EARLY STAGE OF THE CENTRAL ASIAN OROGENIC BELT BUILDING: EVIDENCES FROM THE SOUTHERN SIBERIAN CRATON

The origin of the Central-Asian Orogenic Belt (CAOB), especially of its northern segment nearby the southern margin of the Siberian craton (SC) is directly related to development and closure of the Paleo-Asian Ocean (PAO). Signatures of early stages of the PAO evolution are recorded in the Late Precambrian sedimentary successions of the Sayan-Baikal-Patom Belt (SBPB) on the southern edge of SC. These successions are spread over 2000 km and can be traced along this edge from north-west (Sayan area) to south-east (Baikal area) and further to north-east (Patom area). Here we present the synthesis of all available and reliable LA-ICP-MS U-Pb geochronological studies of detrital zircons from these sedimentary successions.The origin of the Central-Asian Orogenic Belt (CAOB), especially of its northern segment nearby the southern margin of the Siberian craton (SC) is directly related to development and closure of the Paleo-Asian Ocean (PAO). Signatures of early stages of the PAO evolution are recorded in the Late Precambrian sedimentary successions of the Sayan-Baikal-Patom Belt (SBPB) on the southern edge of SC. These successions are spread over 2000 km and can be traced along this edge from north-west (Sayan area) to south-east (Baikal area) and further to north-east (Patom area). Here we present the synthesis of all available and reliable LA-ICP-MS U-Pb geochronological studies of detrital zircons from these sedimentary successions

Determination of water content in clay and organic soil using microwave oven

The article deals with the techniques of soil water content determination using microwave radiation. Its practical application would allow solving the problems of resource efficiency in geotechnical survey due to reduction of energy and resource intensity of laboratory analysis as well as its acceleration by means of decreasing labour intensity and, as a result, cost reduction. The article presents a detail analysis of approaches to soil water content determination and soil drying, considers its features and application. The study in soil of different composition, typical for Western Siberia including organic and organic-mineral ones, is a peculiarity of the given article, which makes it rather topical. The article compares and analyzes the results of the investigation into soil water content, which are obtained via conventional techniques and the original one developed by the authors, consisting in microwave drying. The authors also give recommendation on microwave technique application to dry soil

ВАЛЕНТИН СЕРГЕЕВИЧ ФЕДОРОВСКИЙ – КОРИФЕЙ CИБИРСКОЙ ГЕОЛОГИИ

The publication is devoted to the 80 anniversary of Valentin S. Fedorovsky, the coryphaeus of Siberian geology.Cтатья посвящена 80-летнему юбилею Валентина Сергеевича Федоровского, корифея Сибирской геологии

Влияние нозокомиальной инфекции на тяжесть течения и исход заболевания у пациентов с COVID-19 тяжелого и крайне тяжелого течения

