Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity.

The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), that promotes pulmonary type 2 immunity. Mechanistically, SAA1 interacted directly with allergenic mite FABPs (Der p 13 and Blo t 13). The interaction between mite FABPs and SAA1 activated the SAA1-binding receptor, formyl peptide receptor 2 (FPR2), which drove the epithelial release of the type-2-promoting cytokine interleukin (IL)-33 in a SAA1-dependent manner. Importantly, the SAA1-FPR2-IL-33 axis was upregulated in nasal epithelial cells from patients with chronic rhinosinusitis. These findings identify an unrecognized role for SAA1 as a soluble pattern recognition receptor for conserved FABPs found in common mite allergens that initiate type 2 immunity at mucosal surfaces.

Winners vs. losers: Schistosoma mansoni intestinal and liver eggs exhibit striking differences in gene expression and immunogenicity.

The eggs of the blood fluke Schistosoma mansoni are the main cause of the clinical manifestations of chronic schistosomiasis. After laying, the egg "winners" attach to the endothelium of the mesenteric vein and, after a period of development, induce the growth of a small granuloma, which facilitates their passage to the intestinal lumen. Egg "losers" carried by the bloodstream to non-specific tissues also undergo full development and induce large granuloma formation, but their life ends there. Although these trapped eggs represent a dead end in the parasite life cycle, the vast majority of studies attempting to describe the biology of the S. mansoni eggs have studied these liver-trapped "losers" instead of migrating intestinal "winners". This raises the fundamental question of how these eggs differ. With robust comparative transcriptomic analysis performed on S. mansoni eggs isolated 7 weeks post infection, we show that gene expression is critically dependent on tissue localization, both in the early and late stages of development. While mitochondrial genes and venom allergen-like proteins are significantly upregulated in mature intestinal eggs, well-described egg immunomodulators IPSE/alpha-1 and omega-1, together with micro-exon genes, are predominantly expressed in liver eggs. In addition, several proteases and protease inhibitors previously implicated in egg-host interactions display clear tissue-specific gene expression patterns. These major differences in gene expression could be then reflected in the observed different ability of liver and intestinal soluble egg antigens to elicit host immune responses and in the shorter viability of miracidia hatched from liver eggs. Our comparative analysis provides a new perspective on the biology of parasite's eggs in the context of their development and tissue localization. These findings could contribute to a broader and more accurate understanding of parasite eggs interactions with the host, which have historically been often restricted to liver eggs and sometimes inaccurately generalized.

Evaluation of adherence to abiraterone therapy in prostate cancer patients based on a population pharmacokinetic model.

AIMS: Abiraterone treatment requires regular drug intake under fasting conditions due to pronounced food effect, which may impact patient adherence. The aim of this prospective study was to evaluate adherence to abiraterone treatment in patients with prostate cancer. To achieve this aim, an abiraterone population pharmacokinetic model was developed and patients' adherence has been estimated by comparison of measured levels of abiraterone with population model-based simulations. METHODS: A total of 1469 abiraterone plasma levels from 83 healthy volunteers collected in a bioequivalence study were analysed using a nonlinear mixed-effects model. Monte Carlo simulation was used to describe the theoretical distribution of abiraterone pharmacokinetic profiles at a dose of 1000 mg once daily. Adherence of 36 prostate cancer patients treated with abiraterone was then evaluated by comparing the real abiraterone concentration measured in each patient during follow-up visit with the theoretical distribution of profiles based on simulations. Patients whose abiraterone levels were ˂5th or ˃95th percentile of the distribution of simulated profiles were considered to be non-adherent. RESULTS: Based on this evaluation, 13 patients (36%) have been classified as non-adherent. We observed significant association (P = .0361) between richness of the breakfast and rate of non-adherence. Adherent patients reported significantly better overall condition in self-assessments (P = .0384). A trend towards a higher occurrence of adverse effects in non-adherent patients was observed. CONCLUSIONS: We developed an abiraterone population pharmacokinetic model and proposed an advanced approach to medical adherence evaluation. Due to the need for administration under fasting conditions, abiraterone therapy is associated with a relatively high rate of non-adherence.

