Shifting molecular localization by plasmonic coupling in a single-molecule mirage

Over the last decade, two fields have dominated the attention of sub-diffraction photonics research: Plasmonics and fluorescence nanoscopy. Nanoscopy based on single-molecule localization offers a practical way to explore plasmonic interactions with nanometre resolution. However, this seemingly straightforward technique may retrieve false positional information. Here, we make use of the DNA origami technique to both control a nanometric separation between emitters and a gold nanoparticle, and as a platform for super-resolution imaging based on single-molecule localization. This enables a quantitative comparison between the position retrieved from single-molecule localization, the true position of the emitter and full-field simulations. We demonstrate that plasmonic coupling leads to shifted molecular localizations of up to 30 nm: A single-molecule mirage.Fil: Raab, Mario. Technical University Of Braunschweig; AlemaniaFil: Vietz, Carolin. Technical University of Braunschweig; Alemania; ArgentinaFil: Stefani, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Acuna, Guillermo Pedro. Technical University Of Braunschweig; AlemaniaFil: Tinnefeld, Philip. Technical University Of Braunschweig; Alemani

CEACAM1 regulates TIM-3-mediated tolerance and exhaustion

T-cell immunoglobulin domain and mucin domain-3 (TIM-3, also known as HAVCR2) is an activation-induced inhibitory molecule involved in tolerance and shown to induce T-cell exhaustion in chronic viral infection and cancers[superscript 1, 2, 3, 4, 5]. Under some conditions, TIM-3 expression has also been shown to be stimulatory. Considering that TIM-3, like cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), is being targeted for cancer immunotherapy, it is important to identify the circumstances under which TIM-3 can inhibit and activate T-cell responses. Here we show that TIM-3 is co-expressed and forms a heterodimer with carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on activated T cells and involved in T-cell inhibition[superscript 6, 7, 8, 9, 10]. Biochemical, biophysical and X-ray crystallography studies show that the membrane-distal immunoglobulin-variable (IgV)-like amino-terminal domain of each is crucial to these interactions. The presence of CEACAM1 endows TIM-3 with inhibitory function. CEACAM1 facilitates the maturation and cell surface expression of TIM-3 by forming a heterodimeric interaction in cis through the highly related membrane-distal N-terminal domains of each molecule. CEACAM1 and TIM-3 also bind in trans through their N-terminal domains. Both cis and trans interactions between CEACAM1 and TIM-3 determine the tolerance-inducing function of TIM-3. In a mouse adoptive transfer colitis model, CEACAM1-deficient T cells are hyper-inflammatory with reduced cell surface expression of TIM-3 and regulatory cytokines, and this is restored by T-cell-specific CEACAM1 expression. During chronic viral infection and in a tumour environment, CEACAM1 and TIM-3 mark exhausted T cells. Co-blockade of CEACAM1 and TIM-3 leads to enhancement of anti-tumour immune responses with improved elimination of tumours in mouse colorectal cancer models. Thus, CEACAM1 serves as a heterophilic ligand for TIM-3 that is required for its ability to mediate T-cell inhibition, and this interaction has a crucial role in regulating autoimmunity and anti-tumour immunity.American Association for Cancer Research. Pancreatic Cancer Action Networ

Using DNA origami nanorulers as traceable distance measurement standards and nanoscopic benchmark structures

Abstract In recent years, DNA origami nanorulers for superresolution (SR) fluorescence microscopy have been developed from fundamental proof-of-principle experiments to commercially available test structures. The self-assembled nanostructures allow placing a defined number of fluorescent dye molecules in defined geometries in the nanometer range. Besides the unprecedented control over matter on the nanoscale, robust DNA origami nanorulers are reproducibly obtained in high yields. The distances between their fluorescent marks can be easily analysed yielding intermark distance histograms from many identical structures. Thus, DNA origami nanorulers have become excellent reference and training structures for superresolution microscopy. In this work, we go one step further and develop a calibration process for the measured distances between the fluorescent marks on DNA origami nanorulers. The superresolution technique DNA-PAINT is used to achieve nanometrological traceability of nanoruler distances following the guide to the expression of uncertainty in measurement (GUM). We further show two examples how these nanorulers are used to evaluate the performance of TIRF microscopes that are capable of single-molecule localization microscopy (SMLM)

