Dystrophin Orchestrates the Epigenetic Profile of Muscle Cells Via miRNAs

Mammalian musculature is a very robust and dynamic tissue that goes through many rounds of degeneration and regeneration in an individual’s lifetime. There is a biological program that maintains muscle progenitor cells that, when activated, give rise to intermediate myoblast progeny that consequently differentiate into mature muscle cells. Recent works have provided a picture of the role that microRNAs (miRNAs) play in maintaining aspects of this program. Intriguingly, a subset of these miRNAs is de-regulated in muscular dystrophies (MDs), a group of fatal inherited neuromuscular disorders that are often associated with deficiencies in the Dystrophin (Dys) complex. Apparently, transcriptional expression of many of the muscle specific genes and miRNAs is dependent on chromatin state regulated by the Dys–Syn–nNOS pathway. This puts Dystrophin at the epicenter of a highly regulated program of muscle gene expression in which miRNAs help to coordinate networking between multiple phases of muscle maintenance, degeneration, and regeneration. Therefore, understanding the role of miRNAs in physiology of normal and diseased muscle tissue could be useful for future applications in improving the MD therapies and could open new clinical perspectives

Exocyst-mediated membrane trafficking of the lissencephaly-associated ECM receptor dystroglycan is required for proper brain compartmentalization

To assemble a brain, differentiating neurons must make proper connections and establish specialized brain compartments. Abnormal levels of cell adhesion molecules disrupt these processes. Dystroglycan (Dg) is a major non-integrin cell adhesion receptor, deregulation of which is associated with dramatic neuroanatomical defects such as lissencephaly type II or cobblestone brain. The previously established Drosophila model for cobblestone lissencephaly was used to understand how Dg is regulated in the brain. During development, Dg has a spatiotemporally dynamic expression pattern, fine-tuning of which is crucial for accurate brain assembly. In addition, mass spectrometry analyses identified numerous components associated with Dg in neurons, including several proteins of the exocyst complex. Data show that exocyst-based membrane trafficking of Dg allows its distinct expression pattern, essential for proper brain morphogenesis. Further studies of the Dg neuronal interactome will allow identification of new factors involved in the development of dystroglycanopathies and advance disease diagnostics in humans

Notch-dependent Fizzy-related/Hec1/Cdh1 expression is required for the mitotic-to-endocycle transition in Drosophila follicle cells.

AbstractDuring Drosophila oogenesis, Notch function regulates the transition from mitotic cell cycle to endocycle in follicle cells at stage 6 [1, 2]. Loss of either Notch function or its ligand Delta (Dl) disrupts the normal transition; this disruption causes mitotic cycling to continue and leads to an overproliferation phenotype [1, 2]. In this context, the only known cell cycle component that responds to the Notch pathway is String/Cdc25 (Stg), a G2/M cell cycle regulator [1]. We found that prolonged expression of string is not sufficient to keep cells efficiently in mitotic cell cycle past stage 6, suggesting that Notch also regulates other cell cycle components in the transition. By using an expression screen, we found such a component: Fizzy-related/Hec1/Cdh1 (Fzr), a WD40 repeat protein. Fzr regulates the anaphase-promoting complex/cyclosome (APC/C) and is expressed at the mitotic-to-endocycle transition in a Notch-dependent manner. Mutant clones of Fzr revealed that Fzr is dispensable for mitosis but essential for endocycles. Unlike in Notch clones, in Fzr mutant cells mitotic markers are absent past stage 6. Only a combined reduction of Fzr and ectopic Stg expression prolongs mitotic cycles in follicle cells, suggesting that these two cell cycle regulators, Fzr and Stg, are important mediators of the Notch pathway in the mitotic-to-endocycle transition

TfAP-2 is required for night sleep in Drosophila.

BACKGROUND: The AP-2 transcription factor APTF-1 is crucially required for developmentally controlled sleep behavior in Caenorhabditis elegans larvae. Its human ortholog, TFAP-2beta, causes Char disease and has also been linked to sleep disorders. These data suggest that AP-2 transcription factors may be highly conserved regulators of various types of sleep behavior. Here, we tested the idea that AP-2 controls adult sleep in Drosophila. RESULTS: Drosophila has one AP-2 ortholog called TfAP-2, which is essential for viability. To investigate its potential role in sleep behavior and neural development, we specifically downregulated TfAP-2 in the nervous system. We found that neuronal TfAP-2 knockdown almost completely abolished night sleep but did not affect day sleep. TfAP-2 insufficiency affected nervous system development. Conditional TfAP-2 knockdown in the adult also produced a modest sleep phenotype, suggesting that TfAP-2 acts both in larval as well as in differentiated neurons. CONCLUSIONS: Thus, our results show that AP-2 transcription factors are highly conserved regulators of development and sleep

Tissue-specific regulation of translational readthrough tunes functions of the traffic jam transcription factor

Translational readthrough (TR) occurs when the ribosome decodes a stop codon as a sense codon, resulting in two protein isoforms synthesized from the same mRNA. TR has been identified in several eukaryotic organisms; however, its biological significance and mechanism remain unclear. Here, we quantify TR of several candidate genes in Drosophila melanogaster and characterize the regulation of TR in the large Maf transcription factor Traffic jam (Tj). Using CRISPR/Cas9-generated mutant flies, we show that the TR-generated Tj isoform is expressed in a subset of neural cells of the central nervous system and is excluded from the somatic cells of gonads. Control of TR in Tj is critical for preservation of neuronal integrity and maintenance of reproductive health. The tissue-specific distribution of a release factor splice variant, eRF1H, plays a critical role in modulating differential TR of leaky stop codon contexts. Finetuning of gene regulatory functions of transcription factors by TR provides a potential mechanism for cell-specific regulation of gene ex-pression

Partnership development between universities and IT-companies in staffing sector

У статті досліджено актуальні питання співробітництва між ВНЗ та ІТ-компаніями України в кадровій підготовці. Розглянуто сучасний стан ринку інформаційних технологій. Досліджено особливості процесу та основні етапи розроблення ІТ-продукту. Виділено завдання, результати та необхідні кадрові ресурси для реалізації кожної складової програмного продукту. Визначено потреби та вимоги щодо кваліфікаційного рівня випускників. Надано загальні рекомендації для вищих навчальних закладів щодо підготовки кадрів для ІТ-компаній. Наведено приклади успішної співпраці Національного Університету «Львівська Політехніка» з ІТ-компаніями у рамках навчальних програм, студентських практик, наукових гуртків, тематичних олімпіад.В статье исследованы актуальные вопросы сотрудничества между ВУЗами и IТ-компаниями Украины в подготовке специалистов. Рассмотрено состояние рынка информационных технологий. Исследованы особенности процесса и основные этапы разработки IТ-продукта. Выделены задания, результаты и необходимые кадровые ресурсы для реализации каждой составляющей программного продукта. Определены потребности и требования, а также предоставлены общие рекомендации относительно подготовки кадров для IТ-компаний. Представлены примеры успешного сотрудничества Национального университета «Львовская Политехника» с IТ-компаниями в рамках обучающих программ, студенческих практик, научных кружков, тематических олимпиад.The aim of the research work is to analyze partnership development between Universities and IT-companies in Ukraine in the field of staffing. The IT market situation and IT-company performance in Ukraine are considered. The features of the process and steps of IT-product development are analyzed. The main tasks, results and necessary team members for each step of product development are imposed. The main recommendation for the graduates preparation for IT departments based on market needs for Universities are given. Successful examples of «University-Company» cooperation of Lviv Polytechnic National University are shown. The main ways of cooperation consist of student practices on software development for partner IT-company, International Olympiads, workshops with partner representatives

Optimization of infectious disease processes modelled by nonlinear delay differential equations

In this paper the numerical approach to the solution of optimization problems of processes which are modelled by nonlinear delay differential equations (DDEs) with constant delays is presented. Based on DDEs solution the different characteristics of the modelled process are calculated. One of them is selected as the objective functional. Other characteristics can play a role of constraints. The control is made by the functions, which define the coefficients of DDEs. As a result of piecewise-linear approximation of control function the non-linear mathematical programming problems are obtained. The efficiency of the software developed for solution of nonlinear DDEs and optimization of DDE systems is illustrated on the infectious disease process model.У роботі запропоновано числовий підхід до розв’язування задач оптимізації процесів, поведінка яких моделюється нелінійними диференціальними рівняннями із запізненням (ДРЗ) з постійним кроком запізнення. На основі отриманого розв’язку для ДРЗ обчислюються відповідні характеристики процесу, що розглядається. Одна з цих характеристик вибирається за критерій оптимізації, а інші виконують роль обмежень. За керуючі вибрано функції, від яких залежать коефіцієнти ДРЗ. У результаті апроксимації функцій керування кусково-лінійними функціями отримуємо задачі нелінійного математичного програмування. Ефективність створеного програмного забезпечення для розв’язування нелінійних ДРЗ і задач оптимізації систем, поведінка яких моделюється ДРЗ, проілюстровано на прикладі моделі інфекційного захворювання.В работе предложен численный подход к решению задач оптимизации процессов, поведение которых моделируется нелинейными дифференциальными уравнениями с запаздывающим аргументом (ДУЗ) с постоянным шагом запаздывания. На основе полученного решения для ДУЗ исчисляются соответствующие характеристики рассматриваемого процесса. Одна из этих характеристик выбирается критерием оптимизации, а другие выполняют роль ограничений. В качестве управляющих выбрано функции, от которых зависят коэффициенты ДУЗ. В результате аппроксимации функций управления кусочно-линейными функциями получаем задачи нелинейного математического программирования. Эффективность созданного программного обеспечения для решения нелинейных ДУЗ и задач оптимизации систем, поведение которых моделируется ДУЗ, проиллюстрировано на примере модели инфекционного заболевания