Investigation of neuronal activity in a murine model of Alzheimer’s disease using in vivo two-photon calcium imaging

Alzheimer’s disease (AD) is one of the biggest challenges for biomedical research nowadays as with the growth of life span more and more people are affected by this disorder. Etiology of AD is unknown, yet growing evidence identifies alterations in neuronal activity as of the great importance for pathology. Although several significant studies of neuronal activity alteration in AD were done during the last decade, none of them addressed the question of the time course of these changes over the disease progression. Alzheimer’s disease (AD) is characterized by impairments of brain neurons that are responsible for the storage and processing of information. Studies have revealed decrease in the activity of neurons (Silverman et al., 2001; Prvulovic et al., 2005) and it was proposed that generalized hypoactivity and silencing of brain circuits takes place as formulated in the synaptic failure hypothesis (Selkoe, 2002). However, more recent studies also reported opposite effects – hyperexcitability and hyperactivity of neurons in the AD models (Busche et al., 2008; Sanchez et al., 2012; Liebscher et al., 2016). It still remains unclear if these are two sides of the same coin or if these are two stages, that follow each other. Moreover, it is not clear if observed neuronal activity alterations are caused by the dysfunction of individual neurons or if overall circuitry is disturbed because the crucial “activity controllers” (most probably - inhibitory neurons) alter their activity. This project aimed to examine spontaneous neuronal activity in the murine model of AD at the early stages of disease progression using chronic in vivo imaging to address the character and the stability of neuronal activity alterations as well relation of the activity alterations to amyloid plaque proximity. Compared to earlier studies the approach of in vivo awake calcium imaging used in the current study has many benefits for brain research. The main advantage is that brain activity can be measured without artifacts generated by anesthesia, which can exaggerate or mitigate experimental readouts. In this project, I used genetically encoded calcium indicator GCaMP6 that enables prolonged repetitive imaging of the same neurons in an intact environment. Recording of calcium transients in cell bodies of neurons was accompanied by in vivo imaging of Aβ plaques and followed by immunohistochemical staining of GCaMP6-expressing neurons to investigate how activity changes are correlated with proximity to the plaque. All the experiments were done in awake mice to ensure the absence of anesthesia-derived impact on spontaneous neuronal activity. My results support previously published reports of the increased proportion of hyperactive excitatory neurons in the AD mouse model. Importantly, my results also demonstrate that this increased activity is present in the awake state, is stable over a longer period of time (one month) and does not depend on the distance to the closest plaque. These findings support the hypothesis of permanent network alterations driving aberrant activity patterns that appear early in the disease progression, resulting in a chronic excitation/inhibition disbalance. Another important finding of my project is that individual neurons do not stay in the silent state and most of them remain functional demonstrating normal activity at the later time points. This finding requires further research as it has important implication for the development of the AD treatment, as in case many neurons remain functional and their normal neuronal activity can be recovered by addressing the cause of the circuit dysfunction with treatment. To summarize, the study presented in this PhD thesis is the first longitudinal study of neuronal activity changes in an AD mouse model, and while it provides important insight into pathology, it also emphasizes the importance of chronic in vivo studies to investigate neuronal activity and its role in the disease progression

