On selection of foxes for enhanced aggressiveness and its correlated implications

The results of a 35-year selection of foxes for aggressive response to humans are reported. Averaged estimates of the phenotypic manifestation of aggressiveness in all selection generations are presented. The dynamics of these estimates shows that the phenotypic response to the selection was obvious only in the first 12 generations. Subsequent selection did not alter the mean aggressiveness score. Analysis of variance was performed for the intergroup variability (among descendants of different mothers) and intragroup variability (among the offspring within a family). The intragroup variability was constantly low. Most likely, the trait is stabilized by maternal prenatal and early neonatal factors. The general tendency in the dynamics of intergroup variability is that it does not decrease over time during selection, no matter how long the population has been under it. It follows from the statistical indices of the phenotypic similarity between parents and offspring that additive interactions are insufficient for the explanation of the persisting variability. The contribution of epistatic interactions is not ruled out, though. Emphasis is laid on the correlated consequences of the selection for aggressiveness and their coordination with the consequences of the selection in the opposite direction, for elimination of aggressive response to humans, or for tameness. The parallelism of correlated changes in the selection in contrasting directions is illustrated by the examples of some physiological and morphological traits. The phenomenon is discussed in the light of classical notions of the resource of cryptic genetic variation and the role of selection in its phenotypic manifestation. Its interpretation also invokes molecular data pointing that some genetic pathways may regulate parameters of both aggression and tameness and that the selection processes in both directions may have some genetic targets in common

Spin Texture in a Cold Exciton Gas

We report on the observation of a spin texture in a cold exciton gas in a GaAs/AlGaAs coupled quantum well structure. The spin texture is observed around the exciton rings. The observed phenomena include: a ring of linear polarization, a vortex of linear polarization with polarization perpendicular to the radial direction, an anisotropy in the exciton flux, a skew of the exciton fluxes in orthogonal circular polarizations and a corresponding four-leaf pattern of circular polarization, a periodic spin texture, and extended exciton coherence in the region of the polarization vortex. The data indicate a transport regime where the spin polarization is locked to the direction of particle propagation and scattering is suppressed.Comment: version 2 contains updated supplementary materia

Evolution of climate, glaciation and subglacial environments of Antarctica from the deep ice core and Lake Vostok water sample studies (Key results of implementation of the Russian Science Foundation project, 2014–2016)

Work on the project focused on the following five areas: 1)  field works in Antarctica at Vostok and Concordia stations; 2)  experimental and theoretical studies in the field of ice core and paleoclimate research; 3) experimental and theoretical works related to the exploration of subglacial Lake Vostok; 4) development of technology and drilling equipment for deep ice coring and exploration of subglacial lakes; 5) upgrading the analytical instrumentation in the Climate and Environmental Research Laboratory (CERL) of the Arctic and Antarctic Research Institute. The main achievements in the field of ice core and paleoclimate research include 1) further elaboration of a new method of ice core dating, which is based on the link between air content of ice and local insolation, 2) investigation of the possible applications of the 17O-excess measurements in ice core to the paleoclimate research, 3)  a better understanding of the mechanisms of the formation of relief-related variations in the isotopic content of an ice core drilled in the area of Antarctic megadunes, and 4) obtaining the first reliable data set on the variations of the 17O-excess in the Vostok core corresponding to marine isotope stage 11. As part of our studies of subglacial Lake Vostok, we have obtained a large body of new experimental data from the new ice core recovered from the 5G-3 borehole to the surface of the subglacial lake. Stacked profiles of isotopic composition, gas content and the size and orientation of the ice crystals in the lake ice have been composed from the data of three replicate cores from boreholes 5G-1, 5G-2 and 5G-3. The study reveals that the concentration of gases in the lake water beneath Vostok is unexpectedly low. A clear signature of the melt water in the surface layer of the lake, which is subject to refreezing on the icy ceiling of Lake Vostok, has been discerned in the three different properties of the accreted ice (the ice texture, the isotopic and gas content of the ice). These sets of data indicate in concert that poor mixing of the melt (and hydrothermal) water with the resident lake water and pronounced spatial and/or temporal variability of local hydrological conditions are likely to be the characteristics of the southern end of the lake. A considerable part of the funding allocated by the RSF to this project was used for upgrading the analytical instrumentation for ice core studies in the CERL of AARI. Using this grant, we purchased and started working with the Picarro L-2140i, a new-generation laser mass analyzer, and set the upgraded mass spectrometer Delta V Plus into operation. The new equipment was used to carry out research planned as part of the project, including the setting up and carrying out of new measurements of 17О in ice cores

SYNTHESIS OF NEW PHOSPHORS BASED ON Tm3+, Nd3+ OR Ho3+ DOPED GERMANATES BY “WET” CHEMICAL ROUTES

Various “wet” synthetic chemical techniques are widely used for the production of multifunctional inorganic materials. In contrast to the standard high-temperature solid state route, methods based on the dissolution of starting reagents allow one to obtain phases with given particle morphology and particle size distribution. Besides, with this approach, the defect structure can be efficiently controlled by varying the synthesis conditions and solution preparation. These advantages are important for producing luminescent materials.This work was supported by the Russian Science Foundation, project № 16-13-10111

Функциональная активность нейтрофилов при ожоговом сепсисе

A complex effect of thermal trauma on the immune system triggers the tendency to develop and generalize infection in patients with severe thermal trauma. The phagocytic system, which is represented, first of all, by neutrophilic granulocytes, is significantly altered. Objective: to determine the dynamics of changes in the functional activity of neutrophils in patients with thermal trauma, as well as its prognostic significance in the development of purulent-septic complications of a burn disease. Materials and methods. The functional activity of neutrophils was assessed by spontaneous and induced chemiluminescence responses of whole blood sequentially stimulated with phorbol-12-myristate"13-acetate(PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). 34 patients with a burn disease of different severity were dynamically examined during observation. Results. The newly developed technique was applied to study the responses of whole blood of patients with burn disease to stimuli; data on the functional activity of neutrophils depending on various severities of the disease and response dynamics were obtained. Analysis of chemiluminescent curves of the development of respiratory explosion of neutrophils helped to reveal parameters of the immune system state, namely: a one— or two-phase response to a stimulus, a «rapid phase» neutrophil specific activity, and a «slow phase» neutrophil specific activity. Conclusion. The results revealed trends in alterations of functional activity of neutrophils in burn disease. Diagnostic and prognostic indices of the functional activity of neutrophils for assessing the severity of the disease and the prognosis of the septic process were suggested.Тенденция к развитию и генерализации инфекции у пациентов с тяжелой термической травмой реализуется за счет комплексного влияния термической травмы на иммунную систему. Особенно страдает фагоцитарная система, представленная, в первую очередь, нейтрофильными гранулоцитами. Цель исследования: определение динамики изменения функциональной активности нейтрофилов у пациентов с термической травмой, а также ее прогностической значимости при развитии гнойно-септических осложнений ожоговой болезни. Материалы и методы. Функциональную активность нейтрофилов оценивали на основе спонтанного и индуцированного хемилюминесцентного ответа цельной крови при последовательной стимуляции форбол-12-миристат-13-ацетатом (ФМА) и N-формил-метионил-лейцил-фенилаланином (фМЛФ). Было обследовано 34 пациента с ожоговой болезнью при разной тяжести течения ожоговой болезни и в динамике наблюдения. Результаты. Разработанная новая методика была использована для исследования цельной крови пациентов с ожоговой болезнью, получены данные о функциональной активности нейтрофилов при разной тяжести течения болезни и в динамике. В результате анализа хемилюминесцентных кривых развития респираторного взрыва нейтрофилов выявлены показатели, характеризующие состояние иммунной системы, а именно: одно— или двухфазный ответ на стимул, удельная активность нейтрофила «быстрой фазы», удельная активность нейтрофила «медленной фазы». Заключение. Результаты позволили выделить тенденции изменения функциональной активности нейтрофилов при ожоговой болезни. Предложены диагностические и прогностические показатели функциональной активности нейтрофилов для оценки тяжести болезни и прогноза септического процесса

Resolution on the results of Advisory Board “Searching the effective methods of testing and treating patients with NSCLC caused by <i>NTRK</i> gene fusions“

The Advisory Board was held on December 24, 2021. The molecular genetic research lead specialists and national lead oncologists discussed issues of diagnosis of NTRK gene translocations in patients with non-small cell lung cancer (NSCLC), as well as current opportunities for the treatment of patients with NSCLC caused by NTRK gene fusions. The experts reaffirmed the necessity to identify timely patients with NSCLC caused by NTRK gene fusions, as the correct diagnosis of the disease, including the use of modern diagnostic methods of NTRK gene fusion (NGS is the most sensitive and specific method) determines the success of patient treatment. In this regard, it is critical that physicians know the advantages and disadvantages of each molecular diagnostic method used to have the opportunity to choose the best approach in each clinical case. In order to have a clear, well-functioning strategy for managing patients with suspected NSCLC caused by NTRK gene fusion, it is necessary to use molecular genetic tests, as well as include TRK inhibitors (in particular, the drug larotrectinib; at the time publication of the Resolution, the drug larotrectinib is not registered in the territory of the Russian Federation) in the clinical guidelines for the treatment of lung cancer. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor. The clinical studies on larotrectinib have demonstrated high response rates and durable responses in adults and children with tumours associated with NTRK gene fusions, including primary CNS tumours and brain metastases. The objective response rate observed with larotrectinib was 79%, with 16% achieving a complete response and 64% achieving a partial response. At the same time, the median progression-free survival on larotrectinib was 28.3 months, and the median overall survival was 44.4 months

ОТЕЧЕСТВЕННЫЙ ОПЫТ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ ПРОЯВЛЕНИЙ КОЖНОЙ ТОКСИЧНОСТИ У ПАЦИЕНТОВ МКРР, ПОЛУЧАЮЩИХ ИНГИБИТОРЫ EGFR, НА ПРИМЕРЕ ПРЕПАРАТА ПАНИТУМУМАБ

The results of the first national experience of skin toxicity correction in patients with metastatic colorectal cancer (mCRC) receiving EGRF-inhibitors shown on the example of using of Panitumumab. The collection and evaluation of the data were produced in the framework of the project of the working group on maintenance therapy of Russian society of clinical oncologists and chemotherapeutists (RUSSCO) to develop recommendations for the prevention and treatment of dermatological toxicity in patients receiving EGFR-inhibitors. The project involved 10 centers in Russia.  In 58 patients receiving Panitumumab, the efficacy of prophylactic medication and symptomatic treatment of clinical manifestations of dermatological toxicity using available remedies was evaluated. The results confirm the effectiveness of preventive therapy. Optimal correction schemes of various manifestations of dermal toxicity were developed depending on the clinical manifestations and severity.Освещены результаты первого отечественного опыта коррекции кожной токсичности у пациентов мКРР, получающих ингибиторы EGRF, на примере препарата Панитумумаб. Сбор и оценка данных произведены в рамках проекта рабочей группы по поддерживающей терапии Профессионального Общества онкологов-химиотерапевтов (RUSSCO) по разработке рекомендаций для профилактики и лечения дерматологической токсичности у пациентов, получающих ингибиторы EGFR. В проекте принимали участие 10 центров РФ. У 58 пациентов, получавших Панитумумаб, оценивалась эффективность профилактической медикаментозной и симптоматической терапии клинических проявлений дерматологической токсичности доступными средствами. Полученные результаты подтверждают эффективность профилактической терапии. Разработаны оптимальные схемы коррекции различных проявлений кожной токсичности в зависимости от клинических проявлений и степени тяжести

Eribulin-trastuzumab combination in HER2-positive metastatic breast cancer: updated results from a Russian observational study

