bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mineral signature of the Anthropocene in its deep-time context
Authors: Zalasiewicz Jan , Kryza Ryszard , Williams Mark 
Published: December 2013

Abstract

The Earth has shown a systematic increase in mineral species through its history, with three ‘eras’ comprising ten ‘stages’ identified by Robert Hazen and his colleagues (

Hazen
et al.
2008

), the eras being associated with planetary accretion, crust and mantle reworking and the influence of life, successively. We suggest that a further level in this form of evolution has now taken place of at least ‘stage’ level, where humans have engineered a large and extensive suite of novel, albeit not formally recognized minerals, some of which will leave a geologically significant signal in strata forming today. These include the great majority of metals (that are not found natively), tungsten carbide, boron nitride, novel garnets and many others. A further stratigraphic signal is of minerals that are rare in pre-industrial geology, but are now common at the surface, including mullite (in fired bricks and ceramics), ettringite, hillebrandite and portlandite (in cement and concrete) and ‘mineraloids’ (novel in detail) such as anthropogenic glass. These have become much more common at the Earth's surface since the mid-twentieth century. However, the scale and extent of this new phase of mineral evolution, which represents part of the widespread changes associated with the proposed Anthropocene Epoch, remains uncharted. The
International Mineralogical Association (IMA)
list of officially accepted minerals explicitly excludes synthetic minerals, and no general inventory of these exists. We propose that the growing geological and societal significance of this phenomenon is now great enough for human-made minerals to be formally listed and catalogued by the IMA, perhaps in conjunction with materials science societies. Such an inventory would enable this phenomenon to be placed more effectively within the context of the 4.6 billion year history of the Earth, and would help characterize the strata of the Anthropocene.
Characterization of LY2228820 Dimesylate, a Potent and Selective Inhibitor of p38 MAPK with Antitumor Activity
Authors: Campbell Robert M. , Anderson Bryan D. , Brooks Nathan A. , Brooks Harold B. , Chan Edward M. , De Dios Alfonso , Gilmour Raymond , Graff Jeremy R. , Jambrina Enrique , Mader Mary , McCann Denis , Na Songqing , Parsons Stephen H. , Pratt Susan E. , Shih Chuan , Stancato Louis F. , Starling James J. , Tate Courtney , Velasco Juan A. , Wang Yong , Ye Xiang S. 
Published: December 2013

Abstract
p38α mitogen-activated protein kinase (MAPK) is activated in cancer cells in response to environmental factors, oncogenic stress, radiation, and chemotherapy. p38α MAPK phosphorylates a number of substrates, including MAPKAP-K2 (MK2), and regulates the production of cytokines in the tumor microenvironment, such as TNF-α, interleukin-1β (IL-1β), IL-6, and CXCL8 (IL-8). p38α MAPK is highly expressed in human cancers and may play a role in tumor growth, invasion, metastasis, and drug resistance. LY2228820 dimesylate (hereafter LY2228820), a trisubstituted imidazole derivative, is a potent and selective, ATP-competitive inhibitor of the α- and β-isoforms of p38 MAPK in vitro (IC50 = 5.3 and 3.2 nmol/L, respectively). In cell-based assays, LY2228820 potently and selectively inhibited phosphorylation of MK2 (Thr334) in anisomycin-stimulated HeLa cells (at 9.8 nmol/L by Western blot analysis) and anisomycin-induced mouse RAW264.7 macrophages (IC50 = 35.3 nmol/L) with no changes in phosphorylation of p38α MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc ≤ 10 μmol/L. LY2228820 also reduced TNF-α secretion by lipopolysaccharide/IFN-γ–stimulated macrophages (IC50 = 6.3 nmol/L). In mice transplanted with B16-F10 melanoma, tumor phospho-MK2 (p-MK2) was inhibited by LY2228820 in a dose-dependent manner [threshold effective dose (TED)70 = 11.2 mg/kg]. Significant target inhibition (&gt;40% reduction in p-MK2) was maintained for 4 to 8 hours following a single 10 mg/kg oral dose. LY2228820 produced significant tumor growth delay in multiple in vivo cancer models (melanoma, non–small cell lung cancer, ovarian, glioma, myeloma, breast). In summary, LY2228820 is a p38 MAPK inhibitor, which has been optimized for potency, selectivity, drug-like properties (such as oral bioavailability), and efficacy in animal models of human cancer. Mol Cancer Ther; 13(2); 364–74. ©2013 AACR.
Cancer-Associated CD43 Glycoforms as Target of Immunotherapy
Authors: Tuccillo Franca Maria , Palmieri Camillo , Fiume Giuseppe , de Laurentiis Annamaria , Schiavone Marco , Falcone Cristina , Iaccino Enrico , Galandrini Ricciarda , Capuano Cristina , Santoni Angela , D'Armiento Francesco Paolo , Arra Claudio , Barbieri Antonio , Dal Piaz Fabrizio , Venzon David , Bonelli Patrizia , Buonaguro Franco Maria , Scala Iris , Mallardo Massimo , Quinto Ileana , Scala Giuseppe 
Published: December 2013

Abstract
CD43 is a sialoglycosylated membrane protein that is involved in cell proliferation and differentiation. CD43 glycoforms that are recognized by the UN1 monoclonal antibody (mAb) were expressed in lymphoblastoid T-cell lines and solid tumors, such as breast, colon, gastric, and squamous cell lung carcinomas, while unexpressed in the normal counterparts. The cancer association of UN1/CD43 epitope suggested the possibility to use the UN1 mAb for tumor diagnosis and therapy. In this study, we show that the UN1 mAb was endowed with antitumor activity in vivo because its passive transfer inhibited the growth of UN1-positive HPB-ALL lymphoblastoid T cells in mice. Furthermore, we demonstrate that tumor inhibition was due to UN1 mAb-dependent natural killer–mediated cytotoxicity. By screening a phage-displayed random peptide library, we identified the phagotope 2/165 as a mimotope of the UN1 antigen, as it harbored a peptide sequence that was specifically recognized by the UN1 mAb and inhibited the binding of the UN1 mAb to UN1-positive tumor cells. On the basis of sequence homology with the extracellular region of CD43 (amino acids 64 to 83), the 2/165 peptide sequence was likely mimicking the protein core of the UN1/CD43 epitope. When used as vaccine in mice, the 2/165 phagotope raised antibodies against the UN1/CD43 antigen, indicating that the 2/165 phagotope mimicked the UN1 antigen structure, and could represent a novel immunogen for cancer immunotherapy. These findings support the feasibility of using monoclonal antibodies to identify cancer-associated mimotopes for immunotherapy. Mol Cancer Ther; 13(3); 752–62. ©2013 AACR.
Glioblastoma Cells Containing Mutations in the Cohesin Component STAG2 Are Sensitive to PARP Inhibition
Authors: Bailey Melanie L. , O'Neil Nigel J. , van Pel Derek M. , Solomon David A. , Waldman Todd , Hieter Philip 
Published: December 2013

Abstract
Recent data have identified STAG2, a core subunit of the multifunctional cohesin complex, as a highly recurrently mutated gene in several types of cancer. We sought to identify a therapeutic strategy to selectively target cancer cells harboring inactivating mutations of STAG2 using two independent pairs of isogenic glioblastoma cell lines containing either an endogenous mutant STAG2 allele or a wild-type STAG2 allele restored by homologous recombination. We find that mutations in STAG2 are associated with significantly increased sensitivity to inhibitors of the DNA repair enzyme PARP. STAG2-mutated, PARP-inhibited cells accumulated in G2 phase and had a higher percentage of micronuclei, fragmented nuclei, and chromatin bridges compared with wild-type STAG2 cells. We also observed more 53BP1 foci in STAG2-mutated glioblastoma cells, suggesting that these cells have defects in DNA repair. Furthermore, cells with mutations in STAG2 were more sensitive than cells with wild-type STAG2 when PARP inhibitors were used in combination with DNA-damaging agents. These data suggest that PARP is a potential target for tumors harboring inactivating mutations in STAG2, and strongly recommend that STAG2 status be determined and correlated with therapeutic response to PARP inhibitors, both prospectively and retrospectively, in clinical trials. Mol Cancer Ther; 13(3); 724–32. ©2013 AACR.
Low Integrated DNA Repair Score and Lung Cancer Risk
Authors: Sevilya Ziv , Leitner-Dagan Yael , Pinchev Mila , Kremer Ran , Elinger Dalia , Rennert Hedy S. , Schechtman Edna , Freedman Laurence S. , Rennert Gad , Paz-Elizur Tamar , Livneh Zvi 
Published: December 2013

