iVici: Interrelational Visualization and Correlation Interface

Affiliation: Département de Biochimie, Faculté de médecine, Université de MontréalWe have developed an application, iVici, to analyze cellular networks represented as addressable symmetric or asymmetric two-dimensional matrices. iVici was designed to permit simultaneous visualization and correlation of multiple datasets, representing any relationship between a set of genes, mRNAs, or proteins. Visual overlay of datasets and addressable access to gene annotations permits comparison of networks of different types (for example protein-protein interactions and genetic networks) or investigation of the dynamic reorganization of a particular network

Ensemble inequivalence in long-range interacting systems

Treballs Finals de Grau de Física, Facultat de Física, Universitat de Barcelona, Curs: 2022, Tutor: Ivan LatellaAn important result we learn in the statistical physics course is that statistical ensembles are equivalent in the thermodynamic limit. However, a key assumption behind this result is that interactions in the system are short-range. When interactions are long-range, ensemble equivalence cannot be taken for granted. In this TFG, a simplified self-gravitating system is studied as an example of long-range interacting systems. By introducing the Thirring model, we will be able to see how negative specific heat appears in the microcanonical ensemble while in the canonical ensemble this region is replaced with an isothermal first-order phase transitio

Integrated intelligent systems for industrial automation: the challenges of Industry 4.0, information granulation and understanding agents .

The objective of the paper consists in considering the challenges of new automation paradigm Industry 4.0 and reviewing the-state-of-the-art in the field of its enabling information and communication technologies, including Cyberphysical Systems, Cloud Computing, Internet of Things and Big Data. Some ways of multi-dimensional, multi-faceted industrial Big Data representation and analysis are suggested. The fundamentals of Big Data processing with using Granular Computing techniques have been developed. The problem of constructing special cognitive tools to build artificial understanding agents for Integrated Intelligent Enterprises has been faced

Исторический процесс в свете христианской антропологии Ф. М. Достоевского

На основе фундаментальных для творческого сознания Достоевского понятий «тайны человека» и христианского реализма, «закона Я» и «закона любви» в статье рассмотрена односторонность биологизаторских и социализаторских концепций человеческой природы с эпохи Просвещения и их связь с энтропийными процессами в духовно-нравственном мире людей и снижающими тенденциями в ходе истории. Показаны, как уходящие из поля зрения рационалистического и прагматического сознания духовные законы жизни трансформируют социально-прогрессистское проектирование и планирование, вносят в них нигилистические элементы. Подчеркнуто, что методология христианского реализма носит универсальный характер, соединяет «тайну человека» с тайной истории, и становится одним из главных принципов для оценки иерархии ценностей в различных мировоззренческих, идеологических и социальных системах.Based on the fundamental concepts of the "mystery of man" and Christian realism, the "law of the Ego" and the "law of love" for Dostoevsky's creative consciousness, the article examines the one-sidedness of biologizing and socializing concepts of human nature since the Enlightenment and their connection with entropic processes in the spiritual and moral world of people and declining trends in the course of history. It is shown how the spiritual laws of life, which are leaving the field of view of rationalistic and pragmatic consciousness, transform social-progressive design and planning, and introduce nihilistic elements into them. It is emphasized that the methodology of Christian realism is universal, that it connects the "mystery of man" with the mystery of history, and becomes one of the main principles for assessing the hierarchy of values in various ideological and social systems.Based on the fundamental concepts of the "mystery of man" and Christian realism, the "law of the Ego" and the "law of love" for Dostoevsky's creative consciousness, the article examines the one-sidedness of biologizing and socializing concepts of human nature since the Enlightenment and their connection with entropic processes in the spiritual and moral world of people and declining trends in the course of history. It is shown how the spiritual laws of life, which are leaving the field of view of rationalistic and pragmatic consciousness, transform social-progressive design and planning, and introduce nihilistic elements into them. It is emphasized that the methodology of Christian realism is universal, that it connects the "mystery of man" with the mystery of history, and becomes one of the main principles for assessing the hierarchy of values in various ideological and social systems

Inhibitory effects of polar and non-polar organic substances on activated sludge activity

As is well known, several organic compounds, more often found in industrial wastewater, exhibit inhibitory effects on biomass activity, therefore, leading to poor wastewater treatment efficiency. This study presents the experimental results on the inhibition effects of 14 polar and non-polar organic compounds on the activity of activated sludge in the concentration range of 50–1,000 ppm. Two different activated sludge samples used, one of low activity and another of high activity. The organic compounds tested are: phenol, 2-chlorophenol, nitrophenol, resorcinol, dioxane, acetonitrile and benzotriazole (polar); and toluene, styrene, cyclohexane, tetrachloromethane, paraxylene, benzene and hexane (non-polar). The results demonstrate that polar compounds exhibit higher toxicity than non-polar compounds and hydrophobicity plays a crucial role. The effects of polarity, hydrophobicity, solubility and volatility are discussed and the conclusion is that inhibition is complex phenomenon requiring extensive theoretical and experimental studies