The mechanisms of development of nosocomial infectious complications in COVID-19 and the contribution of bacterial and mycotic superinfection to the formation of extremely high mortality among patients with severe and extremely severe course of this disease have not yet been fully revealed. The objective: to study epidemiology, risk factors for the development of nosocomial superinfection, and its effect on the severity and outcome of the disease in patients with COVID-19.Subjects and Methods. 383 cases of severe and extremely severe COVID-19 were retrospectively analyzed. Demographic data, the presence of concomitant diseases, community-acquired co-infection at the time of hospitalization, data on the methods used to treat new coronavirus infection, severity of the course of the disease, developed infectious complications and their etiology, and the disease outcome were studied. Risk factors for the development of secondary infectious complications and the contribution of nosocomial superinfection to the severity of COVID-19 and the disease outcome were evaluated.Results. Risk factors for the development of secondary infectious complications include age over 65 years (OR 1.04; 95% CI 1.03–1.06; p < 0.0001), concomitant cardiovascular pathology (OR 3.82; 95% CI 2.02‒7.19; p < 0.0001), chronic kidney disease, including requiring renal replacement therapy (OR 2.01; 95% CI 1.33–3.02; p = 0.0007), and glucocorticoid therapy (OR 1.62; 95% CI 1.02–2.69; p = 0.04). The development of nosocomial infectious complications in patients with COVID-19 is associated with a more severe course of the disease and unfavorable prognosis (OR 13.44; 95% CI 8.23‒21.92; p < 0.0001).Conclusion. Identification of risk factors for the development of secondary infectious complications in COVID-19 allows developing differentiated approaches to the pathogenetic treatment of patients with severe COVID-19, increasing alertness in terms of the development of nosocomial infections, ensuring their timely diagnosis and treatment.Механизмы развития нозокомиальных инфекционных осложнений при COVID-19 и вклад бактериальной и микотической суперинфекции в формирование крайне высокой смертности среди пациентов с тяжелым и крайне тяжелым течением этого заболевания до сих пор в полной мере не раскрыты.Цель исследования: изучить эпидемиологию, факторы риска развития нозокомиальной суперинфекции и ее влияние на тяжесть течения и исход заболевания у пациентов с COVID-19.Материал и методы. Ретроспективно проанализировано 383 случая COVID-19 тяжелого и крайне тяжелого течения. Изучены демографические данные, наличие сопутствующих заболеваний, внебольничной коинфекции на момент госпитализации, данные о примененных методах лечения новой коронавирусной инфекции, тяжести течения заболевания, развившихся инфекционных осложнениях и их этиологии, исходе заболевания. Оценке подвергнуты факторы риска развития вторичных инфекционных осложнений и вклад нозокомиальной суперинфекции в тяжесть течения COVID-19 и исход заболевания.Результаты. К факторам риска развития вторичных инфекционных осложнений можно отнести возраст более 65 лет (ОШ 1,04; 95%-ный ДИ 1,03–1,06; p < 0,0001), сопутствующую сердечно-сосудистую патологию (ОШ 3,82; 95%-ный ДИ 2,02–7,19; p < 0,0001), хроническую болезнь почек, в том числе требующую заместительной почечной терапии (ОШ 2,01; 95%-ный ДИ 1,33–3,02; p = 0,0007), терапию глюкокортикоидами (ОШ 1,62; 95%-ный ДИ 1,02–2,69; p = 0,04). Развитие нозокомиальных инфекционных осложнений у пациентов с COVID-19 ассоциировано с более тяжелым течением заболевания и неблагоприятным прогнозом (ОШ 13,44; 95%-ный ДИ 8,23–21,92; p < 0,0001).Заключение. Выявление факторов риска развития вторичных инфекционных осложнений при COVID-19 позволит выработать дифференцированные подходы к патогенетическому лечению больных с тяжелым течением COVID-19, повысить настороженность в плане развития нозокомиальных инфекций, обеспечить их своевременную диагностику и лечение

Characterizing model errors in chemical transport modeling of methane: using GOSAT XCH4_{4} data with weak-constraint four-dimensional variational data assimilation

We examined biases in the global GEOS-Chem chemical transport model for the period of February–May 2010 using weak-constraint (WC) four-dimensional variational (4D-Var) data assimilation and dry-air mole fractions of CH$_{4}$ (XCH$_{4}$) from the Greenhouse gases Observing SATellite (GOSAT). The ability of the observations and the WC 4D-Var method to mitigate model errors in CH$_{4}$ concentrations was first investigated in a set of observing system simulation experiments (OSSEs). We then assimilated the GOSAT XCH$_{4}$ retrievals and found that they were capable of providing information on the vertical structure of model errors and of removing a significant portion of biases in the modeled CH$_{4}$ state. In the WC 4D-Var assimilation, corrections were added to the modeled CH$_{4}$ state at each model time step to account for model errors and improve the model fit to the assimilated observations. Compared to the conventional strong-constraint (SC) 4D-Var assimilation, the WC method was able to significantly improve the model fit to independent observations. Examination of the WC state corrections suggested that a significant source of model errors was associated with discrepancies in the model CH$_{4}$ in the stratosphere. The WC state corrections also suggested that the model vertical transport in the troposphere at middle and high latitudes is too weak. The problem was traced back to biases in the uplift of CH$_{4}$ over the source regions in eastern China and North America. In the tropics, the WC assimilation pointed to the possibility of biased CH$_{4}$ outflow from the African continent to the Atlantic in the mid-troposphere. The WC assimilation in this region would greatly benefit from glint observations over the ocean to provide additional constraints on the vertical structure of the model errors in the tropics. We also compared the WC assimilation at 4° × 5° and 2° × 2.5° horizontal resolutions and found that the WC corrections to mitigate the model errors were significantly larger at 4° × 5° than at 2° × 2.5° resolution, indicating the presence of resolution-dependent model errors. Our results illustrate the potential utility of the WC 4D-Var approach for characterizing model errors. However, a major limitation of this approach is the need to better characterize the specified model error covariance in the assimilation scheme

