Spontaneous emission enhancement of a single molecule by a double-sphere nanoantenna across an interface

We report on two orders of magnitude reduction in the fluorescence lifetime when a single molecule placed in a thin film is surrounded by two gold nanospheres across the film interface. By attaching one of the gold particles to the end of a glass fiber tip, we could control the modification of the molecular fluorescence at will. We find a good agreement between our experimental data and the outcome of numerical calculations

Resolution and enhancement in nanoantenna-based fluorescence microscopy

Single gold nanoparticles can act as nanoantennas for enhancing the fluorescence of emitters in their near-fields. Here we present experimental and theoretical studies of scanning antenna-based fluorescence microscopy as a function of the diameter of the gold nanoparticle. We examine the interplay between fluorescence enhancement and spatial resolution and discuss the requirements for deciphering single molecules in a dense sample. Resolutions better than 20 nm and fluorescence enhancement up to 30 times are demonstrated experimentally. By accounting for the tip shaft and the sample interface in finite-difference time-domain calculations, we explain why the measured fluorescence enhancements are higher in the presence of an interface than the values predicted for a homogeneous environment.Comment: 10 pages, 3 figures. accepted for publication in Nano Letter

Efficient coupling of photons to a single molecule and the observation of its resonance fluorescence

Single dye molecules at cryogenic temperatures display many spectroscopic phenomena known from free atoms and are thus promising candidates for fundamental quantum optical studies. However, the existing techniques for the detection of single molecules have either sacrificed the information on the coherence of the excited state or have been inefficient. Here we show that these problems can be addressed by focusing the excitation light near to the absorption cross section of a molecule. Our detection scheme allows us to explore resonance fluorescence over 9 orders of magnitude of excitation intensity and to separate its coherent and incoherent parts. In the strong excitation regime, we demonstrate the first observation of the Mollow triplet from a single solid-state emitter. Under weak excitation we report the detection of a single molecule with an incident power as faint as 150 attoWatt, paving the way for studying nonlinear effects with only a few photons.Comment: 6 figure

Early influences on cardiovascular and renal development

The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism

Einfluss von N-Düngermenge und Nitrifikationshemmung auf die direkten N2O-Emissionen eines gemüsebaulich genutzten Ackerbodens

Lachgas (N2O) ist ein klimarelevantes Spurengas, es trägt zum Ozonabbau in der Stratosphäre sowie zu 8% am anthropogenen Treibhauseffekt bei und stammt zum Großteil aus landwirtschaftlich genutzten Böden. Ziel dieser Studie war die Ermittlung belastbarer annueller Daten zur N2O-Freisetzung aus gemüsebaulich genutzten Ackerböden Mitteleuropas, d.h. aus einer Gegend mit ausgeprägten Frost-Tau-Zyklen. Ferner sollte das Potential zur Minderung der direkten N2O-Emissionen untersucht werden. Hierzu wurde sowohl eine reduzierte Düngung als auch der Zusatz eines Nitrifikationshemmstoffs getestet. Die Beiträge von N-Dünger und Ernterückständen an den untersuchten Emissionen wurden mittels 15N-markiertem Dünger ermittelt. Die Emissionsfaktoren der verschiedenen Düngerstufen lagen zwischen 0,9 und 1,7. Durch Düngerreduktion bzw. Zusatz von Nitrifikationshemmstoff wurde bei konstantem Ertrag die N2O-Freisetzung um 24 bzw 43% reduziert. Die Blumenkohlernterückstände verursachten 21% der Jahresemissionen und sorgten für hohe Winteremissionen, während Tau-Peaks kaum ausgeprägt waren

YTHDF proteins and m⁶A-RNA clients undergo autophagic turnover during contact inhibition

