Identification of Nedd4 E3 Ubiquitin Ligase as a Binding Partner and Regulator of MAK-V Protein Kinase

MAK-V/Hunk is a scantily characterized AMPK-like protein kinase. Recent findings identified MAK-V as a pro-survival and anti-apoptotic protein and revealed its role in embryonic development as well as in tumorigenesis and metastasis. However molecular mechanisms of MAK-V action and regulation of its activity remain largely unknown. We identified Nedd4 as an interaction partner for MAK-V protein kinase. However, this HECT-type E3 ubiquitin ligase is not involved in the control of MAK-V degradation by the ubiquitin-proteasome system that regulates MAK-V abundance in cells. However, Nedd4 in an ubiquitin ligase-independent manner rescued developmental defects in Xenopus embryos induced by MAK-V overexpression, suggesting physiological relevance of interaction between MAK-V and Nedd4. This identifies Nedd4 as the first known regulator of MAK-V function

Inflammatory cytokines, goblet cell hyperplasia and altered lung mechanics in Lgl1+/- mice

<p>Abstract</p> <p>Background</p> <p>Neonatal lung injury, a leading cause of morbidity in prematurely born infants, has been associated with arrested alveolar development and is often accompanied by goblet cell hyperplasia. Genes that regulate alveolarization and inflammation are likely to contribute to susceptibility to neonatal lung injury. We previously cloned <it>Lgl1</it>, a developmentally regulated secreted glycoprotein in the lung. In rat, O₂toxicity caused reduced levels of <it>Lgl1</it>, which normalized during recovery. We report here on the generation of an <it>Lgl1 </it>knockout mouse in order to determine whether deficiency of <it>Lgl1 </it>is associated with arrested alveolarization and contributes to neonatal lung injury.</p> <p>Methods</p> <p>An <it>Lgl1 </it>knockout mouse was generated by introduction of a neomycin cassette in exon 2 of the <it>Lgl1 </it>gene. To evaluate the pulmonary phenotype of <it>Lgl1</it>^+/-mice, we assessed lung morphology, <it>Lgl1 </it>RNA and protein, elastin fibers and lung function. We also analyzed tracheal goblet cells, and expression of mucin, interleukin (IL)-4 and IL-13 as markers of inflammation.</p> <p>Results</p> <p>Absence of <it>Lgl1 </it>was lethal prior to lung formation. Postnatal <it>Lgl1</it>^+/-lungs displayed delayed histological maturation, goblet cell hyperplasia, fragmented elastin fibers, and elevated expression of T_H2 cytokines (IL-4 and IL-13). At one month of age, reduced expression of <it>Lgl1 </it>was associated with elevated tropoelastin expression and altered pulmonary mechanics.</p> <p>Conclusion</p> <p>Our findings confirm that <it>Lgl1 </it>is essential for viability and is required for developmental processes that precede lung formation. <it>Lgl1</it>^+/-mice display a complex phenotype characterized by delayed histological maturation, features of inflammation in the post-natal period and altered lung mechanics at maturity. <it>Lgl1 </it>haploinsufficiency may contribute to lung disease in prematurity and to increased risk for late-onset respiratory disease.</p

ESTIMATION OF STATE OF PANCREAS AND CHANGE OF REGIONAL HEMODYNAMICS IN PATIENTS WITH EDEMATOUS FORM OF ACUTE PANCREATITIS WITH RECOVERY OUTCOME

The article shows peculiarities of regional circulation of the blood in patients with acute pancreatitis during conservative treatment. Obtained data allows to estimate state of pancreas objectively and also to control adequacy of the treatment

Expression of Foxm1 Transcription Factor in Cardiomyocytes Is Required for Myocardial Development

Forkhead Box M1 (Foxm1) is a transcription factor essential for organ morphogenesis and development of various cancers. Although complete deletion of Foxm1 in Foxm1−/− mice caused embryonic lethality due to severe abnormalities in multiple organ systems, requirements for Foxm1 in cardiomyocytes remain to be determined. This study was designed to elucidate the cardiomyocyte-autonomous role of Foxm1 signaling in heart development. We generated a new mouse model in which Foxm1 was specifically deleted from cardiomyocytes (Nkx2.5-Cre/Foxm1fl/f mice). Deletion of Foxm1 from cardiomyocytes was sufficient to disrupt heart morphogenesis and induce embryonic lethality in late gestation. Nkx2.5-Cre/Foxm1fl/fl hearts were dilated with thinning of the ventricular walls and interventricular septum, as well as disorganization of the myocardium which culminated in cardiac fibrosis and decreased capillary density. Cardiomyocyte proliferation was diminished in Nkx2.5-Cre/Foxm1fl/fl hearts owing to altered expression of multiple cell cycle regulatory genes, such as Cdc25B, Cyclin B1, Plk-1, nMyc and p21cip1. In addition, Foxm1 deficient hearts displayed reduced expression of CaMKIIδ, Hey2 and myocardin, which are critical mediators of cardiac function and myocardial growth. Our results indicate that Foxm1 expression in cardiomyocytes is critical for proper heart development and required for cardiomyocyte proliferation and myocardial growth

Ефективність дорощування гібридних поросят з різною масою при постановці за рідкої системи їх годівлі

The intensity of growth of piglets, their preservation during rearing, and the payment of feed by the increments of animals that were placed for rearing with a design live weight of 7 kg and 20 % less than the design weight – 5.5 kg were studied. Also, the ratio of consumption of compound feed of different recipes during rearing, their cost, and the efficiency of rearing piglets at different staged live weights were studied. It was established that piglets that weighed 1.58 kg less at the beginning of rearing, when placed on rearing during this period, showed 20.9 % lower growth energy, due to which they had 19.6 % lower absolute growth during this period, which caused together with a lower production weight, a 20.3 % lower weight when transferred to fattening and an 8.8 % worse feed payment in increments, they consumed 31.4 % more of the expensive first pre-starter feed during the growing period, and 11.9 % less than the second cheaper pre-starter compound feed and 42.6 % less than the cheapest starter compound feed, as a result of which the cost of feed consumed by the animals of the experimental group was 10.6 % lower compared to the analogs of the experimental group. But taking into account the significantly lower absolute growth of the animals of the experimental group, the cost of feed for 1 kg of growth was 11.2 % higher in comparison with the similar indicator of animals that were put on growing at a designed live weight of 7.0 kg. At the same time, rearing piglets under the conditions of putting them into this process with the design live weight contributed to a decrease of 11.2 % in the cost of feed per kilogram of growth, an increase of 20.3 % in the cost of one piglet after the completion of rearing, and a 23.1 % increase in the income from its sale and 1.07&nbsp;% higher profitability of raising one head, but resulted in 10.6 % higher feed and operating cost of rearing 1 head and 19.6 % higher operating cost of one piglet at the end of rearing.Вивчались інтенсивність росту поросят, їх збереженість під час дорощування та оплата корму приростами тварин, які були поставлені на дорощування за проектної живої маси 7 кг та на 20 % меншою від проектної – 5,5 кг. Також вивчалось співідношення споживання комбікормів різних рецептур під час дорощування, їхня вартість та ефективність дорощування поросят за різної постановочної живої маси. Встановленно, що поросята, які мали на початок дорощування меншу на 1,58 кг вагу, при постановці на дорощування під час цього періоду виявили на 20,9 % нижчу енергію росту, за рахунок чого мали менші на 19,6&nbsp;% абсолютні прирости за цей період, що спричинило разом з меншою постановочною масою на 20,3 % нижчу масу при переведенні на відгодівлю та гіршу на 8,8 % оплату корму приростами, вони спожили за час дорощування на 31,4 % більше дорогого першого престартерного корму, та на 11,9% менше дешевшого другого престартерного комбікорму і на 42,6% менше найбільш де шевшого стартерного комбікорму, в результаті чого вартість спожитих кормів тваринами дослідної групи виявилось на 10,6 % меншою порівняно з аналогами дослідної групи. Але враховуючи суттєво нижчий абсолютний приріст у тварин дослідної групи, кормова собівартість 1 кг приросту у них виявилась на 11,2 % вищою порівняно з аналогічним показником тварин, яких ставили на дорощування за проектної живої маси 7,0 кг. Водночас дорощування порсят за умов постановки їх на цей процес з проектною живою масою посприяло зменшенню на 11,2 % кормової собівартості одного кілограма приросту, підвищенню на 20,3 % вартості одного поросяти по завершенні дорощування та на 23,1 % доходу від його реалізації і на 1,07 % вищій рентабельності вирощування однієї голови, але спричинило вищу на 10,6 % кормову та операційну собівартість дорощування 1 голови та на 19,6 % операційну собівартість одного підсвинка на кінець дорощування

