bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIK3CA mutations can initiate pancreatic tumorigenesis and are targetable with PI3K inhibitors
Authors: Payne S N , Maher M E , Tran N H , Van De Hey D R , Foley T M , Yueh A E , Leystra A A , Pasch C A , Jeffrey J J , Clipson L , Matkowskyj K A , Deming D A 
Published: October 2015

AbstractAberrations in the phosphoinositide 3-kinase (PI3K) signaling pathway have a key role in the pathogenesis of numerous cancers by altering cell growth, metabolism, proliferation and apoptosis. Interest in targeting the PI3K signaling cascade continues, as new agents are being clinically evaluated. PIK3CA mutations result in a constitutively active PI3K and are present in a subset of pancreatic cancers. Here we examine mutant PIK3CA-mediated pancreatic tumorigenesis and the response of PIK3CA mutant pancreatic cancers to dual PI3K/mammalian target of rapamycin (mTOR) inhibition. Two murine models were generated expressing a constitutively active PI3K within the pancreas. An increase in acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasms (PanINs) was identified. In one model these lesions were detected as early as 10 days of age. Invasive pancreatic ductal adenocarcinoma developed in these mice as early as 20 days of age. These cancers were highly sensitive to treatment with dual PI3K/mTOR inhibition. In the second model, PanINs and invasive cancer develop with a greater latency owing to a lesser degree of PI3K pathway activation in this murine model. In addition to PI3K pathway activation, increased ERK1/2 signaling is common in human pancreatic cancers. Phosphorylation of ERK1/2 was also investigated in these models. Phosphorylation of ERK1/2 is demonstrated in the pre-neoplastic lesions and invasive cancers. This activation of ERK1/2 is diminished with dual PI3K/mTOR inhibition. In summary, PIK3CA mutations can initiate pancreatic tumorigenesis and these cancers are particularly sensitive to dual PI3K/mTOR inhibition. Future studies of PI3K pathway inhibitors for patients with PIK3CA mutant pancreatic cancers are warranted.
Azobenzene Modified Imidacloprid Derivatives as Photoswitchable Insecticides: Steering Molecular Activity in a Controllable Manner
Authors: Xu Zhiping , Shi Lina , Jiang Danping , Cheng Jiagao , Shao Xusheng , Li Zhong 
Published: October 2015

AbstractIncorporating the photoisomerizable azobenzene into imidacloprid produced a photoswitchable insecticidal molecule as the first neonicotinoid example of remote control insecticide performance with spatiotemporal resolution. The designed photoswitchable insecticides showed distinguishable activity against Musca both in vivo and in vitro upon irradiation. Molecular docking study further suggested the binding difference of the two photoisomers. The generation of these photomediated insecticides provides novel insight into the insecticidal activity facilitating further investigation on the functions of insect nicotinic acetylcholine receptors and opens a novel way to control and study insect behavior on insecticide poisoning using light.
Real-time Detection of Breast Cancer Cells Using Peptide-functionalized Microcantilever Arrays
Authors: Etayash Hashem , Jiang Keren , Azmi Sarfuddin , Thundat Thomas , Kaur Kamaljit 
Published: October 2015

AbstractLigand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch®) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. The peptide-functionalized microcantilever allowed efficient capture and detection of cancer cells in MCF7 spiked human blood samples emulating CTCs in human blood. A detection limit of 50–100 cancer cells mL−1 from blood samples was achieved with a capture yield of 80% from spiked whole blood samples. The results emphasize the potential of peptide 18-4 as a novel peptide for capturing and detecting cancer cells in conjunction with nanomechanical cantilever platform. The reported peptide-based cantilever platform represents a new analytical approach that can lead to an alternative to the various detection platforms and can be leveraged to further study CTCs.
The role of putrescine in the regulation of proteins and fatty acids of thylakoid membranes under salt stress
Authors: Shu Sheng , Yuan Yinghui , Chen Jie , Sun Jin , Zhang Wenhua , Tang Yuanyuan , Zhong Min , Guo Shirong 
Published: October 2015

