Numerical modelling of post-seismic rupture propagation after the Sumatra 26.12.2004 earthquake constrained by GRACE gravity data

In the last decades, the development of the surface and satellite geodetic and geophysical observations brought a new insights into the seismic cycle, documenting new features of inter-, co-, and post-seismic processes. In particular since 2002 satellite mission GRACE provides monthly models of the global gravity field with unprecedented accuracy showing temporal variations of the Earth's gravity field, including those caused by mass redistribution associated with earthquake processes. When combined with GPS measurements, these new data have allowed to assess the relative importance of afterslip and viscoelastic relaxation after the Sumatra 26.12.2004 earthquake. Indeed the observed post-seismic crustal displacements were fitted well by a viscoelastic relaxation model assuming Burgers body rheology for the asthenosphere (60-220 km deep) with a transient viscosity as low as 4× 1017 Pas and constant∼1019 Pas steady state viscosity in the 60-660-km depth range. However, even the low-viscosity asthenosphere provides the amplitude of strain which gravity effect does not exceed 50 per cent of the GRACE gravity variations, thus additional localized slip of about 1 m was suggested at downdip extension of the coseismic rupture. Post-seismic slip at coseismic rupture or its downdip extension has been suggested by several authors but the mechanism of the post-seismic fault propagation has never been investigated numerically. Depth and size of localized slip area as well as rate and time decay during the post-seismic stage were either assigned a priory or estimated by fitting real geodesy or gravity data. In this paper we investigate post-seismic rupture propagation by modelling two consequent stages. First, we run a long-term, geodynamic simulation to self-consistently produce the initial stress and temperature distribution. At the second stage, we simulate a seismic cycle using results of the first step as initial conditions. The second short-term simulation involves three substeps, including additional stress accumulation after part of the subduction channel was locked; spontaneous coseismic slip; formation and development of damage zones producing afterslip. During the last substep post-seismic stress leads to gradual∼1 m slip localized at three faults around∼100-km downdip extension of the coseismic rupture. We used the displacement field caused by the slip to calculate pressure and density variations and to simulate gravity field variations. Wavelength of calculated gravity anomaly fits well to that of the real data and its amplitude provides about 60 per cent of the observed GRACE anomaly. Importantly, the surface displacements caused by the estimated afterslip are much smaller than those registered by GPS networks. As a result cumulative effect of Burgers rheology viscoelastic relaxation (which explains measured GPS displacements and about a half of gravity variations) plus post-seismic slip predicted by damage rheology model (which causes much smaller surface displacements but provides another half of the GRACE gravity variations) fits well to both sets of the real data. Hence, the presented numerical modelling based on damage rheology supports the process of post-seismic downdip rupture propagation previously hypothesized from the GRACE gravity dat

Numerical modelling of post-seismic rupture propagation after the Sumatra 26.12.2004 earthquake constrained by GRACE gravity data

International audienceIn the last decades, the development of the surface and satellite geodetic and geophysical observations brought a new insights into the seismic cycle, documenting new features of inter-, co-, and post-seismic processes. In particular since 2002 satellite mission GRACE provides monthly models of the global gravity field with unprecedented accuracy showing temporal variations of the Earth's gravity field, including those caused by mass redistribution associated with earthquake processes. When combined with GPS measurements, these new data have allowed to assess the relative importance of afterslip and viscoelastic relaxation after the Sumatra 26.12.2004 earthquake. Indeed the observed post-seismic crustal displacements were fitted well by a viscoelastic relaxation model assuming Burgers body rheology for the asthenosphere (60–220 km deep) with a transient viscosity as low as 4 × 10^17 Pas and constant ~ 10^19 Pas steady state viscosity in the 60–660-km depth range. However, even the low-viscosity asthenosphere provides the amplitude of strain which gravity effect does not exceed 50 per cent of the GRACE gravity variations, thus additional localized slip of about 1 m was suggested at downdip extension of the coseismic rupture. Post-seismic slip at coseismic rupture or its downdip extension has been suggested by several authors but the mechanism of the post-seismic fault propagation has never been investigated numerically. Depth and size of localized slip area as well as rate and time decay during the post-seismic stage were either assigned a priory or estimated by fitting real geodesy or gravity data. In this paper we investigate post-seismic rupture propagation by modelling two consequent stages. First, we run a long-term, geodynamic simulation to self-consistently produce the initial stress and temperature distribution. At the second stage, we simulate a seismic cycle using results of the first step as initial conditions. The second short-term simulation involves three substeps, including additional stress accumulation after part of the subduction channel was locked; spontaneous coseismic slip; formation and development of damage zones producing afterslip. During the last substep post-seismic stress leads to gradual ~1 m slip localized at three faults around ~100-km downdip extension of the coseismic rupture. We used the displacement field caused by the slip to calculate pressure and density variations and to simulate gravity field variations. Wavelength of calculated gravity anomaly fits well to that of the real data and its amplitude provides about 60 per cent of the observed GRACE anomaly. Importantly, the surface displacements caused by the estimated afterslip are much smaller than those registered by GPS networks. As a result cumulative effect of Burgers rheology viscoelastic relaxation (which explains measured GPS displacements and about a half of gravity variations) plus post-seismic slip predicted by damage rheology model (which causes much smaller surface displacements but provides another half of the GRACE gravity variations) fits well to both sets of the real data. Hence, the presented numerical modelling based on damage rheology supports the process of post-seismic downdip rupture propagation previously hypothesized from the GRACE gravity data

МИКРОСАТЕЛЛИТНАЯ НЕСТАБИЛЬНОСТЬ КАК МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИЙ МАРКЕР НАРУШЕНИЯ СИСТЕМЫ РЕПАРАЦИИ ОШИБОЧНО СПАРЕННЫХ НУКЛЕОТИДОВ ПРИ РАКЕ ПИЩЕВОДА

Esophageal cancer is an aggressive form of cancer. Adenocarcinoma and squamous cell carcinoma are the most common histological types of esophageal cancer, with the incidence rate showing an upward tendency. Although endoscopic biopsy is considered the «gold standard» for diagnosis of esophageal cancer, both falsepositive and false-negative results can occur, therefore, the predictive and prognostic molecular markers in outcome of esophageal cancer are required. Although the molecular events involved in esophageal cancer pathogenesis are still poor understood, there have been reports on histological and genetic changes, such as DNA aberrant methylation and copy number variation, changes in DNA stability, its expression and etc. This review summarizes various investigations aimed at studying genomic instability (microsatellite instability, MSI), which predisposes the cell to malignant transformation. The mechanisms of interaction between the mismatch repair and miRNA expression in esophageal cancer have been studied. Recent advances in genomic and molecular studies of MSI+ cancers can successfully complement the histological assessment and help to develop novel therapeutic approaches to cancer treatment.Рак пищевода (РП) является агрессивной по течению и прогнозу злокачественной эпителиальной опухолью. Аденокарцинома и плоскоклеточный рак относятся к наиболее распространенным гистотипам злокачественных новообразований пищевода с постоянной тенденцией к увеличению роста заболеваемости. Существующая система оценки риска развития онкопатологии с помощью эндоскопической биопсии, оставаясь общепризнанным «золотым стандартом» диагностики, приводит как к ложноположительным, так и ложноотрицательным результатам и поэтому нуждается в дополнительных методах предиктивной диагностики и выявлении фундаментальных механизмов онкотрансформации тканей. Молекулярные события, которые контролируют процессы малигнизации тканей пищевода, не полностью ясны, однако описаны несколько гистологических и одновременно генетических изменений, характерных для аденокарциномы и плоскоклеточного рака пищевода: аберрантные метилирование и копийность ДНК, изменение стабильности ДНК, её экспрессии и т. п. В настоящем обзоре обобщены исследования, направленные на изучение нестабильности генома клеток (микросателлитной нестабильности, MSI), трансформированных в опухолевые. Рассмотрены механизмы взаимодействия между комплексом мисматч-репарации и микро-РНК, NGS исследования микросателлитной нестабильности при раке пищевода. Последние достижения геномных и молекулярных исследований MSI+ раков могут успешно дополнить гистологический анализ на уровне предиктивной диагностики и помочь в разработке новых терапевтических подходов к лечению

Rapid ecological change in the coastal zone of Lake Baikal (East Siberia): Is the site of the world\u27s greatest freshwater biodiversity in danger?

Ecological degradation of the benthic littoral zone is an emerging, urgent problem at Lake Baikal (East Siberia), the most species-rich lake on Earth. Within the last five years, multiple changes have occurred in the nearshore benthos where most of the lake\u27s endemic species reside. These changes include proliferation of benthic algae, deaths of snails and endemic sponges, large coastal wash-ups of dead benthic algae and macrophytes, blooms of toxin-producing benthic cyanobacteria, and inputs of industrial contaminants into parts of the lake. Some changes, such as massive coastal accumulations of benthic algae, are currently shared with the Laurentian Great Lakes (LGLs); however, the drivers of these changes differ between Lake Baikal and the LGLs. Coastal eutrophication from inputs of untreated sewage is causing problems at multiple sites in Lake Baikal, whereas in the LGLs, invasive dreissenid mussels redirect pelagic nutrients to the littoral substrate. At other locations in Lake Baikal, ecological degradation may have different causes including water level fluctuations and the input of toxic industrial contaminants. Importantly, the recent deterioration of the benthic littoral zone in both Lake Baikal and the LGLs has occurred while little change has occurred offshore. This highlights the necessity of monitoring both the littoral and pelagic zones of large lakes for assessing ecosystem health, change and conservation

АБЕРРАНТНОЕ МЕТИЛИРОВАНИЕ ПРОМОТОРНЫХ УЧАСТКОВ ГЕНОВ APC, CDH13 И MGMT У БОЛЬНЫХ КОЛОРЕКТАЛЬНЫМ РАКОМ

Aberrant methylation of gene promoter regions is the main epigenetic change characterizing colorectal cancer. Methylation levels of 42 CpG-sites of promoter regions of the MGMT, APC and CDH13 genes in colorectal cancer were studied in comparison with methylation levels of the adjacent normal tissue in 25 patients. Pyrosequencing showed an increase in methylation levels of promoter regions of the MGMT, APC and CDH13 genes in tumor samples by 3 to 5 times. These tumor samples were screened for activating SNP-mutations in the KRAS (40 %), NRAS (0 %) and BRAF (0 %) oncogenes. SNP-mutations in the KRAS gene were accompanied by hypermethylation of one or more promoters of the studied genes. Association of this epigenetic index with tumor metastasis was proved. The data on an increase in methylation of the promoter regions of oncosupressor genes can be used as sensitive prognostic markers of progression and metastasis of colorectal cancer.Аберрантное метилирование промоторных участков генов – основное эпигенетическое изменение, характеризующее колоректальные неопластические образования. В настоящей работе был исследован количественный уровень метилирования 42 CpG-сайтов промоторных участков генов MGMT, APC и CDH13 в опухолях толстой кишки по отношению к уровню метилирования прилежащей условно нормальной ткани 25 пациентов. С помощью метода пиросеквенирования выявлено повышение уровня метилирования промоторных участков генов MGMT, APC и CDH13 в опухолевых образцах от 3 до 5 раз. В этих же образцах опухолей проведен скрининг активирующих SNP-мутаций в онкогенах KRAS (40 %), NRAS (0 %) и BRAF (0 %). Наличие SNP-мутаций в гене KRAS сопровождалось гиперметилированием одного или более промоторов исследованных генов. Доказана ассоциация этого эпигенетического показателя с метастазированием опухоли. Полученные данные об увеличении метилирования промоторных участков генов-онкосупрессоров могут быть использованы в качестве чувствительных прогностических маркеров прогрессирования и метастазирования колоректального рака

ВЛИЯНИЕ ИМПУЛЬСНЫХ МАГНИТНЫХ ПОЛЕЙ НА ЭКСПРЕССИЮ ГЕНОВ ОНКОСУПРЕССОРОВ В ЭКСПЕРИМЕНТЕ НА КУЛЬТУРЕ КЛЕТОК ГЛИОБЛАСТОМЫ ЧЕЛОВЕКА T98G