The YTHDF protein family plays a critical role in cancer development by recognizing and regulating the stability of N6-methyladenosine (m6A)-modified RNA. Here, we reveal an autophagy-dependent mechanism controlling YTHDF protein levels. Using contact inhibition as a cellular model system, we show YTHDF proteins to be rapidly degraded, coinciding with increased autophagy and decreased mTOR activity. Upon pharmacological mTOR inhibition, YTHDF2 is also downregulated via lysosomal degradation. YTHDF2 selectively interacts with the autophagy modifier GABARAP L2 through LC3-interacting region (LIR) motifs in its unstructured N- and C-terminal regions. Autophagic YTHDF2 downregulation results in the co-degradation of its bound m6A-modified RNA clients. While YTHDF depletion induces cell death in contact-inhibition-deficient HCT116 cancer cells, contact-inhibited MRC5 and RPE1 cells remain unaffected. Our findings uncover a regulatory pathway that governs YTHDF protein stability with significant implications for cancer biology and cell fate determination and suggest the existence of an autophagy-mediated degradation pathway for m6A-modified RNA

Strontium isoscapes for provenance, mobility and migration: the way forward

Strontium isotopes (87Sr/86Sr) are increasingly used as a provenance tool in multiple disciplines. Application to biological materials requires knowledge of the variation in bioavailable 87Sr/86Sr across the landscape, potentially in the form of an isoscape (a quantitative model of spatial isotopic variability). This paper summarizes and provides advice on our current understanding of the main concerns in creating and interpreting isoscapes of bioavailable 87Sr/86Sr. Isoscape creation approaches include domain mapping, geostatistical contour mapping and machine learning, the last becoming more readily achievable with the availability of software packages. It is critically important to develop isoscapes at a resolution appropriate for addressing the research questions. Choice of sample materials depends on the research questions and availability: plants or fauna with small ranges are favoured, with some analytes (snails, soil leachates) posing challenges. Interpreting 87Sr/86Sr in biological tissues requires considering Sr metabolism and the timing of tissue formation, thus far underappreciated. The numerous sources of error involved in developing and applying isoscapes must be recognized to avoid over-interpreting data and spurious provenance precision. We hope this paper will help researchers investigating provenance, mobility, landscape use and migration to develop the most appropriate isoscapes for their purposes, and possible future use by others.1. Introduction 2. Approaches to isoscape development: are machine-learning isoscapes better than other types? 3. What is the best sample collection methodology for creating isoscapes? 4. Are plants the best samples for isoscape creation? 5. How should samples be prepared and analysed? 5.1. Sample measurement metadata 5.2. Soil samples 5.3. Plant samples 5.4. Bone and enamel samples 6. What are the complications with assigning provenance? 7. What are the influences of biology and metabolism on consumer tissue Sr? 8. Do specific applications require custom isoscapes? 9. What are the remaining uncertainties and limitations of strontium isoscapes? 9.1. Sources of error 10. Where to from here? 10.1. Adding other isotopes 10.2. Isoscapes for forensics 10.3. Data repositories 10.4. Ethics and accessibility 11. Conclusion

Pathophysiology of the endothelin system - lessons from genetically manipulated animal models

Shortly after discovery of ET-1 in 1988, the entire endothelin system was characterized. The endothelin system consists of the three peptides ET-1, ET-2 and ET-3, their G-protein-coupled receptors endothelin receptor A and B (ETRA and ETRB) and the two endothelin-converting enzymes (ECE-1 and ECE-2). Genetically modified animal models are an important tool in biomedical research. Here we describe the key findings obtained from genetically modified animal models either over-expressing compounds of the ET system or lacking these compounds (knockout mice). Results from the different transgenic and knockout models disclose that the ET system plays a major role in embryonic development. Two ET system-dependent neural crest-driven developmental pathways become obvious: one of them being an ET-1/ETAR axis, responsible for cardio-renal function and development as well as cranial development; the other seems to be an ET-3/ETBR mediated signalling pathway. Mutations within this axis are associated with disruptions in epidermal melanocytes and enteric neurons. These findings led to the discovery of similar findings in humans with Hirschsprung disease. In adult life the ET system is most important in the cardiovascular system and plays a role in fibrotic remodelling of the heart, lung and kidney as well as in the regulation of water and salt excretion