Особенностью течения тяжелых форм СOVID-19 является высокий уровень воспаления, требующий применения дополнительных диагностических технологий для уточнения вызывающей его причины

Subjects and methods. The retrospective study included 37 patients (n = 37) diagnosed with severe viral pneumonia (SARS-CoV2) who were treated in the intensive care unit of Pavlov First Saint Petersburg State Medical University. To assess the significance of PADM as a biomarker of bacterial infection, patients were divided into two groups: the group of patients with viral pneumonia without sepsis (n = 24) and the group of those who developed sepsis and septic shock complicating the course of the new coronavirus infection (n = 13). PADM was assessed as a criterion for the severity of the disease in the groups of deceased (n = 19) and survivors (n = 18). Data were statistically processed in the computer mathematics system R, version 3.6.2, the prognostic significance of PADM was assessed using linear regression.Results. The median PADM in the group without sepsis was higher than the reference value – 1.1 (0.5; 4.3) nmol/L, in patients with sepsis that complicated the course of viral pneumonia – 2.8 (1.1; 5.7) nmol/L (p = 0.0019). Significant differences were revealed between the baseline levels of PADM in patients with different outcomes: in the surviving group, the median was 0.99 (0.5; 3.14) nmol/L, and in the group of deceased – 2.70 (0.94; 5.86 ) nmol/L. In surviving patients, the changes in PADM levels had a linear distribution throughout the entire period of stay in the intensive care unit. In deceased patients, within 20 days before death, PADM tended to grow significantly and reached its maximum by the time of the outcome.Conclusion. The assessment of the PADM blood level can be used to clarify the addition of a bacterial infection in patients with pneumonia caused by the SARS-CoV2 virus. The study of changes in its level makes it possible to objectify the prediction of the course of COVID-19 – favorable or unfavorable. Data accumulation is required to clarify specific PADM values that predict the outcome in COVID-19 patients. Цель: изучить информационную значимость проадреномедуллина (ПАДМ) у пациентов с новой коронавирусной инфекцией COVID-19.Материалы и методы. В ретроспективное исследование включено 37 пациентов (n = 37) с подтвержденным диагнозом вирусной пневмонии (SARS-CoV2) тяжелого течения, проходивших лечение в отделении реанимации и интенсивной терапии ПСПбГМУ им. акад. И. П. Павлова. Для оценки значимости ПАДМ как биомаркера бактериальной инфекции пациентов разделили на две группы: с вирусной пневмонией без сепсиса (n = 24) и с развитием сепсиса и септического шока, осложнивших течение новой коронавирусной инфекции (n = 13). Оценку ПАДМ как критерия тяжести течения заболевания проводили в группах умерших (n = 19) и выживших (n = 18). Статистическую обработку данных выполняли в системе компьютерной математики R версии 3.6.2, оценку прогностической значимости ПАДМ ‒ с помощью линейной регрессии.Результаты. Медиана ПАДМ в группе без сепсиса была выше референсного значения ‒ 1,1 (0,5; 4,3) нмоль/л, у пациентов с сепсисом, осложнившим течение вирусной пневмонии, ‒ 2,8 (1,1; 5,7) нмоль/л (p = 0,0019). Выявлены значимые различия между исходными уровнями ПАДМ у больных с разным исходом: в группе выживших медиана составила 0,99 (0,5;3,14) нмоль/л, а в группе умерших ‒ 2,70 (0,94; 5,86) нмоль/л. У выживших пациентов динамика показателя имела линейное распределение в течение всего периода пребывания в отделении реанимации и интенсивной терапии. У умерших пациентов в течение 20 сут до летального исхода наблюдалась тенденция к значимому нарастанию показателя, который достигал максимума к моменту исхода.Заключение. Оценку уровня ПАДМ в крови можно использовать для уточнения факта присоединения бактериальной инфекции у пациентов с пневмонией, вызванной вирусом SARS-CoV2. Исследование его концентрации в динамике позволяет объективизировать представление о направленности течения COVID-19 – благоприятном или неблагоприятном. Для уточнения конкретных значений ПАДМ, позволяющих прогнозировать исход у пациентов с COVID-19, требуется накопление данных.

