Facing the wind of the pre-FUor V1331 Cyg

The mass outflows in T Tauri stars (TTS) are thought to be an effective mechanism to remove angular momentum during the pre-main-sequence contraction of a low-mass star. The most powerful winds are observed at the FUor stage of stellar evolution. V1331 Cyg has been considered as a TTS at the pre-FUor stage. We analyse high-resolution spectra of V1331 Cyg collected in 1998-2007 and 20-d series of spectra taken in 2012. For the first time the photospheric spectrum of the star is detected and stellar parameters are derived: spectral type G7-K0 IV, mass 2.8 Msun, radius 5 Rsun, vsini < 6 km/s. The photospheric spectrum is highly veiled, but the amount of veiling is not the same in different spectral lines, being lower in weak transitions and much higher in strong transitions. The Fe II 5018, Mg I 5183, K I 7699 and some other lines of metals are accompanied by a `shell' absorption at radial velocity of about -240 km/s. We show that these absorptions form in the post-shock gas in the jet, i.e. the star is seen though its jet. The P Cyg profiles of H-alpha and H-beta indicate the terminal wind velocity of about 500 km/s, which vary on time-scales from several days to years. A model of the stellar wind is developed to interpret the observations. The model is based on calculation of hydrogen spectral lines using the radiative transfer code TORUS. The observed H-alpha and H-beta line profiles and their variability can be well reproduced with a stellar wind model, where the mass-loss rate and collimation (opening angle) of the wind are variable. The changes of the opening angle may be induced by small variability in magetization of the inner disc wind. The mass-loss rate is found to vary within (6-11)x10^{-8} Msun/yr, with the accretion rate of 2.0x10^{-6} Msun/yr.Comment: 11 pages, 12 figures; accepted for publication in MNRAS. Typographical errors have been corrected after the proof stag

In vivo characterization of RNA cis-regulators in bacteria

Thesis advisor: Michelle M. MeyerBacteria commonly utilize cis-acting mRNA structures that bind specific molecules to control gene expression in response to changing cellular conditions. Examples of these ligand-sensing RNA cis-regulators are found throughout the bacterial world and include riboswitches, which interact with small metabolites to modulate the expression of fundamental metabolic genes, and the RNA structures that bind select ribosomal proteins to regulate entire ribosomal protein operons. Despite advances in both non-coding RNA discovery and validation, many predicted regulatory RNA motifs remain uncharacterized and little work has examined how RNA cis-regulators behave within their physiological context in the cell. Furthermore, it is not well understood how structured RNA regulators emerge and are maintained within bacterial genomes. In this thesis, I validate the biological function of a conserved RNA cis-regulator of ribosomal protein synthesis previously discovered by my group using bioinformatic approaches. I then investigate how bacteria respond to the loss of two different cis-regulatory RNA structures. Using Bacillus subtilis as a model organism, I introduce point mutations into the native loci of the ribosomal protein L20-interacting RNA cis-regulator and the tandem glycine riboswitch and assay the strains for fitness defects. I find that disrupting these regulatory RNA structures results in severe mutant phenotypes, especially under harsh conditions such as low temperatures or high glycine concentrations. Together, this body of work highlights the advantages of examining RNA behavior within its biological context and emphasizes the important role RNA cis-regulators play in overall organismal viability. My studies shed light on the selective pressures that impact structured RNA evolution in vivo and reinforce the potential of cis-regulatory RNAs as novel antimicrobial targets.Thesis (PhD) — Boston College, 2017.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Biology

Важкі дихальні шляхи. Клінічний випадок: Лімфангіома шиї у дитини до року

The article describes an interesting clinical case of neck lymphangioma in a child under one year, as the cause of difficult airway during surgery. This case deserves the attention of anesthesiologists, surgeons, interns, considering the clinical features, these additional examination methods and features of anesthesia patients. There was emphasized the importance of pre-operative examination of patients, the use of additional tests and examination methods to determine further tactics. Based on this case, it was concluded that each anesthesiologist must have the skills and clearly know the clinical protocols for managing “difficult airway” and predict severe tracheal intubation.В статье рассмотрен интересный клинический случай лимфангиомы шеи у ребенка до года как причины тяжелых дыхательных путей во время операции. Данный случай заслуживает внимания врачей-анестезиологов, хирургов, врачей-интернов, учитывая особенности клиники, данных дополнительных методов обследования и особенности проведения анестезиологического обеспечения у таких пациентов. Подчеркнута важность предоперационного осмотра пациентов, использование дополнительных тестов и методов обследования для решения дальнейшей тактики. На основе этого случая сделаны выводы, что каждый врач-анестезиолог должен обладать навыками и четко знать клинические протоколы для ведения “тяжелых дыхательных путей” и прогнозировать тяжелую интубацию трахеи.У статті розглянуто цікавий клінічний випадок лімфангіоми шиї у дитини до року як причини важких дихальних шляхів під час операції. Даний випадок заслуговує на увагу лікарів-анестезіологів, хірургів, лікарів-інтернів, з огляду на особливості клініки, даних додаткових методів обстеження та особливості проведення анестезіологічного забезпечення у таких пацієнтів. Підкреслено важливість передопераційного огляду пацієнтів, використання додаткових тестів та методів обстеження для вирішення подальшої тактики. На основі цього випадку зроблено висновки, що кожний лікар-анестезіолог повинен володіти навиками і чітко знати клінічні протоколи для ведення “тяжкого дихального шляху” та прогнозувати тяжку інтубацію трахеї

MRGPRX2 Is the Codeine Receptor of Human Skin Mast Cells: Desensitization through β-Arrestin and Lack of Correlation with the FcεRI Pathway

Codeine stimulates skin mast cells and is therefore used in skin tests and as an inducer of experimental itch.MRGPRX2 responds to various drugs, including opioids, to elicit pseudoallergic reactions, but whether it represents the main opiate receptor of skin mast cells remains unknown. By combining a number of approaches, including the silencing of MRGPRX2, we now report that MRGPRX2 is indeed the dominant codeine receptor of dermal mast cells. Activation by codeine displayed profound subject variability and correlated with secretion elicited by compound 48/80 or substance P but not by FcεRI aggregation. Degranulation by codeine was attenuated by stem cell factor, whereas the opposite was found for FcεRI. Compound 48/80 or codeinealone was able to achieve maximum MRGPRX2 activation. MRGPRX2 was rapidly internalized on codeine binding in a b-arrestin-1‒dependent manner. Codeine-triggered b-arrestin activation was also established by the Tango assay. Prestimulation with MRGPRX2 agonists (but not C3a or FcεRI aggregation) resulted in refractoriness to further stimulation by the same or another MRGPRX2 ligand (cross desensitization). This was duplicated in a cell line (RBL-MRGPRX2). Collectively, codeine degranulates skin mast cells through MRGPRX2, at which it acts as a balanced ligand. It has yet to be determined whether codeine-induced refractoriness could be exploited to desensitize MRGPRX2 to prevent severe pseudoallergic reactions

The SCF/KIT axis in human mast cells: capicua acts as potent KIT repressor and ERK predominates PI3K

BACKGROUND: The SCF/KIT axis regulates nearly all aspects of mast cell (MC) biology. A comprehensive view of SCF-triggered phosphorylation dynamics is lacking. The relationship between signaling modules and SCF-supported functions likewise remains ill-defined. METHODS: MCs were isolated from human skin; upon stimulation by SCF, global phosphoproteomic changes were analyzed by LC-MS/MS and selectively validated by immunoblotting. MC survival was inspected by YoPro; BrdU incorporation served to monitor proliferation. Gene expression was quantified by RT-qPCR and cytokines by ELISA. Pharmacological inhibitors were supplemented by ERK1 and/or ERK2 knock-down. CIC translocation and degradation were studied in nuclear and cytoplasmic fractions. CIC's impact on KIT signaling and function was assessed following RNA interference. RESULTS: ≈5,400 out of ≈10,500 phosphosites experienced regulation by SCF. The MEK/ERK cascade was strongly induced surpassing STAT5>PI3K/Akt>p38>JNK. Comparison between MEK/ERK's and PI3K's support of basic programs (apoptosis, proliferation) revealed equipotency between modules. In functional outputs (gene expression, cytokines), ERK was the most influential kinase. OSM and LIF production was identified in skin MCs. Strikingly, SCF triggered massive phosphorylation of a protein not associated with KIT previously: CIC. Phosphorylation was followed by CIC's cytoplasmic appearance and degradation, the latter sensitive to protease- but not preoteasome-inhibition. Both shuttling and degradation were ERK-dependent. Conversely, CIC-siRNA facilitated KIT-signaling, functional outputs and survival. CONCLUSION: The SCF/KIT axis shows notable strength in MCs, and MEK/ERK as most prominent module. An inhibitory circuit exists between KIT and CIC. CIC stabilization in MCs may turn out as a therapeutic option to interfere with allergic and MC-driven diseases

Density streams in the disc winds of Classical T Tauri stars

Spectral and photometric variability of the Classical T Tauri stars RY Tau and SU Aur from 2013 to 2022 is analyzed. We find that in SU Aur the H-alpha line's flux at radial velocity RV = -50 +- 7 km/s varies with a period P = 255 +- 5 days. A similar effect previously discovered in RY Tau is confirmed with these new data: P = 21.6 days at RV = -95 +- 5 km/s. In both stars, the radial velocity of these variations, the period, and the mass of the star turn out to be related by Kepler's law, suggesting structural features on the disc plane orbiting at radii of 0.2 AU in RY Tau and 0.9 AU in SU Aur, respectively. Both stars have a large inclination of the accretion disc to the line of sight - so that the line of sight passes through the region of the disc wind. We propose there is an azimuthal asymmetry in the disc wind, presumably in the form of 'density streams', caused by substructures of the accretion disc surface. These streams cannot dissipate until they go beyond the Alfven surface in the disc's magnetic field. These findings open up the possibility to learn about the structure of the inner accretion disc of CTTS on scales less than 1 AU and to reveal the orbital distances related to the planet's formation.Comment: 9 pages, 10 figure