Computational analyses of eukaryotic promoters

Computational analysis of eukaryotic promoters is one of the most difficult problems in computational genomics and is essential for understanding gene expression profiles and reverse-engineering gene regulation network circuits. Here I give a basic introduction of the problem and recent update on both experimental and computational approaches. More details may be found in the extended references. This review is based on a summer lecture given at Max Planck Institute at Berlin in 2005

A polarimetrically oriented X-ray stare at the accreting pulsar EXO 2030+375

Accreting X-ray pulsars (XRPs) are presumed to be ideal targets for polarization measurements, as their high magnetic field strength is expected to polarize the emission up to a polarization degree of 80%. However, such expectations are being challenged by recent observations of XRPs with the Imaging X-ray Polarimeter Explorer (IXPE). Here, we report on the results of yet another XRP, namely, EXO 2030+375, observed with IXPE and contemporarily monitored with Insight-HXMT and SRG/ART-XC. In line with recent results obtained with IXPE for similar sources, an analysis of the EXO 2030+375 data returns a low polarization degree of 0%- 3% in the phase-averaged study and a variation in the range of 2%- 7% in the phase-resolved study. Using the rotating vector model, we constrained the geometry of the system and obtained a value of 60 for the magnetic obliquity. When considering the estimated pulsar inclination of 130, this also indicates that the magnetic axis swings close to the observera's line of sight. Our joint polarimetric, spectral, and timing analyses hint toward a complex accreting geometry, whereby magnetic multipoles with an asymmetric topology and gravitational light bending significantly affect the behavior of the observed source

Complex variations in X-ray polarization in the X-ray pulsar LS V +44 17/RX J0440.9+4431

We report on Imaging X-ray polarimetry explorer (IXPE) observations of the Be-transient X-ray pulsar LS V +44 17/RX J0440.9+4431 made at two luminosity levels during the giant outburst in January- February 2023. Considering the observed spectral variability and changes in the pulse profiles, the source was likely caught in supercritical and subcritical states with significantly different emission-region geometry, associated with the presence of accretion columns and hot spots, respectively. We focus here on the pulse-phase-resolved polarimetric analysis and find that the observed dependencies of the polarization degree and polarization angle (PA) on the pulse phase are indeed drastically different for the two observations. The observed differences, if interpreted within the framework of the rotating vector model (RVM), imply dramatic variations in the spin axis inclination, the position angle, and the magnetic colatitude by tens of degrees within the space of just a few days. We suggest that the apparent changes in the observed PA phase dependence are predominantly related to the presence of an unpulsed polarized component in addition to the polarized radiation associated with the pulsar itself. We then show that the observed PA phase dependence in both observations can be explained with a single set of RVM parameters defining the pulsar s geometry. We also suggest that the additional polarized component is likely produced by scattering of the pulsar radiation in the equatorial disk wind

Discovery of strongly variable X-ray polarization in the neutron star low-mass X-ray binary transient XTE J1701-462

CONTEXT: After about 16 years since its first outburst, the transient neutron star low-mass X-ray binary XTE J1701−462 turned on again in September 2022, allowing for the first study of its X-ray polarimetric characteristics by a dedicated observing program with the Imaging X-ray Polarimeter Explorer (IXPE). AIMS: Polarimetric studies of XTE J1701−462 have been expected to improve our understanding of accreting weakly magnetized neutron stars, in particular, the physics and the geometry of the hot inner regions close to the compact object. METHOD: The IXPE data of two triggered observations were analyzed using time-resolved spectroscopic and polarimetric techniques, following the source along its Z-track of the color–color diagram. RESULTS: During the first pointing on 2022 September 29, an average 2–8 keV polarization degree of (4.6 ± 0.4)% was measured, the highest value found up to now for this class of sources. Conversely, only a ∼0.6% average degree was obtained during the second pointing ten days later. CONCLUSIONS: The polarimetric signal appears to be strictly related to the higher energy blackbody component associated with the boundary layer (BL) emission and its reflection from the inner accretion disk, and it is as strong as 6.1% and 1.2% (> 95% significant) above 3–4 keV for the two measurements, respectively. The variable polarimetric signal is apparently related to the spectral characteristics of XTE J1701−462, which is the strongest when the source was in the horizontal branch of its Z-track and the weakest in the normal branch. These IXPE results provide new important observational constraints on the physical models and geometry of the Z-sources. Here, we discuss the possible reasons for the presence of strong and variable polarization among these sources

Sequence Motifs in MADS Transcription Factors Responsible for Specificity and Diversification of Protein-Protein Interaction

Protein sequences encompass tertiary structures and contain information about specific molecular interactions, which in turn determine biological functions of proteins. Knowledge about how protein sequences define interaction specificity is largely missing, in particular for paralogous protein families with high sequence similarity, such as the plant MADS domain transcription factor family. In comparison to the situation in mammalian species, this important family of transcription regulators has expanded enormously in plant species and contains over 100 members in the model plant species Arabidopsis thaliana. Here, we provide insight into the mechanisms that determine protein-protein interaction specificity for the Arabidopsis MADS domain transcription factor family, using an integrated computational and experimental approach. Plant MADS proteins have highly similar amino acid sequences, but their dimerization patterns vary substantially. Our computational analysis uncovered small sequence regions that explain observed differences in dimerization patterns with reasonable accuracy. Furthermore, we show the usefulness of the method for prediction of MADS domain transcription factor interaction networks in other plant species. Introduction of mutations in the predicted interaction motifs demonstrated that single amino acid mutations can have a large effect and lead to loss or gain of specific interactions. In addition, various performed bioinformatics analyses shed light on the way evolution has shaped MADS domain transcription factor interaction specificity. Identified protein-protein interaction motifs appeared to be strongly conserved among orthologs, indicating their evolutionary importance. We also provide evidence that mutations in these motifs can be a source for sub- or neo-functionalization. The analyses presented here take us a step forward in understanding protein-protein interactions and the interplay between protein sequences and network evolution

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease