Development, Diversity, and Neurogenic Capacity of Enteric Glia

Enteric glia are a fascinating population of cells. Initially identified in the gut wall as the “support” cells of the enteric nervous system, studies over the past 20 years have unveiled a vast array of functions carried out by enteric glia. They mediate enteric nervous system signalling and play a vital role in the local regulation of gut functions. Enteric glial cells interact with other gastrointestinal cell types such as those of the epithelium and immune system to preserve homeostasis, and are perceptive to luminal content. Their functional versatility and phenotypic heterogeneity are mirrored by an extensive level of plasticity, illustrated by their reactivity in conditions associated with enteric nervous system dysfunction and disease. As one of the hallmarks of their plasticity and extending their operative relationship with enteric neurons, enteric glia also display neurogenic potential. In this review, we focus on the development of enteric glial cells, and the mechanisms behind their heterogeneity in the adult gut. In addition, we discuss what is currently known about the role of enteric glia as neural precursors in the enteric nervous system.

Evolutionary plasticity and functional versatility of CRISPR systems

The principal biological function of bacterial and archaeal CRISPR systems is RNA-guided adaptive immunity against viruses and other mobile genetic elements (MGEs). These systems show remarkable evolutionary plasticity and functional versatility at multiple levels, including both the defense mechanisms that lead to direct, specific elimination of the target DNA or RNA and those that cause programmed cell death (PCD) or induction of dormancy. This flexibility is also evident in the recruitment of CRISPR systems for nondefense functions. Defective CRISPR systems or individual CRISPR components have been recruited by transposons for RNA-guided transposition, by plasmids for interplasmid competition, and by viruses for antidefense and interviral conflicts. Additionally, multiple highly derived CRISPR variants of yet unknown functions have been discovered. A major route of innovation in CRISPR evolution is the repurposing of diverged repeat variants encoded outside CRISPR arrays for various structural and regulatory functions. The evolutionary plasticity and functional versatility of CRISPR systems are striking manifestations of the ubiquitous interplay between defense and “normal” cellular functions.

Molecular Mechanisms and Regulation of Mammalian Mitophagy

Mitochondria in the cell are the center for energy production, essential biomolecule synthesis, and cell fate determination. Moreover, the mitochondrial functional versatility enables cells to adapt to the changes in cellular environment and various stresses. In the process of discharging its cellular duties, mitochondria face multiple types of challenges, such as oxidative stress, protein-related challenges (import, folding, and degradation) and mitochondrial DNA damage. They mitigate all these challenges with robust quality control mechanisms which include antioxidant defenses, proteostasis systems (chaperones and proteases) and mitochondrial biogenesis. Failure of these quality control mechanisms leaves mitochondria as terminally damaged, which then have to be promptly cleared from the cells before they become a threat to cell survival. Such damaged mitochondria are degraded by a selective form of autophagy called mitophagy. Rigorous research in the field has identified multiple types of mitophagy processes based on targeting signals on damaged or superfluous mitochondria. In this review, we provide an in-depth overview of mammalian mitophagy and its importance in human health and diseases. We also attempted to highlight the future area of investigation in the field of mitophagy.

FUNCTIONAL-SEMANTIC CHARACTERISTICS OF THE SWEDISH MODAL PARTICLE VÄL

Статья посвящена изучению семантики и функций шведской модальной частицы väl в диалогических текстах на материале пьесы современного шведского драматурга Ларса Нурена «Тихая музыка» (Lars Norén «Tyst musik»). Актуальность статьи обусловлена отсутствием исследований шведских модальных частиц на таком материале. Анализ примеров показал, что частица väl отличается функциональной многоплановостью и обладает множеством прагматических значений, которые раскрываются в диалоге и зависят от контекста. Проявление интерактивной функции в большинстве примеров дает право говорить о väl как о диалогической частице, ориентированной на адресата высказывания. The article studies semantics and functions of the Swedish modal particle väl in dialogic texts based on the play of the modern Swedish playwright Lars Norén called «Tyst musik» («Silent Music»). The relevance of the article is due to the lack of studies of Swedish modal particles based on such material. The analysis of the examples showed that väl is distinguished by its functional versatility and has many pragmatic meanings, which are revealed in the dialogue and depend on the context. As the interactive function of väl appears in most examples, the author speaks of väl as a dialogical particle focused on the addressee of the utterance.

