Siberian Exile and Its Reformation during Reign of Peter Great (XVII—XVIII)

The history of the formation and development of the Siberian criminal exile, the main link in the all-Russian system of execution of punishment in the Russian Empire during the 18th— 19th centuries is discussed in the article. It is shown that the exile to Siberia appeared already at the end of the 16th century, however, during this period, called “Moscow”, it did not yet have a proper organization. The study provides examples that convincingly prove that it was only under Peter I and thanks to his efforts that the Siberian exile began to acquire a legal and organized character, began to play an important role in the protective and punitive system of the state. The novelty of the study lies in the fact that for the first time an attempt was made to comprehensively study the transformations of Peter the Great in the field of legal regulation of the system of hard labor and exile, which is shown on the example of Siberia in the 17th—18th centuries. It is shown that it was under Peter that criminal exile and hard labor became not only forms of punishment for criminals, but also the main way to use free labor in the construction of strategically important facilities for the country located on the borders of the Russian Empire

ПОКАЗНИКИ ЕНЕРГЕТИЧНОГО ОБМІНУ В СЕРЦЕВІЙ ТКАНИНІ ЕКСПЕРИМЕНТАЛЬНИХ ТВАРИН ЗА УМОВ ВПЛИВУ КАДМІЙ ХЛОРИДУ

Introduction. Cadmium chloride can enter the body of humans and animals with food, drinking water and atmospheric air. Their effect is to suppress the functional state of mitochondria, which leads to the depletion of energy resources and the violation of a number of vital processes. Cadmium, penetrating into cells, interacts with mercaptogroups, suppresses enzyme systems of energy supply, by replacing bivalent metals that are part of enzymes. The aim of the study – to determine the state of energy metabolism in the cardiac muscle of experimental animals (rats) under conditions of cadmium chloride. Research Methods. Intoxication was carried out by intravenous administration of cadmium chloride at a dose of 1/10 LD50 for 10 days. Animals were divided into two groups: intact and experimental, which were injected with cadmium chloride. The material was collected after decapitation under tiopental anesthesia at 1st, 14th, 28th day after the completion of the administration of the toxicant. Indicators of energy metabolism were determined as follows: the activity of ATPase, lactate dehydrogenase was determined by the enzymatic method; concentration of glucose – glucoxidase method, the level of pyruvate, lactate and adenosine triphosphate (ATP) was determined spectrophotometrically. The content of macro- and micronutrients (Cd, Zn, Cu, Mg) was determined using an atomic absorption spectrophotometer. Results and Discussion. The obtained results testify to the increased use of glucose by the cardiac muscle in anaerobic way, as there is an increase in the concentration of lactic acid. This is confirmed by the literature sources on the development of hypoxia under the conditions of cadmium ions. At that time, the level of adenosine triphosphoric acid decreases as well as the activity of ATPase in the heart tissue. We also observed the increase in the content of magnesium (the activator of ATPase) and zinc (the activator of lactate dehydrogenase) in the heart of experimental animals. Conclusion. The conducted studies indicate a violation of the energy supply of tissue of the heart muscle for cadmium intoxication, which is confirmed by the activation of glucose anaerobic oxidation, a decrease in its level and the content of ATP in the myocardium.