Red meat consumption is considered a risk factor for colorectal cancer (CRC) development and stimulated isolation of plasmid-like DNA molecules from bovine serum and milk, termed bovine meat and milk factors (BMMFs). BMMFs encode a conserved replication protein (Rep). Increased populations of Rep-expressing macrophages have been identified in the peritumor of CRC patients and pre-cancerous tissues when compared to the tissues of healthy individuals. This supports the concept that BMMFs increase cancer risk by indirect carcinogenesis, upon induction of chronic inflammation. However, the spread of Rep+ immune cells in tissues at greater distances from primary tumors has not yet been assessed. Here, we immunohistologically analyzed the presence of Rep+ immune cells in sets of tumor, peritumor and, additionally, distant tissues of CRC patients (n = 13). We identified consistently high numbers of BMMF-positive macrophages in mucosal tissues at distances of as much as 25 cm away from the primary tumors, at levels comparable to peritumors and associated with M2-like macrophage polarization. The broad distribution of BMMFs suggests that BMMF+ macrophages might already exist at stages of pre-cancerous dysplasia or before. Quantification of BMMF tissue expression during colonoscopy might help to preventively stratify individuals at risk of developing polyps/CRC and recommend them for enhanced surveillance and/or changes in dietary lifestyle.

The formation of a conditional connection allows the organism to change its reactions to various environmental factors, combining and mobilizing the necessary internal adaptive processes. It is assumed that there are common mechanisms underlying the formation of adaptive processes including stress response and learning. To develop methods for non-invasive correction of nervous system pathologies in a model object of genetics Drosophila, the relationship of adaptive mechanisms of the formation of a conditional connection and the development of a stressor reaction to the weakening of the Earth’s magnetic field in light: dark conditions was studied. We a role of learning and lighting in stress coping due to the formation of long-term memory in the paradigm of conditioned courtship suppression. Within the framework of quantum dynamics of electronic and nuclear spins of transition states of radical molecules, the hypothesis of their participation in the formation of long-term memory is considered.

Here, we describe the effects of double knockout (KO) of the cbs and cse genes, which are responsible for H2S synthesis through the transsulfuration pathway, and KO of the sulfurtransferase gene (dtst1) in Drosophila melanogaster females. The analysis of H2S production in flies showed minimal levels in the double- and triple-knockout strains. The double- (cbs-/-; cse-/-) and triple- (cbs-/-; cse-/-; dtst-/-) KO flies exhibited a shortened lifespan and reduced fecundity, and showed dramatic changes in Malpighian tubule morphology. The transcriptomic analysis revealed a profound increase in the expression levels of several genes involved in excretory system function in the double-KO and especially the triple-KO flies. Importantly, major groups of differentially expressed genes (DEGs) in the whole bodies of females and ovaries of KO strains included genes responsible for detoxification, reproduction, mitochondrial activity, excretion, cell migration, and muscle system function. The reduced fecundity observed in the double- and triple-KO flies correlated with pronounced changes in the ovarian transcriptome. At the same time, the single knockout of dtst1 increased the flies’ fecundity and lifespan. Our experiments exploring unique Drosophila strains with KO of major H2S-related genes revealed several new pathways controlled by this ancient adaptogenic system that is involved in various human diseases and aging.

Modern concepts hold that intellectual problems in neurological brain damage are based on active forgetting, which is regulated by actin remodeling signal cascades dependent on small GTPases Rac and Rho. The key enzyme in these cascades is LIM kinase 1 (LIMK1). Changes in limk1 gene expression lead to neurocognitive pathologies. There is a need to create and validate simple animal models for rapid screening and testing of targeted therapeutic agents altering the protein–protein interactions of GTPases and components of signal cascades. One opportunity for this is provided by Drosophila, mutant strains of which allow the key points of the intersections of biochemical and neural networks which accompany active forgetting to be identifi ed.

Nickel oxide semiconductor is a good p -type material for fabricating a p - n -heterojunction with n -type GaN semiconductor. The p -NiO/ n -GaN heterojunction, which produces a type II band bias, has significant prospects for creating photosensitive devices. Herein, it is shown that a selective ultraviolet photodetector can be created based on this heterojunction. p -NiO films were formed using magnetron sputtering onto n -doped GaN epitaxial layers grown by plasma assisted molecular beam epitaxy. The structural, optical, and electronic properties of the formed nickel oxide films were studied. A mechanism for reducing dislocation density and conductivity and increasing transparency due to film annealing is proposed. It has been established that the current-voltage characteristics of the p -NiO/ n -GaN heterojunction are typical for diode structures and show selective sensitivity to ultraviolet radiation. The band model and sensitivity of the fabricated ultraviolet photodiode were evaluated. The photosensitivity at zero voltage was 3.11 mA/W, the quantum yield was 0.011, and the detection ability was 8.69 x 10 9 Jones. The work shows the potential of using the p -NiO/ n -GaN heterojunction to create ultraviolet photodetectors.

