metabolic and proteomic analyses, we showed that the Slc25a46 disruption caused a fusion/fission imbalance and an abnormal mitochondrial architecture that disturbed mitochondrial metabolism. These data extended the range of phenotypes associated with Slc25a46 dysfunction. Moreover, this Slc25a46 knock-out mouse model should be useful to further elucidate the role of SLC25A46 in mitochondrial dynamics.

Spectroscopic and theoretical investigations of phenolic acids in white wines.

Model solutions of white wines containing phenolic acids have been investigated by means of UV-vis, laser induced fluorescence and Raman spectroscopic techniques. In order to interpret the spectra, density functional theory calculations of phenolic acids have been performed. This work demonstrates that only hydroxynamic acids are in resonance with a laser excitation line with 325nm wavelength and are therefore at the origin of the strong enhancement of the Raman light scattering. Real white wines also display such resonance Raman scattering so that their content in hydroxycinnamic acids may be quite precisely determined. The analysis of the Raman spectrum of a real dry white wine reveals qualitatively the preponderance in its composition of p-coumaric and caftaric acids.

NGS-based reverse genetic screen for common embryonic lethal mutations compromising fertility in livestock.

We herein report the result of a large-scale, next generation sequencing (NGS)-based screen for embryonic lethal (EL) mutations in Belgian beef and New Zealand dairy cattle. We estimated by simulation that cattle might carry, on average, ∼0.5 recessive EL mutations. We mined exome sequence data from >600 animals, and identified 1377 stop-gain, 3139 frame-shift, 1341 splice-site, 22,939 disruptive missense, 62,399 benign missense, and 92,163 synonymous variants. We show that cattle have a comparable load of loss-of-function (LoF) variants (defined as stop-gain, frame-shift, or splice-site variants) as humans despite having a more variable exome. We genotyped >40,000 animals for up to 296 LoF and 3483 disruptive missense, breed-specific variants. We identified candidate EL mutations based on the observation of a significant depletion in homozygotes. We estimated the proportion of EL mutations at 15% of tested LoF and 6% of tested disruptive missense variants. We confirmed the EL nature of nine candidate variants by genotyping 200 carrier × carrier trios, and demonstrating the absence of homozygous offspring. The nine identified EL mutations segregate at frequencies ranging from 1.2% to 6.6% in the studied populations and collectively account for the mortality of ∼0.6% of conceptuses. We show that EL mutations preferentially affect gene products fulfilling basic cellular functions. The resulting information will be useful to avoid at-risk matings, thereby improving fertility.

Virtual collaboration: effect of spatial configuration on spatial statements production.

When guiding a remote collaborator in a virtual environment, people often take an addressee-perspective, which may have a high cognitive cost. In order to improve collaborative virtual environments, a better understanding of how operators share spatial information is needed. This work aimed to study the cognitive workload linked to spatial statements production in situations in which the relative positions of speaker, addressee and target were varied. Twenty-two participants were asked to give--in one go--instructions to a virtual collaborator on how to find a target in a 3D environment. The scene showed an avatar in the center of eight tables. Sixty-four configurations of avatar orientation (eight possibilities) and target location (on the eight tables) were tested. We measured the delay in starting the instruction once the target appeared, the instruction duration and the subjective evaluation of mental demand. Each instruction was classified according to the spatial reference frame used. The delay was influenced by the processing of spatial information in ego-centered and addressee-centered reference frames. All subsequent measures were determined by mental transformations in addressee-centered coordinates. One condition in particular, when the target was situated diagonally behind the addressee, gave rise to a higher mental demand for the speaker, which points to the investment made by the speaker in achieving the least collaborative effort. Further work should seek to develop efficient tools to facilitate spatial communication in situations that induce the most mental workload.

Cu Nanoparticles Have Different Impacts in Escherichia coli and Lactobacillus brevis than Their Microsized and Ionic Analogues.