Structural Basis for the Functional Diversity of Centrins: A Focus on Calcium Sensing Properties and Target Recognition

Centrins are a family of small, EF hand-containing proteins that are found in all eukaryotes and are often complexed with centrosome-related structures. Since their discovery, centrins have attracted increasing interest due to their multiple, diverse cellular functions. Centrins are similar to calmodulin (CaM) in size, structure and domain organization, although in contrast to CaM, the majority of centrins possess at least one calcium (Ca2+) binding site that is non-functional, thus displaying large variance in Ca2+ sensing abilities that could support their functional versatility. In this review, we summarize current knowledge on centrins from both biophysical and structural perspectives with an emphasis on centrin-target interactions. In-depth analysis of the Ca2+ sensing properties of centrins and structures of centrins complexed with target proteins can provide useful insight into the mechanisms of the different functions of centrins and how these proteins contribute to the complexity of the Ca2+ signaling cascade. Moreover, it can help to better understand the functional redundancy of centrin isoforms and centrin-binding proteins.

Draft Genome Sequence of Cupriavidus sp. Strain IK-TO18, Isolated from Antimony-Contaminated Sediment

Cupriavidus sp. strain IK-TO18 was isolated from antimony-contaminated sediment. The draft genome sequence of the isolate contains 6,605 predicted protein-coding sequences, including genes associated with heavy metal resistance and the aerobic degradation of aromatic hydrocarbons. This sequence will provide valuable information regarding the functional versatility of the genus Cupriavidus .

Multifunctionality of the French Verb Finir ‘to Finish’ Based Constructions: a Corpus-Based Study of French and Lithuanian

Based on the Corpus parallèle de Textes Littéraires (CTLFR-LT), consisting of French fiction texts and their translations into Lithuanian, the present article aims toshow the functional versatility of the French verb finir ‘to finish’. The paper focuses on the following particular constructions:S((in)anim) + finir + (GN);S((in)anim) + (en) finir de + V(inf);S ((in)anim) + finir par + V(inf);pour finir.While retaining its literal meaning, the verb finir ‘to finish’ exhibits a great range of modally marked uses. These uses, considered peripheral in the majority of French monolingual and bilingual grammars or dictionaries, nevertheless appear to be statistically very significant in the present dataset. The study shows that the verb finir ‘to finish’ can be used as a component of various constructions in which it loses its core lexical meaning and functions as an adverbial or discourse connector. The analysis of the data of the corpus Corpus parallèle de Textes Littéraires merely confirms the fact that the constructions under consideration can have a two-fold reading: the adverbial function of time and the function of a sentence adverbial.

Structural basis for the therapeutic advantage of dual and triple agonists at the human GIP, GLP-1 or GCG receptors

Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed to maximize metabolic benefits with reduced side-effects, are in clinical trials to treat type 2 diabetes and obesity. To elucidate the molecular mechanisms by which tirzepatide, a GIPR/GLP-1R dualagonist, and peptide 20, a GIPR/GLP-1R/GCGR triagonist, manifest their superior efficacies over monoagonist such as semaglutide, we determined cryo-electron microscopy structures of tirzepatide-bound GIPR and GLP-1R as well as peptide 20-bound GIPR, GLP-1R and GCGR The structures reveal both common and unique features for the dual and triple agonism by illustrating key interactions of clinical relevance at the atomic level. Retention of glucagon function is required to achieve such an advantage over GLP-1 monotherapy. Our findings provide valuable insights into the structural basis of functional versatility and therapeutic supremacy of tirzepatide and peptide 20.