Aim: to study the effect of a pulsed magnetic field (PMF) on the expression of key tumor suppressor genes, such as aPc, MLH, and MGMt in human t98G glioblastoma cell line. material and methods. the PMF with the intensity of 15 and 300 mt was used alone and in combination with ionizing radiation at a single dose of 10 Gy. to perform ionizing radiation, theratron Equinox 60co unit Best theratronics Ltd., Ottawa, canada) was used. the source of the pulsed magnetic field was Neuro-Ms / D therapeutic advanced device of the Neurosoft company. Live and dead cells were determined in NanoEntekJuliFl cell counter (Korea) using a 0.4 % trypan blue solution to stain dead cells. total RNa was extracted according to the protocol of the manufacturer trizol with changes: the aqueous phase was separated with trizol reagent twice. the quantitative measurement of the isolated RNa was carried out on a Qubit 2.0 fluorimeter using a kit of reagents with the Quant-it RNa assayKit RNa intercalating dye (Life technologies, usa). the expression of MLH, aPc, and MGMt genes was evaluated by Rt-PcR using a cFx96 amplifier (BioRad, usa). Data were analyzed using the cycle threshold (ct) method with normalization for tBP gene expression in each sample. Relative expression of the genetic locus (Exp) was calculated by the 2-Δct method. statistical analysis of the results was carried out using the statictica v10 software package. Results. One day after exposure to PMF, significant differences in the MGMt expression level compared to the control were found (p<0.05). a significant decrease in the transcriptional activity of the MGMt gene in glioblastoma cells was observed with PMF intensity of 15 mt, and correlated with the cell mortality rate. No changes in the mortality rate were observed after radiation exposure combined with 15 mt PMF. However, the mortality rate decreased from 18.7 % to 15 % after radiation exposure combined with 300 mt PMF. Conclusion. the effect of reduction in the transcriptional activity of MGMt in t98G glioblastoma cells and the effect of PMF as a monofactor on their viability characterize the magnetic susceptibility of tumor cell mechanisms. Given the multidirectional nature of the combined interaction of ionizing radiation and PMF, it is necessary to emphasize the importance of choosing and justifying the role of biotropic parameters of PMF in order to exclude a negative effect on the treatment.Цель исследования – изучить влияние импульсного магнитного поля (ИМП) на экспрессию ключевых генов онкосупрессоров aPc, MLH, MGMt клеточной линии глиобластомы человека t98G. Материал и методы. На культуре клеток t98G проведено воздействие ИМП с параметрами индукции 15 и 300 mt как самостоятельно, так и в сочетании с воздействием ионизирующего излучения (РОД 10 Гр). Ионизирующее излучение проводилось на аппарате theratronEquinox фирмы Besttheratronics, где в качестве источника излучения использовался 60Со. Источником импульсного магнитного поля служил аппарат «Нейро-МС/Д терапевтический расширенный» компании «Нейрософт». Определение живых/мертвых клеток проводили в счетчике клеток NanoEntekJuliFl (Корея) с использованием 0,4 % раствора трипанового синего для окраски мертвых клеток. Экстракцию тотальной РНК проводили по протоколу изготовителя trizol с изменениями: водную фазу сепарировали с реагентом trizol дважды. Количественное измерение выделенной РНК проводили на флюориметре Qubit 2.0 с использованием набора реактивов с РНК-интеркалирующим красителем Quant-it RNa assayKit (Lifetechnologies, США). Оценку экспрессии генов MLH, aPc, MGMt проводили методом Rt-PcR на амплификаторе cFx96 (BioRad, США). Данные анализировали с использованием метода порогового значения цикла (ct) с нормализацией по экспрессии гена tBP в каждом образце. Относительную экспрессию генетического локуса (Еxp) рассчитывали по методу 2-Δct. Статистический анализ результатов осуществляли с помощью пакета программ statictica v10. Результаты. Установлено, что через сутки после воздействия ИМП индукцией 15 mt и 300 mt отношение уровня экспрессии MGMt к контролю имело значимые различия (p<0,05). Наиболее выраженное снижение транскрипционной активности гена MGMt в клетках глиобластомы отмечалось при ИМП 15 mt и коррелировало с показателем летальности клеток. Уровень летальности, достигнутый после лучевого воздействия и ИМП 15 mt, не изменялся, а при сочетании с ИМП 300 mt снижался с 18,7 до 15 %. Заключение. Эффекты снижения транскрипционной активности MGMt в клетках глиобластомы t98G и способность влияния ИМП как монофактора на их жизнеспособность характеризуют магнитовосприимчивость клеточных механизмов опухоли. При сочетании ИМП с ионизирующим излучением характер их взаимовлияния меняется от индифферентного до антагонистического, что указывает на необходимость подбора и обоснования ключевых биотропных параметров

A postseismic process in the area of the Simushir 11/2006 Earthquake recovered by the GRACE data

International audienceThe GRACE data make it possible to detect the areas where the earthquakes initiate postseismic creep in regions much larger than the focal area. This information is important for estimation of the seismic potential and position of the locked segments in the subduction zones