Anthropogenic transformation of the valleys of small rivers of the Chuvash Republic

The object of the study is the valleys of small rivers of the Chuvash Republic. The type of economic use, the degree of anthropogenic contamination, modern slope processes are analyzed. The need for research is justified by the deterioration of the ecological state of the landscapes of river valleys, water quality in the watercourses of the Chuvash Republic. In order to collect factual material on the current state of the landscapes of river valleys, expeditions were conducted to the rivers Tsivil, Kubnya, Kirya. Lyulya. The choice of the selected key objects is explained by the fact that they are typical for the physical and geographical regions of the region: the Kubnya River - the Southeastern and Zasursky districts; the Lyulya and Kirya rivers - the Prisursky and Zavolzhsky districts; the Tsivil River – the Volga and Central districts. The data obtained were interpreted for the entire territory of the Chuvash Republic. The analysis of the collected material made it possible to conduct zoning of the region according to the ecological state of river valleys. Four districts were identified: Volga, Central, Forest, Steppe. These areas differ in the degree and types of economic development. The valleys of the Volga region are industrial and agricultural territories, intensively developed. The valleys of the Central District are experiencing an average anthropogenic load from industrial enterprises and irrational agriculture. The valleys of the Forest zone are distinguished by the preservation of natural landscapes and the absence of negative slope processes. The river valleys of the Steppe region are experiencing critical indicators of agricultural development: plowing up to 90% of agricultural land, the absence of natural steppe landscapes. Individual recommendations were developed for each district to improve the ecological state of river valley landscapes and prevent the development of negative processes and emergencies

Release and targeting of polycystin-2-carrying ciliary extracellular vesicles

Extracellular vesicles (EVs) are emerging as a universal means of cell-to-cell communication and hold great potential in diagnostics and regenerative therapies [1]. An urgent need in the field is a fundamental understanding of physiological mechanisms driving EV generation and function. Ciliary EVs act as signaling devices in Chlamydomonas and Caenorhabditis elegans [2, 3, 4]. Mammalian cilia shed EVs to eliminate unwanted receptors [5] or to retract cilia before entering the cell cycle [6]. Here, we used our established C. elegans model to study sensory-evoked ciliary EV release and targeting using a fluorescently labeled EV cargo polycystin-2 (PKD-2). In C. elegans and mammals, the autosomal dominant polycystic kidney disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation [7]. We find that males deposit PKD-2-carrying EVs onto the vulva of the hermaphrodite during mating. We also show that mechanical stimulation triggers release of PKD-2-carrying EVs from cilia. To our knowledge, this is the first report of mechanoresponsive ciliary EV release and of the directional transfer of ciliary EVs from one animal to another animal. Since the polycystins are evolutionarily conserved ciliary EV cargoes, our findings suggest that similar mechanisms for EV release and targeting may occur in other systems and biological contexts

Agroindastrial complex of the Chuvash Republic: intra-regional and All-Russian significance

This paper reveals the current state of various areas of the agro-industrial complex of the Russian region of the Chuvash Republic. Particular attention was paid to comparing a number of parameters characterizing the agro-industrial production of the republic with the corresponding parameters of other areas of the economy of the region, the role of the agro-industrial complex of Chuvashia in the all-Russian agro-industrial production. In the Chuvash Republic, the importance of the agro-industrial complex for the regional economy is often emphasized. Moreover, in the typology of Russian regions in terms of the level and type of economic development, the Chuvash Republic is quite often referred to the category of agro-industrial regions. The paper describes the absence of exceptional natural and climatic advantages for the development of the agro-industrial complex of the region, the relative weakness of the agricultural and agro-industrial sectors of the republic against the background of a number of other regions of Russia. The share of the industry in the structure of GRP and employment in the region is analyzed, while its importance is highlighted against the background of manufacturing industries and the service sector. It also stands out that the modern agro-industrial complex of the Chuvash Republic is of great importance for the socio-economic development of the region and the prospects for further development. However, it is not possible to classify Chuvashia as an agrarian and even agro-industrial region. The most important in the republic is not the agro-industrial complex, but the social infrastructure, industrial infrastructure and industry

