Sex Specific Changes in Tryptophan Breakdown Over a 6 Week Treatment Period

Introduction: Despite the knowledge of sex differences concerning neurobiological parameters as well as clinical course of illness in individuals with mood disorders, the literature concerning tryptophan (Trp) breakdown, specific for women and men, is sparse to date. The current study aimed to evaluate sex differences in Trp, kynurenine (Kyn) and Kyn/Trp concentrations in general, as well as differences in changes of those concentrations over the course of a 6-week rehabilitation program in individuals with life-time unipolar affective disorder. For this purpose changes in Trp and Kyn as well as the Kyn/Trp concentrations between the time of admission (t1) and discharge (t2) were analyzed in dependence of sex. Furthermore, correlations between Trp and Kyn levels and clinical parameters were performed separately for male and female participants.Material and Methods:Results: For the current analysis 426 individuals with lifetime affective disorder completing a 6-week rehabilitation program were included. In both sexes, psychiatric symptoms decreased significantly over time. There was a significant difference between women (n = 242) and men (n = 184) regarding the changes in Trp, Kyn, and Kyn/Trp over time even if controlled for relevant covariates [multivariate: F(3, 380) = 2.663, η2 = 0.021, p = 0.048]. Kyn as well as Kyn/Trp concentrations increased significantly in men over time (Kyn F = 4.809, η2 = 0.012, p = 0.029; Kyn/Trp F = 7.923, η2 = 0.020, p = 0.005). Results remained the same when controlled for psychiatric symptoms.Discussion: The main finding of the present study is the significant difference between women and men regarding the change in Trp, Kyn, and Kyn/Trp over a 6-week psychiatric treatment period, while the depression severity scores as well as general psychiatric symptoms decreased. Sex specific changes in Trp-Kyn pathways have only been explored to a very small extent to date in the literature but are of high clinical relevance in the context of personalized medicine

Molecular details of quinolone–DNA interactions: solution structure of an unusually stable DNA duplex with covalently linked nalidixic acid residues and non-covalent complexes derived from it

Quinolones are antibacterial drugs that are thought to bind preferentially to disturbed regions of DNA. They do not fall into the classical categories of intercalators, groove binders or electrostatic binders to the backbone. We solved the 3D structure of the DNA duplex (ACGCGU-NA)(2), where NA denotes a nalidixic acid residue covalently linked to the 2′-position of 2′-amino-2′-deoxyuridine, by NMR and restrained torsion angle molecular dynamics (MD). In the complex, the quinolones stack on G:C base pairs of the core tetramer and disrupt the terminal A:U base pair. The displaced dA residues can stack on the quinolones, while the uracil rings bind in the minor groove. The duplex-bridging interactions of the drugs and the contacts of the displaced nucleotides explain the high UV-melting temperature for d(ACGCGU-NA)(2) of up to 53°C. Further, non-covalently linked complexes between quinolones and DNA of the sequence ACGCGT can be generated via MD using constraints obtained for d(ACGCGU-NA)(2). This is demonstrated for unconjugated nalidixic acid and its 6-fluoro derivative. The well-ordered and tightly packed structures thus obtained are compatible with a published model for the quinolone–DNA complex in the active site of gyrases

Ultra-bright and efficient single photon generation based on N-V centres in nanodiamonds on a solid immersion lens

Single photons are fundamental elements for quantum information technologies such as quantum cryptography, quantum information storage and optical quantum computing. Colour centres in diamond have proven to be stable single photon sources and thus essential components for reliable and integrated quantum information technology. A key requirement for such applications is a large photon flux and a high efficiency. Paying tribute to various attempts to maximise the single photon flux we show that collection efficiencies of photons from colour centres can be increased with a rather simple experimental setup. To do so we spin-coated nanodiamonds containing single nitrogen-vacancy colour centres on the flat surface of a ZrO2 solid immersion lens. We found stable single photon count rates of up to 853 kcts/s at saturation under continuous wave excitation while having excess to more than 100 defect centres with count rates from 400 kcts/s to 500 kcts/s. For a blinking defect centre we found count rates up to 2.4 Mcts/s for time intervals of several ten seconds. It seems to be a general feature that very high rates are accompanied by a blinking behaviour. The overall collection efficiency of our setup of up to 4.2% is the highest yet reported for N-V defect centres in diamond. Under pulsed excitation of a stable emitter of 10 MHz, 2.2% of all pulses caused a click on the detector adding to 221 kcts/s thus opening the way towards diamond based on-demand single photon sources for quantum applications

Nanoimplantation and Purcell enhancement of single nitrogen-vacancy centers in photonic crystal cavities in diamond

We present the controlled creation of single nitrogen-vacancy (NV) centers via ion implantation at the center of a photonic crystal cavity which is fabricated in an ultrapure, single crystal diamond membrane. High-resolution placement of NV centers is achieved using collimation of a 5 keV-nitrogen ion beam through a pierced tip of an atomic force microscope. We demonstrate coupling of the implanted NV centers’ broad band fluorescence to a cavity mode and observe Purcell enhancement of the spontaneous emission. The results are in good agreement with a master equation model for the cavity coupling

