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

Therapeutic effect of all-trans-retinoic acid (at-RA) on an autoimmune nephritis experimental model: role of the VLA-4 integrin

BACKGROUND: Mercuric chloride (HgCl(2)) induces an autoimmune nephritis in the Brown Norway (BN) rats characterized by anti-glomerular basement membrane antibodies (anti-GBM Ab) deposition, proteinuria and a severe interstitial nephritis, all evident at day 13 of the disease. We assessed the effects of all-trans retinoic acid (at-RA) in this experimental model. At-RA is a vitamin A metabolite which has shown beneficial effects on several nephropathies, even though no clear targets for at-RA were provided. METHODS: We separated animals in four different experimental groups (HgCl(2), HgCl(2)+at-RA, at-RA and vehicle). From each animal we collected, at days 0 and 13, numerous biological samples: urine, to measure proteinuria by colorimetry; blood to determine VLA-4 expression by flow citometry; renal tissue to study the expression of VCAM-1 by Western blot, the presence of cellular infiltrates by immunohistochemistry, the IgG deposition by immunofluorescence, and the cytokines expression by RT-PCR. Additionally, adhesion assays to VCAM-1 were performed using K562 α4 transfectant cells. ANOVA tests were used for statistical significance estimation. RESULTS: We found that at-RA significantly decreased the serum levels of anti-GBM and consequently its deposition along the glomerular membrane. At-RA markedly reduced proteinuria as well as the number of cellular infiltrates in the renal interstitium, the levels of TNF-α and IL-1β cytokines and VCAM-1 expression in renal tissue. Moreover, we reported here for the first time in an in vivo model that at-RA reduced, to basal levels, the expression of VLA-4 (α4β1) integrin induced by mercury on peripheral blood leukocytes (PBLs). In addition, using K562 α4 stable transfectant cells, we found that at-RA inhibited VLA-4 dependent cell adhesion to VCAM-1. CONCLUSION: Here we demonstrate a therapeutic effect of at-RA on an autoimmune experimental nephritis model in rats. We report a significant reduction of the VLA-4 integrin expression on PBLs as well as the inhibition of the VLA4/VCAM1-dependent leukocyte adhesion by at-RA treatment. Thereby we point out the VLA-4 integrin as a target for at-RA in vivo

Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3

GATA-3 is essential for T cell development from the earliest stages. However, abundant GATA-3 can drive T lineage precursors to a non–T cell fate, depending on Notch signaling and developmental stage. Here, overexpression of GATA-3 blocked the survival of pro–T cells when Notch-Delta signals were present but enhanced viability in their absence. In fetal thymocytes at the double-negative 1 (DN1) stage and DN2 stage but not those at the DN3 stage, overexpression of GATA-3 rapidly induced respecification to the mast cell lineage with high frequency by direct transcriptional 'reprogramming'. Normal DN2 thymocytes also showed mast cell potential when interleukin 3 and stem cell factor were added in the absence of Notch signaling. Our results suggest a close relationship between the pro–T cell and mast cell programs and a previously unknown function for Notch in T lineage fidelity

Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation

Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that Treg-specific DNA hypomethylated regions were closely associated with Treg up-regulated transcriptional start site clusters, whereas Foxp3 binding regions had no significant correlation with either up- or down-regulated clusters in nonactivated Treg cells. However, in activated Treg cells, Foxp3 binding regions showed a strong correlation with down-regulated clusters. In accordance with these findings, the above two features of activation-dependent gene regulation in Treg cells tend to occur at different locations in the genome. The results collectively indicate that Treg-specific DNA hypomethylation is instrumental in gene up-regulation in steady state Treg cells, whereas Foxp3 down-regulates the expression of its target genes in activated Treg cells. Thus, the two events seem to play distinct but complementary roles in Treg-specific gene expression

Superoutburst of CR Bootis: Estimation of mass ratio of a typical AMCVn star by stage A superhumps

© The Author 2016.We report on two superoutbursts of the AMCVn-type object CR Boo in 2014 April-March and 2015 May-June. A precursor outburst accompanied both of these superoutbursts. During the rising branch of the main superoutburst in 2014, we detected growing superhumps (stage A superhumps) whose period was 0.017669(24) d. Assuming that this period reflects the dynamical precession rate at the radius of the 3:1 resonance, we could estimate the mass ratio (q = M2/M1) of 0.101(4) by using the stage A superhump period and the orbital period of 0.0170290(6) d. This mass ratio is consistent with that expected from the theoretical evolutionary model of AMCVn-type objects. The detection of precursor outbursts and stage A superhumps is the second case in AMCVn-type objects. There are two interpretations of the outbursts of AMCVn-type objects. One is a dwarf nova (DN) outbursts analogy, which suggets that the outbursts are caused by thermal and tidal instabilities. Another is the VY Scl-type variation, which suggests that the outbursts are caused by the variation of the mass-transfer rate of the secondary. This detection of the superhump variations strongly supports the former interpretation

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Survey of period variations of superhumps in SU UMa-type dwarf novae. VIII. The eighth year (2015-2016)

© The Author 2016.Continuing the project described by Kato et al. (2009, PASJ, 61, S395), we collected times of superhump maxima for 128 SUUMa-type dwarf novae observed mainly during the 2015-2016 season and characterized these objects. The data have improved the distribution of orbital periods, the relation between the orbital period and the variation of superhumps, and the relation between period variations and the rebrightening type in WZSge-type objects. Coupled with new measurements of mass ratios using growing stages of superhumps, we now have a clearer and statistically greatly improved evolutionary path near the terminal stage of evolution of cataclysmic variables. Three objects (V452 Cas, KK Tel, and ASASSN-15cl) appear to have slowly growing superhumps, which is proposed to reflect the slow growth of the 3 : 1 resonance near the stability border. ASASSN-15sl, ASASSN-15ux, SDSSJ074859.55+312512.6, and CRTS J200331.3-284941 are newly identified eclipsing SUUMa-type (or WZ Sge-type) dwarf novae. ASASSN- 15cy has a short (0.050 d) superhump period and appears to belong to EI Psc-type objects with compact secondaries having an evolved core. ASASSN-15gn, ASASSN- 15hn, ASASSN-15kh, and ASASSN-16bu are candidate period bouncers with superhump periods longer than 0.06 d. We have newly obtained superhump periods for 79 objects and 13 orbital periods, including periods from early superhumps. In order that future observations will be more astrophysically beneficial and rewarding to observers, we propose guidelines on how to organize observations of various superoutbursts

Reciprocal priming between receptor tyrosine kinases at recycling endosomes orchestrates cellular signalling outputs

From Wiley via Jisc Publications RouterHistory: received 2020-10-29, rev-recd 2021-04-27, accepted 2021-04-28, pub-electronic 2021-06-04Article version: VoRPublication status: PublishedFunder: Wellcome Trust; Grant(s): 107636/Z/15/Z, 210002/Z/17/ZFunder: UKRI | Biotechnology and Biological Sciences Research Council (BBSRC); Id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/R015864/1, BB/M011208/1Funder: UKRI | Medical Research Council (MRC); Id: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/T016043/1Funder: Cancer Research UK (CRUK); Id: http://dx.doi.org/10.13039/501100000289; Grant(s): A27445Funder: NIHR Manchester Biomedical Research Centre; Grant(s): IS‐BRC‐1215‐20007Funder: Breast Cancer Now; Grant(s): MAN‐Q2‐Y4/5Abstract: Integration of signalling downstream of individual receptor tyrosine kinases (RTKs) is crucial to fine‐tune cellular homeostasis during development and in pathological conditions, including breast cancer. However, how signalling integration is regulated and whether the endocytic fate of single receptors controls such signalling integration remains poorly elucidated. Combining quantitative phosphoproteomics and targeted assays, we generated a detailed picture of recycling‐dependent fibroblast growth factor (FGF) signalling in breast cancer cells, with a focus on distinct FGF receptors (FGFRs). We discovered reciprocal priming between FGFRs and epidermal growth factor (EGF) receptor (EGFR) that is coordinated at recycling endosomes. FGFR recycling ligands induce EGFR phosphorylation on threonine 693. This phosphorylation event alters both FGFR and EGFR trafficking and primes FGFR‐mediated proliferation but not cell invasion. In turn, FGFR signalling primes EGF‐mediated outputs via EGFR threonine 693 phosphorylation. This reciprocal priming between distinct families of RTKs from recycling endosomes exemplifies a novel signalling integration hub where recycling endosomes orchestrate cellular behaviour. Therefore, targeting reciprocal priming over individual receptors may improve personalized therapies in breast and other cancers

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism