INFLUENCE OF ELECTRON-BEAM PROCESSING ON CHANGES IN THE STRUCTURE OF Al-Mg ALLOY OBTAINED BY COLD METAL TRANSFER

Investigations of the structure Al-Mg alloy samples produced by 3D technologies have been carried out. Tests up to failure were carried. Deformation of samples irradiated with a pulsed electron beam is accompanied by brittle destruction of the modified surface layer.Исследование выполнено при поддержке гранта Российского научного фонда (проект № 20-79-00194)

Фонд университетской библиотеки в XXI в.: основные тенденции и факторы успешного комплектования

The necessity for studies and sharing the experience of Russian academic university libraries in collection development is substantiated. The main trends for the collection development in the 21-st century are revealed and examined as the case study of Novosibirsk State University Library.NovosibirskUniversityis among the nation’s leading research universities. The authors specify the trends of modernization, globalization, collection development with digital publications, and the increasing share of the latter in the Library’s acquisitions and, correspondingly, in the collection, on the whole. They also emphasize the relations and mutual dependence of these and other trends within the collection development process. The factors of successful collection development at the Library are recommended to be implemented by other libraries. High professional competences of collection development specialists and other librarians, the wide range of the collection development sources and their stability, and university administration’s special care of the library collections are specified among these factors. The authors conclude that Novosibirsk State University Library has accumulated great experience in collection development in the circumstances of information society, advance of information technologies, expanding globalization, university integration into the global education, science and research environment. This experience can be shared with many other university libraries.Обоснована необходимость изучения и распространения положительного опыта, накопленного отдельными научными библиотеками российских университетов, по комплектованию своих фондов. Выявлены основные тенденции комплектования фонда университетской библиотеки в XXI в. и рассмотрены их проявления на примере Научной библиотеки Новосибирского государственного университета, входящего в число лидеров исследовательских вузов страны. Отмечены тенденции модернизации, глобализации, активного комплектования фонда электронными изданиями и возрастания их доли в общем количестве вновь приобретаемых изданий и, соответственно, в фонде в целом. Подчёркнуты взаимосвязь и взаимозависимость этих и других тенденций в процессе комплектования фонда. Представлены и проанализированы факторы, которые позволяют сотрудникам НБ НГУ следовать современным тенденциям и успешно решить задачи по комплектованию фонда, а также опыт, который могут перенять другие библиотеки. Особого внимания заслуживают высокий профессионализм сотрудников отдела комплектования и всей библиотеки в целом, созданный ими широкий стабильный круг источников пополнения фонда, забота ректората о состоянии библиотечного фонда. Результаты исследования показывают, что сотрудники НБ НГУ накопили положительный опыт комплектования библиотечного фонда в условиях развития информационного общества, внедрения информационных технологий, нарастающей глобализации, интеграции вуза в мировое образовательное и научно-исследовательское пространство. Этот опыт может быть использован другими вузовскими библиотеками

A Yersinia Effector with Enhanced Inhibitory Activity on the NF-κB Pathway Activates the NLRP3/ASC/Caspase-1 Inflammasome in Macrophages

A type III secretion system (T3SS) in pathogenic Yersinia species functions to translocate Yop effectors, which modulate cytokine production and regulate cell death in macrophages. Distinct pathways of T3SS-dependent cell death and caspase-1 activation occur in Yersinia-infected macrophages. One pathway of cell death and caspase-1 activation in macrophages requires the effector YopJ. YopJ is an acetyltransferase that inactivates MAPK kinases and IKKβ to cause TLR4-dependent apoptosis in naïve macrophages. A YopJ isoform in Y. pestis KIM (YopJKIM) has two amino acid substitutions, F177L and K206E, not present in YopJ proteins of Y. pseudotuberculosis and Y. pestis CO92. As compared to other YopJ isoforms, YopJKIM causes increased apoptosis, caspase-1 activation, and secretion of IL-1β in Yersinia-infected macrophages. The molecular basis for increased apoptosis and activation of caspase-1 by YopJKIM in Yersinia-infected macrophages was studied. Site directed mutagenesis showed that the F177L and K206E substitutions in YopJKIM were important for enhanced apoptosis, caspase-1 activation, and IL-1β secretion. As compared to YopJCO92, YopJKIM displayed an enhanced capacity to inhibit phosphorylation of IκB-α in macrophages and to bind IKKβ in vitro. YopJKIM also showed a moderately increased ability to inhibit phosphorylation of MAPKs. Increased caspase-1 cleavage and IL-1β secretion occurred in IKKβ-deficient macrophages infected with Y. pestis expressing YopJCO92, confirming that the NF-κB pathway can negatively regulate inflammasome activation. K+ efflux, NLRP3 and ASC were important for secretion of IL-1β in response to Y. pestis KIM infection as shown using macrophages lacking inflammasome components or by the addition of exogenous KCl. These data show that caspase-1 is activated in naïve macrophages in response to infection with a pathogen that inhibits IKKβ and MAPK kinases and induces TLR4-dependent apoptosis. This pro-inflammatory form of apoptosis may represent an early innate immune response to highly virulent pathogens such as Y. pestis KIM that have evolved an enhanced ability to inhibit host signaling pathways