Time-resolved analysis of amino acid stress identifies eIF2 phosphorylation as necessary to inhibit mTORC1 activity in liver

Amino acid availability is sensed by GCN2 (general control nonderepressible 2) and mechanistic target of rapamycin complex 1 (mTORC1), but how these two sensors coordinate their respective signal transduction events remains mysterious. In this study we utilized mouse genetic models to investigate the role of GCN2 in hepatic mTORC1 regulation upon amino acid stress induced by a single injection of asparaginase. We found that deletion of Gcn2 prevented hepatic phosphorylation of eukaryotic initiation factor 2α to asparaginase and instead unleashed mTORC1 activity. This change in intracellular signaling occurred within minutes and resulted in increased 5'-terminal oligopyrimidine mRNA translation instead of activating transcription factor 4 synthesis. Asparaginase also promoted hepatic mRNA levels of several genes which function as mTORC1 inhibitors, and these genes were blunted or blocked in the absence of Gcn2, but their timing could not explain the early discordant effects in mTORC1 signaling. Preconditioning mice with a chemical endoplasmic reticulum stress agent before amino acid stress rescued normal mTORC1 repression in the liver of Gcn2-/- mice but not in livers with both Gcn2 and the endoplasmic reticulum stress kinase, Perk, deleted. Furthermore, treating wildtype and Gcn2-/- mice with ISRIB, an inhibitor of PERK signaling, also failed to alter hepatic mTORC1 responses to asparaginase, although administration of ISRIB alone had an inhibitory GCN2-independent effect on mTORC1 activity. Taken together, the data show that activating transcription factor 4 is not required, but eukaryotic initiation factor 2α phosphorylation is necessary to prevent mTORC1 activation during amino acid stress

Role of activating transcription factor 4 in the hepatic response to amino acid depletion by asparaginase

The anti-leukemic agent asparaginase activates the integrated stress response (ISR) kinase GCN2 and inhibits signaling via mechanistic target of rapamycin complex 1 (mTORC1). The study objective was to investigate the protective role of activating transcription factor 4 (ATF4) in controlling the hepatic transcriptome and mediating GCN2-mTORC1 signaling during asparaginase. We compared global gene expression patterns in livers from wildtype, Gcn2 -/-, and Atf4 -/- mice treated with asparaginase or excipient and further explored selected responses in livers from Atf4 +/- mice. Here, we show that ATF4 controls a hepatic gene expression profile that overlaps with GCN2 but is not required for downregulation of mTORC1 during asparaginase. Ingenuity pathway analysis indicates GCN2 independently influences inflammation-mediated hepatic processes whereas ATF4 uniquely associates with cholesterol metabolism and endoplasmic reticulum (ER) stress. Livers from Atf4 -/- or Atf4 +/- mice displayed an amplification of the amino acid response and ER stress response transcriptional signatures. In contrast, reduction in hepatic mTORC1 signaling was retained in Atf4 -/- mice treated with asparaginase

Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice

Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress. Genetic loss of Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR gene targets such as Atf5 and Trib3 failed to increase. Instead, mechanistic target of rapamycin complex 1 (mTORC1) signal transduction was unleashed, and this coincided with liver dysfunction reflected by a failure to maintain hydrogen sulfide production or apolipoprotein B100 (ApoB100) expression. In contrast, obese mice lacking hepatic activating transcription factor 4 (Atf4) showed an exaggerated ISR and greater loss of endogenous hydrogen sulfide but normal inhibition of mTORC1 and maintenance of ApoB100 during asparaginase exposure. In both genetic mouse models, expression and phosphorylation of Sestrin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestrin2. In conclusion, obesity promotes a maladaptive ISR during asparaginase exposure. GCN2 functions to repress mTORC1 activity and maintain ApoB100 protein levels independently of Atf4 expression, whereas hydrogen sulfide production is promoted via GCN2-ATF4 pathway

Anthropogenic transformation of the valleys of small rivers of the Chuvash Republic

