Whether we emphasize the notion of 'sign' or the notion of 'code', either way the main interest of biosemiotics and Code Biology is the same, and we argue that the idea of the lower threshold is what still unifies these two groups. Code Biology concentrates on the notion of code: living organisms are defined as code-users or code-makers, and so it may be called the 'lower coding threshold' in this case. The semiotic threshold on the other hand is a concept without a specific definition. There are many possible ways of understanding this term. In order to maintain the lower threshold as the unifying concept between Code Biology and biosemiotics, it is important to be very clear about where this threshold is located and how it is defined. We focus on establishing the lower semiotic threshold at protein biosynthesis, and we propose basing the semiotic understanding of the lowest life forms on the following criteria: arbitrariness, representation, repetition, historicity and self-replication. We also offer that this definition of the lower threshold need not include the notion of interpretation, in the hope that this newly specified common principle of the lower threshold be accepted as a way forward in the conversation between Code Biology and biosemiotics.

• Klíčová slova
• Arbitrariness, Code biology, Evolutionarity, Protein synthesis, Repetition, Representation, Semiosis, Semiotic threshold,
• MeSH
• genetický kód fyziologie   MeSH
• lidé MeSH
• molekulární evoluce * MeSH
• robotika metody   trendy   MeSH
• systémová biologie metody   trendy   MeSH
• umělá inteligence trendy   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In the philosophy of science, we can consider debates about the nature of non-causal explanations in general (e.g. Reutlinger, Saatsi 2018; Lange 2017) and then especially those in the life sciences (e.g. Huneman, 2018; Kostić 2020). These debates are accompanied by the development of a new mechanism that is becoming the major response to the nature of scientific explanation in the life sciences (e.g. Craver, Darden 2013; Craver 2006); and also by the development of a design explanation (e.g. Eck, Mennes 2016) that represents a modern variant of a functional explanation. In this paper, we will methodically: 1. evaluate the plurality of explanatory strategies in contemporary science (chapter 2). 2. describe the mechanical philosophy and mechanistic explanation (Glennan 2016; Craver, Darden 2013, etc.) (chapter 3). 3. explicate the role of mechanisms in code biology (Barbieri 2015, 2002, etc.) and its relation to the new mechanism (chapter 4). 4. fulfill the main goal of the paper - to apply mechanistic explanations in code biology (Barbieri 2019, etc.) and to apply their suitability for this scientific domain (chapter 5).

• Klíčová slova
• Biological sciences, Causal and non-causal explanation, Code biology, Mechanistic and design explanation, ‘Why’-questions,
• MeSH
• biologická evoluce MeSH
• biologické modely * MeSH
• biologické vědy metody   MeSH
• biologie metody   MeSH
• filozofie * MeSH
• kauzalita * MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Arbitrariness in the genetic code is one of the main reasons for a linguistic approach to molecular biology: the genetic code is usually understood as an arbitrary relation between amino acids and nucleobases. However, from a semiotic point of view, arbitrariness should not be the only condition for definition of a code, consequently it is not completely correct to talk about "code" in this case. Yet we suppose that there exist a code in the process of protein synthesis, but on a higher level than the nucleic bases chains. Semiotically, a code should be always associated with a function and we propose to define the genetic code not only relationally (in basis of relation between nucleobases and amino acids) but also in terms of function (function of a protein as meaning of the code). Even if the functional definition of meaning in the genetic code has been discussed in the field of biosemiotics, its further implications have not been considered. In fact, if the function of a protein represents the meaning of the genetic code (the sign's object), then it is crucial to reconsider the notion of its expression (the sign) as well. In our contribution, we will show that the actual model of the genetic code is not the only possible and we will propose a more appropriate model from a semiotic point of view.

• Klíčová slova
• Arbitrariness, Biosemiotics, Genetic code, Protein function, Semiotics,
• MeSH
• aminokyseliny chemie   MeSH
• bodová mutace MeSH
• DNA chemie   MeSH
• genetický kód * MeSH
• histony chemie   MeSH
• modely genetické MeSH
• nukleotidy genetika   MeSH
• RNA chemie   MeSH
• sbalování proteinů MeSH
• teoretické modely MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny MeSH
• DNA MeSH
• histony MeSH
• nukleotidy MeSH
• RNA MeSH

The African trypanosome, Trypanosoma brucei, has developed into a flexible and robust experimental model for molecular and cellular parasitology, allowing us to better combat these and related parasites that cause worldwide suffering. Diminishing case numbers, due to efficient public health efforts, and recent development of new drug treatments have reduced the need for continued study of T. brucei in a disease context. However, we argue that this pathogen has been instrumental in revolutionary discoveries that have widely informed molecular and cellular biology and justifies continuing research as an experimental model. Ongoing work continues to contribute towards greater understanding of both diversified and conserved biological features. We discuss multiple examples where trypanosomes pushed the boundaries of cell biology and hope to inspire researchers to continue exploring these remarkable protists as tools for magnifying the inner workings of cells.