Вступление. Катионы кадмия могут поступать в организм человека и животных с пищей, питьевой водой и атмосферным воздухом. Их действие заключается в угнетении функционального состояния митохондрий, что приводит к истощению энергетических ресурсов и нарушению ряда жизненно важных процессов. Кадмий, проникая в клетки, взаимодействует с меркаптогруппами, подавляет энзимные системы энергообеспечения путем замещения двухвалентных металлов, входящих в состав энзимов. Цель исследования – выяснить состояние энергетического обмена в сердечной мышце экспериментальных животных (крыс) в условиях влияния кадмий хлорида. Методы исследования. Интоксикацию осуществляли путем внутримышечного введения кадмий хлорида в дозе 1/10 LD50 в течение 10-ти дней. Животные были разделены на 2 группы: 1-я интактные; 2-я – экспериментальные, которым вводили кадмий хлорид. Забор материала проводили после декапитации под тиопенталовым наркозом на 1-е, 14-е, 28-е сутки после завершения ввода токсиканта. Показатели энергетического обмена определяли следующим образом: активность АТФ-азы, лактатдегидрогеназы – энзиматическим методом; концентрацию глюкозы – глюкооксидазным методом; уровень пировиноградной, молочной аденозинтрифосфорной (АТФ) кислот – спектрофотометрически; содержание макро- и микроэлементов (Cd, Zn, Cu, Mg) – с помощью атомно-абсорбционного спектрофотометра. Результаты и обсуждение. Полученные результаты свидетельствуют об усиленном использовании глюкозы сердечной мышцей анаэробным путем, так как наблюдали повышение концентрации молочной кислоты. Это подтверило литературные данные о развитии гипоксии в условиях действия ионов кадмия. В то же время отмечено снижение уровня аденозинтрифосфорной кислоты, а также активности АТФ-азы в ткани сердца. Установлено увеличение содержания магния (активатора АТФ-азы) и цинка (активатора лактатдегидрогеназы) в сердце экспериментальных животных. Вывод. Результаты проведенных исследований указывают на нарушение энергетического обеспечения тканей сердечной мышцы в условиях кадмиевой интоксикации, что подтверждается активацией анаэробного окисления глюкозы, снижением ее уровня и содержания аденозинтрифосфорной кислоты в миокарде.Вступ. Катіони кадмію можуть надходити в організм людини і тварин з їжею, питною водою й атмосферним повітрям. Їх дія полягає у пригніченні функціонального стану мітохондрій, що призводить до виснаження енергетичних ресурсів та порушення ряду життєво важливих процесів. Кадмій, проникаючи в клітини, взаємодіє з меркаптогрупами, пригнічує ензимні системи енергозабезпечення шляхом заміщення двовалентних металів, які входять до складу ензимів. Мета дослідження – з’ясувати стан енергетичного обміну в серцевому м’язі експериментальних тварин (щурів) за умов впливу кадмій хлориду. Методи дослідження. Інтоксикацію здійснювали шляхом внутрім’язового введення кадмій хлориду в дозі 1/10 LD50 протягом 10-ти днів. Тварин було поділено на 2 групи: 1-ша – інтактні; 2-га – експериментальні, яким вводили кадмій хлорид. Забір матеріалу проводили після декапітації під тіопенталовим наркозом на 1-шу, 14-ту, 28-му доби після завершення введення токсиканту. Показники енергетичного обміну визначали таким чином: активність АТФ-ази, лактатдегідрогенази – ензиматичним методом; концентрацію глюкози – глюкооксидазним методом; рівень піровиноградної, молочної, аденозинтрифосфорної (АТФ) кислот – спектрофотометрично; вміст макро- та мікроелементів (Cd, Zn, Cu, Mg) – за допомогою атомно-абсорбційного спектрофотометра. Результати й обговорення. Отримані результати свідчать про посилене використання глюкози серцевим м’язом за анаеробним шляхом, оскільки спостерігали підвищення концентрації молочної кислоти. Це підтвердило літературні дані про розвиток гіпоксії за умов дії іонів кадмію. Водночас відмічено зниження рівня аденозинтрифосфорної кислоти, а також активності АТФ-ази у тканині серця. Встановлено збільшення вмісту магнію (активатора АТФ-ази) та цинку (активатора лактатдегідрогенази) в серці експериментальних тварин. Висновок. Результати проведених досліджень вказують на порушення енергетичного забезпечення тканин серцевого м’яза за умов кадмієвої інтоксикації, що підтверджується активацією анаеробного окиснення глюкози, зниженням її рівня та вмісту аденозинтрифосфорної кислоти в міокарді