Introduction. The standard of 1st line treatment of HER2+ metastatic breast cancer (mBC) is double blockade with trastuzumab and pertuzumab + taxane, 2nd line – Trastuzumab-emtazine. There are no standards for further treatment, as well as the optimal drug sequence. Expansion of the arsenal of therapeutic possibilities and the use of new combinations will certainly improve the results of treatment of this category of patients and increase their life expectancy.Aim. We sought to describe treatment patterns of  eribulin  and clinical outcomes of  metastatic HER2-positive breast cancer treated with eribulin  plus trastuzumab combination in  academic institutions and community oncology practices across the Russian Federation.Materials and methods. Patients treated with eribulin anytime between Jan, 2014 and Sep, 2019 with a diagnosis of MBC were identified by 23 providers from Russia. Providers retrospectively reviewed the health records and abstracted selected data points into an electronic case report form for each eligible patient.Results. 100 HER2-positive pts received eribulin in combination with trastuzumab. Median age was 55 (31–80) yrs and ECOG status 0–3. 67% pts had visceral metastases. Eribulin was administered as 1st and 2nd line to 23 (23%) pts, 3rd line to 31 (31%) pts, 4th line and later to 46 (46%). Median number of cycles was 5 (2–27). ORR was 12%, SD – 72%, SD &gt; 6 months – 23%, PD – 16%. Clinical efficacy rate achieved in 35%. Median PFS was 5.07 months (95% CI 4.021–6.119). According to the ER-status the response to eribulin and trastuzumab was different. ORR was 18.8%, SD 72.9% in pts with ER-positive MBC (n = 48) and 5.8% and 71.2% respectively in ER-negative MBC (n = 52). Median PFS was 6.97 months (95% CI 3.924–10.016) in pts with ER-positive MBC and 4.67 months (95% CI 3.841–5.499) in ER-negative MBC (р = 0.3). The combination was well tolerated: dose reductions were required in 12% pts, withdrawal due to toxicity in 4% pts. The most common type of toxicity was hematological with neutropenia Gr III-IV in 14 (14%) pts. Peripheral neuropathy Gr III was observed in 5 (5%) pts. No cardiotoxicity was detected.Conclusions. This is the real-life data of clinical outcomes for patients receiving eribulin plus trastuzumab for HER2-positive MBC throughout the Russian Federation. Our experience with eribulin plus trastuzumab demonstrates that this combination may be a potential effective treatment option for HER-2 positive MBC patients

Эволюция климата, оледенения и подледниковой среды Антарктиды по данным исследований ледяных кернов и проб воды озера Восток (Основные итоги работ по проекту РНФ, 2014–2016 гг.)

Work on the project focused on the following five areas: 1)  field works in Antarctica at Vostok and Concordia stations; 2)  experimental and theoretical studies in the field of ice core and paleoclimate research; 3) experimental and theoretical works related to the exploration of subglacial Lake Vostok; 4) development of technology and drilling equipment for deep ice coring and exploration of subglacial lakes; 5) upgrading the analytical instrumentation in the Climate and Environmental Research Laboratory (CERL) of the Arctic and Antarctic Research Institute. The main achievements in the field of ice core and paleoclimate research include 1) further elaboration of a new method of ice core dating, which is based on the link between air content of ice and local insolation, 2) investigation of the possible applications of the 17O-excess measurements in ice core to the paleoclimate research, 3)  a better understanding of the mechanisms of the formation of relief-related variations in the isotopic content of an ice core drilled in the area of Antarctic megadunes, and 4) obtaining the first reliable data set on the variations of the 17O-excess in the Vostok core corresponding to marine isotope stage 11. As part of our studies of subglacial Lake Vostok, we have obtained a large body of new experimental data from the new ice core recovered from the 5G-3 borehole to the surface of the subglacial lake. Stacked profiles of isotopic composition, gas content and the size and orientation of the ice crystals in the lake ice have been composed from the data of three replicate cores from boreholes 5G-1, 5G-2 and 5G-3. The study reveals that the concentration of gases in the lake water beneath Vostok is unexpectedly low. A clear signature of the melt water in the surface layer of the lake, which is subject to refreezing on the icy ceiling of Lake Vostok, has been discerned in the three different properties of the accreted ice (the ice texture, the isotopic and gas content of the ice). These sets of data indicate in concert that poor mixing of the melt (and hydrothermal) water with the resident lake water and pronounced spatial and/or temporal variability of local hydrological conditions are likely to be the characteristics of the southern end of the lake. A considerable part of the funding allocated by the RSF to this project was used for upgrading the analytical instrumentation for ice core studies in the CERL of AARI. Using this grant, we purchased and started working with the Picarro L-2140i, a new-generation laser mass analyzer, and set the upgraded mass spectrometer Delta V Plus into operation. The new equipment was used to carry out research planned as part of the project, including the setting up and carrying out of new measurements of 17О in ice cores.Изложены основные результаты работ, выполненных Лабораторией изменений климата и окружающей среды ААНИИ по проекту Российского научного фонда в 2014–2016 гг. Показано, что поддержка фонда способствовала получению научных результатов международного уровня в двух приоритетных направлениях антарктических исследований  – реконструкции палеоклимата по ледяным кернам и изучении подледниковой среды Антарктиды