Abstract
DNA repair is a prime mechanism for preventing DNA damage, mutation, and cancers. Adopting a functional approach, we examined the association with lung cancer risk of an integrated DNA repair score, measured by a panel of three enzymatic DNA repair activities in peripheral blood mononuclear cells. The panel included assays for AP endonuclease 1 (APE1), 8-oxoguanine DNA glycosylase (OGG1), and methylpurine DNA glycosylase (MPG), all of which repair oxidative DNA damage as part of the base excision repair pathways. A blinded population-based case–control study was conducted with 96 patients with lung cancer and 96 control subjects matched by gender, age (±1 year), place of residence, and ethnic group (Jews/non-Jews). The three DNA repair activities were measured, and an integrated DNA repair OMA (OGG1, MPG, and APE1) score was calculated for each individual. Conditional logistic regression analysis revealed that individuals in the lowest tertile of the integrated DNA repair OMA score had an increased risk of lung cancer compared with the highest tertile, with OR = 9.7; 95% confidence interval (CI), 3.1–29.8; P &lt; 0.001, or OR = 5.6; 95% CI, 2.1–15.1; P &lt; 0.001 after cross-validation. These results suggest that pending validation, this DNA repair panel of risk factors may be useful for lung cancer risk assessment, assisting prevention and referral to early detection by technologies such as low-dose computed tomography scanning. Cancer Prev Res; 7(4); 398–406. ©2013 AACR.
Associations Between Dietary Patterns and Skin Microcirculation in Healthy Subjects
Authors: Karatzi Kalliopi , Protogerou Athanase , Kesse-Guyot Emmanuelle , Fezeu Leopold K. , Carette Claire , Blacher Jacques , Levy Bernard I. , Galan Pilar , Hercberg Serge , Czernichow Sebastien 
Published: December 2013

Objective—
Microvascular dysfunction is suggested to be a marker of common pathophysiological mechanisms in the development of insulin resistance, cardiovascular diseases, and type 2 diabetes mellitus. Given the established relationship of diet with the macrovascular disease, the aim of this study was to investigate for the first time the possible associations between dietary patterns and microcirculation.

Approach and Results—

Two hundred ninety-one healthy men and women selected from the Supplementation en Vitamines et Mineraux Antioxydants 2’ cohort were assessed for anthropometric, nutritional, biochemical, and microcirculation parameters using finger skin capillaroscopy. Dietary intake was assessed cross-sectionally using a food frequency questionnaire, and principal component analysis was used to identify dietary patterns from 40 food groups. Six dietary patterns were identified. A dietary pattern characterized by increased consumption of vegetable oils, poultry, and fish and seafood was positively associated with both functional and anatomic capillary density after adjusting for confounders (
β
=0.13,
P
=0.05 and
β=
0.20,
P=
0.00, respectively). A second dietary pattern with increased consumption of sweets was inversely associated with functional and anatomic capillary density in all multivariate models (
β
=−0.14,
P
=0.03 and
β=
−0.17,
P=
0.01). There were no associations between any of the derived dietary patterns and capillary recruitment.

Conclusions—
In healthy subjects, a dietary pattern characterized by an increased consumption of vegetable oils, poultry, and fish and seafood and low consumption of sweets was associated with better microvascular function. Further prospective studies are needed to confirm the present association.
Novel Lipid Droplet–Associated Serine Hydrolase Regulates Macrophage Cholesterol Mobilization
Authors: Goo Young-Hwa , Son Se-Hee , Kreienberg Paul B. , Paul Antoni 
Published: December 2013

Objective—
Lipid-laden macrophages or foam cells are characterized by massive cytosolic lipid droplet (LD) deposition containing mostly cholesterol ester (CE) derived from the lipoproteins cleared from the arterial wall. Cholesterol efflux from foam cells is considered to be atheroprotective. Because cholesterol is effluxed as free cholesterol, CE accumulation in LDs may limit free cholesterol efflux. Our objective was to identify proteins that regulate cholesterol trafficking through LDs.

Approach and Results—
In a proteomic analysis of the LD fraction of RAW 264.7 macrophages, we identified an evolutionarily conserved protein with a canonical GXSXG lipase catalytic motif and a predicted α/β-hydrolase fold, the RIKEN cDNA 1110057K04 gene, which we named LD-associated hydrolase (LDAH). LDAH association with LDs was confirmed by immunoblotting and immunocytochemistry. LDAH was labeled with a probe specific for active serine hydrolases. LDAH showed relatively weak in vitro CE hydrolase activity. However, cholesterol measurements in intact cells supported a significant role of LDAH in CE homeostasis because LDAH upregulation and downregulation decreased and increased, respectively, intracellular cholesterol and CE in human embryonic kidney-293 cells and RAW 264.7 macrophages. Mutation of the putative nucleophilic serine impaired active hydrolase probe binding, in vitro CE hydrolase activity, and cholesterol-lowering effect in cells, whereas this mutant still localized to the LD. LDAH upregulation increased CE hydrolysis and cholesterol efflux from macrophages, and, interestingly, LDAH is highly expressed in macrophage-rich areas within mouse and human atherosclerotic lesions.

