РЕЙТИНГУВАННЯ ДІЯЛЬНОСТІ НАУКОВО-ПЕДАГОГІЧНИХ ПРАЦІВНИКІВ ТА КАФЕДР – ВАГОМА СКЛАДОВА СИСТЕМИ ВНУТРІШНЬОГО ЗАБЕЗПЕЧЕННЯ ЯКОСТІ ОСВІТИ У ВИЩОМУ ДЕРЖАВНОМУ НАВЧАЛЬНОМУ ЗАКЛАДІ УКРАЇНИ «БУКОВИНСЬКИЙ ДЕРЖАВНИЙ МЕДИЧНИЙ УНІВЕРСИТЕТ»

The system of rating evaluation of academic staff and departments in the Higher State Educational Establishment of Ukraine “Bukovinian State Medical University” under the monitoring of proper quality of scientific-pedagogical staff is covered. The most significant indicators of activity among the major areas of work are defined; the advantages of remote rating report submission are proved.У статті висвітлено роботу системи рейтингового оцінювання діяльності викладачів та кафедр у ВДНЗ України «Буковинський державний медичний університет» у рамках моніторингу належної якості науково-педагогічного персоналу, визначені найбільш вагомі індикатори діяльності серед основних напрямів роботи, підтверджені переваги дистанційної форми рейтингової звітності

Evaluation of interferon β-1b therapy effects on the level and abnormal nature of immunoglobulin G in patients with multiple sclerosis

Aim: to study and evaluate the interferon β-1b (INF) therapy efficiency on the level and abnormal nature of immunoglobulin G in patients with multiple sclerosis (MS). Materials and methods. This scientific work was performed at the Neurology Department and the Department of Histology, Cytology and Embryology of theLvivNationalMedicalUniversity named after Danylo Halytsky and in theLvivRegionalResearchCenter for the Study of Multiple Sclerosis and Other Demyelinating Diseases on the basis of theLvivRegionalClinicalHospital. The inclusion criteria for patients were age between 18 and 65 years as well as definite diagnosis of MS according to McDonald Diagnostic Criteria for MS (2010). 32 patients with MS and 23 practically healthy persons were enrolled in the study. After a written informed consent obtaining from the patient there was a peripheral venous blood sampling using a blood-collection tube system Vacuette. Serum samples were prepared for antibodies to myelin basic protein (MBP) determination and identification of immunoglobulin glycosylation by means of lectin-immunoenzymatic assay. Results. Elevated levels of anti-MBP IgG and IgM in the treatment-naive MS patients were determined in comparison with the healthy persons. At the same time, higher exposure of anti-inflammatory sialic acid residues on IgG molecules and associated native immune complexes were observed in the group of patients who received INF therapy as well as higher exposure of fucosylated tri-mannose residues on measles IgG molecules and associated native immune complexes in comparison with the untreated patients. Conclusions: The blood serum of MS patients who received INF therapy were characterized by lower levels of IgG and IgM antibodies to MBP and higher exposure of sialic acid terminal residues on IgG and IgM molecules in comparison with the untreated patients. It is reasonable to assume that INF therapy could lead to anti-inflammatory native IgG complexes formation and / or decrease in IgG and IgM autoantibodies against the nervous system components, as it has been shown for autoantibodies to MBP

Functional Connection between Rad51 and PML in Homology-Directed Repair

The promyelocytic leukemia protein (PML) is a tumor suppressor critical for formation of nuclear bodies (NBs) performing important functions in transcription, apoptosis, DNA repair and antiviral responses. Earlier studies demonstrated that simian virus 40 (SV40) initiates replication near PML NBs. Here we show that PML knockdown inhibits viral replication in vivo, thus indicating a positive role of PML early in infection. SV40 large T antigen (LT) induces DNA damage and, consequently, nuclear foci of the key homologous recombination repair protein Rad51 that colocalize with PML. PML depletion abrogates LT-induced Rad51 foci. LT may target PML NBs to gain access to DNA repair factors like Rad51 that are required for viral replication. We have used the SV40 model to gain insight to DNA repair events involving PML. Strikingly, even in normal cells devoid of viral oncoproteins, PML is found to be instrumental for foci of Rad51, Mre11 and BRCA1, as well as homology-directed repair after double-strand break (DSB) induction. Following LT expression or external DNA damage, PML associates with Rad51. PML depletion also causes a loss of RPA foci following γ-irradiation, suggesting that PML is required for processing of DSBs. Immunofluorescent detection of incorporated BrdU without prior denaturation indicates a failure to generate ssDNA foci in PML knockdown cells upon γ-irradiation. Consistent with the lack of RPA and BrdU foci, γ-irradiation fails to induce Chk1 activation, when PML is depleted. Taken together, we have discovered a novel functional connection between PML and the homologous recombination-mediated repair machinery, which might contribute to PML tumor suppressor activity

