Dynamics of cubic-tetragonal phase transition in KNbO3_3 perovskite

The low-energy part of the vibration spectrum in KNbO$_3$ was studied by cold neutron inelastic scattering in the cubic phase. In addition to acoustic phonons, we observe strong diffuse scattering, which consists of two components. The first one is quasi-static and has a temperature-independent intensity. The second component appears as quasi-elastic scattering in the neutron spectrum indicating a dynamic origin. From analysis of the inelastic data we conclude that the quasi-elastic component and the acoustic phonon are mutually coupled. The susceptibility associated with the quasi-elastic component grows as the temperature approaches T$_C$

Gamma phonons and microscopic structure of orthorhombic KNbO3 from first-principles calculations

{}From a series of total energy calculations by the full-potential linear muffin-tin orbital method, the total energy hypersurface as function of atomic displacements from equilibrium positions has been fitted for different Gamma phonon modes in orthorhombic KNbO3. Frequencies and eigenvectors of all TO Gamma phonons have been calculated in the harmonic approximation, and in the quantum oscillator scheme -- for A2 and B2 modes. The microscopic structure of the orthorhombic phase has been analyzed in a series of supercell calculations for different patterns of Nb displacements, providing indications in favour of the chain structure, with oppositely directed neighboring chains.Comment: 10 pages, including 3 LaTeX figure

Hypomineralized Second Primary Molars as Predictor of Molar Incisor Hypomineralization

Molar incisor hypomineralization (MIH) is a developmental defect of dental enamel that shares features with hypomineralized second primary molars (HSPM). Prior to permanent tooth eruption, second primary molars could have predictive value for permanent molar and incisor hypomineralization. To assess this possible relationship, a cross-sectional study was conducted in a sample of 414 children aged 8 and 9 years from the INMA cohort in Valencia (Spain). A calibrated examiner (linear-weighted Kappa 0.83) performed the intraoral examinations at the University of Valencia between November 2013 and 2014, applying the diagnostic criteria for MIH and HSPM adopted by the European Academy of Paediatric Dentistry. 100 children (24.2%) presented MIH and 60 (14.5%) presented HSPM. Cooccurrence of the two defects was observed in 11.1% of the children examined. The positive predictive value was 76.7% (63.9-86.6) and the negative predictive value 84.7% (80.6-88.3). The positive likelihood ratio (S/1-E) was 10.3 (5.9-17.9) and the negative likelihood ratio (1-S/E) 0.57 (0.47-0.68). The odds ratio was 18.2 (9.39-35.48). It was concluded that while the presence of HSPM can be considered a predictor of MIH, indicating the need for monitoring and control, the absence of this defect in primary dentition does not rule out the appearance of MIH

Cystatin A, a Potential Common Link for Mutant Myocilin Causative Glaucoma

Myocilin (MYOC) is a 504 aa secreted glycoprotein induced by stress factors in the trabecular meshwork tissue of the eye, where it was discovered. Mutations in MYOC are linked to glaucoma. The glaucoma phenotype of each of the different MYOC mutation varies, but all of them cause elevated intraocular pressure (IOP). In cells, forty percent of wild-type MYOC is cleaved by calpain II, a cysteine protease. This proteolytic process is inhibited by MYOC mutants. In this study, we investigated the molecular mechanisms by which MYOC mutants cause glaucoma. We constructed adenoviral vectors with variants Q368X, R342K, D380N, K423E, and overexpressed them in human trabecular meshwork cells. We analyzed expression profiles with Affymetrix U133Plus2 GeneChips using wild-type and null viruses as controls. Analysis of trabecular meshwork relevant mechanisms showed that the unfolded protein response (UPR) was the most affected. Search for individual candidate genes revealed that genes that have been historically connected to trabecular meshwork physiology and pathology were altered by the MYOC mutants. Some of those had known MYOC associations (MMP1, PDIA4, CALR, SFPR1) while others did not (EDN1, MGP, IGF1, TAC1). Some, were top-changed in only one mutant (LOXL1, CYP1B1, FBN1), others followed a mutant group pattern. Some of the genes were new (RAB39B, STC1, CXCL12, CSTA). In particular, one selected gene, the cysteine protease inhibitor cystatin A (CSTA), was commonly induced by all mutants and not by the wild-type. Subsequent functional analysis of the selected gene showed that CSTA was able to reduce wild-type MYOC cleavage in primary trabecular meshwork cells while an inactive mutated CSTA was not. These findings provide a new molecular understanding of the mechanisms of MYOC-causative glaucoma and reveal CSTA, a serum biomarker for cancer, as a potential biomarker and drug for the treatment of MYOC-induced glaucoma

The impact of sex on gene expression across human tissues

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation

Contrasting Biogeographic and Diversification Patterns in Two Mediterranean-Type Ecosystems

