Reevesmalmberg8680

CDX2 directly bound to the promoter of PTEN and transactivated its expression.

Our study first uncovered that CDX2 inhibits EMT and metastasis of CRC by regulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression.

Our study first uncovered that CDX2 inhibits EMT and metastasis of CRC by regulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression.Although substantial progress has been made over the past 40 years in treating patients with cancer, effective therapies for those who are diagnosed with advanced metastatic disease are still few and far between. Cancer cells do not exist in isolation rather, they exist within a complex microenvironment composed of stromal cells and extracellular matrix. Within this tumour microenvironment exists an interplay between the two main stromal cell subtypes, cancer-associated fibroblasts (CAFs) and immune cells, that are important in controlling metastasis. A complex network of paracrine signalling pathways between CAFs, immune cells and tumour cells are involved at multiple stages of the metastatic process, from invasion and intravasation at the primary tumour site to extravasation and colonisation in the metastatic site. Heterogeneity and plasticity within stromal cell populations also contribute to the complexity. Although many of these processes are likely to be common to a number of metastatic sites, we will describe in detail the interplay within the liver, a preferred site of metastasis for many tumours. A greater understanding of these networks provides opportunities for the design of new therapeutic approaches for targeting the metastatic disease.

The investigation of underlying mechanism and the exploitation of novel therapies for metastatic prostate cancer (PCa) are still urgently needed. miR-199b-5p has been suggested to function as tumour suppressor in various human cancers. However, the clinical significance and role of miR-199b-5p in PCa remain unclear.

The current study sought to investigate the expression status of miR-199b-5p in PCa and the involved molecular mechanisms in PCa metastasis by using bioinformatics analyses, loss-and gain-of-functions and rescue experiments in vitro and in vivo.

We demonstrated that miR-199b-5p was significantly downregulated in metastatic PCa tissues and cells when compared with the normal prostate tissue, the localised disease, the weakly metastatic and androgen-dependent PCa cell and the normal prostate epithelial cell. We also found that miR-199b-5p drastically suppressed PCa cell proliferation, migration and invasion in vitro and inhibited xenografts tumour growth and metastasis in vivo. 2,3-Butanedione-2-monoxime Mechanistically mechanism of regulating EMT in PCa metastases.

Our study, for the first time, provide evidence of a tumour-suppressive function of miR-199b-5p in the invasion and metastasis of PCa, supporting the translational exploitation of miR-199b-5p-based therapeutic approaches for PCa metastases. Also, the miR-199b-5p-DDR1-ERK signalling axis identified in this study represents a novel mechanism of regulating EMT in PCa metastases.A rich assemblage of various types of bromalites from the lower Carnian "Konservat-Lagerstätte" from the Reingraben Shales in Polzberg (Northern Calcareous Alps, Lower Austria) is described for the first time in detail. They comprise large regurgitalites consisting of numerous entire shells of ammonoid Austrotrachyceras or their fragments and rare teuthid arm hooks, and buccal cartilage of Phragmoteuthis. Small coprolites composed mainly of fish remains were also found. The size, shape and co-occurrence with vertebrate skeletal remains imply that regurgitalites were likely produced by large durophagous fish (most likely by cartilaginous fish Acrodus). Coprolites, in turn, were likely produced by medium-sized piscivorous actinopterygians. link2 Our findings are consistent with other lines of evidence suggesting that durophagous predation has been intense during the Triassic and that the so-called Mesozoic marine revolution has already started in the early Mesozoic.White spot syndrome virus (WSSV) causes major worldwide losses in shrimp aquaculture. The development of resistant shrimp populations is an attractive option for management of the disease. However, heritability for WSSV resistance is generally low and genetic improvement by conventional selection has been slow. This study was designed to determine the power and accuracy of genomic selection to improve WSSV resistance in Litopenaeus vannamei. Shrimp were experimentally challenged with WSSV and resistance was evaluated as dead or alive (DOA) 23 days after infestation. All shrimp in the challenge test were genotyped for 18,643 single nucleotide polymorphisms. Breeding candidates (G0) were ranked on genomic breeding values for WSSV resistance. Two G1 populations were produced, one from G0 breeders with high and the other with low estimated breeding values. A third population was produced from "random" mating of parent stock. The average survival was 25% in the low, 38% in the random and 51% in the high-genomic breeding value groups. Genomic heritability for DOA (0.41 in G1) was high for this type of trait. The realised genetic gain and high heritability clearly demonstrates large potential for further genetic improvement of WSSV resistance in the evaluated L. vannamei population using genomic selection.Herein, we combine titania layers with gold species in a laser-supported process and report a substantial change of properties of the resulting heterostructures depending on the major processing parameters. Electrodes were fabricated via an anodisation process complemented with calcination to ensure a crystalline phase, and followed by magnetron sputtering of metallic films. The obtained TiO2 nanotubes with deposited thin (5, 10 nm) Au films were treated with a UV laser (355 nm) to form Au nanoparticles on top of the nanotubes. It was proven that selected laser working parameters ensure not only the formation of Au nanoparticles, but also simultaneously provide preservation of the initial tubular architecture, while above-threshold laser fluences result in partial destruction (melting) of the top layer of the nanotubes. For almost all of the samples, the crystalline phase of the nanotubes observed in Raman spectra was maintained independently of the laser processing parameters. Enhanced photoresponse up to ca 6 mA/cm2 was demonstrated by photoelectrochemical measurements on samples obtained by laser annealing of the 10 nm Au coating on a titania support. Moreover, a Mott-Schottky analysis indicated the dramatically increased (two orders of magnitude) concentration of donor density in the case of a laser-treated Au-TiO2 heterojunction compared to reference electrodes.Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. link3 Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P = 3.2 × 10-8, odds ratio (OR) = 1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF = 6.4%, P = 1.3 × 10-8, OR = 1.7; rs143445068, MAF = 0.8%, P = 5.2 × 10-9, OR = 3.4; rs183453668, MAF = 0.5%, P = 2.8 × 10-8, OR = 3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Despite recent advances, the myocardial microstructure remains imperfectly understood. In particular, bundles of cardiomyocytes have been observed but their three-dimensional organisation remains debated and the associated mechanical consequences unknown. One of the major challenges remains to perform multiscale observations of the mechanical response of the heart wall. For this purpose, in this study, a full-field Mueller polarimetric imager (MPI) was combined, for the first time, with an in-situ traction device. The full-field MPI enables to obtain a macroscopic image of the explored tissue, while providing detailed information about its structure on a microscopic scale. Specifically it exploits the polarization of the light to determine various biophysical quantities related to the tissue scattering or anisotropy properties. Combined with a mechanical traction device, the full-field MPI allows to measure the evolution of such biophysical quantities during tissue stretch. We observe separation lines on the tissue, which are associated with a fast variation of the fiber orientation, and have the size of cardiomyocyte bundles. Thus, we hypothesize that these lines are the perimysium, the collagen layer surrounding these bundles. During the mechanical traction, we observe two mechanisms simultaneously. On one hand, the azimuth shows an affine behavior, meaning the orientation changes according to the tissue deformation, and showing coherence in the tissue. On the other hand, the separation lines appear to be resistant in shear and compression but weak against traction, with a forming of gaps in the tissue.Crop productivity must increase at unprecedented rates to meet the needs of the growing worldwide population. Exploiting natural variation for the genetic improvement of crops plays a central role in increasing productivity. Although current genomic technologies can be used for high-throughput identification of genetic variation, methods for efficiently exploiting this genetic potential in a targeted, systematic manner are lacking. Here, we developed a haplotype-based approach to identify genetic diversity for crop improvement using genome assemblies from 15 bread wheat (Triticum aestivum) cultivars. We used stringent criteria to identify identical-by-state haplotypes and distinguish these from near-identical sequences (~99.95% identity). We showed that each cultivar shares ~59 % of its genome with other sequenced cultivars and we detected the presence of extended haplotype blocks containing hundreds to thousands of genes across all wheat chromosomes. We found that genic sequence alone was insufficient to fully differentiate between haplotypes, as were commonly used array-based genotyping chips due to their gene centric design. We successfully used this approach for focused discovery of novel haplotypes from a landrace collection and documented their potential for trait improvement in modern bread wheat. This study provides a framework for defining and exploiting haplotypes to increase the efficiency and precision of wheat breeding towards optimising the agronomic performance of this crucial crop.