Non3 is an essential Drosophila gene required for proper nucleolus assembly

The nucleolus is a dynamic non-membrane-bound nuclear organelle, which plays key roles not only in ribosome biogenesis but also in many other cellular processes. Consistent with its multiple functions, the nucleolus has been implicated in many human diseases, including cancer and degenerative pathologies of the nervous system and heart. Here, we report the characterization of the Drosophila Non3 (Novel nucleolar protein 3) gene, which encodes a protein homologous to the human Brix domain-containing Rpf2 that has been shown to control ribosomal RNA (rRNA) processing. We used imprecise P-element excision to generate four new mutant alleles in the Non3 gene. Complementation and phenotypic analyses showed that these Non3 mutations can be arranged in an allelic series that includes both viable and lethal alleles. The strongest lethal allele (Non3∆600) is a genetically null allele that carries a large deletion of the gene and exhibits early lethality when homozygous. Flies heterozygous for Non3∆600 occasionally exhibit a mild reduction in the bristle size, but develop normally and are fertile. However, heteroallelic combinations of viable Non3 mutations (Non3197, Non3310 and Non3259) display a Minute-like phenotype, consisting in delayed development and short and thin bristles, suggesting that they are defective in ribosome biogenesis. We also demonstrate that the Non3 protein localizes to the nucleolus of larval brain cells and it is required for proper nucleolar localization of Fibrillarin, a protein important for post-translational modification and processing of rRNAs. In summary, we generated a number of genetic and biochemical tools that were exploited for an initial characterization of Non3, and will be instrumental for future functional studies on this gene and its protein product

Moonlighting in Mitosis: Analysis of the Mitotic Functions of Transcription and Splicing Factors

Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different cellular compartments. Transcription factors (TFs) and splicing factors (SFs) control processes that occur in interphase nuclei and are strongly reduced during cell division, and are therefore in a favorable situation to evolve moonlighting mitotic functions. However, recently published moonlighting protein databases, which comprise almost 400 proteins, do not include TFs and SFs with secondary mitotic functions. We searched the literature and found several TFs and SFs with bona fide moonlighting mitotic functions, namely they localize to specific mitotic structure(s), interact with proteins enriched in the same structure(s), and are required for proper morphology and functioning of the structure(s). In addition, we describe TFs and SFs that localize to mitotic structures but cannot be classified as moonlighting proteins due to insufficient data on their biochemical interactions and mitotic roles. Nevertheless, we hypothesize that most TFs and SFs with specific mitotic localizations have either minor or redundant moonlighting functions, or are evolving towards the acquisition of these functions

Moonlighting in mitosis:Analysis of the mitotic functions of transcription and splicing factors

Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different cellular compartments. Transcription factors (TFs) and splicing factors (SFs) control processes that occur in interphase nuclei and are strongly reduced during cell division, and are therefore in a favorable situation to evolve moonlighting mitotic functions. However, recently published moonlighting protein databases, which comprise almost 400 proteins, do not include TFs and SFs with secondary mitotic functions. We searched the literature and found several TFs and SFs with bona fide moonlighting mitotic functions, namely they localize to specific mitotic structure(s), interact with proteins enriched in the same structure(s), and are required for proper morphology and functioning of the structure(s). In addition, we describe TFs and SFs that localize to mitotic structures but cannot be classified as moonlighting proteins due to insufficient data on their biochemical interactions and mitotic roles. Nevertheless, we hypothesize that most TFs and SFs with specific mitotic localizations have either minor or redundant moonlighting functions, or are evolving towards the acquisition of these functions

Влияние мексидола на состав и перекисное окисление липидов миокарда в постреанимационном периоде

An experimental model of clinical death followed by reperfusion was used to study the postresuscitative effects of the anti-hypoxant mexidole on lipid composition and peroxidation rates in the rat myocardium. The use of mexidole in early reperfusion was shown to lead to the altered phospholipid composition of cardiomyocytes, the normalization of the activities of superoxide dismutase and catalase, the lower levels of malonic dialdehyde on postresuscitative day 30. Modifications of the myocardium lipid spectrum appeared as the elevated levels of phosphatidylserine and phosphatidylethanolamine that maintained intracellular ionic homeostasis and myocardial performance, as well as decreases in lysophosphatidylcholine having proarrhythmic activity and in sphingomyelin and phosphatidic acids.На экспериментальной модели клинической смерти с последующей реперфузией исследовано влияние антигипок-санта метаболического типа — мексидола на липидный состав и активность перекисного окисления липидов ткани сердца крыс в отдаленном постреанимационном периоде. Показано, что применение мексидола в раннем реперфу-зионном периоде приводило к изменению фосфолипидного состава кардиомиоцитов, нормализации активности су-пероксиддисмутазы и каталазы, снижению содержания малонового диальдегида на 30-е сутки постреанимационного периода. Модификации спектра липидов ткани сердца проявлялись увеличением содержания фосфатидилсерина, фосфатидилэтаноламина, обеспечивающих поддержание внутриклеточного ионного гомеостаза и деятельности сердечной мышцы, уменьшением лизофосфатидилхолина, обладающего аритмогенным действием, сфингомиелина и фосфатидных кислот

БОЛЕЗНЬ ЛЕБЕРА. КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

Violation of visual functions and oculomotor frustration develop at 90% of patients with MS. More than a half of patients are transferred by the numerous recurrence of an optical neuritis which is coming to an end with a partial atrophy of optic nerve. For well-timed purpose of pathogenetic treatment differential diagnostics with other diseases, being accompanied an atrophy of an optic nerve, in particular with Leber's disease. Нарушение зрительных функций и глазодвигательные расстройства развиваются у 90% больных с рассеянным склерозом. Более половины больных переносят неоднократные рецидивы оптического неврита, заканчивающиеся частичной атрофией зрительного нерва. Для своевременного назначения патогенетического лечения чрезвычайно важным является дифференциальная диагностика с другими заболеваниями, сопровождающимися атрофией зрительного нерва, в частности с болезнью Лебера.