The Routledge Handbook to the History and Society of the Americas

Kaltmeier O, Raab J, Foley MS, Nash A, Rinke S, Rufer M, eds. The Routledge Handbook to the History and Society of the Americas. London / New York: Routledge; 2019.The colonial heritage and its renewed aftermaths – expressed in the inter-American experiences of slavery, indigeneity, dependence, and freedom movements, to mention only a few aspects – form a common ground of experience in the Western Hemisphere. The flow of peoples, goods, knowledge and finances have promoted interdependence and integration that cut across borders and link the countries of North and South America together. The nature of this transversally related and multiply interconnected region can only be captured through a transnational, multidisciplinary, and comprehensive approach. The Routledge Handbook to the History and Society of the Americas explores the history and society of the Americas, placing particular emphasis on collective and intertwined experiences. Forty-four chapters cover a range of concepts and dynamics in the Americas from the colonial period until the present century: The shared histories and dynamics of Inter-American relationships are considered through pre-Hispanic empires, colonization, European hegemony, migration, multiculturalism, and political and economic interdependences. Key concepts are selected and explored from different geopolitical, disciplinary, and epistemological perspectives. Highlighting the contested character of key concepts that are usually defined in strict disciplinary terms, the Handbook provides the basis for a better and deeper understanding of inter-American entanglements. This multidisciplinary approach will be of interest to a broad array of academic scholars and students in history, sociology, political science cultural, postcolonial, gender, literary, and globalization stu

Психологічні стани висококваліфікованих спортсменів у різних країнах

Modern sport characterized as important part of human society. Among different kinds of sport the wrestling is popular and spectacularity especially in younger’s people. In last ten years the Olympic wrestling changes the competition rules. All of this changes concern the higher of intensiveness of wrestling fights. Due of this process the optimization of training preparedness of wrestlers is very topical. The scientific and methodic support is a key component of the system preparedness of elite wrestlers. The main parts of scientific support of elite wrestlers are includes: functional, psychological and technical preparedness.Сучасний спорт характеризується як важлива частина людського суспільства. Серед різних видів спорту боротьба користується популярністю та видовищністю, особливо у молоді. За останні десять років олімпійська боротьба змінила правила змагань. Усі ці зміни стосуються підвищення інтенсивності боротьби. У зв’язку з цим оптимізація тренувальної підготовленості борців є дуже актуальною. Науково-методичне забезпечення є ключовим компонентом системної підготовки борців вищого рівня. До основних складових наукового супроводу борців вищого рівня входять: функціональна, психологічна та технічна підготовленість

History and society in the Americas in the 20th and 21st centuries. Inter-American thresholds and critical key concept

Kaltmeier O, Rufer M, Foley MS. History and society in the Americas in the 20th and 21st centuries. Inter-American thresholds and critical key concept. In: Kaltmeier O, Raab J, Foley MS, Nash A, Rinke S, Rufer M, eds. The Routledge Handbook to the History and Society of the Americas. London / New York: Routledge; 2019: 207-221

Modernization

Schulze F. Modernization. In: Kaltmeier O, Raab J, Foley M, Nash A, Rinke S, Rufer M, eds. The Routledge Handbook to the History and Society of the Americas. London: Routledge; 2019: 355-364

Indigeneity

Kaltmeier O. Indigeneity. In: Kaltmeier O, Raab J, Foley MS, Nash A, Rinke S, Rufer M, eds. Routledge Handbook to the History and Society of the Americas. London / New York: Routledge; 2019: 319-329

Religious Beliefs

Schäfer H. Religious Beliefs. In: Kaltmeier O, Raab J, Foley MS, Nash A, Rinke S, Rufer M, eds. The Routledge Handbook to the History and Society of the Americas. London ; New York: Routledge; 2019: 403-414

Prolonged monitoring of postprandial lipid metabolism after a western meal rich in linoleic acid and carbohydrates

Today, increased awareness has been raised regarding high consumption of n-6 polyunsaturated fatty acids (n-6 PUFA) in western diets. A comprehensive analysis of total and individual postprandial fatty acid (FA) profiles would provide insights into metabolic turnover and related health effects. After an overnight fast, nine healthy adults consumed a mixed meal composed of 97 g carbohydrate and 45 g fat of which 26.4 g was linoleic acid (LA). Non-esterified fatty acids (NEFA), phospholipid fatty acids (PL-FA) and triacylglycerol fatty acids (TG-FA) were monitored in plasma samples, at baseline and hourly over 7 h postprandial. Total TG-FA concentration peaked at 2h postprandial followed by a constant decline. LA from TG18:2n-6 and behenic acid from TG22:0 showed the highest response among TG-FA, with a biphasic response detected for the former. PL-FA exhibited no change. Total NEFA initially decreased reaching nadir at 1h, then increased reaching its maximum value at 7h. The individual NEFA showed the same response curve except LA and some very long chain saturated fatty acids (VLCSFA, â Ľ 20 carbon chain length) that markedly increased shortly after the meal intake. The similarities and dissimilarities in lipid profiles between study subjects at different time points were visualized using non-metric multidimensional scaling (NMDS). Overall, the results indicate that postprandial levels of LA and VLCSFA either as NEFA or TG were most affected by the test meal, which might provide an explanation for the health effects of this dietary lifestyle characterized by high intake of mixed meals rich in n-6 PUFA.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author