According to modern concepts, biochemical cascades activated in response to stress impacts also contribute to cognitive functions, such as learning and memory formation. Considering a conditioned reflex as an adaptation to the external environment, one can assume its occurrence as a reaction to external challenges, which, when reinforced, contribute to the formation of a conditioned connection, and in the absence, cause the development of a stress response. The metabolic activity of the body is inextricably linked with circadian rhythms, which determine the daily fluctuations in light, temperature, oxygen content and magnetic field. The integration of these timers is carried out by a protein of the cryptochrome family (CRY), which functions as a blue light receptor and is known as a repressor of the main circadian transcription complex CLOCK/BMAL1. In order to develop methods for non-invasive correction of pathologies of the nervous system on a model object of genetics – Drosophila using mutant lines, the relationship between adaptive mechanisms for the formation of a conditioned connection and the development of a stress response to a weakening of the magnetic field, hypoxic and temperature effects is studied. The data are discussed in light of the role of the CRY/CLOCK/BMAL1 system as a link in magnetoreception, hypoxia, circadian rhythm regulation, cognitive functions, and DNA double-strand breaks in nerve ganglia (an indicator of the physiological activity of neurons).

Here, we describe the effect of knockout (KO) of two key genes (cbs, cse) responsible for H2S synthesis in the transsulfuration pathway as well as the inactivation of sulfurtransferase gene (dtst1) encoding single domain rhodanese on Drosophila melanogaster genome expression and several life-history traits. The analysis of H2S production in the KO flies showed its minimal level in the strain with double KO (CBS-/-; CSE-/-) while flies with triple KO (CBS-/-; CSE-/-; dTST1-/-) exhibited higher H2S level and improvements in lifespan. The transcriptomic analysis of fly bodies from the double KO strain with maximum disturbances of fitness components revealed a profound increase in the expression of genes involved in the functioning of the excretory system. Besides, double and triple KO flies exhibited drastic changes in Malpighian tubules' appearance. Inactivation of genes related to H2S metabolism resulted in altered expression of numerous loci involved in mitochondrial function. While KO of the dtst1 gene did not affect the genome expression, the triple KO flies exhibited more changes in the whole-body transcriptome than double KO flies. Reduced fecundity in double knockouts correlates with pronounced changes in ovarian transcriptome data. Surprisingly, the knockout of the dtst1 gene affected the flies' memory.

Одно из приоритетных направлений в современной биологии и медицине — изучение регуляторных механизмов повышения жизнеспособности многоклеточных систем. Многие из 20 кодируемых аминокислот стимулируют клеточную пролиферацию в органотипической культуре различных тканей экспериментальных животных. Также известно, что в основе физической жизнеспособности лежит скорость восстановления организма путем стимуляции клеток к пролиферации или апоптозу, осуществляемой под влиянием цитокинов и/или пептидов. В Санкт-Петербургском Институте биорегуляции и геронтологии была разработана технология выделения из различных органов и тканей телят полипептидных комплексов, влияющих на органотипическую культуру тканей экспериментальных животных. В состав полипептидных комплексов входят короткие пептиды — тетра-, три- и дипептиды, которые, являясь минорными компонентами исследованных полипептидных комплексов, обладают высокой биологической активностью. На основе этих данных может быть осуществлена разработка новых лекарственных препаратов, предназначенных для лечения и профилактики общих гериатрических синдромов (например, старческой астении), а также заболеваний различных органов с учетом принципа тканеспецифичности. Целью работы было исследование эффекта различных комбинаций L-аминокислот и дипептидов на жизнеспособность клеток в органотипической культуре ткани нервной и иммунной систем у крыс разного возраста.

Courtship suppression is a behavioral adaptation of the fruit fly. When majority of the females in a fly population are fertilized and non-receptive for mating, a male, after a series of failed attempts, decreases its courtship activity towards all females, saving its energy and reproductive resources. The time of courtship decrease depends on both duration of unsuccessful courtship and genetically determined features of the male nervous system. Thereby, courtship suppression paradigm can be used for studying molecular mechanisms of learning and memory. p-Cofilin, a component of the actin remodeling signaling cascade and product of LIM-kinase 1 (LIMK1), regulates Drosophila melanogaster forgetting in olfactory learning paradigm. Previously, we have shown that limk1 suppression in the specific types of nervous cells differently affects fly courtship memory. Here, we used Gal4 > UAS system to induce limk1 overexpression in the same types of neurons. limk1 activation in the mushroom body, glia, and fruitless neurons decreased learning index compared to the control strain or the strain with limk1 knockdown. In cholinergic and dopaminergic/serotoninergic neurons, both overexpression and knockdown of limk1 impaired Drosophila short-term memory. Thus, proper balance of the limk1 activity is crucial for normal cognitive activity of the fruit fly.