The object of the study is the valleys of small rivers of the Chuvash Republic. The type of economic use, the degree of anthropogenic contamination, modern slope processes are analyzed. The need for research is justified by the deterioration of the ecological state of the landscapes of river valleys, water quality in the watercourses of the Chuvash Republic. In order to collect factual material on the current state of the landscapes of river valleys, expeditions were conducted to the rivers Tsivil, Kubnya, Kirya. Lyulya. The choice of the selected key objects is explained by the fact that they are typical for the physical and geographical regions of the region: the Kubnya River - the Southeastern and Zasursky districts; the Lyulya and Kirya rivers - the Prisursky and Zavolzhsky districts; the Tsivil River – the Volga and Central districts. The data obtained were interpreted for the entire territory of the Chuvash Republic. The analysis of the collected material made it possible to conduct zoning of the region according to the ecological state of river valleys. Four districts were identified: Volga, Central, Forest, Steppe. These areas differ in the degree and types of economic development. The valleys of the Volga region are industrial and agricultural territories, intensively developed. The valleys of the Central District are experiencing an average anthropogenic load from industrial enterprises and irrational agriculture. The valleys of the Forest zone are distinguished by the preservation of natural landscapes and the absence of negative slope processes. The river valleys of the Steppe region are experiencing critical indicators of agricultural development: plowing up to 90% of agricultural land, the absence of natural steppe landscapes. Individual recommendations were developed for each district to improve the ecological state of river valley landscapes and prevent the development of negative processes and emergencies

Geoecological risks in the valleys of small rivers of the forest-steppe zone of the Russian plain (on the example of the Chuvash Republic)

The Chuvash Republic belongs to the territories with a high frequency of occurrence of emergency situations of moderate severity. This is due to the intensive economic development of the region. The probability and intensity of the manifestation of georisks is different for individual landscapes, therefore it needs a detailed study. The study includes the study of the probability of the development of slope, climatic, hydrological risks, and the risk of wildfires on the territory of the Chuvash Republic. The analysis showed that the slope type of geoecological risk is confined to the river valleys of the region and has maximum values in the north of the Chuvash Republic. A high risk of flooding and flooding exists in the valleys of major rivers of the region (Volga, Sura) and their tributaries of the first order. On other watercourses, the hydrological risk is not significant. Climate and weather risks are associated with hurricane winds and dry winds. The southeastern part of the region suffers the most from them. The risk of fires depends on the composition and age of the stand. The maximum risk values are typical for the Prisursky forest area (southern and southwestern parts of the region). Based on the data obtained, the classification of the districts of the Chuvash Republic by the size of the georisks was carried out. Four groups of districts were identified according to the probability of natural emergencies and the main factors of their occurrence were described

Agroindastrial complex of the Chuvash Republic: intra-regional and All-Russian significance

This paper reveals the current state of various areas of the agro-industrial complex of the Russian region of the Chuvash Republic. Particular attention was paid to comparing a number of parameters characterizing the agro-industrial production of the republic with the corresponding parameters of other areas of the economy of the region, the role of the agro-industrial complex of Chuvashia in the all-Russian agro-industrial production. In the Chuvash Republic, the importance of the agro-industrial complex for the regional economy is often emphasized. Moreover, in the typology of Russian regions in terms of the level and type of economic development, the Chuvash Republic is quite often referred to the category of agro-industrial regions. The paper describes the absence of exceptional natural and climatic advantages for the development of the agro-industrial complex of the region, the relative weakness of the agricultural and agro-industrial sectors of the republic against the background of a number of other regions of Russia. The share of the industry in the structure of GRP and employment in the region is analyzed, while its importance is highlighted against the background of manufacturing industries and the service sector. It also stands out that the modern agro-industrial complex of the Chuvash Republic is of great importance for the socio-economic development of the region and the prospects for further development. However, it is not possible to classify Chuvashia as an agrarian and even agro-industrial region. The most important in the republic is not the agro-industrial complex, but the social infrastructure, industrial infrastructure and industry