Проблеми і перспективи розвитку фінансової системи України

Фінансова система України за останні 15 років зазнала суттєвих змін, але багато хто з них не отримали відповідного відображення в законодавстві. Україна потребує чіткої правової та адміністративної основи управління податково-бюджетною сферою. Це означає, що всі функції та механізми такого управління (бюджетною та позабюджетної діяльністю) повинні в повному обсязі регламентуватися законами та відповідними нормативними актами. Зрозуміло, що кошти слід виділяти і витрачати лише за наявності відповідних на це правових повноважень. Фінансову систему держави можна розглядати в декількох аспектах. Зокрема, фінансова система - це сукупність фінансових інститутів, кожний з яких сприяє утворенню та використанню відповідних централізованих та децентралізованих фондів грошових коштів для здійснення фінансової діяльності держави, тобто діяльності з приводу мобілізації, розподілу і використання централізованих і децентралізованих фондів грошових коштів для виконання завдань і функцій держави та органів місцевого самоврядування. Державні фінанси, відіграючи винятково важливу роль в економіці, не можуть розглядатися як єдиний або найголовніший інструмент економічної політики. Сам стан державних фінансів та формування доходної і видаткової частин бюджету залежать від багатьох чинників, хоч недооцінювати його вплив на економіку країни також не слід. Фінансова система України як предмет дослідження фінансового права складається з таких основних ланок: державний бюджет та місцеві фінанси, фінанси державних підприємств, установ та організацій, спеціальні цільові фонди та кредит.The financial system of Ukraine for the past 15 years has undergone significant changes, but many of them had the appropriate reflection in the legislation. Ukraine needs a clear legal and administrative foundations fiscal management area. This means that all of the features and mechanisms of the administration (budgetary and extrabudgetary activities) should be fully governed by the laws and of this legal authority. The financial system of the state can be seen in several aspects. In particular, the financial system - a set of financial institutions, each of which contributes to the formation and use of appropriate centralized and decentralized funds of funds for financing activities of the state, ie of about mobilization, distribution and use of centralized and decentralized funds of funds to the tasks and functions of state and local governments. Public finances, playing a crucial role in the economy, can not be regarded as the only or the most important instrument of economic policy. The very public finances and budget revenues and budget expenditures depend on many factors, though underestimate its impact on the economy and should not be. The financial system of Ukraine as a subject of study Finance consists of the following main parts: the state budget and local finances, finances of state enterprises, institutions and organizations, special trust funds and credit

Investigation of neuronal activity in a murine model of Alzheimer’s disease using in vivo two-photon calcium imaging

Alzheimer’s disease (AD) is one of the biggest challenges for biomedical research nowadays as with the growth of life span more and more people are affected by this disorder. Etiology of AD is unknown, yet growing evidence identifies alterations in neuronal activity as of the great importance for pathology. Although several significant studies of neuronal activity alteration in AD were done during the last decade, none of them addressed the question of the time course of these changes over the disease progression. Alzheimer’s disease (AD) is characterized by impairments of brain neurons that are responsible for the storage and processing of information. Studies have revealed decrease in the activity of neurons (Silverman et al., 2001; Prvulovic et al., 2005) and it was proposed that generalized hypoactivity and silencing of brain circuits takes place as formulated in the synaptic failure hypothesis (Selkoe, 2002). However, more recent studies also reported opposite effects – hyperexcitability and hyperactivity of neurons in the AD models (Busche et al., 2008; Sanchez et al., 2012; Liebscher et al., 2016). It still remains unclear if these are two sides of the same coin or if these are two stages, that follow each other. Moreover, it is not clear if observed neuronal activity alterations are caused by the dysfunction of individual neurons or if overall circuitry is disturbed because the crucial “activity controllers” (most probably - inhibitory neurons) alter their activity. This project aimed to examine spontaneous neuronal activity in the murine model of AD at the early stages of disease progression using chronic in vivo imaging to address the character and the stability of neuronal activity alterations as well relation of the activity alterations to amyloid plaque proximity. Compared to earlier studies the approach of in vivo awake calcium imaging used in the current study has many benefits for brain research. The main advantage is that brain activity can be measured without artifacts generated by anesthesia, which can exaggerate or mitigate experimental readouts. In this project, I used genetically encoded calcium indicator GCaMP6 that enables prolonged repetitive imaging of the same neurons in an intact environment. Recording of calcium transients in cell bodies of neurons was accompanied by in vivo imaging of Aβ plaques and followed by immunohistochemical staining of GCaMP6-expressing neurons to investigate how activity changes are correlated with proximity to the plaque. All the experiments were done in awake mice to ensure the absence of anesthesia-derived impact on spontaneous neuronal activity. My results support previously published reports of the increased proportion of hyperactive excitatory neurons in the AD mouse model. Importantly, my results also demonstrate that this increased activity is present in the awake state, is stable over a longer period of time (one month) and does not depend on the distance to the closest plaque. These findings support the hypothesis of permanent network alterations driving aberrant activity patterns that appear early in the disease progression, resulting in a chronic excitation/inhibition disbalance. Another important finding of my project is that individual neurons do not stay in the silent state and most of them remain functional demonstrating normal activity at the later time points. This finding requires further research as it has important implication for the development of the AD treatment, as in case many neurons remain functional and their normal neuronal activity can be recovered by addressing the cause of the circuit dysfunction with treatment. To summarize, the study presented in this PhD thesis is the first longitudinal study of neuronal activity changes in an AD mouse model, and while it provides important insight into pathology, it also emphasizes the importance of chronic in vivo studies to investigate neuronal activity and its role in the disease progression

Theoretical Aspects of Interdisciplinary Communications Between Mathematical Disciplines and Disciplines of Professional Training of Future Specialists in Organization of Information Security

Стаття присвячена дослідженню проблеми міжпредметних зв’язків у системі професійної підготовки майбутніх фахівців із організації інформаційної безпеки у вищих навчальних закладах України. На основі результатів аналізу науково-педагогічних джерел уточнено суть поняття «міжпредметні зв’язки». Проаналізовані особливості міжпредметних зв’язків математичних дисциплін із дисциплінами циклу професійної підготовки бакалаврів галузі знань 12 «Інформаційні технології» спеціальності 125 «Кібербезпека». Розкрито роль математичної освіти у професійній підготовці майбутніх фахівців із кібербезпеки. Наведені основні розділи математичних дисциплін (вищої математики, теорія ймовірностей і математичної статистики, дискретної математики, числових методів), які використовуються під час вивчення професійно-орієнтованих дисциплін. Доведено, що математичні знання виконують роль методологічної основи наукового знання, базової складової більшості профілюючих дисциплін майбутніх фахівців із організації інформаційної безпеки.The article is devoted to problems of interdisciplinary relations in the system of professional training of future specialists in information security in higher educational institutions of Ukraine. Based on the results of the analysis of scientific pedagogical sources clarified the essence of the concept of "interdisciplinary connections". The article analyses the peculiarities of interdisciplinary connections of mathematics with the disciplines of professional cycle of training of bachelors science 12 Information technology specialty 125 "Cybersecurity". The role of mathematics education in professional training of future experts in cybersecurity. The main topics of mathematical disciplines (higher mathematics, probability theory and mathematical statistics, discrete mathematics, numerical methods) used in the study of professionally oriented disciplines. It is proved that mathematical knowledge perform the role of methodological bases of scientific knowledge, the basic component of most of the main subjects of future specialists in information security

Проблеми і перспективи розвитку фінансової системи України

Фінансова система України за останні 15 років зазнала суттєвих змін, але багато хто з них не отримали відповідного відображення в законодавстві. Україна потребує чіткої правової та адміністративної основи управління податково-бюджетною сферою. Це означає, що всі функції та механізми такого управління (бюджетною та позабюджетної діяльністю) повинні в повному обсязі регламентуватися законами та відповідними нормативними актами. Зрозуміло, що кошти слід виділяти і витрачати лише за наявності відповідних на це правових повноважень. Фінансову систему держави можна розглядати в декількох аспектах. Зокрема, фінансова система - це сукупність фінансових інститутів, кожний з яких сприяє утворенню та використанню відповідних централізованих та децентралізованих фондів грошових коштів для здійснення фінансової діяльності держави, тобто діяльності з приводу мобілізації, розподілу і використання централізованих і децентралізованих фондів грошових коштів для виконання завдань і функцій держави та органів місцевого самоврядування. Державні фінанси, відіграючи винятково важливу роль в економіці, не можуть розглядатися як єдиний або найголовніший інструмент економічної політики. Сам стан державних фінансів та формування доходної і видаткової частин бюджету залежать від багатьох чинників, хоч недооцінювати його вплив на економіку країни також не слід. Фінансова система України як предмет дослідження фінансового права складається з таких основних ланок: державний бюджет та місцеві фінанси, фінанси державних підприємств, установ та організацій, спеціальні цільові фонди та кредит.The financial system of Ukraine for the past 15 years has undergone significant changes, but many of them had the appropriate reflection in the legislation. Ukraine needs a clear legal and administrative foundations fiscal management area. This means that all of the features and mechanisms of the administration (budgetary and extrabudgetary activities) should be fully governed by the laws and of this legal authority. The financial system of the state can be seen in several aspects. In particular, the financial system - a set of financial institutions, each of which contributes to the formation and use of appropriate centralized and decentralized funds of funds for financing activities of the state, ie of about mobilization, distribution and use of centralized and decentralized funds of funds to the tasks and functions of state and local governments. Public finances, playing a crucial role in the economy, can not be regarded as the only or the most important instrument of economic policy. The very public finances and budget revenues and budget expenditures depend on many factors, though underestimate its impact on the economy and should not be. The financial system of Ukraine as a subject of study Finance consists of the following main parts: the state budget and local finances, finances of state enterprises, institutions and organizations, special trust funds and credit

НАВЧАЛЬНО-ДОСЛІДНИЦЬКА ДІЯЛЬНІСТЬ ЯК ФАКТОР ПРОФЕСІЙНОГО СТАНОВЛЕННЯ МАЙБУТНІХ ПЕДАГОГІВ

No abstract

Use of traffic calming measures in the Republic of Belarus

Traffic calming is one of the main approaches to ensuring safety in city streets and it is based on the concept of speed containment. The aim of this approach is to minimize passing transit flows through the streets of district importance, to ensure the safety of pedestrians and cyclists, as well as to impact the behavior of drivers in urban conditions. City streets should be designed taking into account the restriction of "extra" speed, in accordance with the category and purpose. It is necessary to have regard to the functionality of the street, the uniformity of the traffic flow, the appropriateness of the imposed limitations, and the predictability of the technical means used to organize traffic. The main criteria for the use of traffic calming measures can be: accident rate, speed through traffic, and specific traffic conditions. The article presents practical results of studies on traffic conditions in the pedestrian crossings areas equipped with humps. It discusses alternative measures of physical and psychological effects on the traffic participants in the context of the traffic calming approach

The analysis of various measures of the speed control of the traffic in the cities and settlements of the Republic of Belarus

The results of the analysis of various measures of calm of movement in cities and settlements are presented in the article. The alternative measures of physical and psychological effects on the traffic participants are considered. Particular attention is paid to the application of speed humps. They are installed on the streets of cities and settlements widely. The statistics of road traffic accidents at sites with humps in Minsk are considered. Various aspects of the effect of speed humps on accident rate have been established. And experimental studies of the instantaneous speeds of road vehicles in the installation area of speed humps have been performed. New modifications of speed humps are proposed, the design of which was developed on the basis of research of interactions with the car. Also the study investigated the effect of hump on the accident rate, delays in transportation, changes of speed and flow density. In addition, specific proposals have been developed. They are included in the technical normative legal acts in our country partially. That proposals allows to increase the overall quality of traffic (minimize the total economic, environmental and emergency losses from installation of speed humps). For example, alternative variants of design decisions on improvement of quality traffic safety are considered. In addition, the article considers other measures of forced speed control on streets network of cities and settlements in the country

Аналіз професійної діяльності майбутніх інженерів-педагогів з проектування баз даних

The paper analyzes the characteristics of teaching the subject «Principles of Information Security and databases» in terms of the training of future engineers and educators; it elucidated components of professional activity on designing databases and consider the substantive and procedural components of the profession of the future engineers and educators to design databases based on program course «Principles of information Security and databases» and professional experts in database design.У статті проаналізовано особливості викладання дисципліни «Принципи побудови і захист інформації баз даних» в аспекті професійної підготовки майбутніх інженерів-педагогів; з’ясовано компоненти професійної діяльності з проектування баз даних; розглянуто змістову та процедурну компоненти професійної діяльності майбутніх інженерів-педагогів з проектування баз даних на основі програми дисципліни «Принципи побудови і захист інформації баз даних» та професійної діяльності фахівців з проектування баз даних

ДОСЛІДНИЦЬКІ УМІННЯ ЯК ПОКАЗНИК ГОТОВНОСТІ СТУДЕНТІВ ВИЩОЇ ШКОЛИ ДО ТВОРЧОЇ РОБОТИ

The article deals with the specificity o f investigating skills as an exponent o f future teachers’ readiness to the creative professional activities, their classification is given