Copper formulations have been used for decades for antimicrobial and antifouling applications. With the development of nanoformulations of copper that are more effective than their ionic and microsized analogues, a key regulatory question is whether these materials should be treated as new or existing materials. To address this issue, here we compare the magnitude and mechanisms of toxicity of a series of Cu species (at concentration ranging from 2 to 250 µg/mL), including nano Cu, nano CuO, nano Cu(OH)2 (CuPro and Kocide), micro Cu, micro CuO, ionic Cu(2+) (CuCl2 and CuSO4) in two species of bacteria (Escherichia coli and Lactobacillus brevis). The primary size of the particles studied ranged from 10 nm to 10 µm. Our results reveal that Cu and CuO nanoparticles (NPs) are more toxic than their microsized counterparts at the same Cu concentration, with toxicities approaching those of the ionic Cu species. Strikingly, these NPs showed distinct differences in their mode of toxicity when compared to the ionic and microsized Cu, highlighting the unique toxicity properties of materials at the nanoscale. In vitro DNA damage assays reveal that both nano Cu and microsized Cu are capable of causing complete degradation of plasmid DNA, but electron tomography results show that only nanoformulations of Cu are internalized as intact intracellular particles. These studies suggest that nano Cu at the concentration of 50 µg/mL may have unique genotoxicity in bacteria compared to ionic and microsized Cu.

Raman spectroscopy of white wines.

The feasibility of exploiting Raman scattering to analyze white wines has been investigated using 3 different wavelengths of the incoming laser radiation in the near-UV (325 nm), visible (532 nm) and near infrared (785 nm). To help in the interpretation of the Raman spectra, the absorption properties in the UV-visible range of two wine samples as well as their laser induced fluorescence have also been investigated. Thanks to the strong intensity enhancement of the Raman scattered light due to electronic resonance with 325 nm laser excitation, hydroxycinnamic acids may be detected and analyzed selectively. Fructose and glucose may also be easily detected below ca. 1000 cm(-1). This feasibility study demonstrates the potential of the Raman spectroscopic technique for the analysis of white wines.

Implantes cocleares: aspectos tecnológicos e papel socioeconômico / Cochlear implants: technological aspects and socioeconomic role

INTRODUÇÃO: O grande número de deficientes auditivos faz da perda auditiva um sério problema social, econômico e de saúde pública. Próteses auditivas e implantes cocleares representam os principais dispositivos utilizados como paliativos por pessoas com deficiência auditiva, sendo que os implantes cocleares são muitas vezes a única opção nos casos de deficiência auditiva severa e profunda. Nesse artigo discute-se de maneira geral os diferentes aspectos envolvendo implantes cocleares, tanto de âmbito tecnológico como seu papel socioeconômico. MÉTODOS: Baseado em dados do SUS, IBGE e outras fontes, um levantamento qualitativo e quantitativo é feito pela primeira vez especificamente para a população brasileira. O artigo discute ainda o estado da arte das tecnologias envolvidas no implante coclear, com base em literatura científica e informações de fabricantes, bem como as perspectivas para as próximas gerações de implantes cocleares. CONCLUSÃO: Há potencial e demanda para evoluções nos implantes atuais. A implantação precoce é benéfica para pacientes e sociedade, compensando os custos econômica e socialmente. No entanto, as políticas públicas de reabilitação necessitam se adequar para atender com eficácia à crescente população afetada pela deficiência auditiva.

INTRODUCTION: Due to the great number of affected people, hearing loss is considered a serious social, economic and public health problem. Hearing aids and cochlear implants are the primary devices used as palliatives for people with hearing loss, and cochlear implants are often the only option in cases of severe to profound hearing impairment. This paper covers both technological and socio-economic aspects of cochlear implant, which is considered as one of most recommended treatments to alleviate severe to profound hearing loss. METHODS: Brazilian unified health system data is used to display qualitative and quantitative analysis impact on Brazilian population and government. A state-of-art review based on scientific literature and manufacturer data is provided, as well as perspectives for the next cochlear implant generation. CONCLUSION: There is potential and demand for evolutions in current implants. Early implantation is beneficial for patients and society, compensating the costs economic and socially. However, public programs need to adapt in order to efficiently attend the increasing affected population.

Determination of subject-specific muscle fatigue rates under static fatiguing operations.