Plasma-borne indicators of inflammasome activity in Parkinson’s disease patients

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms and loss of dopaminergic neurons of the substantia nigra. Inflammation and cell death are recognized aspects of PD suggesting that strategies to monitor and modify these processes may improve the management of the disease. Inflammasomes are pro-inflammatory intracellular pattern recognition complexes that couple these processes. The NLRP3 inflammasome responds to sterile triggers to initiate pro-inflammatory processes characterized by maturation of inflammatory cytokines, cytoplasmic membrane pore formation, vesicular shedding, and if unresolved, pyroptotic cell death. Histologic analysis of tissues from PD patients and individuals with nigral cell loss but no diagnosis of PD identified elevated expression of inflammasome-related proteins and activation-related “speck” formation in degenerating mesencephalic tissues compared with controls. Based on previous reports of circulating inflammasome proteins in patients suffering from heritable syndromes caused by hyper-activation of the NLRP3 inflammasome, we evaluated PD patient plasma for evidence of inflammasome activity. Multiple circulating inflammasome proteins were detected almost exclusively in extracellular vesicles indicative of ongoing inflammasome activation and pyroptosis. Analysis of plasma obtained from a multi-center cohort identified elevated plasma-borne NLRP3 associated with PD status. Our findings are consistent with others indicating inflammasome activity in neurodegenerative disorders. Findings suggest mesencephalic inflammasome protein expression as a histopathologic marker of early-stage nigral degeneration and suggest plasma-borne inflammasome-related proteins as a potentially useful class of biomarkers for patient stratification and the detection and monitoring of inflammation in PD

Tracking tracer motion in a 4-D electrical resistivity tomography experiment

A new framework for automatically tracking subsurface tracers in electrical resistivity tomography (ERT) monitoring images is presented. Using computer vision and Bayesian inference techniques, in the form of a Kalman filter, the trajectory of a subsurface tracer is monitored by predicting and updating a state model representing its movements. Observations for the Kalman filter are gathered using the maximally stable volumes algorithm, which is used to dynamically threshold local regions of an ERT image sequence to detect the tracer at each time step. The application of the framework to the results of 2-D and 3-D tracer monitoring experiments show that the proposed method is effective for detecting and tracking tracer plumes in ERT images in the presence of noise, without intermediate manual intervention

Spatial monitoring of groundwater drawdown and rebound associated with quarry dewatering using automated time-lapse electrical resistivity tomography and distribution guided clustering

Dewatering systems used for mining and quarrying operations often result in highly artificial and complex groundwater conditions, which can be difficult to characterise and monitor using borehole point sampling approaches. Here automated time-lapse electrical resistivity tomography (ALERT) is considered as a means of monitoring subsurface groundwater dynamics associated with changes in the dewatering regime in an operational sand and gravel quarry. We considered two scenarios: the first was unplanned interruption to dewatering due to a pump failure for a period of several days, which involved comparing ALERT monitoring results before and after groundwater rebound; the second involved a planned interruption to pumping over a period of 6 h, for which near-continuous ALERT monitoring of groundwater rebound and drawdown was undertaken. The results of the second test were analysed using distribution guided clustering (DGC) to provide a more quantitative and objective assessment of changes in the subsurface over time. ALERT successfully identified groundwater level changes during both monitoring scenarios. It provided a more useful indication of the rate of water level rise and maximum water levels than piezometer monitoring results. This was due to the piezometers rapidly responding to pressure changes at depth, whilst ALERT/DGC provided information of slower changes associated with the storage and delayed drainage of water within the sediment. By applying DGC we were able to automatically and quantitatively define changes in the resistivity sections, which correlated well with the direct observations of groundwater at site. For ERT monitoring applications that generate numerous time series, the use of DGC could significantly enhance the efficiency of data interpretation, and provide a means of automating groundwater monitoring through assigning alarm thresholds associated with rapid changes in groundwater conditions