Genome sequence of the progenitor of the wheat D genome Aegilops tauschii.

Aegilops tauschii is the diploid progenitor of the D genome of hexaploid wheat (Triticum aestivum, genomes AABBDD) and an important genetic resource for wheat. The large size and highly repetitive nature of the Ae. tauschii genome has until now precluded the development of a reference-quality genome sequence. Here we use an array of advanced technologies, including ordered-clone genome sequencing, whole-genome shotgun sequencing, and BioNano optical genome mapping, to generate a reference-quality genome sequence for Ae. tauschii ssp. strangulata accession AL8/78, which is closely related to the wheat D genome. We show that compared to other sequenced plant genomes, including a much larger conifer genome, the Ae. tauschii genome contains unprecedented amounts of very similar repeated sequences. Our genome comparisons reveal that the Ae. tauschii genome has a greater number of dispersed duplicated genes than other sequenced genomes and its chromosomes have been structurally evolving an order of magnitude faster than those of other grass genomes. The decay of colinearity with other grass genomes correlates with recombination rates along chromosomes. We propose that the vast amounts of very similar repeated sequences cause frequent errors in recombination and lead to gene duplications and structural chromosome changes that drive fast genome evolution.

Current-induced bond rupture in single-molecule junctions: Effects of multiple electronic states and vibrational modes.

Current-induced bond rupture is a fundamental process in nanoelectronic architectures, such as molecular junctions, and scanning tunneling microscopy measurements of molecules at surfaces. The understanding of the underlying mechanisms is important for the design of molecular junctions that are stable at higher bias voltages and is a prerequisite for further developments in the field of current-induced chemistry. In this work, we analyze the mechanisms of current-induced bond rupture employing a recently developed method, which combines the hierarchical equations of motion approach in twin space with the matrix product state formalism and allows accurate, fully quantum mechanical simulations of the complex bond rupture dynamics. Extending previous work [Ke et al. J. Chem. Phys. 154, 234702 (2021)], we consider specifically the effect of multiple electronic states and multiple vibrational modes. The results obtained for a series of models of increasing complexity show the importance of vibronic coupling between different electronic states of the charged molecule, which can enhance the dissociation rate at low bias voltages profoundly.

Effect of pelvic floor status on the outcome of pelvic organ prolapse surgery.

Pelvic organ prolapse (POP) is a common diagnosis with an incidence in the population of up to 50%. POP causes restrictions in everyday life and reduces patients' quality of life. Therapy is either conservative in the form of physiotherapy or the use of different types of pessaries, possibly. in case of inappropriateness or failure of conservative treatment, an operative solution is chosen. Avulsion injury of the levator ani muscle (MLA) is a strong factor in the development of POP. Some patients undergo repeated surgeries for POP, negatively impacting their quality of life. Studies show that the stage of POP and avulsion injury is associated with an increased risk of recurrence after index prolapse surgery. Ultrasound diagnosis of MLA injuries might help in predicting the risk of recurrence. Assessment of pelvic floor function is crucial for the success of surgical management of POP.

Optical maps refine the bread wheat Triticum aestivum cv. Chinese Spring genome assembly.

Until recently, achieving a reference-quality genome sequence for bread wheat was long thought beyond the limits of genome sequencing and assembly technology, primarily due to the large genome size and > 80% repetitive sequence content. The release of the chromosome scale 14.5-Gb IWGSC RefSeq v1.0 genome sequence of bread wheat cv. Chinese Spring (CS) was, therefore, a milestone. Here, we used a direct label and stain (DLS) optical map of the CS genome together with a prior nick, label, repair and stain (NLRS) optical map, and sequence contigs assembled with Pacific Biosciences long reads, to refine the v1.0 assembly. Inconsistencies between the sequence and maps were reconciled and gaps were closed. Gap filling and anchoring of 279 unplaced scaffolds increased the total length of pseudomolecules by 168 Mb (excluding Ns). Positions and orientations were corrected for 233 and 354 scaffolds, respectively, representing 10% of the genome sequence. The accuracy of the remaining 90% of the assembly was validated. As a result of the increased contiguity, the numbers of transposable elements (TEs) and intact TEs have increased in IWGSC RefSeq v2.1 compared with v1.0. In total, 98% of the gene models identified in v1.0 were mapped onto this new assembly through development of a dedicated approach implemented in the MAGAAT pipeline. The numbers of high-confidence genes on pseudomolecules have increased from 105 319 to 105 534. The reconciled assembly enhances the utility of the sequence for genetic mapping, comparative genomics, gene annotation and isolation, and more general studies on the biology of wheat.