С 1910 года генетические исследования с привлечением мутанта white Drosophila melanogaster сыграли фундаментальную роль в современной биологии. Бурное развитие такие эксперименты получили после разработки методов трансформации зародышевой линии, позволивших создавать трансгенные линии дрозофилы, что существенно расширило возможности исследования многих биологических процессов, в том числе и поведения. Ген white характеризуется плейотропным действием, затрагивающим не только зрение, но и другие важные аспекты жизнедеятельности, включая различные формы поведения, обучения и памяти. Сопоставляя результаты наших предыдущих работ, направленных на изучение способности к обучению и формированию памяти у мутанта w 1118 в интактном контроле и при действии теплового шока на имаго, с настоящей работой, нацеленной на анализ влияния на эти процессы стадиеспецифичных температурных воздействий, можно констатировать сохранность процессов обучения и памяти у мутанта w1118 как в интактном контроле, так и при действии теплового шока на различных стадиях онтогенеза в парадигме условно-рефлекторного подавления ухаживания. Это важно учитывать при выборе методических подходов при планировании поведенческих экспериментов с привлечением трансгенных линий на генетическом фоне white.

Актуальной проблемой современной физиологии и медицины является выявление биологически активных молекул, влияющих на клеточные процессы пролиферации и апоптоза. В Санкт-Петербургском институте биорегуляции и геронтологии разработана технология выделения ряда полипептидных комплексов из различных органов и тканей телят, оказывающих стимулирующее влияние в культуре разных тканей организма на клеточную пролиферацию. В составе полипептидных комплексов содержатся короткие пептиды, имеющие сходную с полипептидами биологическую активность. Целью настоящего исследования было выявление действия коротких пептидов на клеточную пролиферацию в органотипической культуре тканей коры головного мозга, селезенки, печени молодых (3-месячных) и старых (18-месячных) крыс. При исследовании влияния в эффективных концентрациях трипептидов Glu-Asp-Arg, Glu-Asp-Pro, Glu-Asp-Leu и дипептидов Asp-Ser, Asp-Leu, Asp-Ala, Asp-Gly, Asp-Arg, Ala-Gly установлено, что эти пептиды статистически достоверно (p < 0,05) cтимулируют клеточную пролиферацию в эксплантатах коры головного мозга, печени, селезенки, как молодых, так и старых крыс. Полученные данные о коротких пептидах, стимулирующих клеточную пролиферацию в культивируемых тканях коры головного мозга, печени, селезенки молодых и старых организмов, создают базу для целенаправленной разработки новых лекарственных препаратов, том числе геропротекторов.

Bovine milk and meat factors (BMMFs) are plasmid‐like DNA molecules isolated from bovine milk and serum, as well as the peritumor of colorectal cancer (CRC) patients. BMMFs have been proposed as zoonotic infectious agents and drivers of indirect carcinogenesis of CRC, inducing chronic tissue inflammation, radical formation and increased levels of DNA damage. Data on expression of BMMFs in large clinical cohorts to test an association with co‐markers and clinical parameters were not previously available and were therefore assessed in this study. Tissue sections with paired tumor‐adjacent mucosa and tumor tissues of CRC patients [individual cohorts and tissue microarrays (TMAs) (n = 246)], low‐/high‐grade dysplasia (LGD/HGD) and mucosa of healthy donors were used for immunohistochemical quantification of the expression of BMMF replication protein (Rep) and CD68/CD163 (macrophages) by co‐immunofluorescence microscopy and immunohistochemical scoring (TMA). Rep was expressed in the tumor‐adjacent mucosa of 99% of CRC patients (TMA), was histologically associated with CD68+/CD163+ macrophages and was increased in CRC patients when compared to healthy controls. Tumor tissues showed only low stromal Rep expression. Rep was expressed in LGD and less in HGD but was strongly expressed in LGD/HGD‐adjacent tissues. Albeit not reaching statistical significance, incidence curves for CRC‐specific death were increased for higher Rep expression (TMA), with high tumor‐adjacent Rep expression being linked to the highest incidence of death. BMMF Rep expression might represent a marker and early risk factor for CRC. The correlation between Rep and CD68 expression supports a previous hypothesis that BMMF‐specific inflammatory regulations, including macrophages, are involved in the pathogenesis of CRC.

