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

Lake-size dependency of wind shear and convection as controls on gas exchange

High-frequency physical observations from 40 temperate lakes were used to examine the relative contributions of wind shear (u*) and convection (w*) to turbulence in the surface mixed layer. Seasonal patterns of u* and w* were dissimilar; u* was often highest in the spring, while w * increased throughout the summer to a maximum in early fall. Convection was a larger mixed-layer turbulence source than wind shear (u */w*-1 for lakes* and w* differ in temporal pattern and magnitude across lakes, both convection and wind shear should be considered in future formulations of lake-air gas exchange, especially for small lakes. © 2012 by the American Geophysical Union.Jordan S. Read, David P. Hamilton, Ankur R. Desai, Kevin C. Rose, Sally MacIntyre, John D. Lenters, Robyn L. Smyth, Paul C. Hanson, Jonathan J. Cole, Peter A. Staehr, James A. Rusak, Donald C. Pierson, Justin D. Brookes, Alo Laas, and Chin H. W

Diffuse cutaneous systemic sclerosis following SARS-Co V-2 vaccination

The largest world-wide vaccination rollout ever is currently underway to tackle the covid-19 pandemic. We report a case of diffuse cutaneous systemic sclerosis (SSc) in a 70-year-old male with rapidly progressive skin thickening which developed two weeks after receiving the first dose of the ChAdOx1 nCOV-19 vaccine. As the onset of SSc skin was in close temporal proximity to the administration of the first dose vaccine with no other triggers, we suspected a possible adverse reaction to the ChAdOx1 nCOV-19 vaccine. We hypothesise that the recombinant adenoviral vector encoding the spike protein antigen of SARS-CoV-2 triggered an unexpected immune activation resulting in an atypical presentation of late-onset SSc, within the well-recognised ANA positive, ENA negative subgroup of patients.We review the possible mechanisms underlying autoimmunity when provoked by vaccination and other published rheumatological phenomenon occurring shortly after COVID vaccination

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

Genomics reveals historic and contemporary transmission dynamics of a bacterial disease among wildlife and livestock

Whole-genome sequencing has provided fundamental insights into infectious disease epidemiology, but has rarely been used for examining transmission dynamics of a bacterial pathogen in wildlife. In the Greater Yellowstone Ecosystem (GYE), outbreaks of brucellosis have increased in cattle along with rising seroprevalence in elk. Here we use a genomic approach to examine Brucella abortus evolution, cross-species transmission and spatial spread in the GYE. We find that brucellosis was introduced into wildlife in this region at least five times. The diffusion rate varies among Brucella lineages (∼3 to 8 km per year) and over time. We also estimate 12 host transitions from bison to elk, and 5 from elk to bison. Our results support the notion that free-ranging elk are currently a self-sustaining brucellosis reservoir and the source of livestock infections, and that control measures in bison are unlikely to affect the dynamics of unrelated strains circulating in nearby elk populations

Origin and evolution of the octoploid strawberry genome.

Cultivated strawberry emerged from the hybridization of two wild octoploid species, both descendants from the merger of four diploid progenitor species into a single nucleus more than 1 million years ago. Here we report a near-complete chromosome-scale assembly for cultivated octoploid strawberry (Fragaria × ananassa) and uncovered the origin and evolutionary processes that shaped this complex allopolyploid. We identified the extant relatives of each diploid progenitor species and provide support for the North American origin of octoploid strawberry. We examined the dynamics among the four subgenomes in octoploid strawberry and uncovered the presence of a single dominant subgenome with significantly greater gene content, gene expression abundance, and biased exchanges between homoeologous chromosomes, as compared with the other subgenomes. Pathway analysis showed that certain metabolomic and disease-resistance traits are largely controlled by the dominant subgenome. These findings and the reference genome should serve as a powerful platform for future evolutionary studies and enable molecular breeding in strawberry

Intermittent glucocorticoid treatment improves muscle metabolism via the PGC1α/Lipin1 axis in an aging-related sarcopenia model