Cumulative local muscle fatigue may lead to potential musculoskeletal disorder (MSD) risks, and subject-specific muscle fatigability needs to be considered to reduce potential MSD risks. This study was conducted to determine local muscle fatigue rate at shoulder joint level based on an exponential function derived from a muscle fatigue model. Forty male subjects participated in a fatiguing operation under a static posture with a range of relative force levels (14-33%). Maximum muscle strengths over time were measured after different fatiguing sessions. The time course of strength decline was fitted to the exponential function. Subject-specific fatigue rates of shoulder joint moment strength were determined. Good correspondence ([Formula: see text]) was found in the regression of the majority (35 out of 40 subjects). Substantial inter-individual variability in fatigue rate was found and discussed.

Controlling spatial distributions of molecules in multicomponent organic crystals, with quantitative mapping by confocal Raman microspectrometry.

We report four experimental strategies for controlling the three-dimensional arrangement of molecules in multicomponent organic crystals, exploiting confocal Raman microspectrometry to quantify the three-dimensional spatial distributions. Specifically, we focus on controlling the distribution of two types of guest molecule in solid organic inclusion compounds to produce composite core-shell crystals, crystals with a homogeneous distribution of the components, crystals with continuous compositional variation from the core to the surface, and crystals with alternating shells of the components. In this context, confocal Raman microspectrometry is particularly advantageous over optical microscopy as it is nondestructive, offers micrometric spatial resolution, and relies only on the component molecules having different vibrational properties.

High-density marker imputation accuracy in sixteen French cattle breeds.

BACKGROUND: Genotyping with the medium-density Bovine SNP50 BeadChip® (50K) is now standard in cattle. The high-density BovineHD BeadChip®, which contains 777,609 single nucleotide polymorphisms (SNPs), was developed in 2010. Increasing marker density increases the level of linkage disequilibrium between quantitative trait loci (QTL) and SNPs and the accuracy of QTL localization and genomic selection. However, re-genotyping all animals with the high-density chip is not economically feasible. An alternative strategy is to genotype part of the animals with the high-density chip and to impute high-density genotypes for animals already genotyped with the 50K chip. Thus, it is necessary to investigate the error rate when imputing from the 50K to the high-density chip. METHODS: Five thousand one hundred and fifty three animals from 16 breeds (89 to 788 per breed) were genotyped with the high-density chip. Imputation error rates from the 50K to the high-density chip were computed for each breed with a validation set that included the 20% youngest animals. Marker genotypes were masked for animals in the validation population in order to mimic 50K genotypes. Imputation was carried out using the Beagle 3.3.0 software. RESULTS: Mean allele imputation error rates ranged from 0.31% to 2.41% depending on the breed. In total, 1980 SNPs had high imputation error rates in several breeds, which is probably due to genome assembly errors, and we recommend to discard these in future studies. Differences in imputation accuracy between breeds were related to the high-density-genotyped sample size and to the genetic relationship between reference and validation populations, whereas differences in effective population size and level of linkage disequilibrium showed limited effects. Accordingly, imputation accuracy was higher in breeds with large populations and in dairy breeds than in beef breeds. More than 99% of the alleles were correctly imputed if more than 300 animals were genotyped at high-density. No improvement was observed when multi-breed imputation was performed. CONCLUSION: In all breeds, imputation accuracy was higher than 97%, which indicates that imputation to the high-density chip was accurate. Imputation accuracy depends mainly on the size of the reference population and the relationship between reference and target populations.

Spin crossover complexes [Fe(NH2trz)3](X)2·nH2O investigated by means of polarized Raman scattering and DFT calculations.

Vibrational spectra of the spin crossover (SCO) polymers [Fe(NH2trz)3](X)2·nH2O where NH2trz = 4-NH2-1,2,4-triazole and X = Cl, Br, BF4, and NO3 have been analyzed. Our results show that the anions and water molecules have no significant influence on the vibrational properties of the Fe(NH2-trz)3 polymer chains. A detailed study of the nitrate derivative, based on the DFT analysis of the polarized spectra of single crystals, has been undertaken to propose the normal mode assignment of the Raman peaks in the low spin state of the compound. Changes in the Raman spectra in the high spin state could therefore be analyzed and interpreted by several Raman bands identified as molecular probes of the SCO phenomenon. Various factors (laser power, humidity, pressure) that influence the transition temperatures and the hysteresis loops have been identified and adjusted for obtaining reliable measurements. We demonstrate in particular that all the techniques used to probe the phase transition process give comparable results providing that the sample environment is well controlled.