Plasma cytokines in patients with COVID-19 during acute phase of the disease and following complete recovery

COVID-19, an infection caused by the new coronavirus SARS-CoV-2, is associated with a number of pathophysiological mechanisms, mobilizing a wide spectrum of biomolecules, mainly, cytokines.The purpose of this study was to evaluate levels of multiple cytokines in blood plasma from the patients with COVID-19 during acute phase of the disease, and upon complete recovery. Samples of peripheral blood plasma of 56 patients with COVID-19, 69 convalescents and 10 healthy individuals were examined. Concentrations of 46 molecules, such as IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A/CTLA8, IL-17-E/IL-25, IL-17F, IL-18, IL-22, IL-27, IFNα2, IFNγ, TNFα, TNFβ/ Lymphotoxin-α (LTA), CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine, IL-1ra, IL-10, EGF, FGF-2/FGF-basic, Flt3 Ligand, G-CSF, M-CSF, GM-CSF, PDGF-AA, PDGF-AB/ BB, TGF-α, VEGF-A were measured via xMAP multiplexing technology. Significantly increased levels of 18 cytokines were found in blood plasma from COVID-19 patients during acute phase of the disease (as compared to control group), i.e., IL-6, IL-7, IL-15, IL-27, TNFα, TNFβ/Lymphotoxin-α (LTA), CCL2/MCP-1, CCL7/MCP-3, CXCL1/GROα, CXCL8/IL-8, CXCL10/IP-10, CXCL9/MIG, IL-1rа, IL-10, M-CSF, GM-CSF, VEGF-A. We found a significant decrease of nearly all the mentioned cytokines in recovered patients, in comparison with those who had moderate, severe/extremely severe disease. Moreover, we revealed a significantly decreased level of 8 cytokines in plasma from convalescents, as compared with control group, i.e., IL-1α, IL-2, IL-9, IL-12 p40, IL-18, CCL22/MDC, Flt3 Ligand, TGF-α. Immune response caused by SARS-CoV-2 infection involves multiple cytokines, mostly, with pro-inflammatory effects. We have shown for the first time that the convalescence phase is characterized by significantly lower levels of cytokines which regulate cellular differentiation and hematopoiesis (in particular, lymphocytes, T-cells and NK-cells). Over acute phase of the disease, the levels of these cytokines did not change. We revealed a significant decrease of most plasma cytokines upon recovery as compared to acute phase. On the contrary, acute phase of the disease is accompanied by significant increase of both pro- and antiinflammatory cytokines in blood plasma

TBC1D3, a Hominoid-Specific Gene, Delays IRS-1 Degradation and Promotes Insulin Signaling by Modulating p70 S6 Kinase Activity