AbstractPolyamines can alleviate the inhibitory effects of salinity on plant growth by regulating photosynthetic efficiency. However, little information is available to explain the specific mechanisms underlying the contribution of polyamines to salt tolerance of the photosynthetic apparatus. Here, we investigated the role of putrescine (Put) on the photosynthetic apparatus of cucumber seedlings under salt stress. We found that NaCl stress resulted in severe ion toxicity and oxidative stress in cucumber chloroplasts. In addition, salinity caused a significant increase in the saturated fatty acid contents of thylakoid membranes. Put altered unsaturated fatty acid content, thereby alleviating the disintegration of thylakoid grana lamellae and reducing the number of plastoglobuli in thylakoid membranes. BN-PAGE revealed Put up-regulated the expression of ATP synthase, CP47, D1, Qb and psbA proteins and down-regulated CP24, D2 and LHCII type III in NaCl-stressed thylakoid membranes. qRT-PCR analysis of gene expression was used to compare transcript and protein accumulation among 10 candidate proteins. For five of these proteins, induced transcript accumulation was consistent with the pattern of induced protein accumulation. Our results suggest that Put regulates protein expression at transcriptional and translational levels by increasing endogenous polyamines levels in thylakoid membranes, which may stabilise photosynthetic apparatus under salt stress.
Analysis of a transgenic Oct4 enhancer reveals high fidelity long-range chromosomal interactions
Authors: Cai Mingyang , Gao Fan , Zhang Peilin , An Woojin , Shi Jiandang , Wang Kai , Lu Wange 
Published: October 2015

AbstractGenome structure or nuclear organization has fascinated researchers investigating genome function. Recently, much effort has gone into defining relationships between specific genome structures and gene expression in pluripotent cells. We previously analyzed chromosomal interactions of the endogenous Oct4 distal enhancer in pluripotent cells. Here, we derive ES and iPS cells from a transgenic Oct4 distal enhancer reporter mouse. Using sonication-based Circularized Chromosome Conformation Capture (4C) coupled with next generation sequencing, we determined and compared the genome-wide interactome of the endogenous and transgenic Oct4 distal enhancers. Integrative genomic analysis indicated that the transgenic enhancer binds to a similar set of loci and shares similar key enrichment profiles with its endogenous counterpart. Both the endogenous and transgenic Oct4 enhancer interacting loci were enriched in the open nucleus compartment, which is associated with active histone marks (H3K4me1, H3K27ac, H3K4me3 and H3K9ac), active cis-regulatory sequences (DNA hypersensitivity sites (DHS)), 5-hydroxymethylcytosine (5-hmc) and early DNA replication domains. In addition, binding of some pluripotency-related transcription factors was consistently enriched in our 4C sites and genes in those sites were generally more highly expressed. Overall, our work reveals critical features that may function in gene expression regulation in mouse pluripotent cells.
Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection
Authors: Mooney Jason P. , Lokken Kristen L. , Byndloss Mariana X. , George Michael D. , Velazquez Eric M. , Faber Franziska , Butler Brian P. , Walker Gregory T. , Ali Mohamed M. , Potts Rashaun , Tiffany Caitlin , Ahmer Brian M. M. , Luckhart Shirley , Tsolis Renée M. 
Published: October 2015

AbstractChildhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection. Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory macrophages and T cells into the intestinal mucosa and increased expression of inflammatory cytokines. These mucosal responses were also observed in germ-free mice, showing that they are independent of the resident microbiota. Remarkably, P. yoelii infection reduced colonization resistance of mice against S. enterica serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal microbiota revealed marked changes in the community structure. Shifts in the microbiota increased susceptibility to intestinal colonization by S. Typhimurium, as demonstrated by microbiota reconstitution of germ-free mice. These results show that P. yoelii infection, via alterations to the microbial community in the intestine, decreases resistance to intestinal colonization with NTS. Further they raise the possibility that decreased colonization resistance may synergize with effects of malaria on systemic immunity to increase susceptibility to disseminated NTS infections.
mirPRo–a novel standalone program for differential expression and variation analysis of miRNAs
Authors: Shi Jieming , Dong Min , Li Lei , Liu Lin , Luz-Madrigal Agustin , Tsonis Panagiotis A. , Del Rio-Tsonis Katia , Liang Chun 
Published: October 2015

AbstractBeing involved in many important biological processes, miRNAs can regulate gene expression by targeting mRNAs to facilitate their degradation or translational inhibition. Many miRNA sequencing studies reveal that miRNA variations such as isomiRs and “arm switching” are biologically relevant. However, existing standalone tools usually do not provide comprehensive, detailed information on miRNA variations. To deepen our understanding of miRNA variability, we developed a new standalone tool called “mirPRo” to quantify known miRNAs and predict novel miRNAs. Compared with the most widely used standalone program, miRDeep2, mirPRo offers several new functions including read cataloging based on genome annotation, optional seed region check, miRNA family expression quantification, isomiR identification and categorization and “arm switching” detection. Our comparative data analyses using three datasets from mouse, human and chicken demonstrate that mirPRo is more accurate than miRDeep2 by avoiding over-counting of sequence reads and by implementing different approaches in adapter trimming, mapping and quantification. mirPRo is an open-source standalone program (https://sourceforge.net/projects/mirpro/).
Control of a chemical reaction (photodegradation of the p3ht polymer) with nonlocal dielectric environments
Authors: Peters V. N. , Tumkur T. U. , Zhu G. , Noginov M. A. 
Published: October 2015