Fine tuning genomic evaluations in dairy cattle through SNP pre-selection with the Elastic-Net algorithm.

For genomic selection methods, the statistical challenge is to estimate the effect of each of the available single-nucleotide polymorphism (SNP). In a context where the number of SNPs (p) is much higher than the number of bulls (n), this task may lead to a poor estimation of these SNP effects if, as for genomic BLUP (gBLUP), all SNPs have a non-null effect. An alternative is to use approaches that have been developed specifically to solve the 'p >> n' problem. This is the case of variable selection methods and among them, we focus on the Elastic-Net (EN) algorithm that is a penalized regression approach. Performances of EN, gBLUP and pedigree-based BLUP were compared with data from three French dairy cattle breeds, giving very encouraging results for EN. We tried to push further the idea of improving SNP effect estimates by considering fewer of them. This variable selection strategy was considered both in the case of gBLUP and EN by adding an SNP pre-selection step based on quantitative trait locus (QTL) detection. Similar results were observed with or without a pre-selection step, in terms of correlations between direct genomic value (DGV) and observed daughter yield deviation in a validation data set. However, when applied to the EN algorithm, this strategy led to a substantial reduction of the number of SNPs included in the prediction equation. In a context where the number of genotyped animals and the number of SNPs gets larger and larger, SNP pre-selection strongly alleviates computing requirements and ensures that national evaluations can be completed within a reasonable time frame.

A common reference population from four European Holstein populations increases reliability of genomic predictions.

BACKGROUND: Size of the reference population and reliability of phenotypes are crucial factors influencing the reliability of genomic predictions. It is therefore useful to combine closely related populations. Increased accuracies of genomic predictions depend on the number of individuals added to the reference population, the reliability of their phenotypes, and the relatedness of the populations that are combined. METHODS: This paper assesses the increase in reliability achieved when combining four Holstein reference populations of 4000 bulls each, from European breeding organizations, i.e. UNCEIA (France), VikingGenetics (Denmark, Sweden, Finland), DHV-VIT (Germany) and CRV (The Netherlands, Flanders). Each partner validated its own bulls using their national reference data and the combined data, respectively. RESULTS: Combining the data significantly increased the reliability of genomic predictions for bulls in all four populations. Reliabilities increased by 10%, compared to reliabilities obtained with national reference populations alone, when they were averaged over countries and the traits evaluated. For different traits and countries, the increase in reliability ranged from 2% to 19%. CONCLUSIONS: Genomic selection programs benefit greatly from combining data from several closely related populations into a single large reference population.

Raman spectroscopy probing of self-assembled monolayers inside the pores of gold nanotube membranes.

Electroless deposition was used to coat porous alumina membranes with gold. This process reduced the pore diameters and provided a platform suitable for surface modifications with self assembled monolayers (SAMs). The surface enhanced Raman scattering (SERS) effect was employed in order to confirm and characterise the formation of SAMs of 3-mercaptobenzoic acid (mMBA) inside the pores of gold nanotube membranes prepared using porous alumina (PA) templates. The investigation of the coverage and reproducibility of SAMs within porous matrices is of utmost importance in the design of filtration membranes and sensing platforms. Raman spectroscopy is capable of spatially resolved techniques such as mapping which was used to characterise the distribution of mMBA assembly within the pores. Due to the highly ordered structure of porous alumina and well controlled electroless gold deposition, these gold coated membranes have the potential to develop into SERS active substrates for ultrasensitive sensing technologies.

Improved Lasso for genomic selection.