Conclusions—
The data identify a candidate target to promote reverse cholesterol transport from atherosclerotic lesions.
Cystathionine γ-lyase Accelerates Osteoclast Differentiation
Authors: Itou Takahiro , Maldonado Natalia , Yamada Iwao , Goettsch Claudia , Matsumoto Jiro , Aikawa Masanori , Singh Sasha , Aikawa Elena 
Published: December 2013

Objective—
Clinical evidence has linked vascular calcification in advanced atherosclerotic plaques with overt cardiovascular disease and mortality. Bone resorbing monocyte-derived osteoclast-like cells are sparse in these plaques, indicating that their differentiation capability could be suppressed. Here, we seek to characterize the process of osteoclastogenesis by identifying novel regulators and pathways, with the aim of exploring possible strategies to reduce calcification.

Approach and Results—

We used a quantitative mass spectrometry strategy, tandem mass tagging, to quantify changes in the proteome of osteoclast-like cells differentiated from RAW264.7 cells in response to, receptor activator of nuclear factor κ-B ligand induction, a common in vitro model for osteogenesis. More than 4000 proteins were quantified, of which 138 were identified as novel osteoclast-related proteins. We selected 5 proteins for subsequent analysis (cystathionine γ-lyase [Cth/CSE], EGF-like repeat and discoidin I–like domain–containing protein 3, integrin α FG-GAP repeat containing 3, adseverin, and serpinb6b) and show that gene expression levels are also increased. Further analysis of the CSE transcript profile reveals an early onset of an mRNA increase. Silencing of CSE by siRNA and
dl
-propargylglycine, a CSE inhibitor, attenuated receptor activator of nuclear factor κ-B ligand–induced tartrate-resistant acid phosphatase type 5 activity and pit formation, suggesting that CSE is a potent inducer of calcium resorption. Moreover, knockdown of CSE suppressed expression of osteoclast differentiation markers.

Conclusions—
Our large-scale proteomics study identified novel candidate regulators or markers for osteoclastogenesis and demonstrated that CSE may act in early stages of osteoclastogenesis.
Inhibition of Arthritis in the Lewis Rat by Apolipoprotein A-I and Reconstituted High-Density Lipoproteins
Authors: Wu Ben J. , Ong Kwok L. , Shrestha Sudichhya , Chen Kang , Tabet Fatiha , Barter Philip J. , Rye Kerry-Anne 
Published: December 2013

Objective—
This study questions whether high-density lipoproteins (HDLs) and apolipoprotein A-I inhibit joint inflammation in streptococcal cell wall peptidoglycan-polysaccharide (PG-PS)–induced arthritis in female Lewis rats.

Approach and Results—
Administration of PG-PS to female Lewis rats caused acute joint inflammation after 4 days, followed by remission by day 8. The animals subsequently developed chronic joint inflammation that persisted until euthanasia at day 21. Treatment with apolipoprotein A-I 24 hours before and 24 hours after PG-PS administration reduced the acute and chronic joint inflammation. Treatment with apolipoprotein A-I at days 7, 9, and 11 after PG-PS administration reduced the chronic joint inflammation. Treatment with apolipoprotein A-I or reconstituted HDLs consisting of apolipoprotein A-I complexed with phosphatidylcholine 24 hours before and at days 1, 7, 9, and 11 after PG-PS administration reduced acute and chronic joint inflammation. Treatment with apolipoprotein A-I also reduced the inflammatory white blood cell count, synovial fluid proinflammatory cytokine levels, synovial tissue macrophage accumulation, as well as toll-like receptor 2, and inflammatory cytokine expression. At the molecular level, preincubation of human monocyte–derived macrophages with apolipoprotein A-I or reconstituted HDLs before PG-PS stimulation inhibited the PG-PS–induced increase in toll-like receptor 2 and myeloid differentiation primary response gene (88) mRNA levels, nuclear factor-κB activation, and proinflammatory cytokine production. The effects of apolipoprotein A-I and reconstituted HDLs were abolished by transfecting the human monocyte–derived macrophages with ATP-binding cassette transporter A1 or G1 siRNA.

Conclusions—
Apolipoprotein A-I and reconstituted HDLs attenuate PG-PS–induced arthritis in the rat. Studies in human monocyte–derived macrophages indicate that this benefit may be because of the inhibition of toll-like receptor 2 expression and decreased nuclear factor-κB activation in macrophages.
Insulin-Regulated Protein Palmitoylation Impacts Endothelial Cell Function
Authors: Wei Xiaochao , Song Haowei , Semenkovich Clay F. 
Published: December 2013

Objective—
Defects in insulin signaling are associated with abnormal endothelial cell function, which occurs commonly in cardiovascular disease. Targets of insulin signaling in endothelial cells are incompletely understood. Protein S-palmitoylation, the reversible modification of proteins by the lipid palmitate, is a post-translational process relevant to cell signaling, but little is known about the role of insulin in protein palmitoylation.

Approach and Results—
To test the hypothesis that insulin alters protein palmitoylation in endothelial cells, we combined acyl-biotin exchange chemistry with stable isotope labeling by amino acids in cell culture to perform quantitative proteomic profiling of human endothelial cells. We identified ≈380 putative palmitoylated proteins, of which >200 were not known to be palmitoylated; ≈10% of the putative palmitoylated proteins were induced or suppressed by insulin. Of those potentially affected by insulin, <10 have been implicated in vascular function. For one, platelet-activating factor acetylhydrolase IB subunit gamma (PAFAH1b3; not previously known to be palmitoylated), we confirmed that insulin stimulated palmitoylation without affecting PAFAH1b3 protein abundance. Chemical inhibition of palmitoylation prevented insulin-induced angiogenesis in vitro; knockdown of PAFAH1b3 had the same effect. PAFAH1b3 knockdown also disrupted cell migration. Mutagenesis of cysteines at residues 56 and 206 prevented palmitoylation of PAFAH1b3, abolished its capacity to stimulate cell migration, and inhibited its association with detergent-resistant membranes, which are implicated in cell signaling. Insulin promoted the association of wild-type PAFAH1b3 with detergent-resistant membranes.

Conclusions—
These findings provide proof of principle for using proteomics to identify novel insulin-inducible palmitoylation targets relevant to endothelial function.
Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient With Chronic Kidney Disease (RENAL-DES) Study
Authors: Tomai Fabrizio , Ribichini Flavio , De Luca Leonardo , Petrolini Alessandro , Ghini Anna S. , Weltert Luca , Spaccarotella Carmen , Proietti Igino , Trani Carlo , Nudi Francesco , Pighi Michele , Vassanelli Corrado 
Published: December 2013

Background—
Percutaneous coronary interventions in patients with chronic kidney disease have shown suboptimal results. Drug-eluting stents (DES) might reduce the rate of target vessel revascularization in comparison with bare-metal stents (BMS) in patients with chronic kidney disease. However, given the multiple concomitant individual variables present in such patients, the comparison of neointimal growth after percutaneous coronary intervention is complex and difficult to assess.

Methods and Results—

Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient with Chronic Kidney Disease (RENAL-DES) was a prospective, randomized, multicenter study to directly compare the efficacy in the prevention of clinical restenosis of everolimus-eluting stent (Xience V) and BMS with an identical design (Multi-Link Vision), both implanted in the same patient with multivessel coronary artery disease and chronic kidney disease (estimated glomerular filtration rate <60 mL/min). The primary end point of the study was the ischemia-driven target vessel revascularization as detected with myocardial scintigraphy at 12 months. In 215 patients, 512 coronary vessels were successfully treated with the randomly assigned DES (n=257) or BMS (n=255). At 1 year, the rate of ischemia-driven target vessel revascularization for DES and BMS groups was 2.7% (95% confidence interval, 1.1%–5.6%) and 11.4% (95% confidence interval, 7.8% to 16%), respectively,
P
<0.001. For the multivariate analysis, independent predictors of the ischemia-driven target vessel revascularization were BMS implantation (odds ratio, 4.95; 95% confidence interval, 2.1–11.6;
P
<0.001) and vessel size (odds ratio, 0.32; 95% confidence interval, 0.1–0.7;
P
=0.006).

Conclusions—
This is the first randomized trial showing a reduction of clinical restenosis with a new-generation DES in comparison with a BMS of equal design, in patients who have chronic kidney disease with multivessel coronary artery disease.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00818792.