Impaired CK1 Delta Activity Attenuates SV40-Induced Cellular Transformation In Vitro and Mouse Mammary Carcinogenesis In Vivo

Simian virus 40 (SV40) is a powerful tool to study cellular transformation in vitro, as well as tumor development and progression in vivo. Various cellular kinases, among them members of the CK1 family, play an important role in modulating the transforming activity of SV40, including the transforming activity of T-Ag, the major transforming protein of SV40, itself. Here we characterized the effects of mutant CK1δ variants with impaired kinase activity on SV40-induced cell transformation in vitro, and on SV40-induced mammary carcinogenesis in vivo in a transgenic/bi-transgenic mouse model. CK1δ mutants exhibited a reduced kinase activity compared to wtCK1δ in in vitro kinase assays. Molecular modeling studies suggested that mutation N172D, located within the substrate binding region, is mainly responsible for impaired mutCK1δ activity. When stably over-expressed in maximal transformed SV-52 cells, CK1δ mutants induced reversion to a minimal transformed phenotype by dominant-negative interference with endogenous wtCK1δ. To characterize the effects of CK1δ on SV40-induced mammary carcinogenesis, we generated transgenic mice expressing mutant CK1δ under the control of the whey acidic protein (WAP) gene promoter, and crossed them with SV40 transgenic WAP-T-antigen (WAP-T) mice. Both WAP-T mice as well as WAP-mutCK1δ/WAP-T bi-transgenic mice developed breast cancer. However, tumor incidence was lower and life span was significantly longer in WAP-mutCK1δ/WAP-T bi-transgenic animals. The reduced CK1δ activity did not affect early lesion formation during tumorigenesis, suggesting that impaired CK1δ activity reduces the probability for outgrowth of in situ carcinomas to invasive carcinomas. The different tumorigenic potential of SV40 in WAP-T and WAP-mutCK1δ/WAP-T tumors was also reflected by a significantly different expression of various genes known to be involved in tumor progression, specifically of those involved in wnt-signaling and DNA repair. Our data show that inactivating mutations in CK1δ impair SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo

Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors

Acute myeloid leukemia (AML) is mostly driven by oncogenic transcription factors, which have been classically viewed as intractable targets using small molecule inhibitor approaches. Here, we demonstrate that AML driven by repressive transcription factors including AML1-ETO and PML-RARα are extremely sensitive to Poly (ADP-ribose) Polymerase (PARP) inhibitor (PARPi), in part due to their suppressed expression of key homologous recombination genes and thus compromised DNA damage response (DDR). In contrast, leukemia driven by MLL fusions with dominant transactivation ability is proficient in DDR and insensitive to PARP inhibition. Intriguing, depletion of an MLL downstream target, Hoxa9 that activates expression of various HR genes, impairs DDR and sensitizes MLL leukemia to PARPi. Conversely, Hoxa9 over-expression confers PARPi resistance to AML1-ETO and PML-RARα transformed cells. Together, these studies describe a potential utility of PARPi-induced synthetic lethality for leukemia treatment and reveal a novel molecular mechanism governing PARPi sensitivity in AML

УЛЬТРАСТРУКТУРНИЙ СТАН ЛІМБІКО-ГІПОТАЛАМІЧНИХ СТРУКТУР МОЗКУ ЩУРІВ З УСКЛАДНЕННЯМ СТРЕПТОЗОТОЦИНІНДУКОВАНОГО ДІАБЕТУ ГОСТРИМ ПОРУШЕННЯМ КРОВООБІГУ В БАСЕЙНІ СОННИХ АРТЕРІЙ

