Highlights d A deep learning model for AD prediction was derived from a large set of synthetic ADs d The predictor (ADpred) identifies sequence features important for acidic AD function d AD sequence features explain the basis for the fuzzy binding mechanism of acidic ADs d Acidic ADs are enriched in yeast but not in Drosophila or human transcription factors

MotivationWord-based or ‘alignment-free’ algorithms are increasingly used for phylogeny reconstruction and genome comparison, since they are much faster than traditional approaches that are based on full sequence alignments. Existing alignment-free programs, however, are less accurate than alignment-based methods.ResultsWe propose Filtered Spaced Word Matches (FSWM), a fast alignment-free approach to estimate phylogenetic distances between large genomic sequences. For a pre-defined binary pattern of match and don’t-care positions, FSWM rapidly identifies spaced word-matches between input sequences, i.e. gap-free local alignments with matching nucleotides at the match positions and with mismatches allowed at the don’t-care positions. We then estimate the number of nucleotide substitutions per site by considering the nucleotides aligned at the don’t-care positions of the identified spaced-word matches. To reduce the noise from spurious random matches, we use a filtering procedure where we discard all spaced-word matches for which the overall similarity between the aligned segments is below a threshold. We show that our approach can accurately estimate substitution frequencies even for distantly related sequences that cannot be analyzed with existing alignment-free methods; phylogenetic trees constructed with FSWM distances are of high quality. A program run on a pair of eukaryotic genomes of a few hundred Mb each takes a few minutes.Availability and ImplementationThe program source code for FSWM including a documentation, as well as the software that we used to generate artificial genome sequences are freely available at http://fswm.gobics.de/Supplementary information Supplementary data are available at Bioinformatics online.

Liquid-liquid phase separation is a key organizational principle in eukaryotic cells, on par with intracellular membranes. It allows cells to concentrate specific proteins into condensates, increasing reaction rates and achieving switch-like regulation. However, it is unclear how cells trigger condensate formation or dissolution and regulate their sizes. We predict from first principles two mechanisms of active regulation by post-translational modifications such as phosphorylation: In enrichment-inhibition, the regulating modifying enzyme enriches in condensates and the modifications of proteins inhibit their interactions. Stress granules, Cajal bodies, P granules, splicing speckles, and synapsin condensates obey this model. In localization-induction, condensates form around an immobilized modifying enzyme, whose modifications strengthen protein interactions. Spatially targeted condensates formed during transmembrane signaling, microtubule assembly, and actin polymerization conform to this model. The two models make testable predictions that can guide studies into the many emerging roles of biomolecular condensates.Eukaryotic cells contain numerous types of membraneless organelles, which contain between a few and thousands of protein and RNA species that are highly enriched in comparison to the surrounding nucleoplasm or cytoplasm. These biomolecular condensates are held together by weak, multivalent and highly collaborative interactions, often between intrinsically disordered regions of their constituent proteins (Banani et al., 2017;Shin and Brangwynne, 2017).In contrast to membrane-bound organelles, cells can regulate the formation and size of condensates by posttranslational modifications of one or a few key proteins, most prominently by phosphorylation. The modifications usually lie within intrinsically disordered regions and modulate the strength of attractive interactions with other condensate components (Bah and Forman-Kay, 2016; Fung et al., 2018). Due to the highly cooperative nature of phase transitions, small changes in interaction strengths can result in the formation or dissolution of condensates, and this switch-like, dynamic nature makes them ideal for regulation.For instance the nucleolus, Cajal bodies, splicing speckles, paraspeckles, and PML bodies in the nucleus and P-bodies in the cytoplasm have to be dissolved during mitosis and reformed afterwards to ensure a balanced distribution of their content to daughter cells (Rai et al., 2018;Dundr and Misteli, 2010). Stress granules form upon cellular stress and are dissolved when the stress ceases (Wippich et al., 2013).Whereas these long-known, floating droplet or-ganelles are large enough to be visible using simpler 31 light microscopic techniques, in the past years liquid-32 liquid phase separation has been implicated in mul-33 tifarious processes in which -often sub-micrometer-34 sized -condensates are formed at particular sites in the 35 cell: at sites of DNA repair foci (Altmeyer et al., 2015), 36 Polycomb-mediated chromatin silencing (Tatavo...

Current tissue regenerative strategies rely mainly on tissue repair by transplantation of the synthetic/natural implants. However, limitations of the existing strategies have increased the demand for tissue engineering approaches. Appropriate cell source, effective cell modification, and proper supportive matrices are three bases of tissue engineering. Selection of appropriate methods for cell stimulation, scaffold synthesis, and tissue transplantation play a definitive role in successful tissue engineering. Although the variety of the players are available, but proper combination and functional synergism determine the practical efficacy. Hence, in this review, a comprehensive view of tissue engineering and its different aspects are investigated.

No abstract