Solid-state nanopores are single-molecule sensors that hold great potential for rapid protein and nucleic-acid analysis. Despite their many opportunities, the conventional ionic current detection scheme that is at the heart of the sensor suffers inherent limitations. This scheme intrinsically couples signal strength to the driving voltage, requires the use of high-concentration electrolytes, suffers from capacitive noise, and impairs high-density sensor integration. Here, we propose a fundamentally different detection scheme based on the enhanced light transmission through a plasmonic nanopore. We demonstrate that translocations of single DNA molecules can be optically detected, without the need of any labeling, in the transmitted light intensity through an inverted-bowtie plasmonic nanopore. Characterization and the cross-correlation of the optical signals with their electrical counterparts verify the plasmonic basis of the optical signal. We demonstrate DNA translocation event detection in a regime of driving voltages and buffer conditions where traditional ionic current sensing fails. This label-free optical detection scheme offers opportunities to probe native DNA–protein interactions at physiological conditions.

No abstract

Decreased expression of mitochondrial frataxin (FXN) causes Friedreich's ataxia (FRDA), a neurodegenerative disease with type 2 diabetes (T2D) as severe comorbidity. Brown adipose tissue (BAT) is a mitochondria-enriched and antidiabetic tissue that turns excess energy into heat to maintain metabolic homeostasis. Here we report that the FXN knock-in/knock-out (KIKO) mouse shows hyperlipidemia, reduced energy expenditure and insulin sensitivity, and elevated plasma leptin, recapitulating T2D-like signatures. FXN deficiency leads to disrupted mitochondrial ultrastructure and oxygen consumption as well as lipid accumulation in BAT. Transcriptomic data highlights cold intolerance in association with iron-mediated cell death (ferroptosis). Impaired PKA-mediated lipolysis and expression of genes controlling mitochondrial metabolism, lipid catabolism and adipogenesis were observed in BAT of KIKO mice as well as in FXN-deficient T37i brown and primary adipocytes. Significant susceptibility to ferroptosis was observed in adipocyte precursors that showed increased lipid peroxidation and decreased glutathione peroxidase 4. Collectively our data point to BAT dysfunction in FRDA and suggest BAT as promising therapeutic target to overcome T2D in FRDA.

Phase singularities are dislocations widely studied in optical fields as well as in other areas of physics. With experiment and theory we show that the vectorial nature of light affects the spatial distribution of phase singularities in random light fields. While in scalar random waves phase singularities exhibit spatial distributions reminiscent of particles in isotropic liquids, in vector fields their distribution for the different vector components becomes anisotropic due to the direct relation between propagation and field direction. By incorporating this relation in the theory for scalar fields by Berry and Dennis, we quantitatively describe our experiments.PACS numbers: 02.40.Xx Finding correlations in chaotic systems is the first step towards understanding. Many are the fields where such predictions could be exploited, from weather forecast to economic modeling [1,2]. The study of random phenomena is a topic of great interest and inspiration for many branches of physics as well. In electromagnetism, for example, random wave fields have been a topic of intense studies since decades, an outstanding example being Anderson localization of light [3]. More recently the scientific interest on random wave fields has continued intensively, ranging from useful techniques as noninvasive imaging with speckle correlation [4] to fascination concerning the observation of rogue waves in optical fields [5,6]. Zooming into the structure of a random wave field, attention has been pointed to deep-subwavelength dislocations known as phase singularities [7].Phase singularities are locations in which the phase of a scalar complex field is not defined. In two-dimensional fields these locations are points in the plane. Although they are just a discrete set of points, phase singularities can describe the basic properties of the field in which they arise. For this reason they are widely studied in wave fields [8][9][10][11][12][13][14], as well as in many areas of physics, where they are better-known as topological defects in nematics [15] or as vortices in superfluids [16].For a single frequency phase singularities are fixed in space, and their spatial distribution in a scalar field of monochromatic random waves has been analytically modeled by Berry and Dennis [17]. The hallmark of such a distribution is a clear pair correlation, reminiscent of that of particles in liquids. By realizing random waves ensembles in microwave billiards [18][19][20], the correlation of phase singularities was tested for a field perpendicular to the plane of the billiard, showing excellent agreement with the theoretical expectations [21]. For such a field and in that geometry indeed scalar theory was appropriate. However, electromagnetic waves are vectorial in nature, and in a different framework it was already demonstrated how the presence of a spin degree of freedom can affect the correlation properties of a random field [22,23].Here, we show how the vectorial nature of light affects the distribution of its phase singularities. By mapping the in-...

In the yeast Kluyveromyces lactis, the inactivation of structural or regulatory glycolytic and fermentative genes generates obligate respiratory mutants which can be characterized by sensitivity to the mitochondrial drug antimycin A on glucose medium (Rag(-) phenotype). Rag(-) mutations can occasionally be generated by the inactivation of genes not evidently related to glycolysis or fermentation. One such gene is the hypoxic regulatory gene KlMGA2. In this work, we report a study of the many defects, in addition to the Rag(-) phenotype, generated by KlMGA2 deletion. We analyzed the fermentative and respiratory metabolism, mitochondrial functioning and morphology in the Klmga2Δ strain. We also examined alterations in the regulation of the expression of lipid biosynthetic genes, in particular fatty acids, ergosterol and cardiolipin, under hypoxic and cold stress and the phenotypic suppression by unsaturated fatty acids of the deleted strain. Results indicate that, despite the fact that the deleted mutant strain had a typical glycolytic/fermentative phenotype and KlMGA2 is a hypoxic regulatory gene, the deletion of this gene generated defects linked to mitochondrial functions suggesting new roles of this protein in the general regulation and cellular fitness of K. lactis. Supplementation of unsaturated fatty acids suppressed or modified these defects suggesting that KlMga2 modulates membrane functioning or membrane-associated functions, both cytoplasmic and mitochondrial.