CLASH
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Urban environments are inhabited by several types of feline populations, which we can differentiate as feral cats, free-roaming pets, and confined pets. Due to a shift in the cultural representation of cats from pest controllers to companion animals, cats living semi-independently of humans are perceived increasingly negatively, while the pet population has become the object of intense care. A regulative approach converges with a concern for welfare in the operation and educational campaigns of municipal shelters, which through their implementation of neutering policies have proven to be key players in the contemporary relation of urban cats and humans. The generally widespread notion of cat welfare associated with a secure life comes into tension with the fact that the psychobiological needs of feral cats are significantly different than those of pets. It becomes apparent that individual interactions between humans and cats in urban environments in the Anthropocene are increasingly influenced by the intervention of institutions that can be characterized as seeking to administer the wild.
- Klíčová slova
- animal welfare, domestic cat, feral cats, pets, population dynamics, routine neutering, trap-neuter-return,
- Publikační typ
- časopisecké články MeSH
Results of calculations using various empirical potentials suggest that base pair buckling, which commonly occurs in DNA crystal structures, is sufficient to eliminate the steric clash at CpG steps in B-DNA, originating from the base pair propeller twisting. The buckling is formed by an inclination of cytosines while deviations of guanines from a plane perpendicular to the double helix axis are unfavorable. The buckling is accompanied by an increased vertical separation of the base pair centers but the buckled arrangement of base pairs is at least as stable as when the vertical separation is normal and buckle zero. In addition, room is created by the increased vertical separation for the bases to propeller twist as is observed in DNA crystal structures. Further stabilization of base stacking is introduced into the buckled base pair arrangement by roll opening the base pairs into the double helix minor groove. The roll may lead to the double helix bending and liberation of guanines from the strictly perpendicular orientation to the double helix axis. The liberated guanines further contribute to the base pair buckling and stacking improvement. This work also suggests a characteristic very stable DNA structure promoted by nucleotide sequences in which runs of purines follow runs of pyrimidine bases.
MicroRNAs (miRNAs) are small non-coding RNAs that play a central role in the post-transcriptional regulation of biological processes. miRNAs regulate transcripts through direct binding involving the Argonaute protein family. The exact rules of binding are not known, and several in silico miRNA target prediction methods have been developed to date. Deep learning has recently revolutionized miRNA target prediction. However, the higher predictive power comes with a decreased ability to interpret increasingly complex models. Here, we present a novel interpretation technique, called attribution sequence alignment, for miRNA target site prediction models that can interpret such deep learning models on a two-dimensional representation of miRNA and putative target sequence. Our method produces a human readable visual representation of miRNA:target interactions and can be used as a proxy for the further interpretation of biological concepts learned by the neural network. We demonstrate applications of this method in the clustering of experimental data into binding classes, as well as using the method to narrow down predicted miRNA binding sites on long transcript sequences. Importantly, the presented method works with any neural network model trained on a two-dimensional representation of interactions and can be easily extended to further domains such as protein-protein interactions.
- Klíčová slova
- CLASH, deep learning, interpretation, miRNA target prediction, visualization,
- Publikační typ
- časopisecké články MeSH
This document outlines the use of an algorithm to filter out impossible crystal-packing arrangements based on steric considerations. Within an exhaustive grid search frame, the space sample is reduced by analysis of spherical areas where atom pairs from different rigid units might clash. This technique finds areas in the state space where the global energy minimum might lie. The minimum can then be found by the usual methods of molecular modeling restricted to these particular areas. Only a tiny fraction of atom pair distances need to be tested; usually a single quantity on average per one state of model space! For example, a crystal of three rigid molecules, each containing 12 atoms, has 3x12x12=432 atom pairs just in one unit cell but our method needs to test on average 1 to 4 atom pairs per state. Using modern computers, about 10(12-15) models can be tested within several hours or days. For example, a crystal model with six rotational degrees of freedom (two rigid molecules in the unit cell) each with step 3 degrees can be tested in a few hours on a 1-GHz x86 processor-based machine. The method presented here has been implemented in the SUPRAMOL program.
