(4RS)-Methyl 4-cyano-4-cyclo­hexyl-4-phenyl­butano­ate

In the crystal structure of the title compound, C18H23NO2, there are only van der Waals inter­actions present. The cyclo­hexyl ring has a chair conformation. The longer axes of the displacement parameters of the non-H atoms forming the ethyl­methyl­carboxyl­ate skeleton are perpendicular to the plane through the non-H atoms of this skeleton

Arginyltransferase, Its Specificity, Putative Substrates, Bidirectional Promoter, and Splicing-derived Isoforms

Substrates of the N-end rule pathway include proteins with destabilizing N-terminal residues. Three of them, Asp, Glu, and (oxidized) Cys, function through their conjugation to Arg, one of destabilizing N-terminal residues that are recognized directly by the pathway's ubiquitin ligases. The conjugation of Arg is mediated by arginyltransferase, encoded by ATE1. Through its regulated degradation of specific proteins, the arginylation branch of the N-end rule pathway mediates, in particular, the cardiovascular development, the fidelity of chromosome segregation, and the control of signaling by nitric oxide. We show that mouse ATE1 specifies at least six mRNA isoforms, which are produced through alternative splicing, encode enzymatically active arginyltransferases, and are expressed at varying levels in mouse tissues. We also show that the ATE1 promoter is bidirectional, mediating the expression of both ATE1 and an oppositely oriented, previously uncharacterized gene. In addition, we identified GRP78 (glucose-regulated protein 78) and protein-disulfide isomerase as putative physiological substrates of arginyltransferase. Purified isoforms of arginyltransferase that contain the alternative first exons differentially arginylate these proteins in extract from ATE1-/- embryos, suggesting that specific isoforms may have distinct functions. Although the N-end rule pathway is apparently confined to the cytosol and the nucleus, and although GRP78 and protein-disulfide isomerase are located largely in the endoplasmic reticulum, recent evidence suggests that these proteins are also present in the cytosol and other compartments in vivo, where they may become N-end rule substrates

Poly[μ2-aqua-μ4-naphthalene-1,8-dicarboxyl­ato-manganese(II)]

The asymmetric unit of the title complex, [Mn(C12H6O4)(H2O)]n, contains one MnII ion, one 1,8-naphthalene­dicarboxyl­ate (1,8-NDC) ligand and one water mol­ecule. The MnII ion is six-coordinated within a distorted octa­hedral coordination geometry, in which the equatorial sites are occupied by four carboxyl­ate O atoms from four different 1,8-NDC ligands, while the axial positions are occupied by two O atoms of two coordinated water mol­ecules. Adjacent MnII centres are bridged by one coordinated water and two carboxyl­ate groups in a syn–syn mode to form infinite chains along the b axis, which are further cross-linked by the naphthalene spacers of the 1,8-NDC ligands to produce a two-dimensional extended network

Menin prevents liver steatosis through co-activation of peroxisome proliferator-activated receptor alpha

AbstractFatty liver is strongly associated with metabolic syndrome. Here, we show that the impaired hepatic expression of menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, represents a common feature of several fatty liver mouse models. The liver specific ablation of MEN1 gene expression in healthy mice induced hepatic steatosis under high-fat dietary conditions. Moreover, overexpression of menin in livers of steatotic db/db mice reduced liver triglyceride accumulation. At the molecular level, we found that menin acts synergistically with the nuclear receptor PPARα to control gene expression of fatty acid oxidation. Collectively, these data suggest a crucial role for menin as an integrator of the complex transcriptional network controlling hepatic steatosis.Structured summary of protein interactionsMenin physically interacts with PPAR alpha by anti tag coimmunoprecipitation (View Interaction: 1, 2)

The N-end rule pathway as a nitric oxide sensor controlling the levels of multiple regulators

The conjugation of arginine to proteins is a part of the N-end rule pathway of protein degradation. Three amino (N)-terminal residues—aspartate, glutamate and cysteine—are arginylated by ATE1-encoded arginyl-transferases. Here we report that oxidation of N-terminal cysteine is essential for its arginylation. The in vivo oxidation of N-terminal cysteine, before its arginylation, is shown to require nitric oxide. We reconstituted this process in vitro as well. The levels of regulatory proteins bearing N-terminal cysteine, such as RGS4, RGS5 and RGS16, are greatly increased in mouse ATE1^-/- embryos, which lack arginylation. Stabilization of these proteins, the first physiological substrates of mammalian N-end rule pathway, may underlie cardiovascular defects in ATE1^-/- embryos. Our findings identify the N-end rule pathway as a new nitric oxide sensor that functions through its ability to destroy specific regulatory proteins bearing N-terminal cysteine, at rates controlled by nitric oxide and apparently by oxygen as well

Genome-wide transcriptional analysis of temperature shift in L. interrogans serovar lai strain 56601

BACKGROUND: Leptospira interrogans is an important mammalian pathogen. Transmission from an environmental source requires adaptation to a range of new environmental conditions in the organs and tissues of the infected host. Several studies have shown that a shift in culture temperature from 28°C to 37°C, similar to that encountered during infection of a host from an environmental source, is associated with differential synthesis of several proteins of the outer membrane, periplasm and cytoplasm. The whole genome of the Leptospira interrogans serogroup Icterohaemorrhagiae serovar lai type strain #56601 was sequenced in 2003 and microarrays were constructed to compare differential transcription of the whole genome at 37°C and 28°C. RESULTS: DNA microarray analyses were used to investigate the influence of temperature on global gene expression in L. interrogans grown to mid-exponential phase at 28°C and 37°C. Expression of 106 genes differed significantly at the two temperatures. The differentially expressed genes belonged to nine functional categories: Cell wall/membrane biogenesis genes, hemolysin genes, heat shock proteins genes, intracellular trafficking and secretion genes, two-component system and transcriptional regulator genes, information storage and processing genes, chemotaxis and flagellar genes, metabolism genes and genes with no known homologue. Real-time reverse transcription-PCR assays confirmed the microarray data. CONCLUSION: Microarray analyses demonstrated that L. interrogans responds globally to temperature alteration. The data delineate the spectrum of temperature-regulated gene expression in an important human pathogen and provide many new insights into its pathogenesis

Threshold-independent method for single-shot readout of spin qubits in semiconductor quantum dots

The single-shot readout data process is essential for the realization of high-fidelity qubits and fault-tolerant quantum algorithms in semiconductor quantum dots. However, the fidelity and visibility of the readout process is sensitive to the choice of the thresholds and limited by the experimental hardware. By demonstrating the linear dependence between the measured spin state probabilities and readout visibilities along with dark counts, we describe an alternative threshold-independent method for the single-shot readout of spin qubits in semiconductor quantum dots. We can obtain the extrapolated spin state probabilities of the prepared probabilities of the excited spin state through the threshold-independent method. Then, we analyze the corresponding errors of the method, finding that errors of the extrapolated probabilities cannot be neglected with no constraints on the readout time and threshold voltage. Therefore, by limiting the readout time and threshold voltage we ensure the accuracy of the extrapolated probability. Then, we prove that the efficiency and robustness of this method is 60 times larger than that of the most commonly used method. Moreover, we discuss the influence of the electron temperature on the effective area with a fixed external magnetic field and provide a preliminary demonstration for a single-shot readout up to 0.7 K/1.5T in the future.Comment: 18 pages, 6 figure

An Assessment Method for Debris Flow Dam Formation in Taiwan

Debris flows in tributaries rush into and block the main branches of rivers and often result in serious hazards. Dam failures cause large floods in the downstream area and can lead to fatalities and property damage. This study proposes an assessment method to evaluate the formation of a debris flow dam, which includes two conditions: (1) the sediment transported by the debris flow must reach across the river; and (2) the thickness of the deposit by the debris flow must be higher than the in situ water depth. This methodology was used to study the case of a debris flow dam caused by debris flow across the Er River in Taiwan, which blocked the Chishan River and led to the formation of the Namasha debris flow dam. This methodology can also be applied to identify the formation of debris flow dams.El flujo de detritos que cae en los tributarios de los ríos puede bloquear los ramales principales y eventualmente convertirse en un riesgo. El rompimiento de uno de estos represamientos de agua puede causar inundaciones en las zonas de la corriente, además de víctimas y daños a propiedades. Este estudio propone un método para evaluar la formación de represamientos de agua por flujo de detritos bajo dos condiciones: (1) los sedimentos transportados por el flujo de detritos deben alcanzar el lecho del río; (2) el grosor de los depósitos por el flujo de detritos debe ser mayor que la profundidad de agua in situ. Esta metodología se utilizó para estudiar el caso de represamiento por el flujo de detritos en el río Er de Taiwán, el cual bloqueó el río Chishan y que condujo a la formación de la presa Namasha. Esta metodología también puede aplicarse para identificar la formación de represamientos por flujo de detritos