The five Mediterranean regions of the world comprise almost 50,000 plant species (ca 20% of the known vascular plants) despite accounting for less than 5% of the world’s land surface. The ecology and evolutionary history of two of these regions, the Cape Floristic Region and the Mediterranean Basin, have been extensively investigated, but there have been few studies aimed at understanding the historical relationships between them. Here, we examine the biogeographic and diversification processes that shaped the evolution of plant diversity in the Cape and the Mediterranean Basin using a large plastid data set for the geophyte family Hyacinthaceae (comprising ca. 25% of the total diversity of the group), a group found mainly throughout Africa and Eurasia. Hyacinthaceae is a predominant group in the Cape and the Mediterranean Basin both in terms of number of species and their morphological and ecological variability. Using state-of-the-art methods in biogeography and diversification, we found that the Old World members of the family originated in sub-Saharan Africa at the Paleocene–Eocene boundary and that the two Mediterranean regions both have high diversification rates, but contrasting biogeographic histories. While the Cape diversity has been greatly influenced by its relationship with sub-Saharan Africa throughout the history of the family, the Mediterranean Basin had no connection with the latter after the onset of the Mediterranean climate in the region and the aridification of the Sahara. The Mediterranean Basin subsequently contributed significantly to the diversity of neighbouring areas, especially Northern Europe and the Middle East, whereas the Cape can be seen as a biogeographical cul-de-sac, with only a few dispersals toward sub-Saharan Africa. The understanding of the evolutionary history of these two important repositories of biodiversity would benefit from the application of the framework developed here to other groups of plants present in the two regions

Precision of the current methods to measure the alkenone proxy UK'37 and absolute alkenone abundance in sediments : results of an interlaboratory comparison study

Measurements of the UK'37 index and the absolute abundance of alkenones in marine sediments are increasingly used in paleoceanographic research as proxies of past sea surface temperature and haptophyte (mainly coccolith-bearing species) primary productivity, respectively. An important aspect of these studies is to be able to compare reliably data obtained by different laboratories from a wide variety of locations. Hence the intercomparability of data produced by the research community is essential. Here we report results from an anonymous interlaboratory comparison study involving 24 of the leading laboratories that carry out alkenone measurements worldwide. The majority of laboratories produce data that are intercomparable within the considered confidence limits. For the measurement of alkenone concentrations, however, there are systematic biases between laboratories, which might be related to the techniques employed to quantify the components. The maximum difference between any two laboratories for any two single measurements of UK'37 in sediments is estimated, with a probability of 95%, to be <2.18C. In addition, the overall within-laboratory precision for the UK'37 temperature estimates is estimated to be <1.68C (95% probability). Similarly, from the analyses of alkenone concentrations the interlaboratory reproducibility is estimated at 32%, and the repeatability is estimated at 24%. The former is compared to a theoretical estimate of reproducibility and found to be excessively high. Hence there is certainly scope and a demonstrable need to improve reproducibility and repeatability of UK'37 and especially alkenone quantification data across the community of scientists involved in alkenone research

Genetic Structure of the Tree Peony (Paeonia rockii) and the Qinling Mountains as a Geographic Barrier Driving the Fragmentation of a Large Population

Tree peonies are great ornamental plants associated with a rich ethnobotanical history in Chinese culture and have recently been used as an evolutionary model. The Qinling Mountains represent a significant geographic barrier in Asia, dividing mainland China into northern (temperate) and southern (semi-tropical) regions; however, their flora has not been well analyzed. In this study, the genetic differentiation and genetic structure of Paeonia rockii and the role of the Qinling Mountains as a barrier that has driven intraspecific fragmentation were evaluated using 14 microsatellite markers.Twenty wild populations were sampled from the distributional range of P. rockii. Significant population differentiation was suggested (F(ST) value of 0.302). Moderate genetic diversity at the population level (H(S) of 0.516) and high population diversity at the species level (H(T) of 0.749) were detected. Significant excess homozygosity (F(IS) of 0.076) and recent population bottlenecks were detected in three populations. Bayesian clusters, population genetic trees and principal coordinate analysis all classified the P. rockii populations into three genetic groups and one admixed Wenxian population. An isolation-by-distance model for P. rockii was suggested by Mantel tests (r = 0.6074, P<0.001) and supported by AMOVA (P<0.001), revealing a significant molecular variance among the groups (11.32%) and their populations (21.22%). These data support the five geographic boundaries surrounding the Qinling Mountains and adjacent areas that were detected with Monmonier's maximum-difference algorithm.Our data suggest that the current genetic structure of P. rockii has resulted from the fragmentation of a formerly continuously distributed large population following the restriction of gene flow between populations of this species by the Qinling Mountains. This study provides a fundamental genetic profile for the conservation and responsible exploitation of the extant germplasm of this species and for improving the genetic basis for breeding its cultivars

Characterisation of age and polarity at onset in bipolar disorder

Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses

Characterisation of age and polarity at onset in bipolar disorder

Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses