Prediction of Protein Sites and Physicochemical Properties Related to Functional Specificity

Specificity Determining Positions (SDPs) are protein sites responsible for functional specificity within a family of homologous proteins. These positions are extracted from a family’s multiple sequence alignment and complement the fully conserved positions as predictors of functional sites. SDP analysis is now routinely used for locating these specificity-related sites in families of proteins of biomedical or biotechnological interest with the aim of mutating them to switch specificities or design new ones. There are many different approaches for detecting these positions in multiple sequence alignments. Nevertheless, existing methods report the potential SDP positions but they do not provide any clue on the physicochemical basis behind the functional specificity, which has to be inferred a-posteriori by manually inspecting these positions in the alignment. In this work, a new methodology is presented that, concomitantly with the detection of the SDPs, automatically provides information on the amino-acid physicochemical properties more related to the change in specificity. This new method is applied to two different multiple sequence alignments of homologous of the well-studied RasH protein representing different cases of functional specificity and the results discussed in detail.

THE ROLE OF METAPHOR IN LEZGHIN PROVERBS AND SAYINGS

The article analyzes the functional specificity of the metaphor in folk proverbs and sayings of the Lezghins. On the subject-figurative level, Lezghin paremias are characterized by frequent use of metaphor and metaphorical images. Metaphor, with its meaningfulness, best copes with the artistic features of this genre, which requires laconicism and brevity of presentation.

Shared and specific functions of Arfs 1–5 at the Golgi revealed by systematic knockouts

ADP-ribosylation factors (Arfs) are small GTPases regulating membrane traffic in the secretory pathway. They are closely related and appear to have overlapping functions, regulators, and effectors. The functional specificity of individual Arfs and the extent of redundancy are still largely unknown. We addressed these questions by CRISPR/Cas9-mediated genomic deletion of the human class I (Arf1/3) and class II (Arf4/5) Arfs, either individually or in combination. Most knockout cell lines were viable with slight growth defects only when lacking Arf1 or Arf4. However, Arf1+4 and Arf4+5 could not be deleted simultaneously. Class I Arfs are nonessential, and Arf4 alone is sufficient for viability. Upon Arf1 deletion, the Golgi was enlarged, and recruitment of vesicle coats decreased, confirming a major role of Arf1 in vesicle formation at the Golgi. Knockout of Arf4 caused secretion of ER-resident proteins, indicating specific defects in coatomer-dependent ER protein retrieval by KDEL receptors. The knockout cell lines will be useful tools to study other Arf-dependent processes.

The endophilin curvature-sensitive motif requires electrostatic guidance to recycle synaptic vesicles in vivo

Curvature-sensing mechanisms assist proteins in executing particular actions on various membrane organelles. Here, we investigated the functional specificity of curvature-sensing amphipathic motifs through the study of endophilin, an endocytic protein for synaptic vesicle recycling. We generated chimeric endophilin proteins by replacing the endophilin amphipathic motif H0 with other curvature-sensing amphipathic motifs. We found that the role of amphipathic motifs cannot simply be extrapolated from the identity of their parental proteins. For example, the amphipathic motif of the nuclear pore complex protein NUP133 functionally replaced the synaptic role of endophilin H0. Interestingly, non-functional endophilin chimeras had similar defects — producing fewer synaptic vesicles but more endosomes — indicating that the curvature-sensing motifs in these chimeras have a common deficiency at reforming synaptic vesicles. Finally, we converted non-functional endophilin chimeras into functional proteins by changing the cationic property of amphipathic motifs, setting a precedent for reprogramming the functional specificity of curvature-sensing motifs in vivo.

FUNCTIONS OF ANTHROPONYMS IN THE COLLECTION OF MYKOLA BILOKOPYTOV «AND ETERNAL TIME PASSES SLOWLY…»

Purpose. The purpose of the research is to analyze the functions of stylistically marked artistic anthroponyms in the satirical and funny works written by M.Bilokopytov (on the material of the collection “And Eternal Time passes slowly...”).Methods. The method of purposeful sampling (collection of actual material for analysis), descriptive (analysis of collected material), method of systematization and classification (division of anthroponyms into groups), statistical (detection of quantitative ratios of proper names in works), and contextual analysis were used to establish functional specificity of anthroponyms.Results. The article examines the pragmatics of anthroponyms in the satirical and funny works written by M.Bilokopytov. We studied the author's peculiar way to use anthroponyms, their variability, frequency, and functions. Both satirical and funny proper names are classified according to their functions, so we were able to distinguish stylistically neutral anthroponyms from stylistically marked artistic ones. The stylistically neutral anthroponyms are represented by the following groups: proper names related to the depicted epoch; first and last names; first names and patronymics; fist name, patronymic and last name; proper names of famous real people. Among the stylistically marked artistic anthroponyms, we can distinguish evaluative-characteristic names and precedent proper ones. We admit that M.Bilokopytov selected quite skillfully anthroponyms in his satirical and funny works showing his sound individual and authorial ingenuity. It is worth paying attention to the proper names in the author’s scope, to be borrowed from the real anthroponymicon. Such anthroponyms refer to specific people around the writer, his personal acquaintances and friends.Conclusions. Thus, the inexhaustible source of the comic in the satirical and funny works written by M.Bilokopytov are precisely the stylistically marked artistic anthroponyms. Most of the names of the characters are expressive and are used by the author as evaluative-characteristic names. They help to characterize the hero, point out his special features.Key words: emotional coloring, stylistically marked artistic anthroponyms, pragmatic potential, satirical and funny works, function. Мета. Метою розвідки є аналіз функційного навантаження літературно-художніх антропонімів сатирично-гумористичних творів М.Білокопитова (на матеріалі збірки «А Вічний Час непоспіхом тече...»).Методи. У роботі використані метод цілеспрямованої вибірки (збирання фактичного матеріалу для аналізу), описовий (аналіз зібраного матеріалу), метод систематизації та класифікації (поділ антропонімів на групи), статистичний (виявлення кількісних співвідношень власних імен у творах), а також застосовано контекстуальний аналіз для встановлення функціональної специфіки антропонімів.Результати. У статті досліджено функційне навантаження антропонімів в сатирично-гумористичних творах М.Білокопитова. Визначено авторські особливості вживання антропонімів, їх варіативність, частотність та функціональне навантаження. Сатирично-гумористичні власні імена класифіковано відповідно до їх функцій, тому було виділено стилістично-нейтральні та стилістично-марковані літературно-художні антропоніми. Зазначено, що стилістично-нейтральні антропоні-ми представлені такими групами: власні імена, що відповідають зображуваній епосі; імена та прізвища; імена та по батькові; прізвища + імена + імена по батькові; власні імена відомих реальних людей. Серед стилістично-маркованих антропонімів виділено оцінювально-характеризувальні та прецедентні власні імена. Антропоніми у сатирично-гумористичних творах М.Білокопитова дібрані досить майстерно, адже для цього потрібна неабияка індивідуально-авторська винахідливість. Варто звернути увагу на власні імена у спадщині письменника, що запозичені автором із реального антропонімікону. Такі антропоніми називають конкретних людей з оточення письменника, його особистих знайомих та друзів.Висновки. Отже, невичерпним джерелом комічного в сатирично-гумористичних текстах М.Білокопитова є саме літературно-художні антропоніми. Більшість імен персонажів експресивні і використовуються автором як оцінювально-характери-зувальні. Вони допомагають схарактеризувати героя, вказують на його особливі риси.Ключові слова: емоційне забарвлення, літературно-художні антропоніми, прагматичний потенціал, сатирично-гуморис-тичні твори, функціональне навантаження.

Diverse inhibitory projections from the cerebellar interposed nucleus

The cerebellum consists of parallel circuit modules that contribute to diverse behaviors, spanning motor to cognitive. Recent work employing cell-type-specific tracing has identified circumscribed output channels of the cerebellar nuclei (CbN) that could confer tight functional specificity. These studies have largely focused on excitatory projections of the CbN, however, leaving open the question of whether inhibitory neurons also constitute multiple output modules. We mapped output and input patterns to intersectionally restricted cell types of the interposed and adjacent interstitial nuclei in mice. In contrast to the widespread assumption of primarily excitatory outputs and restricted inferior olive-targeting inhibitory output, we found that inhibitory neurons from this region ramified widely within the brainstem, targeting both motor- and sensory-related nuclei, distinct from excitatory output targets. Despite differences in output targeting, monosynaptic rabies tracing revealed largely shared afferents to both cell classes. We discuss the potential novel functional roles for inhibitory outputs in the context of cerebellar theory.

Role of structural specificity of ZnO particles in preserving functionality of proteins in their corona

Reconfiguration of protein conformation in a micro and nano particle (MNP) protein corona due to interaction is an often-overlooked aspect in drug design and nano-medicine. Mostly, MNP-Protein corona studies focus on the toxicity of nano particles (NPs) in a biological environment to analyze biocompatibility. However, preserving functional specificity of proteins in an NP corona becomes critical for effective translation of nano-medicine. This paper investigates the non-classical interaction between insulin and ZnO MNPs using a classical electrical characterization technique at GHz frequency with an objective to understand the effect of the micro particle (MP) and nanoparticle (NP) morphology on the electrical characteristics of the MNP-Protein corona and therefore the conformation and functional specificity of protein. The MNP-Protein corona was subjected to thermal and enzymatic (papain) perturbation to study the denaturation of the protein. Experimental results demonstrate that the morphology of ZnO particles plays an important role in preserving the electrical characteristics of insulin.