Transcriptional regulation of Saccharomyces cerevisiaeCYS3 encoding cystathionine γ-lyase

In studying the regulation of GSH11, the structural gene of the high-affinity glutathione transporter (GSH-P1) in Saccharomyces cerevisiae, a cis-acting cysteine responsive element, CCGCCACAC (CCG motif), was detected. Like GSH-P1, the cystathionine γ-lyase encoded by CYS3 is induced by sulfur starvation and repressed by addition of cysteine to the growth medium. We detected a CCG motif (−311 to −303) and a CGC motif (CGCCACAC; −193 to −186), which is one base shorter than the CCG motif, in the 5′-upstream region of CYS3. One copy of the centromere determining element 1, CDE1 (TCACGTGA; −217 to −210), being responsible for regulation of the sulfate assimilation pathway genes, was also detected. We tested the roles of these three elements in the regulation of CYS3. Using a lacZ-reporter assay system, we found that the CCG/CGC motif is required for activation of CYS3, as well as for its repression by cysteine. In contrast, the CDE1 motif was responsible for only activation of CYS3. We also found that two transcription factors, Met4 and VDE, are responsible for activation of CYS3 through the CCG/CGC and CDE1 motifs. These observations suggest a dual regulation of CYS3 by factors that interact with the CDE1 motif and the CCG/CGC motifs

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

A tryptophan-rich peptide acts as a transcription activation domain

<p>Abstract</p> <p>Background</p> <p>Eukaryotic transcription activators normally consist of a sequence-specific DNA-binding domain (DBD) and a transcription activation domain (AD). While many sequence patterns and motifs have been defined for DBDs, ADs do not share easily recognizable motifs or structures.</p> <p>Results</p> <p>We report herein that the N-terminal domain of yeast valyl-tRNA synthetase can function as an AD when fused to a DNA-binding protein, LexA, and turn on reporter genes with distinct LexA-responsive promoters. The transcriptional activity was mainly attributed to a five-residue peptide, WYDWW, near the C-terminus of the N domain. Remarkably, the pentapeptide <it>per se </it>retained much of the transcriptional activity. Mutations which substituted tryptophan residues for both of the non-tryptophan residues in the pentapeptide (resulting in W₅) significantly enhanced its activity (~1.8-fold), while mutations which substituted aromatic residues with alanine residues severely impaired its activity. Accordingly, a much more active peptide, pentatryptophan (W₇), was produced, which elicited ~3-fold higher activity than that of the native pentapeptide and the N domain. Further study indicated that W₇mediates transcription activation through interacting with the general transcription factor, TFIIB.</p> <p>Conclusions</p> <p>Since W₇shares no sequence homology or features with any known transcription activators, it may represent a novel class of AD.</p

Where Does Mediator Bind In Vivo?

Background: The Mediator complex associates with RNA polymerase (Pol) II, and it is recruited to enhancer regions by activator proteins under appropriate environmental conditions. However, the issue of Mediator association in yeast cells is controversial. Under optimal growth conditions (YPD medium), we were unable to detect Mediator at essentially any S. cerevisiae promoter region, including those supporting very high levels of transcription. In contrast, whole genome microarray experiments in synthetic complete (SC) medium reported that Mediator associates with many genes at both promoter and coding regions. Principal Findings: As assayed by chromatin immunoprecipitation, we show that there are a small number of Mediator targets in SC medium that are not observed in YPD medium. However, most Mediator targets identified in the genome-wide analysis are false positives that arose for several interrelated reasons: the use of overly lenient cut-offs; artifactual differences in apparent IP efficiencies among different genomic regions in the untagged strain; low fold-enrichments making it difficult to distinguish true Mediator targets from false positives that occur in the absence of the tagged Mediator protein. Lastly, apparent Mediator association in highly active coding regions is due to a non-specific effect on accessibility due to the lack of nucleosomes, not to a specific association of Mediator. Conclusions: These results indicate that Mediator does not bind to numerous sites in the yeast genome, but rathe