Molecular profiling of a rare rosette-forming glioneuronal tumor arising in the spinal cord

Rosette-forming glioneuronal tumor (RGNT) of the IV ventricle is a rare and recently recognized brain tumor entity. It is histologically composed by two distinct features: a glial component, resembling pilocytic astrocytoma, and a component forming neurocytic rosettes and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in the spinal cord. Following an immunohistochemistry validation, we further performed an extensive genomic analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. We observed the loss of 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Local amplifications in 9q34.2 and 19p13.3 (encompassing the gene SBNO2) were identified. Moreover, we observed focal gains/losses in several chromosomes. Additionally, on chromosome 7, we identified the presence of the KIAA1549:BRAF gene fusion, which was further validated by RT-PCR and FISH. Across all mutational analyses, we detected and validated the somatic mutations of the genes MLL2, CNNM3, PCDHGC4 and SCN1A. Our comprehensive molecular profiling of this RGNT suggests that MAPK pathway and methylome changes, driven by KIAA1549:BRAF fusion and MLL2 mutation, respectively, could be associated with the development of this rare tumor entity.Conselho Nacional de Desenvolvimento Científico e Tecnológico [475358/2011-2] to RMR (www.cnpq.br); Fundação de Amparo a Pesquisa do Estado de São Paulo [2012/19590-0] to RMR and [2011/08523-7 and 2012/08287-4] to LTB (www.fapesp.br); the Foundation for Science and Technology (FCT) [PTDC/SAU-ONC/115513/2009] to RMR; and the National Cancer Institute [P30CA046934] to MG

Defining murine organogenesis at single-cell resolution reveals a role for the leukotriene pathway in regulating blood progenitor formation.

During gastrulation, cell types from all three germ layers are specified and the basic body plan is established 1 . However, molecular analysis of this key developmental stage has been hampered by limited cell numbers and a paucity of markers. Single-cell RNA sequencing circumvents these problems, but has so far been limited to specific organ systems 2 . Here, we report single-cell transcriptomic characterization of >20,000 cells immediately following gastrulation at E8.25 of mouse development. We identify 20 major cell types, which frequently contain substructure, including three distinct signatures in early foregut cells. Pseudo-space ordering of somitic progenitor cells identifies dynamic waves of transcription and candidate regulators, which are validated by molecular characterization of spatially resolved regions of the embryo. Within the endothelial population, cells that transition from haemogenic endothelial to erythro-myeloid progenitors specifically express Alox5 and its co-factor Alox5ap, which control leukotriene production. Functional assays using mouse embryonic stem cells demonstrate that leukotrienes promote haematopoietic progenitor cell generation. Thus, this comprehensive single-cell map can be exploited to reveal previously unrecognized pathways that contribute to tissue development

Platelet function is modified by common sequence variation in megakaryocyte super enhancers

Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through ex vivo and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions

Existence and uniqueness for non-linear singular integral equations used in fluid mechanics

summary:Non-linear singular integral equations are investigated in connection with some basic applications in two-dimensional fluid mechanics. A general existence and uniqueness analysis is proposed for non-linear singular integral equations defined on a Banach space. Therefore, the non-linear equations are defined over a finite set of contours and the existence of solutions is investigated for two different kinds of equations, the first and the second kind. Moreover, the existence of solutions is further studied for non-linear singular integral equations over a finite number of arbitrarily ordered arcs. An application to fluid mechanics theory is finally given for the determination of the form of the profiles of a turbomachine in two-dimensional flow of an incompressible fluid

Finite-part singular integral approximations in Hilbert spaces

Some new approximation methods are proposed for the numerical evaluation of the finite-part singular integral equations defined on Hilbert spaces when their singularity consists of a homeomorphism of the integration interval, which is a unit circle, on itself. Therefore, some existence theorems are proved for the solutions of the finite-part singular integral equations, approximated by several systems of linear algebraic equations. The method is further extended for the proof of the existence of solutions for systems of finite-part singular integral equations defined on Hilbert spaces, when their singularity consists of a system of diffeomorphisms of the integration interval, which is a unit circle, on itself

Intestinal adaptation in short bowel syndrome: A case report

Short bowel syndrome is a clinical entity that includes loss of energy, fluid, electrolytes or micronutrient balance because of inadequate functional intestinal length. This case report demonstrates the case of a woman who compensated for short bowel syndrome through intestinal adaptation, which is a complex process worthy of further investigation for the avoidance of dependence on total parenteral nutrition and of intestinal transplantation in such patients. © 2015 Arab Journal of Gastroenterology

© Hindawi Publishing Corp. FINITE-PART SINGULAR INTEGRAL APPROXIMATIONS IN HILBERT SPACES

Some new approximation methods are proposed for the numerical evaluation of the finitepart singular integral equations defined on Hilbert spaces when their singularity consists of a homeomorphism of the integration interval, which is a unit circle, on itself. Therefore, some existence theorems are proved for the solutions of the finite-part singular integral equations, approximated by several systems of linear algebraic equations. The method is further extended for the proof of the existence of solutions for systems of finite-part singular integral equations defined on Hilbert spaces, when their singularity consists of a system of diffeomorphisms of the integration interval, which is a unit circle, on itself. 2000 Mathematics Subject Classification: 65L10, 65R20

Small airways’ function in Obstructive Sleep Apnea-Hypopnea Syndrome

Introduction and objectives: Most of the studies of the pathophysiology of Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) focus on the collapsibility and obstruction of the upper airways. The aim of our study was the investigation of small airways’ function in patients with OSAHS. Materials and methods: We studied 23 patients (mean age, 51.6 years) diagnosed with mild to severe OSAHS, without comorbidities and 8 controls (mean age, 45.9 years). All subjects underwent full polysomnography sleep study; spirometry and maximum flow/volume curves while breathing room air and a mixture of 80%He-20%O2. The volume of equal flows (VisoV⋅) of the two curves and the difference of flows at 50% of FVC (ΔV˙max50) were calculated, as indicates of small airways’ function. Results: The results showed that VisoV⋅ was significantly increased in patients with OSAHS compared with controls (18.79 ± 9.39 vs. 4.72 ± 4.68, p = 0.004). No statistically significantly difference was found in ΔV˙max50% (p = 0.551); or the maximum Expiratory flow at 25–75% of FVC (p = 0.067) and the maximum expiratory flow at 50% of FVC (p = 0.174) breathing air. Conclusions: We conclude that at the time of the diagnosis of OSAHS, the function of the small airways is affected. This could be due to breathing at low lung volumes and the cyclic closure/opening of the small airways and may affect the natural history of OSAHS. The findings could lead to new therapeutic implications, targeting directly the small airways. © 2020 Sociedade Portuguesa de Pneumologi