Replication of fifteen loci involved in human plasma protein N-glycosylation in 4,802 samples from four cohorts

Human protein glycosylation is a complex process, and its in vivo regulation is poorly understood. Changes in glycosylation patterns are associated with many human diseases and conditions. Understanding the biological determinants of protein glycome provides a basis for future diagnostic and therapeutic applications. Genome-wide association studies (GWAS) allow to study biology via a hypothesis-free search of loci and genetic variants associated with a trait of interest. Sixteen loci were identified by three previous GWAS of human plasma proteome N-glycosylation. However, the possibility that some of these loci are false positives needs to be eliminated by replication studies, which have been limited so far. Here, we use the largest set of samples so far (4,802 individuals) to replicate the previously identified loci. For all but one locus, the expected replication power exceeded 95%. Of the sixteen loci reported previously, fifteen were replicated in our study. For the remaining locus (near the KREMEN1 gene) the replication power was low, and hence replication results were inconclusive. The very high replication rate highlights the general robustness of the GWAS findings as well as the high standards adopted by the community that studies genetic regulation of protein glycosylation. The fifteen replicated loci present a good target for further functional studies. Among these, eight genes encode glycosyltransferases: MGAT5, B3GAT1, FUT8, FUT6, ST6GAL1, B4GALT1, ST3GAL4, and MGAT3. The remaining seven loci offer starting points for further functional follow-up investigation into molecules and mechanisms that regulate human protein N-glycosylation in vivo

Проспективное исследование выявляемости рака предстательной железы при выполнении мультипараметрической магнитно-резонансной/ ультразвуковой fusion, стандартной и сатурационной биопсии