Empirical experience with genomic selection in dairy cattle suggests that the distribution of the effects of single nucleotide polymorphisms (SNPs) might be far from normality for some traits. An alternative, avoiding the use of arbitrary prior information, is the Bayesian Lasso (BL). Regular BL uses a common variance parameter for residual and SNP effects (BL1Var). We propose here a BL with different residual and SNP effect variances (BL2Var), equivalent to the original Lasso formulation. The λ parameter in Lasso is related to genetic variation in the population. We also suggest precomputing individual variances of SNP effects by BL2Var, to be later used in a linear mixed model (HetVar-GBLUP). Models were tested in a cross-validation design including 1756 Holstein and 678 Montbéliarde French bulls, with 1216 and 451 bulls used as training data; 51 325 and 49 625 polymorphic SNP were used. Milk production traits were tested. Other methods tested included linear mixed models using variances inferred from pedigree estimates or integrated out from the data. Estimates of genetic variation in the population were close to pedigree estimates in BL2Var but not in BL1Var. BL1Var shrank breeding values too little because of the common variance. BL2Var was the most accurate method for prediction and accommodated well major genes, in particular for fat percentage. BL1Var was the least accurate. HetVar-GBLUP was almost as accurate as BL2Var and allows for simple computations and extensions.

A strategy for QTL fine-mapping using a dense SNP map.

BACKGROUND: Dense marker maps require efficient statistical methods for QTL fine mapping that work fast and efficiently with a large number of markers. In this study, the simulated dataset for the XIIth QTLMAS workshop was analyzed using a QTL fine mapping set of tools. METHODS: The QTL fine-mapping strategy was based on the use of statistical methods combining linkage and linkage disequilibrium analysis. Variance component based linkage analysis provided confidence intervals for the QTL. Within these regions, two additional analyses combining both linkage analysis and linkage disequilibrium information were applied. The first method estimated identity-by-descent probabilities among base haplotypes that were used to group them in different clusters. The second method constructed haplotype groups based on identity-by-state probabilities. RESULTS: Two QTL explaining 9.4 and 3.3% of the genetic variance were found with high significance on chromosome 1 at positions 19.5 and 76.6 cM. On chromosome 2, two QTL were also detected at positions 26.0 and 53.2 explaining respectively 9.0 and 7.8 of total genetic variance. The QTL detected on chromosome 3 at position 11.9 cM (5% of variance) was less important. The QTL with the highest effect (37% of variance) was detected on chromosome 4 at position 3.1 cM and another QTL (13.6% of variance) was detected on chromosome 5 at position 93.9 cM. CONCLUSION: The proposed strategy for fine-mapping of QTL combining linkage and linkage disequilibrium analysis allowed detecting the most important QTL with an additive effect in a short period but it should be extended in the future in order to fine-map linked and epistatic QTL.

Fine mapping of quantitative trait loci affecting female fertility in dairy cattle on BTA03 using a dense single-nucleotide polymorphism map.

Fertility quantitative trait loci (QTL) are of high interest in dairy cattle since insemination failure has dramatically increased in some breeds such as Holstein. High-throughput SNP analysis and SNP microarrays give the opportunity to genotype many animals for hundreds SNPs per chromosome. In this study, due to these techniques a dense SNP marker map was used to fine map a QTL underlying nonreturn rate measured 90 days after artificial insemination previously detected with a low-density microsatellite marker map. A granddaughter design with 17 Holstein half-sib families (926 offspring) was genotyped for a set of 437 SNPs mapping to BTA3. Linkage analysis was performed by both regression and variance components analysis. An additional analysis combining both linkage analysis and linkage-disequilibrium information was applied. This method first estimated identity-by-descent probabilities among base haplotypes. These probabilities were then used to group the base haplotypes in different clusters. A QTL explaining 14% of the genetic variance was found with high significance (P < 0.001) at position 19 cM with the linkage analysis and four sires were estimated to be heterozygous (P < 0.05). Addition of linkage-disequilibrium information refined the QTL position to a set of narrow peaks. The use of the haplotypes of heterozygous sires offered the possibility to give confidence in some peaks while others could be discarded. Two peaks with high likelihood-ratio test values in the region of which heterozygous sires shared a common haplotype appeared particularly interesting. Despite the fact that the analysis did not fine map the QTL in a unique narrow region, the method proved to be able to handle efficiently and automatically a large amount of information and to refine the QTL position to a small set of narrow intervals. In addition, the QTL identified was confirmed to have a large effect (explaining 13.8% of the genetic variance) on dairy cow fertility as estimated by nonreturn rate at 90 days.