Digital receivers for low-frequency radio telescopes UTR-2, URAN, GURT

This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. Since 1998, digital receivers performing on-the-fly dynamic spectrum calculations or waveform data recording without data loss have been used at the UTR-2 radio telescope, the URAN VLBI system, and the GURT new generation radio telescope. Here we detail these receivers developed for operation in the strong interference environment that prevails in the decameter wavelength range. Data collected with these receivers allowed us to discover numerous radio astronomical objects and phenomena at low frequencies, a summary of which is also presented.Comment: 24 pages, 15 figure

8-ий семінар з хмарних технологій в освіті: звіт

This is an introductory text to a collection of selected papers from the 8th Workshop on Cloud Technologies in Education (CTE 2020) which was held in Kryvyi Rih, Ukraine, on the December 18, 2020. It consists of short introduction, papers’ review and some observations about the event and its future.Це вступний текст до збірки вибраних доповідей із восьмого семінару з хмарних технологій в освіті (CTE 2020), який відбувся у Кривому Розі, Україна, 18 грудня 2020 р. Він складається з короткого вступу, огляду статей та деякі спостереження щодо події та її майбутнього

AREdu 2021 – Імерсивні технології сьогодні

This is an introductory text to a collection of papers from the AREdu 2021: The 4th International Workshop on Augmented Reality in Education, which was held in Kryvyi Rih, Ukraine, on the May 11, 2021. It consists of short introduction, papers’ review and some observations about the event and its future.Це вступний текст до збірника статей з AREdu 2021: 4-того Міжнародного семінар з питань доповненої реальності в освіті, який відбувся 11 травня 2021 року в Кривому Розі, Україна. Він складається з короткого вступу, огляду статей та деяких спостереження щодо події та її майбутнього

Pixelated full-colour small molecule semiconductor devices towards artificial retinas

Opto-stimulation of semiconductor-biointerfaces provides efficient pathways towards eliciting neural activity through selective spectral excitation. In visual prosthesis, tri-colour stimulation capability is the key to restoring full-colour vision. Here we report on investigation of organic photoactive π-conjugated donor–acceptor small molecules based on triphenylamine whose absorption spectra are similar to those of the photoreceptors of the human eye. Photoactive device fabrication and characterisation towards full colour, pixelated retinal prosthesis based on inkjet printing of these molecules is demonstrated, with round pixels reaching 25 microns in diameter. Photo-response is studied via interfacing with biological electrolyte solution and using long-pulse, narrow-band excitation. Both photo-voltage and photo-current responses in the devices with a ZnO hole-blocking interlayer show clear signatures of capacitive charging at the electrolyte/device interface, also demonstrating spectral selectivity comparable to that of human eye’ cones and rods

FoxM1 Is a General Target for Proteasome Inhibitors

Proteasome inhibitors are currently in the clinic or in clinical trials, but the mechanism of their anticancer activity is not completely understood. The oncogenic transcription factor FoxM1 is one of the most overexpressed genes in human tumors, while its expression is usually halted in normal non-proliferating cells. Previously, we established that thiazole antibiotics Siomycin A and thiostrepton inhibit FoxM1 and induce apoptosis in human cancer cells. Here, we report that Siomycin A and thiostrepton stabilize the expression of a variety of proteins, such as p21, Mcl-1, p53 and hdm-2 and also act as proteasome inhibitors in vitro. More importantly, we also found that well-known proteasome inhibitors such as MG115, MG132 and bortezomib inhibit FoxM1 transcriptional activity and FoxM1 expression. In addition, overexpression of FoxM1 specifically protects against bortezomib-, but not doxorubicin-induced apoptosis. These data suggest that negative regulation of FoxM1 by proteasome inhibitors is a general feature of these drugs and it may contribute to their anticancer properties