Optical characterization of inhomogeneous thin films with randomly rough boundaries exhibiting wide intervals of spatial frequencies.

Results concerning the optical characterization of two inhomogeneous polymer-like thin films deposited by the plasma enhanced chemical vapor deposition onto silicon single crystal substrates are presented. One of these films is deposited onto a smooth silicon surface while the latter film is deposited on a randomly rough silicon surface with a wide interval of spatial frequencies. A combination of variable-angle spectroscopic ellipsometry and spectroscopic reflectometry applied at near-normal incidence are utilized for characterizing both the films. An inhomogeneity of the films is described by the method based on multiple-beam interference of light and method replacing inhomogeneous thin films by multilayer systems. Homogeneous transition layers between the films and substrates are considered. The Campi-Coriasso dispersion model is used to express spectral dependencies of the optical constants of the polymer-like films and transition layers. A combination of the scalar diffraction theory and Rayleigh-Rice theory is used to include boundary roughness into formulae for the optical quantities of the rough polymer-like film. Within the optical characterization, the spectral dependencies of the optical constants at the upper and lower boundaries of both the polymer-like films are determined together with their thickness values and profiles of the optical constants. Roughness parameters are determined for the rough film. The values of the roughness parameters are confirmed by atomic force microscopy. Moreover, the optical constants and thicknesses of both the transition layers are determined. A discussion of the achieved results for both the polymer-like films and transition layers is performed.

Vibronic Coupling through the Continuum in the e+CO_{2} System.

We report two-dimensional electron energy-loss spectra of CO_{2}. The high-resolution experiment reveals a counterintuitive fine structure at energy losses where CO_{2} states form a vibrational pseudocontinuum. Guided by the symmetry of the system, we constructed a four-dimensional nonlocal model for the vibronic dynamics involving two shape resonances (forming a Renner-Teller Π_{u} doublet at the equilibrium geometry) coupled to a virtual Σ_{g}^{+} state. The model elucidates the extremely non-Born-Oppenheimer dynamics of the coupled nuclear motion and explains the origin of the observed structures. It is a prototype of the vibronic coupling of metastable states in continuum.

On Systematic Design of Fractional-Order Element Series.

In this paper a concept for the efficient design of a series of floating fractional-order elements (FOEs) is proposed. Using even single or a very limited number of so-called "seed" FOEs it is possible to obtain a wide set of new FOEs featuring fractional order α being in the range [-n,n], where n is an arbitrary integer number, and hence enables to overcome the lack of commercial unavailability of FOEs. The systematic design stems from the utilization of a general immittance converter (GIC), whereas the concept is further developed by proposing a general circuit structure of the GIC that employs operational transconductance amplifiers (OTAs) as active elements. To show the efficiency of the presented approach, the use of only up to two "seed" FOEs with a properly selected fractional order αseed as passive elements results in the design of a series of 51 FOEs with different α being in the range [-2,2] that may find their utilization in sensor applications and the design of analog signal processing blocks. Comprehensive analysis of the proposed GIC is given, whereas the effect of parasitic properties of the assumed active elements is determined and the optimization process described to improve the overall performance of the GIC. Using OTAs designed in 0.18 µµm TSMC CMOS technology, Cadence Virtuoso post-layout simulation results of the GIC are presented that prove its operability, performance optimization, and robustness of the proposed design concept.

Obstetric anal sphincter injury and anal incontinence.

