The assessment of LIF in uterine flushing--a possible new diagnostic tool in states of impaired fertility

The objective of this study was to assess the LIF (leukemia inhibitory factor) concentration in uterine flushing and serum (ELISA) of women with proven fertility, infertile women and women with recurrent miscarriage. In addition, progesterone level was determined in serum. A decreased production of LIF in the uterine microenvironment was found in states of impaired fertility. With a cut-off point of 8.23 pg/ml for LIF level in uterine flushings we have achieved 86.7% sensitivity and 100% specificity in detection of women with idiopathic infertility compared to fertile controls. No correlation between LIF in serum and uterine flushing was demonstrated, rendering LIF measurements in serum useless for diagnosis of impaired infertility. We conclude that LIF measurement in uterine flushing could be a useful diagnostic tool to predict unsuccessful implantation.     

Molecular,genetic and evolutionary analysis of a paracentric inversion in Arabidopsis thaliana

Chromosomal inversions can provide windows onto the cytogenetic, molecular, evolutionary and demographic histories of a species. Here we investigate a paracentric 1.17‐Mb inversion on chromosome 4 of Arabidopsis thaliana with nucleotide precision of its borders. The inversion is created by Vandal transposon activity, splitting an F‐box and relocating a pericentric heterochromatin segment in juxtaposition with euchromatin without affecting the epigenetic landscape. Examination of the RegMap panel and the 1001 Arabidopsis genomes revealed more than 170 inversion accessions in Europe and North America. The SNP patterns revealed historical recombinations from which we infer diverse haplotype patterns, ancient introgression events and phylogenetic relationships. We find a robust association between the inversion and fecundity under drought. We also find linkage disequilibrium between the inverted region and the early flowering Col‐FRIGIDA allele. Finally, SNP analysis elucidates the origin of the inversion to South‐Eastern Europe approximately 5000 years ago and the FRI‐Col allele to North‐West Europe, and reveals the spreading of a single haplotype to North America during the 17th to 19th century. The ‘American haplotype’ was identified from several European localities, potentially due to return migration.     

Histone H3 lysine 27 acetylation is altered in colon cancer

Background

Histone post-translational modifications (PTMs) play an important role in the regulation of the expression of genes, including those involved in cancer development and progression. However, our knowledge of PTM patterns in human tumours is limited.

Methods

MS-based analyses were used to quantify global alterations of histone PTMs in colorectal cancer (CRC) samples. Histones isolated from 12 CRCs and their corresponding normal mucosa by acidic extraction were separated by SDS-PAGE and analysed by liquid chromatography-mass spectrometry.

Results

Among 96 modified peptides, 41 distinct PTM sites were identified, of which 7, 13, 11, and 10 were located within the H2A, H2B, H3, and H4 sequences, respectively, and distributed among the amino-terminal tails and the globular domain of the four histones. Modification intensities were quantified for 33 sites, of which 4 showed significant (p-value ≤ 0.05) differences between CRC tissues and healthy mucosa samples. We identified histone H3 lysine 27 acetylation (H3K27Ac) as a modification upregulated in CRC, which had not been shown previously.

Conclusions

The present results indicate the usefulness of a bottom-up proteomic approach for the detection of histone modifications at a global scale. The differential abundance of H3K27Ac mark in CRC, a PTM associated with active enhancers, suggests its role in regulating genes whose expression changes in CRC.     

No correlation between pinopode formation and LIF and MMP2 expression in endometrium during implantation window

Implantation depends on two factors - embryo and endometrium. The period of maximal endometrial receptivity is a poorly understood phenomenon. We decided to look at three possible markers of implantation: pinopodes, leukemia inhibitory factor, and matrix metalloproteinase 2 and their correlations. We included in the study 23 idiopathic infertility patients and 21 patients with recurrent spontaneous abortions of unknown etiology. Twenty one fertile patients were also recruited. A biopsy was used for endometrial dating according to the Noyes and Hertig criteria, and assessed for the presence of pinopodes via a scanning electron microscope. Endometria were examined in Real Time-Polymerase Chain Reaction cycles for the mRNA expression of leukemia inhibitory factor (LIF) and matrix metalloproteinase 2 (MMP2). No difference was found in the stage of pinopodes development, nor in the coverage of endometrial surface between the studied groups. The expression level for LIF mRNA was lower in control patients compared to idiopathic infertility and recurrent miscarriage patients. No difference was detected in the expression of MMP2 between all studied groups. No correlation was found between pinopodes development stage and LIF and MMP2 expressions in endometrium. Of the studied factors, LIF and pinopodes show the most promise as potential markers of endometrial receptivity. However, the results achieved suggest that these markers are independent of each other.     

Flexible docking of peptides to proteins using CABS‐dock

Molecular docking of peptides to proteins can be a useful tool in the exploration of the possible peptide binding sites and poses. CABS‐dock is a method for protein–peptide docking that features significant conformational flexibility of both the peptide and the protein molecules during the peptide search for a binding site. The CABS‐dock has been made available as a web server and a standalone package. The web server is an easy to use tool with a simple web interface. The standalone package is a command‐line program dedicated to professional users. It offers a number of advanced features, analysis tools and support for large‐sized systems. In this article, we outline the current status of the CABS‐dock method, its recent developments, applications, and challenges ahead.     

Feather holes and flight performance in the barn swallow Hirundo rustica

Feather holes are small (0.5–1?mm in diameter) deformities that appear on the vanes of flight feathers. Such deformities were found in many bird species, including galliforms and passerines. Holey flight feathers may be more permeable to air, which could have a negative effect on their ability to generate aerodynamic forces. However, to date the effects of feather holes on flight performance in birds remained unclear. In this study we investigated the relationship between the number of feather holes occurring in the wing or tail feathers and short term flight performance traits – aerial manoeuvrability, maximum velocity and maximum acceleration – in barns swallows, which are long distance migrating aerial foragers. We measured short-term flight performance of barn swallows in a standardized manner in flight tunnels. We found that acceleration and velocity were significantly negatively associated with the number of holes in the wing flight feathers, but not with those in the tail feathers. In the case of acceleration the negative relationship was sex specific – while acceleration significantly decreased with the number of feather holes in females, there was no such significant association in males. Manoeuvrability was not significantly associated with the number of feather holes. These results are consistent with the hypothesis that feather holes are costly in terms of impaired flight. We discuss alternative scenarios that could explain the observed relationships. We also suggest directions for future studies that could investigate the exact mechanism behind the negative association between the number of feather holes and flight characteristics.     

Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion

Studies in tissue culture cells have demonstrated a role for the Ras-like GTPase Rap1 in the regulation of integrin-mediated cell-matrix and cadherin-mediated cell-cell contacts. To analyze the function of Rap1 in vivo, we have disrupted the Rap1A gene by homologous recombination. Mice homozygous for the deletion allele are viable and fertile. However, primary hematopoietic cells isolated from spleen or thymus have a diminished adhesive capacity on ICAM and fibronectin substrates. In addition, polarization of T cells from Rap1-/- cells after CD3 stimulation was impaired compared to that of wild-type cells. Despite this, these defects did not result in hematopoietic or cell homing abnormalities. Although it is possible that the relatively mild phenotype is a consequence of functional complementation by the Rap1B gene, our genetic studies confirm a role for Rap1A in the regulation of integrins.     

Innate immunity orchestrates the mobilization and homing of hematopoietic stem/progenitor cells by engaging purinergic signaling—an update

Purinergic Signalling - Bone marrow (BM) as an active hematopoietic organ is highly sensitive to changes in body microenvironments and responds to external physical stimuli from the surrounding...