It has been shown that experimental diabetes, complicated with carotid ischemia-reperfusion, significantly exacerbates changes of the structural components of neurocytes and the pericapillary spaces in the limbic-hypothalamic brain structures.Установлено, что осложнение экспериментального сахарного диабета каротидной ишемией-реперфузией существенно усугубляет изменения структурных компонентов нейронов и перикапиллярних пространств в лимбико-гипоталамических структурах мозга.Установлено, що ускладнення експериментального цукрового діабету каротидною ішемієюреперфузією суттєво поглиблює зміни структурних компонентів нейроцитів та перикапілярних просторів у лімбіко-гіпоталамічних структурах мозку

РЕАКЦІЯ РНК НЕЙРОНІВ ПОЛІВ ГІПОКАМПА ЩУРІВ З ЕКСПЕРИМЕНТАЛЬНИМ ЦУКРОВИМ ДІАБЕТОМ НА ІШЕМІЧНО-РЕПЕРФУЗІЙНЕ ПОШКОДЖЕННЯ ГОЛОВНОГО МОЗКУ

The effect of bilateral carotid ischemia-reperfusion on the RNA content in neurons of the hippocampal fields of animals with diabetes mellitus has been studied. It has been established that four-month diabetes mellitus increases the RNA content in the neurons of the hippocampal fields CA1, CA2, CA3 and decreases – in the field CA4. RNA reaction of the hippocampal neurons (unmodified and with apoptosis signs) on ischemic-reperfusion brain damage in animals without diabetes mellitus and with the presence of this disease has a similar direction in the CA1, CA3, CA4 fields in both terms of ischemic-reperfusional period, but in the CA2 field this type of reaction was detected only on 12th day of observation and was radically different in the early period of observation.Изучено влияние двусторонней каротидной ишемии-реперфузии на содержание РНК в нейронах полей гиппокампа животных с сахарным диабетом. Установлено, что четырехмесячный сахарный диабет повышает содержание РНК в нейронах полей гиппокампа СА1, СА2, СА3 и снижает – в поле СА4. Реакция РНК нейронов гиппокампа (неизмененных и с признаками апоптоза) на ишемически-реперфузионное повреждение головного мозга у животных без сахарного диабета и с наличием данной патологии имеет подобную направленность в полях СА1, СА3, СА4 в оба термина ишемически-реперфуйного периода, а в поле СА2 – на 12-е сутки, кардинально отличаясь в раннем сроке наблюдения.Вивчено вплив двобічної каротидної ішемії-реперфузії на вміст РНК у нейронах полів гіпокампа тварин із цукровим діабетом. Встановлено, що чотиримісячний цукровий діабет підвищує вміст РНК у нейронах полів гіпокампа СА1, СА2, СА3 та знижує – у полі СА4. Реакція РНК нейронів гіпокампа (незмінених та з ознаками апоптозу) на ішемічно-реперфузійне ушкодження головного мозку у тварин без цукрового діабету та з наявністю даної патології носить подібне спрямування в полях СА1, СА3, СА4 в обидва терміни ішемічно-реперфуйного періоду, а в полі СА2 – лише на 12-ту добу, кардинально відрізняючись у ранньому терміні спостереження

Функціональний стан нирок за сумісного застосування ксантинолу нікотинату з L-аргініном

It has been shown in experiments on rats that under the conditions of a nitrogen oxide increase in the organism by means of an L-arginine (100 mg/kg) injection a prolonged use (for 7 days) of xanthinol nicotinate (3 mg/kg) significantly intensifies the clearance of sodium ions and the renal exeretion of this cation.В опытах на крысах показано, что при увеличении оксида азота в организме введением L-аргинина (100 мг/кг) длительное (семь дней) применение ксантинола никотината (3 мг/кг) значительно усиливает клиренс ионов натрия и почечную экскрецию данного катиона.У дослідах на щурах показано, що за умов збільшення оксиду азоту в організмі уведенням L-аргініну (100 мг/кг) тривале (7 днів) застосування ксантинолу нікотинату (3 мг/кг) значно підсилює кліренс іонів натрію та ниркову екскрецію даного катіона