One- and two-dimensional photonic crystal micro-cavities in single crystal diamond

The development of solid-state photonic quantum technologies is of great interest for fundamental studies of light-matter interactions and quantum information science. Diamond has turned out to be an attractive material for integrated quantum information processing due to the extraordinary properties of its colour centres enabling e.g. bright single photon emission and spin quantum bits. To control emitted photons and to interconnect distant quantum bits, micro-cavities directly fabricated in the diamond material are desired. However, the production of photonic devices in high-quality diamond has been a challenge so far. Here we present a method to fabricate one- and two-dimensional photonic crystal micro-cavities in single-crystal diamond, yielding quality factors up to 700. Using a post-processing etching technique, we tune the cavity modes into resonance with the zero phonon line of an ensemble of silicon-vacancy centres and measure an intensity enhancement by a factor of 2.8. The controlled coupling to small mode volume photonic crystal cavities paves the way to larger scale photonic quantum devices based on single-crystal diamond

Reversal of diastereoselectivity in the synthesis of Peptidomimetic 3‑Carboxamide-1,4-benzodiazepin-5-ones

Enantiopure 3-carboxamide-1,4-benzodiazepin-5-ones were synthesized via the Ugi reaction followed by the Staudinger/aza-Wittig or reduction reactions in only two steps. A complete reversal of diastereoselectivity was achieved depending on the cyclization methodology employed. The different orientation of the C3 substituent in our 3-substituted 1,4-benzodiazepin-5-ones with respect to the most studied 1,4-benzodiazepin-2-ones makes them complementary in the development of new drugs because the primary source of binding selectivity of 1,4-benzodiazepines is the selective recognition of ligand conformations by the receptor.Ministerio de Economía y Competitividad, Spain (Project CTQ2012-31611), Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Project BU246A12-1) and the European Commission, Seventh Framework Programme (Project SNIFFER FP7-SEC-2012-312411)

Laser writing of coherent colour centres in diamond

Optically active point defects in crystals have gained widespread attention as photonic systems that can find use in quantum information technologies [1,2]. However challenges remain in the placing of individual defects at desired locations, an essential element of device fabrication. Here we report the controlled generation of single nitrogen-vacancy (NV) centres in diamond using laser writing [3]. The use of aberration correction in the writing optics allows precise positioning of vacancies within the diamond crystal, and subsequent annealing produces single NV centres with up to 45% success probability, within about 200 nm of the desired position. Selected NV centres fabricated by this method display stable, coherent optical transitions at cryogenic temperatures, a pre-requisite for the creation of distributed quantum networks of solid-state qubits. The results illustrate the potential of laser writing as a new tool for defect engineering in quantum technologies

Gold(I)-Catalyzed Coupling Reactions for the Synthesis of Diverse Small Molecules Using the Build/Couple/Pair Strategy

The build/couple/pair strategy has yielded small molecules with stereochemical and skeletal diversity by using short reaction sequences. Subsequent screening has shown that these compounds can achieve biological tasks considered challenging if not impossible (‘undruggable’) for small molecules. We have developed gold(I)-catalyzed cascade reactions of easily prepared propargyl propiolates as a means to achieve effective intermolecular coupling reactions for this strategy. Sequential alkyne activation of propargyl propiolates by a cationic gold(I) catalyst yields an oxocarbenium ion that we previously showed is trapped by C-based nucleophiles at an extrannular site to yield α-pyrones. Here, we report O-based nucleophiles react by ring opening to afford a novel polyfunctional product. In addition, by coupling suitable building blocks, we subsequently performed intramolecular pairing reactions that yield diverse and complex skeletons. These pairing reactions include one based on a novel aza-Wittig-6π-electrocyclization sequence and others based on ring-closing metathesis reactions.Chemistry and Chemical Biolog

Superconducting single photon detectors integrated with diamond nanophotonic circuits

Photonic quantum technologies promise to repeat the success of integrated nanophotonic circuits in non-classical applications. Using linear optical elements, quantum optical computations can be performed with integrated optical circuits and thus allow for overcoming existing limitations in terms of scalability. Besides passive optical devices for realizing photonic quantum gates, active elements such as single photon sources and single photon detectors are essential ingredients for future optical quantum circuits. Material systems which allow for the monolithic integration of all components are particularly attractive, including III-V semiconductors, silicon and also diamond. Here we demonstrate nanophotonic integrated circuits made from high quality polycrystalline diamond thin films in combination with on-chip single photon detectors. Using superconducting nanowires coupled evanescently to travelling waves we achieve high detection efficiencies up to 66 % combined with low dark count rates and timing resolution of 190 ps. Our devices are fully scalable and hold promise for functional diamond photonic quantum devices.Comment: 28 pages, 5 figure