The binding of microRNAs (miRNAs) to their target sites is a complex process, mediated by the Argonaute (Ago) family of proteins. The prediction of miRNA:target site binding is an important first step for any miRNA target prediction algorithm. To date, the potential for miRNA:target site binding is evaluated using either co-folding free energy measures or heuristic approaches, based on the identification of binding 'seeds', i.e., continuous stretches of binding corresponding to specific parts of the miRNA. The limitations of both these families of methods have produced generations of miRNA target prediction algorithms that are primarily focused on 'canonical' seed targets, even though unbiased experimental methods have shown that only approximately half of in vivo miRNA targets are 'canonical'. Herein, we present miRBind, a deep learning method and web server that can be used to accurately predict the potential of miRNA:target site binding. We trained our method using seed-agnostic experimental data and show that our method outperforms both seed-based approaches and co-fold free energy approaches. The full code for the development of miRBind and a freely accessible web server are freely available.
- Klíčová slova
- CLASH, convolutional neural network, miRNA binding, miRNA:target prediction,
- MeSH
- algoritmy MeSH
- Argonaut proteiny genetika metabolismus MeSH
- deep learning * MeSH
- mikro RNA * genetika metabolismus MeSH
- výpočetní biologie metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Argonaut proteiny MeSH
- mikro RNA * MeSH
There is a lesion of aortic thoracic complex in car-passengers during the frontal clash to a static or to a dynamic antipodal obstacle is described in this study. It is a retrospective analysis. Facts were noted especially from dissectional documents. All from 298 men died. The main cause of car-passengers death was a weighty traumatic lesion of cardiovascular system in 58.7%. The aortic rupture was noted in 98 (32.9%) people, the death was in 90.8% directly on the road and 9.2% at hospital. From the whole people who were accepted to a hospital were 9 (8.9%) with a traumatic aortic rupture. But nobody of them was transported to a special center and everyone died due to traumatic lesion of cardiovascular system. Statistical significant cofactors of aortic rupture were atherosclerosis of aortic wall and intensity of clash. Therefore we can expect an aortic rupture in every third dead frontal car crash participant on a dynamic or static obstacle. Nearly 10% from men with traumatic aortic rupture were transported to a hospital. No aortic rupture was diagnosed.
- MeSH
- aorta thoracica zranění MeSH
- dopravní nehody * MeSH
- dospělí MeSH
- lidé MeSH
- ruptura aorty epidemiologie etiologie patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
In this work the author is trying to show some problems related to informed consent in psychiatry. It deals especially with problems of medical research, sterilisation, involuntary therapy, treatment of drug addition etc. In each of these areas there can come to a clash of interests between the society and the patient. The informed consent turns our attention to the patient.
- MeSH
- informovaný souhlas pacienta * MeSH
- lidé MeSH
- psychiatrie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
Molecular dynamics (MD) simulations represent an established tool to study RNA molecules. The outcome of MD studies depends, however, on the quality of the force field (ff). Here we suggest a correction for the widely used AMBER OL3 ff by adding a simple adjustment of the nonbonded parameters. The reparameterization of the Lennard-Jones potential for the -H8···O5'- and -H6···O5'- atom pairs addresses an intranucleotide steric clash occurring in the type 0 base-phosphate interaction (0BPh). The nonbonded fix (NBfix) modification of 0BPh interactions (NBfix0BPh modification) was tuned via a reweighting approach and subsequently tested using an extensive set of standard and enhanced sampling simulations of both unstructured and folded RNA motifs. The modification corrects minor but visible intranucleotide clash for the anti nucleobase conformation. We observed that structural ensembles of small RNA benchmark motifs simulated with the NBfix0BPh modification provide better agreement with experiments. No side effects of the modification were observed in standard simulations of larger structured RNA motifs. We suggest that the combination of OL3 RNA ff and NBfix0BPh modification is a viable option to improve RNA MD simulations.
- MeSH
- fosfáty * MeSH
- molekulární konformace MeSH
- nukleotidové motivy MeSH
- RNA * chemie MeSH
- simulace molekulární dynamiky MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfáty * MeSH
- RNA * MeSH
