Palladium-catalyzed heteroallylation of unactivated alkenes – synthesis of citalopram

A palladium-catalyzed difunctionalization of unactivated alkenes with tethered nucleophiles is reported. The versatile reaction occurs with simple allylic halides and can be carried out under air. The methodology provides rapid access to a wide array of desirable heterocyclic targets, as illustrated by a concise synthesis of the widely prescribed antidepressant citalopram

Effects of Low-Dose Gestational TCDD Exposure on Behavior and on Hippocampal Neuron Morphology and Gene Expression in Mice.

BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent and toxic environmental pollutant. Gestational exposure to TCDD has been linked to cognitive and motor deficits, and increased incidence of autism spectrum disorder (ASD) traits in children. Most animal studies of these neurodevelopmental effects involve acute TCDD exposure, which does not model typical exposure in humans. OBJECTIVES: The aim of the study was to establish a dietary low-dose gestational TCDD exposure protocol and performed an initial characterization of the effects on offspring behavior, neurodevelopmental phenotypes, and gene expression. METHODS: Throughout gestation, pregnant C57BL/6J mice were fed a diet containing a low dose of TCDD (9 ng TCDD/kg body weight per day) or a control diet. The offspring were tested in a battery of behavioral tests, and structural brain alterations were investigated by magnetic resonance imaging. The dendritic morphology of pyramidal neurons in the hippocampal Cornu Ammonis (CA)1 area was analyzed. RNA sequencing was performed on hippocampi of postnatal day 14 TCDD-exposed and control offspring. RESULTS: TCDD-exposed females displayed subtle deficits in motor coordination and reversal learning. Volumetric difference between diet groups were observed in regions of the hippocampal formation, mammillary bodies, and cerebellum, alongside higher dendritic arborization of pyramidal neurons in the hippocampal CA1 region of TCDD-exposed females. RNA-seq analysis identified 405 differentially expressed genes in the hippocampus, enriched for genes with functions in regulation of microtubules, axon guidance, extracellular matrix, and genes regulated by SMAD3. DISCUSSION: Exposure to 9 ng TCDD/kg body weight per day throughout gestation was sufficient to cause specific behavioral and structural brain phenotypes in offspring. Our data suggest that alterations in SMAD3-regulated microtubule polymerization in the developing postnatal hippocampus may lead to an abnormal morphology of neuronal dendrites that persists into adulthood. These findings show that environmental low-dose gestational exposure to TCDD can have significant, long-term impacts on brain development and function. https://doi.org/10.1289/EHP7352

Counter‐Credit‐Risk Yield Spreads: A Puzzle in China's Corporate Bond Market

yesIn this paper, using China’s risk-free and corporate zero yields together with aggregate credit risk measures and various control variables from 2006 to 2013, we document a puzzle of counter-credit-risk corporate yield spreads. We interpret this puzzle as a symptom of the immaturity of China’s credit bond market, which reveals a distorted pricing mechanism latent in the fundamental of this market. We also find interesting results about relationships between corporate yield spreads and interest rates as well as risk premia and the stock index, and these results are somewhat attributed to this puzzle

Past, present, and future geo-biosphere interactions on the Tibetan Plateau and implications for permafrost

This manuscript resulted from a Workshop in 2019 at the Senckenberg Research Institute and Natural History Museum Frankfurt, Germany, supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDA20100300). J. Liu also thanks the support of the Henan Provincial Key Laboratory of Hydrosphere and Watershed Water Security. T. Ehlers thanks the California Institute of Technology Moore Distinguished Scholar Program for support in completing this manuscript during a sabbatical. J. Liu and T. Bolch thank the support from the Strategic Priority Research Program of the Chinese Academy of Sciences (grants no. XDA20060402, XDA20100300). We thank the German Science Foundation (DFG) for support of the TiP (Tibetan Plateau: Formation-Climate-Ecoystems) priority research program (SPP-1372) for initiating the collaborations that led to this manuscript.Interactions between the atmosphere, biosphere, cryosphere, hydrosphere, and geosphere are most active in the critical zone, a region extending from the tops of trees to the top of unweathered bedrock. Changes in one or more of these spheres can result in a cascade of changes throughout the system in ways that are often poorly understood. Here we investigate how past and present climate change have impacted permafrost, hydrology, and ecosystems on the Tibetan Plateau. We do this by compiling existing climate, hydrologic, cryosphere, biosphere, and geologic studies documenting change over decadal to glacial-interglacial timescales and longer. Our emphasis is on showing present-day trends in environmental change and how plateau ecosystems have largely flourished under warmer and wetter periods in the geologic past. We identify two future pathways that could lead to either a favorable greening or unfavorable degradation and desiccation of plateau ecosystems. Both paths are plausible given the available evidence. We contend that the key to which pathway future generations experience lies in what, if any, human intervention measures are implemented. We conclude with suggested management strategies that can be implemented to facilitate a future greening of the Tibetan Plateau.Publisher PDFPeer reviewe

Increased numbers of oligodendrocyte lineage cells in the optic nerves of cerebroside sulfotransferase knockout mice

Sulfatide is a myelin glycolipid that functions in the formation of paranodal axo-glial junctions in vivo and in the regulation of oligodendrocyte differentiation in vitro. Cerebroside sulfotransferase (CST) catalyzes the production of two sulfated glycolipids, sulfatide and proligodendroblast antigen, in oligodendrocyte lineage cells. Recent studies have demonstrated significant increases in oligodendrocytes from the myelination stage through adulthood in brain and spinal cord under CST-deficient conditions. However, whether these result from excess migration or in situ proliferation during development is undetermined. In the present study, CST-deficient optic nerves were used to examine migration and proliferation of oligodendrocyte precursor cells (OPCs) under sulfated glycolipid-deficient conditions. In adults, more NG2-positive OPCs and fully differentiated cells were observed. In developing optic nerves, the number of cells at the leading edge of migration was similar in CST-deficient and wild-type mice. However, BrdU+ proliferating OPCs were more abundant in CST-deficient mice. These results suggest that sulfated glycolipids may be involved in proliferation of OPCs in vivo

Automated Home-Cage Behavioural Phenotyping of Mice

Neurobehavioral analysis of mouse phenotypes requires the monitoring of mouse behavior over long periods of time. Here, we describe a trainable computer vision system enabling the automated analysis of complex mouse behaviors. We provide software and an extensive manually annotated video database used for training and testing the system. Our system performs on par with human scoring, as measured from ground-truth manual annotations of thousands of clips of freely behaving mice. As a validation of the system, we characterized the home-cage behaviors of two standard inbred and two non-standard mouse strains. From this data we were able to predict in a blind test the strain identity of individual animals with high accuracy. Our video-based software will complement existing sensor based automated approaches and enable an adaptable, comprehensive, high-throughput, fine-grained, automated analysis of mouse behavior.McGovern Institute for Brain ResearchCalifornia Institute of Technology. Broad Fellows Program in Brain CircuitryNational Science Council (China) (TMS-094-1-A032

False discovery rate estimation and heterobifunctional cross-linkers

<div><p>False discovery rate (FDR) estimation is a cornerstone of proteomics that has recently been adapted to cross-linking/mass spectrometry. Here we demonstrate that heterobifunctional cross-linkers, while theoretically different from homobifunctional cross-linkers, need not be considered separately in practice. We develop and then evaluate the impact of applying a correct FDR formula for use of heterobifunctional cross-linkers and conclude that there are minimal practical advantages. Hence a single formula can be applied to data generated from the many different non-cleavable cross-linkers.</p></div