Visible Light Mediated Aryl Migration by Homolytic C−N Cleavage of Aryl Amines

The photocatalytic preparation of aminoalkylated heteroarenes from haloalkylamides via a 1,4‐aryl migration from nitrogen to carbon, conceptually analogous to a radical Smiles rearrangement, is reported. This method enables the substitution of amino groups in heteroaromatic compounds with aminoalkyl motifs under mild, iridium(III)‐mediated photoredox conditions. It provides rapid access to thienoazepinone, a pharmacophore present in multiple drug candidates for potential treatment of different conditions, including inflammation and psychotic disorders.Aminoalkylated heteroarenes are synthesized by a radical Smiles rearrangement of haloalkylamides through a key C−N cleavage under mild, iridium(III)‐mediated photoredox conditions. The method provides rapid access to the pharmaceutically relevant thienoazepinone scaffold.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146419/1/anie201806659_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146419/2/anie201806659.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146419/3/anie201806659-sup-0001-misc_information.pd

Data from the paper: Valence and Arosual: A comparison of two sets of Emotional Facial Expressions

Supplementary material to our publication: Adolph, D. & Alpers, G.W. (2010). Valence and Arosual: A comparison of two sets of Emotional Facial Expressions. Amer J Psychol, 123: 209-219. Supplementary material in MADATA contains: Table 1: Valence and Arousal Ratings in response to Nim-Stim pics (Tottenham, N., Tanaka, J. W., Leon, A. C., McCarry, T., Nurse, M., Hare, T. A., Marcus, D. J., Westerlund, A., Casey, B. J., & Nelson, C. (2009). The NimStim set of facial expressions: Judgments from untrained research participants. Psychiatry Research, 168, 242-249.); Means (+ SD) of Valence and Arousal Ratings. Table 2: Valence and Arousal Ratings in response to KDEF pics (Lundqvist, D., Flykt, A., & Öhman, A. (1998). Karolinska Directed Emotional Faces. Stockholm, Sweden: Department of Neurosciences, Karolinska Hospital); Means (+ SD) of Valence and Arousal Rating

Rapid transcriptional and metabolic regulation of the deacclimation process in cold acclimated Arabidopsis thaliana

Background: During low temperature exposure, temperate plant species increase their freezing tolerance in a process termed cold acclimation. This is accompanied by dampened oscillations of circadian clock genes and disrupted oscillations of output genes and metabolites. During deacclimation in response to warm temperatures, cold acclimated plants lose freezing tolerance and resume growth and development. While considerable effort has been directed toward understanding the molecular and metabolic basis of cold acclimation, much less information is available about the regulation of deacclimation.Results: We report metabolic (gas chromatography-mass spectrometry) and transcriptional (microarrays, quantitative RT-PCR) responses underlying deacclimation during the first 24 h after a shift of Arabidopsis thaliana (Columbia-0) plants cold acclimated at 4 °C back to warm temperature (20 °C). The data reveal a faster response of the transcriptome than of the metabolome and provide evidence for tightly regulated temporal responses at both levels. Metabolically, deacclimation is associated with decreasing contents of sugars, amino acids, glycolytic and TCA cycle intermediates, indicating an increased need for carbon sources and respiratory energy production for the activation of growth. The early phase of deacclimation also involves extensive down-regulation of protein synthesis and changes in the metabolism of lipids and cell wall components. Hormonal regulation appears particularly important during deacclimation, with extensive changes in the expression of genes related to auxin, gibberellin, brassinosteroid, jasmonate and ethylene metabolism. Members of several transcription factor families that control fundamental aspects of morphogenesis and development are significantly regulated during deacclimation, emphasizing that loss of freezing tolerance and growth resumption are transcriptionally highly interrelated processes. Expression patterns of some clock oscillator components resembled those under warm conditions, indicating at least partial re-activation of the circadian clock during deacclimation.Conclusions: This study provides the first combined metabolomic and transcriptomic analysis of the regulation of deacclimation in cold acclimated plants. The data indicate cascades of rapidly regulated genes and metabolites that underlie the developmental switch resulting in reduced freezing tolerance and the resumption of growth. They constitute a large-scale dataset of genes, metabolites and pathways that are crucial during the initial phase of deacclimation. The data will be an important reference for further analyses of this and other important but under-researched stress deacclimation processes

Arylmigration durch sichtbares Licht unter homolytischer C‐N‐Spaltung in Arylaminen

Die photokatalytische Synthese von aminoalkylierten Heteroaromaten aus Halogenalkylamiden gelingt durch die einer Smiles‐Umlagerung konzeptionell analogen 1,4‐Arylmigration von Stickstoff zu Kohlenstoff. Mit dieser neuartigen Methode kann die Substitution von Aminogruppen in Heteroaromaten durch Aminoalkylmotive unter milden, Iridium(III)‐vermittelten Photoredox‐Bedingungen realisiert werden. Sie bietet einen schnellen Zugang zum Thienoazepinon‐Bicyclus, einem Pharmakophor, der in unterschiedlichen Verbindungen mit potentiellen Anwendungen bei der Behandlung von bestimmten Entzündungen und psychischen Krankheiten vorkommt.Aminoalkylierte Heteroarene werden durch Smiles‐Umlagerung von Halogenalkylamiden über eine C‐N‐Spaltung unter milden, Iridium(III)‐vermittelten Photoredox‐Bedingungen synthetisiert. Das Verfahren bietet einen schnellen Zugang zu dem pharmazeutisch relevanten Thienoazepinon‐Grundgerüst.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146369/1/ange201806659.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146369/2/ange201806659_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146369/3/ange201806659-sup-0001-misc_information.pd

Quantitative High-Resolution Genomic Analysis of Single Cancer Cells

During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics

GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation : a potential neurogenetic pathway to panic disorder

The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG - related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1,370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, p=3.3x10-8; rs191260602, p=3.9x10-8). We followed up on this finding in a larger dimensional ACQ sample (N=2,547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3,845) and a case control sample with the categorical phenotype PD/AG (Ncombined =1,012) obtaining highly significant p-values also for GLRB single nucleotide variants rs17035816 (p=3.8x10-4) and rs7688285 (p=7.6x10-5). GLRB gene expression was found to be modulated by rs7688285 in brain tissue as well as cell culture. Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network as well as general sensory activation by GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout-mice demonstrated an agoraphobic phenotype. In conjunction withthe clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, though functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.PostprintPeer reviewe

Outbreaks of virulent diarrheagenic Escherichia coli - are we in control?

Shiga toxin-producing Escherichia coli (STEC) are the most virulent diarrheagenic E. coli known to date. They can be spread with alarming ease via food as exemplified by a large sprout-borne outbreak of STEC O104:H4 in 2011 that was centered in northern Germany and affected several countries. Effective control of such outbreaks is an important public health task and necessitates early outbreak detection, fast identification of the outbreak vehicle and immediate removal of the suspected food from the market, flanked by consumer advice and measures to prevent secondary spread