Отдаленные результаты эмболизации артериовенозных мальформаций головного мозга гистоакрилом

N-butyl cyanoacrylate (Hystoacryl) is one of the most frequently used glues for the treatment of cerebral arteriovenous malformation. However, long-term results of its treatment with Hystoacryl are insufficiently studied. 136 patients were examined. Catamnesis was (4 ± 1) year. The quality of life is reduced due to cognitive and motor disorders.В последнее время наиболее распространенным эмболизирующим веществом является смесь гистоакрила с липиодолом. При этом в системе комплексного лечения артериовенозных мальформаций отдаленные результаты эмболизации изучены недостаточно. Проведено обследование 136 пациентов со средним сроком катамнеза (4 ± 1) год. Установлено, что снижение качества жизни пациентов обусловлено когнитивными, двигательными нарушениями

Drosophila SUMM4 complex couples insulator function and DNA replication control

Asynchronous replication of chromosome domains during S phase is essential for eukaryotic genome function, but the mechanisms establishing which domains replicate early versus late in different cell types remain incompletely understood. Intercalary heterochromatin domains replicate very late in both diploid chromosomes of dividing cells and in endoreplicating polytene chromosomes where they are also underrelicated. Drosophila SNF2-related factor SUUR imparts locus-specific underreplication of polytene chromosomes. SUUR negatively regulates DNA replication fork progression; however, its mechanism of action remains obscure. Here we developed a novel method termed MS-Enabled Rapid protein Complex Identification (MERCI) to isolate a stable stoichiometric native complex SUMM4 that comprises SUUR and a chromatin boundary protein Mod(Mdg4)-67.2. Mod(Mdg4) stimulates SUUR ATPase activity and is required for a normal spatiotemporal distribution of SUUR in vivo. SUUR and Mod(Mdg4)-67.2 together mediate the activities of gypsy insulator that prevent certain enhancer-promoter interactions and establish euchromatin-heterochromatin barriers in the genome. Furthermore, SuUR or mod(mdg4) mutations reverse underreplication of intercalary heterochromatin. Thus, SUMM4 can impart late replication of intercalary heterochromatin by attenuating the progression of replication forks through euchromatin/heterochromatin boundaries. Our findings implicate a SNF2 family ATP-dependent motor protein SUUR in the insulator function, reveal that DNA replication can be delayed by a chromatin barrier and uncover a critical role for architectural proteins in replication control. They suggest a mechanism for the establishment of late replication that does not depend on an asynchronous firing of late replication origins

Диагностика и мониторинг нейронального повреждения при тяжелой черепно-мозговой травме

Objective: to search for an accessible, valid, and easy-to-use method for the diagnosis and monitoring of a neuronal lesion in severe brain injury (SBI). Subjects and methods. Thirty-three patients aged 18—55 years with isolated SBI (the Glasgow coma scores for admission consciousness were 6±2) were examined; the serum content of neuron-specific protein S-100B was further analyzed. Results and discussion. The cell damage marker concentration was substantially increased in the acute period of brain injury. When the pathological process followed a favorable course, S-100B was considerably decreased just on day 2 of the disease. When the changes were negative, S-100B concentrations remained virtually unchanged or even increased, which was indicative of secondary brain reperfusion/ischemic lesions. The mean baseline marker level varied with the type of brain injury diagnosed by computed tomography; the highest figures being noted in the groups where significant brain tissue lesion was detected. Key words: severe brain injury, prognosis, S-100B protein.Цель исследования — поиск доступного, надежного и простого метода диагностики и мониторинга нейронального повреждения при ТЧМТ. Материалы и методы. Проведено обследование 33 пациентов с изолированной ТЧМТ в возрасте 18—55 лет (уровень сознания при поступлении в стационар 6±2 балла по ШКГ), с последующим анализом содержания нейронспецифического протеина S-100В в сыворотке крови. Результаты и обсуждение. Концентрация маркера клеточного повреждения значительно повышалась в остром периоде черепно-мозговой травмы. При благоприятном течении патологического процесса уровень S-100В значительно снижался уже на 2-е сутки болезни. При отрицательной динамике концентрация S-100В оставалась практически неизменной или даже повышалась, что свидетельствовало о вторичных реперфузионных повреждениях головного мозга. Показано, что средние значения начального уровня маркера различались в зависимости от вида ЧМТ, диагностированного КТ, причем наибольшие цифры отмечались в группах, где выявлялось значительное повреждение мозговой ткани. Ключевые слова: тяжелая черепно-мозговая травма, прогноз, белок S-100В

Cравнительная характеристика когнитивных нарушений у больных с токсической (ртутной) и сосудистой (дисциркуляторной) энцефалопатией

The neurophysiological (the registration of induced potentials P300) and the psychological examinations of 70 patients, males, with chronic mercury intoxications (ChMI) and discirculatory encephalopathy (DE) have been performed with aim to reveal the features of cognitive disorders (CD). The study results have shown the presence of light CD and small demention in the patients of both groups, preferably, of subcork type for the patients with ChMI and preferably of cork type – for the patients with DE.Проведено нейрофизиологическое (регистрация вызванных потенциалов Р300) и психологическое обследование 70 мужчин с хронической ртутной интоксикацией (ХРИ) и дисциркуляторной энцефалопатией (ДЭ) с целью выявления особенностей когнитивных нарушений (КН). Результаты исследования показали наличие легких КН и легкой деменции у пациентов обеих групп, преимущественно подкоркового типа для больных ХРИ и коркового - для пациентов с ДЭ