Sarcopenia burdens the older population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are lacking. The glucocorticoid prednisone remodels muscle metabolism on the basis of frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once-weekly intermittent prednisone administration rescued muscle quality in aged 24-month-old mice to a level comparable to that seen in young 4-month-old mice. We discovered an age- and sex-independent glucocorticoid receptor transactivation program in muscle encompassing peroxisome proliferator-activated receptor γ coactivator 1 α (PGC1α) and its cofactor Lipin1. Treatment coordinately improved mitochondrial abundance through isoform 1 and muscle mass through isoform 4 of the myocyte-specific PGC1α, which was required for the treatment-driven increase in carbon shuttling from glucose oxidation to amino acid biogenesis. We also probed myocyte-specific Lipin1 as a nonredundant factor coaxing PGC1α upregulation to the stimulation of both oxidative and anabolic effects. Our study unveils an aging-resistant druggable program in myocytes for the coordinated rescue of energy and mass in sarcopenia

A Global lake ecological observatory network (GLEON) for synthesising high-frequency sensor data for validation of deterministic ecological models

A Global Lake Ecological Observatory Network (GLEON; www.gleon.org) has formed to provide a coordinated response to the need for scientific understanding of lake processes, utilising technological advances available from autonomous sensors. The organisation embraces a grassroots approach to engage researchers from varying disciplines, sites spanning geographic and ecological gradients, and novel sensor and cyberinfrastructure to synthesise high-frequency lake data at scales ranging from local to global. The high-frequency data provide a platform to rigorously validate processbased ecological models because model simulation time steps are better aligned with sensor measurements than with lower-frequency, manual samples. Two case studies from Trout Bog, Wisconsin, USA, and Lake Rotoehu, North Island, New Zealand, are presented to demonstrate that in the past, ecological model outputs (e.g., temperature, chlorophyll) have been relatively poorly validated based on a limited number of directly comparable measurements, both in time and space. The case studies demonstrate some of the difficulties of mapping sensor measurements directly to model state variable outputs as well as the opportunities to use deviations between sensor measurements and model simulations to better inform process understanding. Well-validated ecological models provide a mechanism to extrapolate high-frequency sensor data in space and time, thereby potentially creating a fully 3-dimensional simulation of key variables of interest

Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300

It is well established that the coordinated regulation of activity-dependent gene expression by the histone acetyltransferase (HAT) family of transcriptional coactivators is crucial for the formation of contextual fear and spatial memory, and for hippocampal synaptic plasticity. However, no studies have examined the role of this epigenetic mechanism within the infralimbic prefrontal cortex (ILPFC), an area of the brain that is essential for the formation and consolidation of fear extinction memory. Here we report that a postextinction training infusion of a combined p300/CBP inhibitor (Lys-CoA-Tat), directly into the ILPFC, enhances fear extinction memory in mice. Our results also demonstrate that the HAT p300 is highly expressed within pyramidal neurons of the ILPFC and that the small-molecule p300-specific inhibitor (C646) infused into the ILPFC immediately after weak extinction training enhances the consolidation of fear extinction memory. C646 infused 6 h after extinction had no effect on fear extinction memory, nor did an immediate postextinction training infusion into the prelimbic prefrontal cortex. Consistent with the behavioral findings, inhibition of p300 activity within the ILPFC facilitated long-term potentiation (LTP) under stimulation conditions that do not evoke long-lasting LTP. These data suggest that one function of p300 activity within the ILPFC is to constrain synaptic plasticity, and that a reduction in the function of this HAT is required for the formation of fear extinction memory

Talk the talk, walk the walk: Defining Critical Race Theory in research

Over the last decade there has been a noticeable growth in published works citing Critical Race Theory (CRT). This has led to a growth in interest in the UK of practical research projects utilising CRT as their framework. It is clear that research on 'race' is an emerging topic of study. What is less visible is a debate on how CRT is positioned in relation to methodic practice, substantive theory and epistemological underpinnings. The efficacy of categories of data gathering tools, both traditional and non-traditional is a discussion point here to explore the complexities underpinning decisions to advocate a CRT framework. Notwithstanding intersectional issues, a CRT methodology is recognisable by how philosophical, political and ethical questions are established and maintained in relation to racialised problematics. This paper examines these tensions in establishing CRT methodologies and explores some of the essential criteria for researchers to consider in utilising a CRT framework. © 2012 Copyright Taylor and Francis Group, LLC