OBJECTIVE: The aim of our study is to clarify the problems of OASI (obstetric anal sphincter injuries) and anal incontinence and prevention of this injury. METHODS: Review of articles in peer reviewed journals with the usage of Google Scholar function and PubMed. CONCLUSION: OASI is a severe injury which is more commonly associated with assisted vaginal delivery. This injury cannot be fully prevented, but its incidence can be averted by the usage of selective mediolateral episiotomy, or by other precautionary moves in high risk patients. The treatment of anal incontinence after OASI requires a complex approach and thorough examination. At first delivery, OASI is not a stern indication for caesarean section in accordance with current state of knowledge.

Hybrid assembly of the large and highly repetitive genome of Aegilops tauschii, a progenitor of bread wheat, with the MaSuRCA mega-reads algorithm.

Long sequencing reads generated by single-molecule sequencing technology offer the possibility of dramatically improving the contiguity of genome assemblies. The biggest challenge today is that long reads have relatively high error rates, currently around 15%. The high error rates make it difficult to use this data alone, particularly with highly repetitive plant genomes. Errors in the raw data can lead to insertion or deletion errors (indels) in the consensus genome sequence, which in turn create significant problems for downstream analysis; for example, a single indel may shift the reading frame and incorrectly truncate a protein sequence. Here, we describe an algorithm that solves the high error rate problem by combining long, high-error reads with shorter but much more accurate Illumina sequencing reads, whose error rates average <1%. Our hybrid assembly algorithm combines these two types of reads to construct mega-reads, which are both long and accurate, and then assembles the mega-reads using the CABOG assembler, which was designed for long reads. We apply this technique to a large data set of Illumina and PacBio sequences from the species Aegilops tauschii, a large and extremely repetitive plant genome that has resisted previous attempts at assembly. We show that the resulting assembled contigs are far larger than in any previous assembly, with an N50 contig size of 486,807 nucleotides. We compare the contigs to independently produced optical maps to evaluate their large-scale accuracy, and to a set of high-quality bacterial artificial chromosome (BAC)-based assemblies to evaluate base-level accuracy.

Introgression of perennial growth habit from Lophopyrum elongatum into wheat.

KEY MESSAGE: A locus for perennial growth was mapped on Lophopyrum elongatum chromosome arm 4ES and introgressed into the wheat genome. Evidence was obtained that in addition to chromosome 4E, other L. elongatum chromosomes control perennial growth. Monocarpy versus polycarpy is one of the fundamental developmental dichotomies in flowering plants. Advances in the understanding of the genetic basis of this dichotomy are important for basic biological reasons and practically for genetic manipulation of growth development in economically important plants. Nine wheat introgression lines (ILs) harboring germplasm of the Lophopyrum elongatum genome present in the octoploid amphiploid Triticum aestivum cv. Chinese Spring (subgenomes AABBDD) × L. elongatum (genomes EE) were selected from a population of ILs developed earlier. These ILs were employed here in genomic analyses of post-sexual cycle regrowth (PSCR), which is a component of polycarpy in caespitose L. elongatum. Analyses of disomic substitution (DS) lines confirmed that L. elongatum chromosome 4E confers PSCR on wheat. The gene was mapped into a short distal region of L. elongatum arm 4ES and was tentatively named Pscr1. ILs harboring recombined chromosomes with 4ES segments, including Pscr1, incorporated into the distal part of the 4DS chromosome arm were identified. Based on the location, Pscr1 is not orthologous with the rice rhizome-development gene Rhz2 located on rice chromosome Os3, which is homoeologous with chromosome 4E, but it may correspond to the Teosinte branched1 (TB1) gene, which is located in the introgressed region in the L. elongatum and Ae. tauschii genomes. A hexaploid IL harboring a large portion of the E-genome but devoid of chromosome 4E also expressed PSCR, which provided evidence that perennial growth is controlled by genes on other L. elongatum chromosomes in addition to 4E.

Genome-wide introgression from a bread wheat × Lophopyrum elongatum amphiploid into wheat.

KEY MESSAGE: We introgressed wheatgrass germplasm from the octoploid amphiploid Triticum aestivum× Lophopyrum elongatum into wheat by manipulating the wheat Ph1 gene and discovered and characterized 130 introgression lines harboring single or, in various combinations, complete and recombined L. elongatum chromosomes. Diploid wheatgrass Lophopyrum elongatum (genomes EE) possesses valuable traits for wheat genetics and breeding. We evaluated several strategies for introgression of this germplasm into wheat. To detect it, we developed and validated multiplexed sets of Sequenom MassARRAY single nucleotide polymorphism (SNP) markers, which differentiated disomic and monosomic L. elongatum chromosomes from wheat chromosomes. We identified 130 introgression lines (ILs), which harbored 108 complete and 89 recombined L. elongatum chromosomes. Of the latter, 59 chromosomes were recombined by one or more crossovers and 30 were involved in centromeric (Robertsonian) translocations or were telocentric. To identify wheat chromosomes substituted for or recombined with L. elongatum chromosomes, we genotyped the ILs with the wheat 90-K Infinium SNP array. We found that most of the wheat 90-K probes correctly detected their targets in the L. elongatum genome and showed that some wheat SNPs are ancient and had originated prior to the divergence of the wheat and L. elongatum lineages. Of the 130 ILs, 52% were homozygous for Ph1 deletion and thus are staged to be recombined further. We failed to detect in the L. elongatum genome the 4/5 reciprocal translocation that has been reported in Thinopyrum bessarabicum and several other Triticeae genomes.

Structural variation and rates of genome evolution in the grass family seen through comparison of sequences of genomes greatly differing in size.

Homology was searched with genes annotated in the Aegilops tauschii pseudomolecules against genes annotated in the pseudomolecules of tetraploid wild emmer wheat, Brachypodium distachyon, sorghum and rice. Similar searches were performed with genes annotated in the rice pseudomolecules. Matrices of collinear genes and rearrangements in their order were constructed. Optical BioNano genome maps were constructed and used to validate rearrangements unique to the wild emmer and Ae. tauschii genomes. Most common rearrangements were short paracentric inversions and short intrachromosomal translocations. Intrachromosomal translocations outnumbered segmental intrachromosomal duplications. The densities of paracentric inversion lengths were approximated by exponential distributions in all six genomes. Densities of collinear genes along the Ae. tauschii chromosomes were highly correlated with meiotic recombination rates but those of rearrangements were not, suggesting different causes of the erosion of gene collinearity and evolution of major chromosome rearrangements. Frequent rearrangements sharing breakpoints suggested that chromosomes have been rearranged recurrently at some sites. The distal 4 Mb of the short arms of rice chromosomes Os11 and Os12 and corresponding regions in the sorghum, B. distachyon and Triticeae genomes contain clusters of interstitial translocations including from 1 to 7 collinear genes. The rates of acquisition of major rearrangements were greater in the large wild emmer wheat and Ae. tauschii genomes than in the lineage preceding their divergence or in the B. distachyon, rice and sorghum lineages. It is suggested that synergy between large quantities of dynamic transposable elements and annual growth habit have been the primary causes of the fast evolution of the Triticeae genomes.

Recombination between homoeologous chromosomes induced in durum wheat by the Aegilops speltoides Su1-Ph1 suppressor.

KEY MESSAGE: Su1-Ph1, which we previously introgressed into wheat from Aegilops speltoides, is a potent suppressor of Ph1 and a valuable tool for gene introgression in tetraploid wheat. We previously introgressed Su1-Ph1, a suppressor of the wheat Ph1 gene, from Aegilops speltoides into durum wheat cv Langdon (LDN). Here, we evaluated the utility of the introgressed suppressor for inducing introgression of alien germplasm into durum wheat. We built LDN plants heterozygous for Su1-Ph1 that simultaneously contained a single LDN chromosome 5B and a single Ae. searsii chromosome 5Sse, which targeted them for recombination. We genotyped 28 BC1F1 and 84 F2 progeny with the wheat 90-K Illumina single-nucleotide polymorphism assay and detected extensive recombination between the two chromosomes, which we confirmed by non-denaturing fluorescence in situ hybridization (ND-FISH). We constructed BC1F1 and F2 genetic maps that were 65.31 and 63.71 cM long, respectively. Recombination rates between the 5B and 5Sse chromosomes were double the expected rate computed from their meiotic pairing, which we attributed to selection against aneuploid gametes. Recombination rate between 5B and 5Sse was depressed compared to that between 5B chromosomes in the proximal region of the long arm. We integrated ND-FISH signals into the genetic map and constructed a physical map, which we used to map a 172,188,453-bp Ph1 region. Despite the location of the region in a low-recombination region of the 5B chromosome, we detected three crossovers in it. Our data show that Su1-Ph1 is a valuable tool for gene introgression and gene mapping based on recombination between homoeologous chromosomes in wheat.

Correction to: Recombination between homoeologous chromosomes induced in durum wheat by the Aegilops speltoides Su1-Ph1 suppressor.

Unfortunately, the 9th author name was incorrectly published in the original publication. The complete correct name is given below.

Draft genome of the wheat A-genome progenitor Triticum urartu.

Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.

New insights into structural organization and gene duplication in a 1.75-Mb genomic region harboring the α-gliadin gene family in Aegilops tauschii, the source of wheat D genome.

Among the wheat prolamins important for its end-use traits, α-gliadins are the most abundant, and are also a major cause of food-related allergies and intolerances. Previous studies of various wheat species estimated that between 25 and 150 α-gliadin genes reside in the Gli-2 locus regions. To better understand the evolution of this complex gene family, the DNA sequence of a 1.75-Mb genomic region spanning the Gli-2 locus was analyzed in the diploid grass, Aegilops tauschii, the ancestral source of D genome in hexaploid bread wheat. Comparison with orthologous regions from rice, sorghum, and Brachypodium revealed rapid and dynamic changes only occurring to the Ae. tauschii Gli-2 region, including insertions of high numbers of non-syntenic genes and a high rate of tandem gene duplications, the latter of which have given rise to 12 copies of α-gliadin genes clustered within a 550-kb region. Among them, five copies have undergone pseudogenization by various mutation events. Insights into the evolutionary relationship of the duplicated α-gliadin genes were obtained from their genomic organization, transcription patterns, transposable element insertions and phylogenetic analyses. An ancestral glutamate-like receptor (GLR) gene encoding putative amino acid sensor in all four grass species has duplicated only in Ae. tauschii and generated three more copies that are interspersed with the α-gliadin genes. Phylogenetic inference and different gene expression patterns support functional divergence of the Ae. tauschii GLR copies after duplication. Our results suggest that the duplicates of α-gliadin and GLR genes have likely taken different evolutionary paths; conservation for the former and neofunctionalization for the latter.

Uncovering the dispersion history, adaptive evolution and selection of wheat in China.

Wheat was introduced to China approximately 4500 years ago, where it adapted over a span of time to various environments in agro-ecological growing zones. We investigated 717 Chinese and 14 Iranian/Turkish geographically diverse, locally adapted wheat landraces with 27 933 DArTseq (for 717 landraces) and 312 831 Wheat660K (for a subset of 285 landraces) markers. This study highlights the adaptive evolutionary history of wheat cultivation in China. Environmental stresses and independent selection efforts have resulted in considerable genome-wide divergence at the population level in Chinese wheat landraces. In total, 148 regions of the wheat genome show signs of selection in at least one geographic area. Our data show adaptive events across geographic areas, from the xeric northwest to the mesic south, along and among homoeologous chromosomes, with fewer variations in the D genome than in the A and B genomes. Multiple variations in interdependent functional genes such as regulatory and metabolic genes controlling germination and flowering time were characterized, showing clear allelic frequency changes corresponding to the dispersion of wheat in China. Population structure and selection data reveal that Chinese wheat spread from the northwestern Caspian Sea region to South China, adapting during its agricultural trajectory to increasingly mesic and warm climatic areas.