Induced tRNA import into human mitochondria: implication of a host aminoacyl-tRNA-synthetase:

In human cell, a subset of small non-coding RNAs is imported into mitochondria from the cytosol. Analysis of the tRNA import pathway allowing targeting of the yeast tRNA(Lys)(CUU) into human mitochondria demonstrates a similarity between the RNA import mechanisms in yeast and human cells. We show that the cytosolic precursor of human mitochondrial lysyl-tRNA synthetase (preKARS2) interacts with the yeast tRNA(Lys)(CUU) and small artificial RNAs which contain the structural elements determining the tRNA mitochondrial import, and facilitates their internalization by isolated human mitochondria. The tRNA import efficiency increased upon addition of the glycolytic enzyme enolase, previously found to be an actor of the yeast RNA import machinery. Finally, the role of preKARS2 in the RNA mitochondrial import has been directly demonstrated in vivo, in cultured human cells transfected with the yeast tRNA and artificial importable RNA molecules, in combination with preKARS2 overexpression or downregulation by RNA interference. These findings suggest that the requirement of protein factors for the RNA mitochondrial targeting might be a conserved feature of the RNA import pathway in different organisms

A mosaic of RNA binding and protein interaction motifs in a bifunctional mitochondrial tRNA import factor from Leishmania tropica

Proteins that participate in the import of cytosolic tRNAs into mitochondria have been identified in several eukaryotic species, but the details of their interactions with tRNA and other proteins are unknown. In the kinetoplastid protozoon Leishmania tropica, multiple proteins are organized into a functional import complex. RIC8A, a tRNA-binding subunit of this complex, has a C-terminal domain that functions as subunit 6b of ubiquinol cytochrome c reductase (complex III). We show that the N-terminal domain, unique to kinetoplastid protozoa, is structurally similar to the appended S15/NS1 RNA-binding domain of aminoacyl tRNA synthetases, with a helix–turn–helix motif. Structure-guided mutagenesis coupled with in vitro assays showed that helix α1 contacts tRNA whereas helix α2 targets the protein for assembly into the import complex. Inducible expression of a helix 1-deleted variant in L. tropica resulted in formation of an inactive import complex, while the helix 2-deleted variant was unable to assemble in vivo. Moreover, a protein-interaction assay showed that the C-terminal domain makes allosteric contacts with import receptor RIC1 complexed with tRNA. These results help explain the origin of the bifunctionality of RIC8A, and the allosteric changes accompanying docking and release of tRNA during import

Method of carrier-free delivery of therapeutic RNA importable into human mitochondria: Lipophilic conjugates with cleavable bonds:

Defects in mitochondrial DNA often cause neuromuscular pathologies, for which no efficient therapy has yet been developed. MtDNA targeting nucleic acids might therefore be promising therapeutic candidates. Nevertheless, mitochondrial gene therapy has never been achieved because DNA molecules can not penetrate inside mitochondria in vivo. In contrast, some small non-coding RNAs are imported into mitochondrial matrix, and we recently designed mitochondrial RNA vectors that can be used to address therapeutic oligoribonucleotides into human mitochondria. Here we describe an approach of carrier-free targeting of the mitochondrially importable RNA into living human cells. For this purpose, we developed the protocol of chemical synthesis of oligoribonucleotides conjugated with cholesterol residue through cleavable covalent bonds. Conjugates containing pH-triggered hydrazone bond were stable during the cell transfection procedure and rapidly cleaved in acidic endosomal cellular compartments. RNAs conjugated to cholesterol through a hydrazone bond were characterized by efficient carrier-free cellular uptake and partial co-localization with mitochondrial network. Moreover, the imported oligoribonucleotide designed to target a pathogenic point mutation in mitochondrial DNA was able to induce a decrease in the proportion of mutant mitochondrial genomes. This newly developed approach can be useful for a carrier-free delivery of therapeutic RNA into mitochondria of living human cells

Biological significance of 5S rRNA import into human mitochondria: role of ribosomal protein MRP-L18:

5S rRNA is an essential component of ribosomes of all living organisms, the only known exceptions being mitochondrial ribosomes of fungi, animals, and some protists. An intriguing situation distinguishes mammalian cells: Although the mitochondrial genome contains no 5S rRNA genes, abundant import of the nuclear DNA-encoded 5S rRNA into mitochondria was reported. Neither the detailed mechanism of this pathway nor its rationale was clarified to date. In this study, we describe an elegant molecular conveyor composed of a previously identified human 5S rRNA import factor, rhodanese, and mitochondrial ribosomal protein L18, thanks to which 5S rRNA molecules can be specifically withdrawn from the cytosolic pool and redirected to mitochondria, bypassing the classic nucleolar reimport pathway. Inside mitochondria, the cytosolic 5S rRNA is shown to be associated with mitochondrial ribosomes