TOPCAT and Gaia

TOPCAT, and its command line counterpart STILTS, are powerful tools for working with large source catalogues. ESA's Gaia mission, most recently with its second data release, is producing source catalogues of unprecedented quality for more than a billion sources. This paper presents some examples of how TOPCAT and STILTS can be used for analysis of Gaia data.Comment: 4 pages, 2 figures; to appear in the Proceedings of ADASS 2018, Astronomical Society of the Pacific (ASP) Conference Serie

Fatty Acid and Peptide Profiles in Plasma Membrane and Membrane Rafts of PUFA Supplemented RAW264.7 Macrophages

The eukaryotic cell membrane possesses numerous complex functions, which are essential for life. At this, the composition and the structure of the lipid bilayer are of particular importance. Polyunsaturated fatty acids may modulate the physical properties of biological membranes via alteration of membrane lipid composition affecting numerous physiological processes, e.g. in the immune system. In this systematic study we present fatty acid and peptide profiles of cell membrane and membrane rafts of murine macrophages that have been supplemented with saturated fatty acids as well as PUFAs from the n-3, the n-6 and the n-9 family. Using fatty acid composition analysis and mass spectrometry-based peptidome profiling we found that PUFAs from both the n-3 and the n-6 family have an impact on lipid and protein composition of plasma membrane and membrane rafts in a similar manner. In addition, we found a relation between the number of bis-allyl-methylene positions of the PUFA added and the unsaturation index of plasma membrane as well as membrane rafts of supplemented cells. With regard to the proposed significance of lipid microdomains for disease development and treatment our study will help to achieve a targeted dietary modulation of immune cell lipid bilayers

Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis

<p>Abstract</p> <p>Background</p> <p>Lipid-rich tumours have been associated with increased cancer metastasis and aggressive clinical behaviours. Nonetheless, pathologists cannot classify lipid-rich tumours as a clinically distinctive form of carcinoma due to a lack of mechanistic understanding on the roles of lipids in cancer development.</p> <p>Methods</p> <p>Coherent anti-Stokes Raman scattering (CARS) microscopy is employed to study cancer cell behaviours in excess lipid environments <it>in vivo </it>and <it>in vitro</it>. The impacts of a high fat diet on cancer development are evaluated in a Balb/c mice cancer model. Intravital flow cytometry and histology are employed to enumerate cancer cell escape to the bloodstream and metastasis to lung tissues, respectively. Cancer cell motility and tissue invasion capability are also evaluated in excess lipid environments.</p> <p>Results</p> <p>CARS imaging reveals intracellular lipid accumulation is induced by excess free fatty acids (FFAs). Excess FFAs incorporation onto cancer cell membrane induces membrane phase separation, reduces cell-cell contact, increases surface adhesion, and promotes tissue invasion. Increased plasma FFAs level and visceral adiposity are associated with early rise in circulating tumour cells and increased lung metastasis. Furthermore, CARS imaging reveals FFAs-induced lipid accumulation in primary, circulating, and metastasized cancer cells.</p> <p>Conclusion</p> <p>Lipid-rich tumours are linked to cancer metastasis through FFAs-induced physical perturbations on cancer cell membrane. Most importantly, the revelation of lipid-rich circulating tumour cells suggests possible development of CARS intravital flow cytometry for label-free detection of early-stage cancer metastasis.</p

Европейское соглашение по применению ферментной заместительной терапии у взрослых пациентов с болезнью Помпе: 10-летний опыт

.Реферативный перевод из: van der Ploeg A. T., Kruijshaar M. E., Toscano A. et al. European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease: a 10-year experience. Eur J Neurol 2017;4(6):768-e31. DOI: 10.1200/JCO.2016.71.6472.Перевод: Сергей Сергеевич Никитин Введение. Болезнь Помпе – редкое наследственное мышечное заболевание, для лечения которого с 2006 г. применяют ферментную заместительную терапию. В документе представлены последние рекомендации по началу и прекращению ферментной заместительной терапии у взрослых пациентов. Методы. В ходе Европейского консорциума по болезни Помпе эксперты из 11 европейских стран обсудили данные литературы об эффективности ферментной заместительной терапии у взрослых пациентов на основании оценки показателей прогноза клинического течения и качества жизни больных. В данной статье представлены результаты обсуждений 3 согласительных совещаний во время консорциума. Результаты. Специалисты пришли к соглашению относительно подтверждения диагноза болезни Помпе, сроков начала ферментной заместительной терапии, показаний и условий ее прекращения и применения во время беременности. Общее соглашение по перечисленным вопросам принято на основании мнения экспертов и подтверждено данными литературы. При проведении исследований в группах были получены данные о положительном эффекте ферментной заместительной терапии. Анализ проводили при оценке 586 взрослых пациентов из 1 клинического испытания и 43 наблюдательных исследований. Обратили внимание на индивидуальные различия в эффективности лечения, обнаруженные в отдельных сообщениях. В 11 наблюдательных исследованиях, включающих пациентов с тяжелой степенью поражения, также была доказана эффективность ферментной заместительной терапии. Исследования эффектов лечения у больных на доклинической стадии заболевания отсутствуют. Выводы. В ходе 1-го Европейского консорциума на основании международного экспертного мнения составлены рекомендации по началу и прекращению ферментной заместительной терапии у взрослых пациентов с болезнью Помпе

Mechanisms of leukocyte lipid body formation and function in inflammation

An area of increasingly interest for the understanding of cell signaling are the spatio-temporal aspects of the different enzymes involved in lipid mediator generation (eicosanoid-forming enzymes, phospholipases and their regulatory kinases and phosphatases) and pools of lipid precursors. The compartmentalization of signaling components within discrete and dynamic sites in the cell is critical for specificity and efficiency of enzymatic reactions of phosphorilation, enzyme activation and function. We hypothesized that lipid bodies - inducible non-membrane bound cytoplasmic lipid domains - function as specialized intracellular sites of compartmentalization of signaling with major roles in lipid mediator formation within leukocytes engaged in inflammatory process. Over the past years substantial progresses have been made demonstrating that all enzymes involved in eicosanoid synthesis localize at lipid bodies and lipid bodies are distinct sites for eicosanoid generation. Here we will review our current knowledge on the mechanisms of formation and functions of lipid bodies pertinent to inflammation

Modulation of 11β-hydroxysteroid dehydrogenase as a strategy to reduce vascular inflammation

Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macrophage and lymphocyte infiltration. Although acutely glucocorticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorticoid action within the lesion may reduce neointimal proliferation and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating levels due to pre-receptor metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). 11β-HSD2 converts active glucocorticoids into inert 11-keto forms. 11β-HSD1 catalyses the reverse reaction, regenerating active glucocorticoids. 11β-HSD2-deficiency/ inhibition causes hypertension, whereas deficiency/ inhibition of 11β-HSD1 generates a cardioprotective lipid profile and improves glycemic control. Importantly, 11β-HSD1-deficiency/ inhibition is atheroprotective, whereas 11β-HSD2-deficiency accelerates atherosclerosis. These effects are largely independent of systemic risk factors, reflecting modulation of glucocorticoid action and inflammation within the vasculature. Here, we consider whether evidence linking the 11β-HSDs to vascular inflammation suggests these isozymes are potential therapeutic targets in vascular injury and atherosclerosis