Catalysis at the sub-nanoscale: complex CO oxidation chemistry on a few Au atoms

Au has been widely used as jewelry since ancient times due to its bulk, chemically inert properties. During the last three decades, nanoscale Au has attracted remarkable attention and has been shown to be an exceptional catalyst, especially for oxidation reactions. Herein, we elucidate a puzzle in catalysis by using multiscale computational modeling: the experimentally observed “magic number” CO oxidation catalytic behavior of sub-nanoscale Au clusters. Our results demonstrate that support effects (cluster charging), symmetry-induced electronic effects on the clusters, catalyst reconstruction, competing chemical pathways and formation of carbonate contribute to the marked differences in the observed catalytic behavior of Aun− clusters with n = 6, 8 and 10 atoms. This is the first demonstration of multiscale simulations on sub-nanoscale catalysts unraveling the magic number activity for the CO oxidation reaction on Au

An orthogonal biocatalytic approach for the safe generation and use of HCN in a multistep continuous preparation of chiral O-acetylcyanohydrins

An enantioselective preparation of O-acetylcyanohydrins has been accomplished by a three-step telescoped continuous process. The modular components enabled accurate control of two sequential biotransformations, safe handling of an in situ generated hazardous gas, and in-line stabilization of products. This method proved to be advantageous over the batch protocols in terms of reaction time (40 vs 345 min) and ease of operation, opening up access to reactions which have often been neglected due to safety concerns.We gratefully acknowledge the Deutsche Forschungsgemeinschaft (DFG) within the research training group GRK 1166 “Biocatalysis in non-conventional media (BioNoCo)”, and the EPSRC (Award Nos. EP/K009494/1 and EP/K039520/1)This is the final version of the article. It first appeared from Georg Thieme Verlag KG via http://dx.doi.org/10.1055/s-0035-156064

Microchimerism and Renal Transplantation: Doubt Still Persists

Objective: We sought to study microchimerism in a group of kidney transplant recipients. Materials and Methods: In this study, the peripheral blood microchimerism (PBM) after renal transplantation was retrospectively evaluated in 32 male-to-female recipients of living unrelated or cadaveric donor renal transplants. Using a nested polymerase chain reaction (PCR) amplification specific for SRY region of the Y chromosome, microchimerism was detected with a sensitivity of 1:1,000,000. Recipients were compared according to the presence of PBM, acute and chronic rejection episodes, type of allotransplant, recipient and donor age at transplantation, previous male labor or blood transfusion, allograft function (serum creatinine level), and body mass index. Results: Among 32 recipients, 7 (21.9) were positive for PBM upon multiple testing at various posttransplant times. All microchimeric recipients had received kidneys from living unrelated donors. No significant difference was observed with regard to other parameters. In addition the acute rejection rate in the microchimeric group was 3 (42) versus 4 (16) in the nonmicrochimeric recipients (not significant). Conclusion: Our results suggested better establishment of microchimerism after living donor kidney transplantation. However, doubt persists concerning the true effect of microchimerism after renal transplantation. It seems that microchimerism alone has no major protective role upon renal allograft survival. © 2007 Elsevier Inc. All rights reserved

Promiscuous targeting of bromodomains by bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia

Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET (bromo and extra-terminal) inhibitors and their significant activity in diverse tumor models have rapidly translated into clinical studies and have motivated drug development efforts targeting non-BET BRDs. However, the complex multidomain/subunit architecture of BRD protein complexes complicates predictions of the consequences of their pharmacological targeting. To address this issue, we developed a promiscuous BRD inhibitor [bromosporine (BSP)] that broadly targets BRDs (including BETs) with nanomolar affinity, creating a tool for the identification of cellular processes and diseases where BRDs have a regulatory function. As a proof of principle, we studied the effects of BSP on leukemic cell lines known to be sensitive to BET inhibition and found, as expected, strong antiproliferative activity. Comparison of the modulation of transcriptional profiles by BSP after a short exposure to the inhibitor resulted in a BET inhibitor signature but no significant additional changes in transcription that could account for inhibition of other BRDs. Thus, nonselective targeting of BRDs identified BETs, but not other BRDs, as master regulators of context-dependent primary transcription response.The Structural Genomics Consortium is a registered charity (no. 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative (EU/EFPIA) (ULTRA-DD grant 115766), Janssen, Merck & Co., Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, São Paulo Research Foundation (FAPESP), Takeda, and Wellcome Trust (092809/Z/10/Z). P.F., S.P., and C.-Y.W. were supported by a Wellcome Career Development Fellowship (095751/Z/11/Z). A.-C.G. is the Canada Research Chair in Functional Proteomics and the Lea Reichmann Chair in Cancer Proteomics and was supported by the Canadian Institutes of Health Research (foundation grant FDN143301). J.-P.L. was supported by a Cancer Research Society (Canada) Scholarship for the Next Generation of Scientists

Serum IL-17, IL-23, and TGF-β levels in type 1 and type 2 diabetic patients and age-matched healthy controls

Type 1 diabetes is recognized as an autoimmune inflammatory disease and low grade inflammation is also observed in type 2 diabetic patients. Interleukin 17 (IL-17) is a new player in inflammation. Th17 cells, as the main source of IL-17, require transforming growth factor β (TGF-β) and interleukin 23 (IL-23). The aim of this study was to investigate serum IL-17, IL-23 and TGF-β levels in diabetic patients and controls. In this case-control study, serum levels of IL-17, IL-23, and TGF-β were measured in 24 type 1 diabetic patients and 30 healthy controls using the ELISA method. Simultaneously, the same methodology was used to compare serum concentration of these three cytokines in 38 type 2 diabetic patients and 40 healthy controls. There was no significant difference between serum levels of IL-17 and IL-23 cytokines between cases and controls. However, TGF-β was significantly lower in type 1 diabetic patients (P<0.001). Serum IL-17 and IL-23 levels demonstrate no association with type 1 and type 2 diabetes, but, in line with previous studies, TGF-β levels were lower in type 1 diabetic patients. © 2014 Azam Roohi et al

Association of polymorphisms of vasoactive intestinal peptide and its receptor with reproductive traits of turkey hens

The aim of this study was to identify variations of vasoactive intestinal peptide (VIP) and VIP receptor-1 (VIPR-1) genes that might be associated with turkey reproductive traits. One hundred twenty turkey hens were recorded for age at first egg (AFE), first egg weight (FEW), egg number (EN), total egg weight (TEW), laying period (LP), and broodiness. The DNA was isolated from blood samples and subjected to PCR amplification of the meleagrine VIP and VIPR-1 genes. The SNPs were detected by single-strand conformation polymorphism and the variant DNA fragments were sequenced. One mutation in 3’-UTR of VIP (G5846A) and two SNPs in intron 2 of VIPR-1 (C17687T and A17690T) were found, all of them novel. The associations of the three detected SNPs with the reproductive traits of turkeys were evaluated. The detected polymorphisms were used for marker-trait association analyses. The results of association analysis showed that G5846A on 3’ UTR of VIP has a significant association with LP, EN, TEW, and AFE. The G allele of G5846A was the favourable SNP allele for LP, EN, and TEW traits. The AA genotype of A17690T on intron 2 of VIPR-1 was significantly associated with higher LP, EN, and TEW. AGAA haplotype showed association with higher EN and TEW. These results suggest that the SNPs in 3’-UTR of VIP and intron 2 of VIPR-1 genes may influence egg production traits in turkey hens.Keywords: broodiness, candidate gene, egg production, single nucleotide polymorphism, VIPR-