• Klíčová slova
• GPI-anchor, RNA editing, alternative oxidase, endocytosis, genetic code, glycosome, tRNA import,
• MeSH
• molekulární biologie MeSH
• Trypanosoma brucei brucei * genetika   MeSH
• Trypanosoma * genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

A limited number of non-canonical genetic codes have been described in eukaryotic nuclear genomes. Most involve reassignment of one or two termination codons as sense ones [1-4], but no code variant is known that would have reassigned all three termination codons. Here, we describe such a variant that we discovered in a clade of trypanosomatids comprising nominal Blastocrithidia species. In these protists, UGA has been reassigned to encode tryptophan, while UAG and UAA (UAR) have become glutamate encoding. Strikingly, UAA and, less frequently, UAG also serve as bona fide termination codons. The release factor eRF1 in Blastocrithidia contains a substitution of a conserved serine residue predicted to decrease its affinity to UGA, which explains why this triplet can be read as a sense codon. However, the molecular basis for the dual interpretation of UAR codons remains elusive. Our findings expand the limits of comprehension of one of the fundamental processes in molecular biology.

• Klíčová slova
• Blastocrithidia, evolution, genetic code, phylogeny, protists, translation, trypanosomatids,
• MeSH
• buněčné jádro genetika   MeSH
• fylogeneze MeSH
• genetický kód genetika   MeSH
• kodon chemie   genetika   MeSH
• protozoální proteiny chemie   genetika   MeSH
• sekvence aminokyselin MeSH
• terminační kodon chemie   genetika   MeSH
• Trypanosomatina genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kodon MeSH
• protozoální proteiny MeSH
• terminační kodon MeSH

In this paper we investigate the rate coding capabilities of neurons whose input signal are alterations of the base state of balanced inhibitory and excitatory synaptic currents. We consider different regimes of excitation-inhibition relationship and an established conductance-based leaky integrator model with adaptive threshold and parameter sets recreating biologically relevant spiking regimes. We find that given mean post-synaptic firing rate, counter-intuitively, increased ratio of inhibition to excitation generally leads to higher signal to noise ratio (SNR). On the other hand, the inhibitory input significantly reduces the dynamic coding range of the neuron. We quantify the joint effect of SNR and dynamic coding range by computing the metabolic efficiency-the maximal amount of information per one ATP molecule expended (in bits/ATP). Moreover, by calculating the metabolic efficiency we are able to predict the shapes of the post-synaptic firing rate histograms that may be tested on experimental data. Likewise, optimal stimulus input distributions are predicted, however, we show that the optimum can essentially be reached with a broad range of input distributions. Finally, we examine which parameters of the used neuronal model are the most important for the metabolically efficient information transfer.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• akční potenciály fyziologie   MeSH
• excitační postsynaptické potenciály fyziologie   MeSH
• membránové potenciály fyziologie   MeSH
• modely neurologické * MeSH
• nervové vedení fyziologie   MeSH
• nervový přenos fyziologie   MeSH
• nervový útlum fyziologie   MeSH
• neurony fyziologie   MeSH
• počítačová simulace MeSH
• poměr signál - šum MeSH
• výpočetní biologie MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosintrifosfát MeSH

• MeSH
• aminokyseliny MeSH
• biosyntéza peptidů MeSH
• DNA MeSH
• genetický kód * MeSH
• lidé MeSH
• molekulární biologie MeSH
• nukleotidy biosyntéza   MeSH
• ribozomy MeSH
• RNA MeSH
• vrozené poruchy metabolismu enzymologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• aminokyseliny MeSH
• DNA MeSH
• nukleotidy MeSH
• RNA MeSH