Insulin/IGF-1 signaling plays a pivotal role in the regulation of cellular homeostasis through its control of glucose metabolism as well as due to its effects on cell proliferation. Aberrant regulation of insulin signaling has been repeatedly implicated in uncontrolled cell growth and malignant transformations. TBC1D3 is a hominoid specific gene previously identified as an oncogene in breast and prostate cancers. Our efforts to identify the molecular mechanisms of TBC1D3-induced oncogenesis revealed the role of TBC1D3 in insulin/IGF-1 signaling pathway. We document here that TBC1D3 intensifies insulin/IGF-1-induced signal transduction through intricate, yet elegant fine-tuning of signaling mechanisms. We show that TBC1D3 expression substantially delayed ubiquitination and degradation of insulin receptor substrate-1 (IRS-1). This effect is achieved through suppression of serine phosphorylation at S636/639, S307 and S312 of IRS-1, which are key phosphorylation sites required for IRS-1 degradation. Furthermore, we report that the effect of TBC1D3 on IRS-1:S636/639 phosphorylation is mediated through TBC1D3-induced activation of protein phosphatase 2A (PP2A), followed by suppression of T389 phosphorylation on p70 S6 kinase (S6K). TBC1D3 specifically interacts with PP2A regulatory subunit B56γ, indicating that TBC1D3 and PP2A B56γ operate jointly to promote S6K:T389 dephosphorylation. These findings suggest that TBC1D3 plays an unanticipated and potentially unique role in the fine-tuning of insulin/IGF-1 signaling, while providing novel insights into the regulation of tumorigenesis by a hominoid-specific protein

Glucose-induced posttranslational activation of protein phosphatases PP2A and PP1 in yeast

The protein phosphatases PP2A and PP1 are major regulators of a variety of cellular processes in yeast and other eukaryotes. Here, we reveal that both enzymes are direct targets of glucose sensing. Addition of glucose to glucose-deprived yeast cells triggered rapid posttranslational activation of both PP2A and PP1. Glucose activation of PP2A is controlled by regulatory subunits Rts1, Cdc55, Rrd1 and Rrd2. It is associated with rapid carboxymethylation of the catalytic subunits, which is necessary but not sufficient for activation. Glucose activation of PP1 was fully dependent on regulatory subunits Reg1 and Shp1. Absence of Gac1, Glc8, Reg2 or Red1 partially reduced activation while Pig1 and Pig2 inhibited activation. Full activation of PP2A and PP1 was also dependent on subunits classically considered to belong to the other phosphatase. PP2A activation was dependent on PP1 subunits Reg1 and Shp1 while PP1 activation was dependent on PP2A subunit Rts1. Rts1 interacted with both Pph21 and Glc7 under different conditions and these interactions were Reg1 dependent. Reg1-Glc7 interaction is responsible for PP1 involvement in the main glucose repression pathway and we show that deletion of Shp1 also causes strong derepression of the invertase gene SUC2. Deletion of the PP2A subunits Pph21 and Pph22, Rrd1 and Rrd2, specifically enhanced the derepression level of SUC2, indicating that PP2A counteracts SUC2 derepression. Interestingly, the effect of the regulatory subunit Rts1 was consistent with its role as a subunit of both PP2A and PP1, affecting derepression and repression of SUC2, respectively. We also show that abolished phosphatase activation, except by reg1Δ, does not completely block Snf1 dephosphorylation after addition of glucose. Finally, we show that glucose activation of the cAMP-PKA (protein kinase A) pathway is required for glucose activation of both PP2A and PP1. Our results provide novel insight into the complex regulatory role of these two major protein phosphatases in glucose regulation

Ruxolitinib versus Dexamethasone in Hospitalized Adults with Covid-19: multicenter matched-controlled study

Abstract Background Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Both janus kinase (JAK) inhibitor, baricitinib, and dexamethasone demonstrated the reduction of mortality. In this matched control study we compared dexamethasone to another JAK inhibitor, ruxolitinib. Methods The study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by 29 clinical and laboratory parameters predicting survival. Results Ruxolitinib treatment in the general cohort of patients was associated with equivalent to dexamethasone mortality rate: 9,6% (95% CI 4,6-14,6%) vs 13,0% (95% CI 7,5-18,5%, superiority p=0.35, non-inferiority p=0.0137), respectively. Time to discharge without oxygen support requirement was also not different between these groups: 13 vs 11 days (p=0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated reduced mortality in ruxolitnib-treated patients with febrile fever (OR 0.33, 95%CI 0.11-1.00). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p=0.042), ruxolitinib therapy was associated with better safety profile due to reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p=0.025). Conclusions Ruxolitinib may be an alternative anti-cytokine therapy with comparable efficacy in patients with potential risks of steroid administration. Patients with febrile fever at admission may benefit from ruxolitinib administration. Funding Ruxolitinib was obtained from Novartis through Managed Access Program (MAP)