Background. Currently, about 80 % of men with low-grade prostate cancer (per ISUP 1 (International Society of Urological Pathology)) have indications for radical treatment. Overdiagnosis of low-grade cancer is associated with the use of systematic biopsy methods (standard transrectal, saturation) under ultrasound control for diagnosis verification. To improve prostate cancer diagnosis, the European Association of Urology (2019) recommended multiparametric magnetic resonance imaging before biopsy, and in case of detection of a suspicious lesion magnetic resonance imaging (MRI)-targeted biopsy. In clinical practice, the most common method of MRI-targeted biopsy is multiparametric MRI ultrasound-guided (mpMRI/US) fusion biopsy. However, some studies show contradictory results in detection of prostate cancer using systematic and MRI-targeted biopsy techniques.Aim. To compare detection of clinically significant prostate cancer (ISUP ≥2) using mpMRI/US fusion, standard, and saturation biopsy.Materials and methods. The study included 96 patients. The following inclusion criteria were applied: prostate-specific antigen >2 ng/mL and/or detection of a suspicious lesion during digital rectal and/or transrectal ultrasound examination, and PI-RADS (Prostate Imaging Reporting and Data System) v.2.1 score ≥3. At the first stage, “unblinded” urologist performed a transperineal mpMRI/US fusion and saturation biopsies. At the second stage, “blinded” urologist performed standard transrectal biopsy. Clinically significant cancer was defined as ISUP ≥2.Results. Median age was 63 years, prostate volume – 47 cm3, prostate-specific antigen – 6.82 ng/mL. MpMRI/US fusion, standard, and saturation biopsies were comparable in regard to the rate of detection of clinically significant (29, 24, 28 %; p = 0.81) and clinically insignificant (25, 26, 35 %; p = 0.43) cancer. Overall prostate cancer detection rates were also similar: 54, 50, 63 %, respectively (p = 0.59). The percentages of positive cores in mpMRI/US fusion, standard, and saturation biopsies were 33, 10 and 13 %, respectively (p <0.01). The maximal core length in mpMRI/US was 6.4 mm, in standard biopsy – 6.35 mm, in saturation biopsy – 5.1 mm (p = 0.7).Conclusion. Detection rates of clinically significant, clinically insignificant prostate cancer and overall detection rate are comparable between systematic biopsy techniques and mpMRI/US fusion biopsy.Введение. В настоящее время до 80 % мужчин с раком предстательной железы (РПЖ) низкой степени злокачественности (ISUP 1 (по классификации Международного общества урологических патологов)) подлежат радикальному лечению. Гипердиагностика РПЖ низкой степени злокачественности обусловлена использованием для верифиации диагноза так называемых систематических методов биопсии предстательной железы, выполняемых под ультразвуковым (УЗ) контролем (стандартная трансректальная, сатурационная). В целях улучшения диагностики РПЖ Европейской ассоциацией урологов рекомендовано (2019) перед биопсией всем пациентам проводить мультипараметрическую магнитно-резонансную томографию, в случае обнаружения подозрительного очага выполнять магнитно-резонансную (МР) прицельную биопсию. Наибольшее распространение получила мультипараметрическая МР/УЗ (мпМР/УЗ) fusion-биопсия. Однако в ряде исследований представлены противоречивые результаты выявляемости РПЖ при сравнении систематических и МР-прицельных методов биопсии.Цель исследования – сравнение выявляемости клинически значимого РПЖ (ISUP ≥2) при проведении мпМР/УЗ fusion, стандартной и сатурационной биопсии.Материалы и методы. В исследование были включены 96 пациентов. Критерии включения: уровень простатического специфического антигена >2 нг/мл, и/или обнаружение подозрительного очага при проведении пальцевого ректального и/или трансректального ультразвукового исследования, и ≥3 баллов по критериям PI-RADS (Prostate Imaging Reporting and Data System) v.2.1. Первым этапом «расслепленный» уролог выполнял трансперинеальную мпМР/УЗ fusion и сатурационную биопсию, вторым этапом «ослепленный» уролог проводил стандартную трансректальную биопсию. Клинически значимый РПЖ определяли как ISUP ≥2.Результаты. Медиана возраста пациентов составила 63 года, объема предстательной железы – 47 см3, уровня простатического специфического антигена – 6,82 нг/мл. При сравнении результатов мпМР/УЗ fusion, стандартной и сатурационной биопсии не обнаружены статистически достоверные различия в отношении выявляемости клинически значимого (29, 24 и 28 % соответственно; p = 0,81) и клинически незначимого (25, 26 и 35 % соответственно; p = 0,43) рака. Общая выявляемость РПЖ также сопоставима – 54, 50 и 63 % соответственно (p = 0,59). Доля положительных биоптатов составила 33, 10 и 13 % соответственно (p <0,01). Максимальная длина биоптата, пораженного раком, при мпМР/УЗ fusion-биопсии – 6,4 мм, при стандартной – 6,35 мм, при сатурационной – 5,1 мм (p = 0,7).Заключение. Выявляемость клинически значимого, клинически незначимого и общая выявляемость РПЖ сопоставимы при проведении как систематических методов биопсии, так и мпМР/УЗ fusion-биопсии.ps

Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I

The defining role of the tonic activity of neural networks in supporting the body's appropriate responses to sensory stimuli has been demonstrated and analyzed in detail by recording spike activity from single neurons and low-frequency EEG activity in the range Tonic gamma activity is known to change in accordance with the ongoing state of the subject and the task being executed. In particular, generation of gamma activity increases in the state of attention and/or mental loading. Thus, studies in 1980 showed that increases in the EEG gamma rhythm in cats occurred at the time point at which they paid full attention to their target prey 567 Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 61, No. 1, pp. 75-84, January-February, 2011. Original article submitted March 10, 2010. Accepted October 18, 2010 Tonic brain activity has significant influences on the nature of a subject's responses to target sensory stimuli. We report here studies of the dynamics of the background activity in the gamma-rhythm range of the EEG in rabbits during execution of an "active oddball" paradigm modified for animals -a task widely used for studies of attention. Increased levels of power and coherence in background gamma activity were found to reflect expectation of a target stimulus, correct responses to stimuli being executed at a particular level of background gamma activity which probably corresponds to the optimum level of sustained (tonic) attention. Decreases in the level of gamma activity led to missed responses to the target stimulus, while excess levels lead to erroneous responses to non-target signals (false anxiety). These dynamics of background gamma activity are interpreted as resulting from oscillations in the level of tonic cholinergic activation of right cerebral cortex. Keywords: attention, operant conditioned reflex, oddball, electroencephalogram, gamma rhythm, rabbit. Faculty of Biology, M. V. Lomonosov Moscow State University; e-mail: [email protected]. Thus, there is currently a set of experimental data showing that changes in the level of sustained, or tonic, attention (defined as a subject's readiness to make a response, appropriate to the conditions of the task, to discrete sensory stimuli over a long period of time) are accompanied by variations in measures of background gamma activity. Nonetheless, data on the phenomenology of this situation remain controversial and contradictory and its mechanisms virtually unknown. The aim of the present work was to study the generation of background gamma activity in the EEG in rabbits in relation to variations in the level of sustained (tonic) attention during execution of the "active oddball" paradigm (a task widely used in studies of attention), including: 1) assessment of background gamma activity at different levels of sustained attention due to changes in the subjectively expected probability that the target stimulus will be presented; 2) assessment of the interaction between background gamma activity and the level of sustained attention influencing the correctness with which the target and non-target stimuli are recognized. METHODS Training of Animals and Recording of Behavior in Experimental Conditions The experimental model based on the active oddball paradigm, developed by ourselves for animals, consists of differential conditioned reflex stimuli, one of which, the target (conditioned) stimulus, is presented significantly less frequently than the non-target (differential, ignored) stimulus. Having executed an operant movement in response to the target stimulus, the animal receives a drink as reinforcement; execution of a movement in response to the non-target stimulus is regarded as an error and is not reinforced Experiments were performed in a screened light-and soundproofed chamber in freely moving rabbits weighing 3-4.5 kg. During experiments, animals were subjected to fluid deprivation without reducing body weight by more than 20% of initial. The animals' operant movements were that the forepart of the head had to break a light beam in the recording device on the floor of the pen. Correct movements performed within 4 sec of stimulus activation were reinforced by delivery of 5 ml of fruit juice from an automatic bowl also fixed to the floor of the pen close to the recording device (method developed by B. V. Chernyshev and Moskvitin). Sound stimuli were delivered via a loudspeaker located above the experimental pen; tone duration was 40 msec, with rise and decay times of 10 msec, and loudness was about 70 dB. For animals of group I (four rabbits), the target (conditioned) stimulus was a tone of 2000 Hz and the non-target (differential) stimulus was at 800 Hz; the same stimuli were used for animals of group II (four rabbits) but with the values reversed (target stimulus at 800 Hz, non-target stimulus at 2000 Hz). Use of two groups of animals allowed the effects of attention to be studied independently of differences in the physical parameters of the target and non-target stimuli. The target and non-target stimuli were presented in quasirandom order at a ratio of 1:4; two target stimuli never followed immediately one after the other and were always separated by at least two presentations of the non-target stimuli. Each experiment involved 150-450 trials (including 30-90 presentations of the target stimulus). The interstimulus interval was 8 ± 1 sec. During experiments, four variants of behavioral responses to stimuli were seen: positive reactions and missed reactions in response to the target stimulus, erroneous responses (false anxiety), and correct refusals to respond to the non-target stimulus. Surgery and EEG Recording Surgery to implant macroelectrodes for EEG recording was performed in a stereotaxic apparatus under general anesthesia (Nembutal, 55 mg/kg) and local anesthesia with 2% novocaine solution. Silver macroelectrodes for EEG recordings were placed on one side above the frontal (F), lateral parietal (lP), and central parietal (cP) areas of the cortex; macroelectrodes were implanted into bone to a depth of 1.5 mm at points with coordinates of A = 7, L = 1-3.5 for recording F; P = 1-2, L = 5.5-6 for recording lP; and A = 0, L = 0 (the bregma) for recording cP, using an atlas The reference electrode was positioned 10-15 mm anterior to the bregma, close to the sagittal suture, and the ground electrode was placed in the posterior part of the skull (A = -10 ± 2, L = 2 ± 1). All electrodes were fixed to bone with fast-setting resin, after which the animal's head was fitted with a 10-way socket. A multicore flexible screened cable was plugged into the socket for EEG recording, with low-noise repeaters. The EEG signal was then delivered to an ISDB biopotentials amplifier (WPI Inc., USA) and then to the analog-to-digital converter (ADC) of an L-305 input-output card (L-Card, Russia) fitted in a standard computer. EEG recordings were made with a time constant of 1.6 sec and an upper frequency cut-off of 70 Hz; the sampling frequency was 512 Hz. Experiments were controlled and recordings were made of the EEG and light beam crossing times automatically using the Emerald Spike program (by B. V. Chernyshev). Analysis and Processing of Experimental Data Artifacts were removed from EEG traces automatically and by visual assessment of traces for all trials. Gamma Panasyuk, Matselepa, Chernyshev, et al. 568 activity power and coherence were calculated in Emerald Spike over the range 28-68 Hz for 500 msec of prestimulus activity using fast Fourier transformation with a superimposed Hann window. Gamma activity parameters were calculated using non-averaged EEG traces