Данный обзор отражает основные направления развития переливания крови в России до открытия групп крови. О переливании крови в допетровской России достоверно неизвестно. Предпосылки возникновения российской трансфузиологии возникают в XVIII веке в связи с формированием систематического отечественного медицинского образования. XIX век знаменуется становлением национальной научной медицинской школы. Этот период можно по праву считать и временем становления переливания крови в России. Первое в России переливание крови от человека к человеку было осуществлено 20 апреля 1832 года в Санкт-Петербурге Андреем Мартыновичем Вольфом, учеником С. Ф. Хотовицкого. Вслед за этим к проблеме гемотрансфузии обращаются многие российские медики. Среди них прежде всего необходимо выделить И. В. Буяльского, стоявшего у истоков трансфузиологии; А. М. Филомафитского, автора первого в России трактата о переливании крови; В. В. Сутугина, заложившего основы консервирования крови. Особое место занимают работы С. П. Коломнина, осуществившего первое в мире переливание дефибринированной крови раненым в военно-полевых условиях. Именно развитие военной трансфузиологии, а также успешное применение гемотрансфузий при заболеваниях и отравлениях составляли отличительные черты российской практики переливания крови.

В статье представлен обзор докладов участников симпозиума «Генетические и эпигенетические механизмы поведенческих функций», включенных в научную программу XXIV Съезда физиологического общества им. И. П. Павлова, состоявшегося в Санкт-Петербурге 11–15 сентября 2023 года. Изложено основное содержание докладов ученых из университетов и научно-исследовательских институтов Москвы, Санкт-Петербурга, Калининграда, Новосибирска, Петрозаводска, Нижнего Новгорода, Ярославля, Ростова-на-Дону, Казани, Красноярска. Отмечен высокий методический и теоретический уровень представленных исследований, лежащих в русле крайне востребованного интегративного подхода к исследованию поведения. Современное понимание механизмов генетической и эпигенетической регуляции нервных сетей мозга при реализации поведенческих функций может быть достигнуто только совместными усилиями физиологии и генетики. Сложная система физиологических реакций, обусловливающая поведенческий фенотип, регулируется как непосредственно геномом, так и изменениями экспрессии генов, в основе которых лежат различные эпигенетические механизмы. Крайне важно учитывать, что пути реализации генетической информации не только регулируются генетическими, эпигенетическими и средовыми факторами, но и сами физиологические процессы опосредуют реализацию генетической программы. Дальнейшая разработка подходов, представленных в докладах симпозиума, открывает новые горизонты исследования поведенческих функций и коррекции патологических поведенческих реакций.

Fabrication of electric contacts is one of the most important stages in the electronic devices manufacturing process. Recently, considerable attention is paid to non-alloyed ohmic contact studies, although the more conventional approach usually involves contact formation by rapid thermal annealing of the sputtered metallization. In this work the contact resistance of alloyed (Ti/Al/Ni/Au and Ti/Al) and non-alloyed (Yb/Au) ohmic contacts to n-GaN epitaxial films is compared. Ti/Al/Ni/Au alloyed ohmic contacts have the lowest resistance. However, it is found that the contact resistance values for non-alloyed Yb/Au and alloyed Ti/Al contacts are similar. Thus, low-resistance non-alloyed Yb/Au-based ohmic contacts to n-GaN are demonstrated.

qPCR is widely used in quantitative studies of plant genomes and transcriptomes. In this article, this method is considered as an auxiliary step in the preparation and selection of markers for FISH analysis. Several cases from the authors' research on populations of the same species were reviewed, and a comparison of the closely related species, as well as the adaptation of the markers, based on satellite tandem repeats (TRs) using quantitative qPCR data was conducted. In the selected cases, TRs with contrast abundance were identified in the cases of the Dasypyrum, Thinopyrum and Aegilops species, and the transfer of TRs between the wheat and related species was demonstrated. TRs with intraspecific copy number variation were revealed in Thinopyrum ponticum and wheat-wheatgrass partial amphidiploids, and the TR showing predominant hybridization to the sea buckthorn Y chromosome was identified. Additionally, problems such as the absence of a reference gene for qPCR, and low-efficiency and self-complementary primers, were illustrated. In the cases considered here, the qPCR results clearly show high correlation with the subsequent results of the FISH analysis, which confirms the value of this method for cytogenetic studies.