BACKGROUND: The most demanding challenge in research on molecular aspects within the flow of biological information is posed by the complex carbohydrates (glycan part of cellular glycoconjugates). How the 'message' encoded in carbohydrate 'letters' is 'read' and 'translated' can only be unraveled by interdisciplinary efforts. SCOPE OF REVIEW: This review provides a didactic step-by-step survey of the concept of the sugar code and the way strategic combination of experimental approaches characterizes structure-function relationships, with resources for teaching. MAJOR CONCLUSIONS: The unsurpassed coding capacity of glycans is an ideal platform for generating a broad range of molecular 'messages'. Structural and functional analyses of complex carbohydrates have been made possible by advances in chemical synthesis, rendering production of oligosaccharides, glycoclusters and neoglycoconjugates possible. This availability facilitates to test the glycans as ligands for natural sugar receptors (lectins). Their interaction is a means to turn sugar-encoded information into cellular effects. Glycan/lectin structures and their spatial modes of presentation underlie the exquisite specificity of the endogenous lectins in counterreceptor selection, that is, to home in on certain cellular glycoproteins or glycolipids. GENERAL SIGNIFICANCE: Understanding how sugar-encoded 'messages' are 'read' and 'translated' by lectins provides insights into fundamental mechanisms of life, with potential for medical applications.

• Klíčová slova
• Conformer, Crystallography, Dendrimer, Glycan, Lectin, Neoglycoconjugate,
• MeSH
• glykoproteiny chemie   MeSH
• konformace proteinů MeSH
• konformace sacharidů MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• oligosacharidy chemie   MeSH
• polysacharidy chemie   MeSH
• sacharidové sekvence MeSH
• sacharidy chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• glykoproteiny MeSH
• oligosacharidy MeSH
• polysacharidy MeSH
• sacharidy MeSH

Cullin-RING ubiquitin ligases (CRLs) represent the largest family of E3 ubiquitin ligases that control most if not all cellular processes. In CUL3-based CRLs, the substrate specificity is conferred by the interaction with one of around 183 existing BTB proteins, implying a broad spectrum of possible ubiquitylation signals and possible direct ubiquitylation substrates. Indeed, CUL3-based E3-ligases can catalyze various proteolytic and non-proteolytic ubiquitin signals regulating many physiological and pathophysiological states. Here, we discuss the recent studies focusing on the non-proteolytic CUL3-based signaling in mammalian cells, which emerge as important pathways during cell division, embryonic development as well as other biological processes. Mechanistically, non-proteolytic ubiquitin signals generated by CUL3 E3-ligases often regulate substrates' interactions with other downstream factors or their subcellular localization. Existing data also demonstrate an interplay with the proteolytic ubiquitylation catalyzed on the same substrates by different E3-ligases or by the same CUL3-BTB CRL3s on different substrates. In future, a deeper understanding of the upstream spatiotemporal regulatory mechanisms will help to dissect this fascinating CUL3 ubiquitin code.

• Klíčová slova
• Cell division, Cullin 3, Development, Non-proteolytic signaling, Substrates, Ubiquitin code,
• MeSH
• kulinové proteiny metabolismus   MeSH
• lidé MeSH
• proteolýza MeSH
• ubikvitin metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• CUL3 protein, human MeSH Prohlížeč
• kulinové proteiny MeSH
• ubikvitin MeSH

The site-specific chemical modification of proteins through incorporation of noncanonical amino acids enables diverse applications, such as imaging, probing, and expanding protein functions, as well as to precisely engineer therapeutics. Here we report a general strategy that allows the incorporation of noncanonical amino acids into target proteins using the amber suppression method and their efficient secretion in the biotechnological relevant expression host Bacillus subtilis. This facilitates efficient purification of target proteins directly from the supernatant, followed by their functionalization using click chemistry. We used this strategy to site-specifically introduce norbornene lysine into a single chain antibody and functionalize it with fluorophores for the detection of human target proteins.

• MeSH
• Bacillus subtilis genetika   metabolismus   MeSH
• CRISPR-Cas systémy MeSH
• ELISA MeSH
• genetické vektory MeSH
• genetický kód MeSH
• isopropylthiogalaktosid farmakologie   MeSH
• kreatinkinasa, forma MM metabolismus   MeSH
• lidé MeSH
• lysin chemie   MeSH
• norbornany chemie   MeSH
• proteinové inženýrství metody   MeSH
• regulace genové exprese u bakterií účinky léků   MeSH
• rekombinantní proteiny chemie   genetika   izolace a purifikace   metabolismus   MeSH
• syntetická chemie okamžité shody MeSH
• zelené fluorescenční proteiny genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2-norbornene MeSH Prohlížeč
• isopropylthiogalaktosid MeSH
• kreatinkinasa, forma MM MeSH
• lysin MeSH
• norbornany MeSH
• rekombinantní proteiny MeSH
• zelené fluorescenční proteiny MeSH