The Outburst of the Blazar AO 0235+164 in 2006 December: Shock-in-Jet Interpretation

We present the results of polarimetric ($R$ band) and multicolor photometric ($BVRIJHK$) observations of the blazar AO 0235+16 during an outburst in 2006 December. The data reveal a short timescale of variability (several hours), which increases from optical to near-IR wavelengths; even shorter variations are detected in polarization. The flux density correlates with the degree of polarization, and at maximum degree of polarization the electric vector tends to align with the parsec-scale jet direction. We find that a variable component with a steady power-law spectral energy distribution and very high optical polarization (30-50%) is responsible for the variability. We interpret these properties of the blazar withina model of a transverse shock propagating down the jet. In this case a small change in the viewing angle of the jet, by $\lesssim 1^o$, and a decrease in the shocked plasma compression by a factor of $\sim$1.5 are sufficient to account for the variability.Comment: 22 pages, 8 figures, accepted for Ap

Определение возможных микроРНК-маркеров злоупотребления препаратами кобальта методом ПЦР в реальном времени с использованием панелей сигнального пути гипоксии

Objectives. Cobalt mimics the state of hypoxia to prevent degradation of the alpha subunit of hypoxia-inducible factor, resulting in an increase in blood oxygen capacity and endurance. Athletes can use this property to gain competitive advantage. Nowadays, direct methods of inductively coupled plasma mass spectrometry and liquid chromatography-tandem mass spectrometry are used to determine total cobalt levels in the body. However, the World Anti-Doping Agency is yet to establish a maximum allowable threshold concentration of this element in biofluids. The lack of clear identification criteria complicates the interpretation of the obtained results for the purposes of doping control. In this regard, the present work proposes a new approach for the indirect determination of possible cobalt abuse based on changes in the expression levels of miRNAs involved in the regulation of hypoxia signaling pathways. Here, the aim is to identify possible microRNA markers whose expression does not depend on exercise-induced hypoxia, but changes markedly when taking cobalt preparations.Methods. MicroRNA isolation was performed from blood plasma samples using the PAXgene Blood miRNA Kit. Quantitative real-time polymerase chain reaction (PCR) was performed on CFX96 Bio-Rad (USA) analyzer using miScript® SYBR® Green PCR Kits and panels for studying the expression profiles of mature microRNAs of the hypoxia signaling pathway miScript® miRNA PCR Array.Results. Based on the statistical analysis of the data, it was found that the expression of hsa-miR-15b-5p in the blood plasma of the subjects does not depend on physical activity, but increases when taking cobalt preparations.Conclusions. The difference in expression levels during anaerobic exercise-induced hypoxia and cobalt-induced hypoxia makes hsa-miR-15b-5p a potential candidate to be a marker of erythropoiesis-stimulating agent abuse.Цели. Кобальт имитирует состояние гипоксии, препятствуя деградации альфасубъединицы гипоксия-индуцируемого фактора, что приводит к увеличению кислородной емкости крови и может использоваться спортсменами в качестве допинга для получения конкурентных преимуществ. На сегодняшний момент для определения общего кобальта в организме используют прямые методы масс-спектрометрии с индуктивно связанной плазмой, жидкостной хроматографиитандемной масс-спектрометрии, однако Всемирным антидопинговым агентством не установлена максимально допустимая пороговая концентрация этого элемента в биожидкостях. Отсутствие четких критериев идентификации осложняет интерпретацию полученных результатов. В связи с этим, в данной статье впервые предлагается подход по косвенному определению возможных злоупотреблений кобальтом для целей допинг-контроля, основанный на изменении уровней экспрессии микроРНК, задействованных в регуляции сигнального пути гипоксии. Цель исследования заключалась в поиске возможных микроРНК-маркеров, экспрессия которых не зависит от гипоксии, вызванной физическими нагрузками, но заметно изменяется при приеме препаратов кобальта.Методы. Выделение микроРНК из образцов плазмы крови проводили при помощи набора PAXgene Blood miRNA Kit. Количественную полимеразную цепную реакцию в реальном времени проводили на амплификаторе CFX96 Bio-Rad (США) с помощью наборов miScript® SYBR® Green PCR Kit и панелей для исследования профилей экспрессии зрелых микроРНК сигнального пути гипоксии Hypoxia Signaling Pathway miScript® miRNA PCR Array.Результаты. На основании статистического анализа данных было установлено, что экспрессия hsa-miR-15b-5p в плазме крови испытуемых не зависит от физической нагрузки, но возрастает при приеме препаратов кобальта.Выводы. Разница в уровнях экспрессии при гипоксии, вызванной анаэробной физической нагрузкой, и имитацией гипоксии за счет применения кобальта делает hsa-miR-15b-5p потенциальным претендентом на роль маркера злоупотребления данным эритропоэзстимулирующим агентом

Another look at the BL Lacertae flux and spectral variability

The GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT) monitored BL Lacertae in 2008-2009 at radio, near-IR, and optical frequencies. During this period, high-energy observations were performed by XMM-Newton, Swift, and Fermi. We analyse these data with particular attention to the calibration of Swift UV data, and apply a helical jet model to interpret the source broad-band variability. The GASP-WEBT observations show an optical flare in 2008 February-March, and oscillations of several tenths of mag on a few-day time scale afterwards. The radio flux is only mildly variable. The UV data from both XMM-Newton and Swift seem to confirm a UV excess that is likely caused by thermal emission from the accretion disc. The X-ray data from XMM-Newton indicate a strongly concave spectrum, as well as moderate flux variability on an hour time scale. The Swift X-ray data reveal fast (interday) flux changes, not correlated with those observed at lower energies. We compare the spectral energy distribution (SED) corresponding to the 2008 low-brightness state, which was characterised by a synchrotron dominance, to the 1997 outburst state, where the inverse-Compton emission was prevailing. A fit with an inhomogeneous helical jet model suggests that two synchrotron components are at work with their self inverse-Compton emission. Most likely, they represent the radiation from two distinct emitting regions in the jet. We show that the difference between the source SEDs in 2008 and 1997 can be explained in terms of pure geometrical variations. The outburst state occurred when the jet-emitting regions were better aligned with the line of sight, producing an increase of the Doppler beaming factor. Our analysis demonstrates that the jet geometry can play an extremely important role in the BL Lacertae flux and spectral variability.Comment: 12 pages, 10 figures, accepted for publication in A&

The brightest gamma-ray flaring blazar in the sky: AGILE and multi-wavelength observations of 3C 454.3 during November 2010

Since 2005, the blazar 3C 454.3 has shown remarkable flaring activity at all frequencies, and during the last four years it has exhibited more than one gamma-ray flare per year, becoming the most active gamma-ray blazar in the sky. We present for the first time the multi-wavelength AGILE, SWIFT, INTEGRAL, and GASP-WEBT data collected in order to explain the extraordinary gamma-ray flare of 3C 454.3 which occurred in November 2010. On 2010 November 20 (MJD 55520), 3C 454.3 reached a peak flux (E>100 MeV) of F_gamma(p) = (6.8+-1.0)E-5 ph/cm2/s on a time scale of about 12 hours, more than a factor of 6 higher than the flux of the brightest steady gamma-ray source, the Vela pulsar, and more than a factor of 3 brighter than its previous super-flare on 2009 December 2-3. The multi-wavelength data make a thorough study of the present event possible: the comparison with the previous outbursts indicates a close similarity to the one that occurred in 2009. By comparing the broadband emission before, during, and after the gamma-ray flare, we find that the radio, optical and X-ray emission varies within a factor 2-3, whereas the gamma-ray flux by a factor of 10. This remarkable behavior is modeled by an external Compton component driven by a substantial local enhancement of soft seed photons.Comment: Accepted for publication in ApJ Letters. 18 Pages, 4 Figures, 1 Tabl

Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia Brain

BACKGROUND: Transcriptomic studies of the brains of schizophrenia (SZ) patients have produced abundant but largely inconsistent findings about the disorders pathophysiology. These inconsistencies might stem not only from the heterogeneous nature of the disorder, but also from the unbalanced focus on particular cortical regions and protein-coding genes. Compared to protein-coding transcripts, long intergenic non-coding RNA (lincRNA) display substantially greater brain region and disease response specificity, positioning them as prospective indicators of SZ-associated alterations. Further, a growing understanding of the systemic character of the disorder calls for a more systematic screening involving multiple diverse brain regions. AIM: We aimed to identify and interpret alterations of the lincRNA expression profiles in SZ by examining the transcriptomes of 35 brain regions. METHODS: We measured the transcriptome of 35 brain regions dissected from eight adult brain specimens, four SZ patients, and four healthy controls, using high-throughput RNA sequencing. Analysis of these data yielded 861 annotated human lincRNAs passing the detection threshold. RESULTS: Of the 861 detected lincRNA, 135 showed significant region-dependent expression alterations in SZ (two-way ANOVA, BH-adjusted p 0.05) and 37 additionally showed significant differential expression between HC and SZ individuals in at least one region (post hoc Tukey test, p 0.05). For these 37 differentially expressed lincRNAs (DELs), 88% of the differences occurred in a cluster of brain regions containing axon-rich brain regions and cerebellum. Functional annotation of the DEL targets further revealed stark enrichment in neurons and synaptic transmission terms and pathways. CONCLUSION: Our study highlights the utility of a systematic brain transcriptome analysis relying on the expression profiles measured across multiple brain regions and singles out white matter regions as a prospective target for further SZ research

Difficulties differential diagnostics of rare skin diseases in practice dermatovenerologist

This article discusses is study of differential diagnostics of rare skin diseases, using the example of Grover's Disease. Various literary sources are analyzed, data on etiology, pathogenesis, clinical picture of typical and atypical forms of GD are presented. The article is of an overview nature and contains up-to-date information on the diagnosis and treatment of Grover's transient acantholytic dermatosis. Based on the description of the clinical case of Grover's disease, differential diagnostics with other skin diseases was carried out.В данной статье рассмотрен вопрос дифференциальной диагностики редких кожных заболеваний, на примере Болезни Гровера. Проанализированы различные литературные источники, представлены данные об этиологии, патогенезе, клинической картине типичной и атипичных форм БГ. Статья носит обзорный характер и содержит современную информацию о диагностике и лечении транзиторного акантолитического дерматоза Гровера. На основании описания клинического случая Болезни Гровера проведена дифференциальная диагностика с другими кожными заболеваниям

ИДЕНТИФИКАЦИЯ ГИБРИДНОГО БЕЛКА ЭПО-Fc МЕТОДАМИ ПОЛИАКРИЛАМИДНОГО ГЕЛЬ-ЭЛЕКТРОФОРЕЗА С ИЗОЭЛЕКТРИЧЕСКИМ ФОКУСИРОВАНЕИМ (IEF-PAGE) И В ПРИСУТСТВИИ ДОДЕЦИЛСУЛЬФАТА (SDS-PAGE)/ЛАУРИЛСАРКОЗИНАТА НАТРИЯ (SAR-PAGE) С ЦЕЛЬЮ АНТИДОПИНГОВОГО КОНТРОЛЯ

The article is devoted to develop of an approach for the identification of new stimulator of ematopoiesis, EPO-Fc fusion protein, which is banned by the World Anti-doping Agency (WADA) to use by athletes since it has become doping. Existing methods of qualitative determination of this substances in routine practice of antidoping laboratories such as polyacrylamide gelelectrophoresis in presence of sodium dodecylsulphate (SDS-PAGE) or lauroylsarcosinate (SARPAGE) are insufficiently specific. The article shows the principal possibility of identification of EPO-Fc fusion protein by means of IEF-PAGE in carrier ampholyte-based gels with a pH range 2-6 after Fc-fragment removal via fermentative hydrolysis.It has been shown that the removing of the crystallizable fragment leads to decrease of molecular weight of whole hybrid molecule and to increase its electrophoretic mobility that allows to detect this banned substances with high specificity by existing methods. During the study the enzyme for hydrolytic cleavage and optimum conditions of hydrolysis of EPO-Fc in serum samples were selected.Статья посвящена разработке подхода по идентификации нового стимулятора кроветворения, гибридного белка ЭПО-Fc, запрещенного Всемирным антидопинговым агентством (ВАДА) для употребления спортсменами и являющегося допингом. Существующие в рутинной практике антидопинговых лабораторий мира методы качественного определения данного вещества с помощью полиакриламидного гель-электрофореза в присутствии додецилсульфата (SDS-PAGE) и лаурилсаркозината (SAR-PAGE) натрия недостаточно специфичны. В статье описана принципиальная возможность идентификации ЭПО-Fc методом изоэлектрического фокусирования в полиакриламидном геле (IEF-PAGE) с градиентом рН 2-6 после удаления Fc-части молекулы посредством ферментативного гидролиза. Показано, что удаление кристаллизуемого фрагмента приводит к уменьшению молекулярной массы всей гибридной молекулы и увеличению ее электрофоретической подвижности, что позволяет специфично детектировать запрещенное вещество существующими методами. В ходе исследования выбран фермент для гидролитического расщепления ЭПО-Fc и подобраны оптимальные условия гидролиза в образцах сыворотки крови