AbstractProximity to metallic surfaces, plasmonic structures, cavities and other inhomogeneous dielectric environments is known to control spontaneous emission, energy transfer, scattering and many other phenomena of practical importance. The aim of the present study was to demonstrate that, in spirit of the Marcus theory, the rates of chemical reactions can, too, be influenced by nonlocal dielectric environments, such as metallic films and metal/dielectric bilayer or multilayer structures. We have experimentally shown that metallic, composite metal/dielectric substrates can, indeed, control ordering as well as photodegradation of thin poly-3-hexylthiophene (p3ht) films. In many particular experiments, p3ht films were separated from metal by a dielectric spacer, excluding conventional catalysis facilitated by metals and making modification of the nonlocal dielectric environment a plausible explanation for the observed phenomena. This first step toward understanding of a complex relationship between chemical reactions and nonlocal dielectric environments is to be followed by the theory development and a broader scope of thorough experimental studies.
An assessment of the amount of untapped fold level novelty in under-sampled areas of the tree of life
Authors: Barry Roche Daniel , Brüls Thomas 
Published: October 2015

AbstractPrevious studies of protein fold space suggest that fold coverage is plateauing. However, sequence sampling has been -and remains to a large extent- heavily biased, focusing on culturable phyla. Sustained technological developments have fuelled the advent of metagenomics and single-cell sequencing, which might correct the current sequencing bias. The extent to which these efforts affect structural diversity remains unclear, although preliminary results suggest that uncultured organisms could constitute a source of new folds. We investigate to what extent genomes from uncultured and under-sampled phyla accessed through single cell sequencing, metagenomics and high-throughput culturing efforts have the potential to increase protein fold space and conclude that i) genomes from under-sampled phyla appear enriched in sequences not covered by current protein family and fold profile libraries, ii) this enrichment is linked to an excess of short (and possibly partly spurious) sequences in some of the datasets, iii) the discovery rate of novel folds among sequences uncovered by current fold and family profile libraries may be as high as 36%, but would ultimately translate into a marginal increase in global discovery of novel folds. Thus, genomes from under-sampled phyla should have a rather limited impact on increasing coarse grained tertiary structure level novelty.
USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination
Authors: Iyengar Prasanna Vasudevan , Jaynes Patrick , Rodon Laura , Lama Dilraj , Law Kai Pong , Lim Yoon Pin , Verma Chandra , Seoane Joan , Eichhorn Pieter Johan Adam 
Published: October 2015

AbstractUbiquitin modification of the TGF-β pathway components is emerging as a key mechanism of TGF-β pathway regulation. To limit TGF-β responses, TGF-β signaling is regulated through a negative feedback loop whereby the E3 ligase SMURF2 targets the TGF-β receptor (TβR) complex for ubiquitin-mediated degradation. Counteracting this process, a number of deubiquitinating (DUBs) enzymes have recently been identified that deubiquitinate and stabilize the TβR. However the precise mechanism by which these DUBs act on TβR function remains poorly defined. Here, we demonstrate that apart from targeting the TβR complex directly, USP15 also deubiquitinates SMURF2 resulting in enhanced TβR stability and downstream pathway activation. Through proteomic analysis, we show that USP15 modulates the ubiquitination of Lys734, a residue required for SMURF2 catalytic activity. Our results show that SMURF2 is a critical target of USP15 in the TGF-β pathway and may also explain how USP15 and SMURF2 target multiple complementary protein complexes in other pathways.
Distinguishing time-delayed causal interactions using convergent cross mapping
Authors: Ye Hao , Deyle Ethan R. , Gilarranz Luis J. , Sugihara George 
Published: October 2015

AbstractAn important problem across many scientific fields is the identification of causal effects from observational data alone. Recent methods (convergent cross mapping, CCM) have made substantial progress on this problem by applying the idea of nonlinear attractor reconstruction to time series data. Here, we expand upon the technique of CCM by explicitly considering time lags. Applying this extended method to representative examples (model simulations, a laboratory predator-prey experiment, temperature and greenhouse gas reconstructions from the Vostok ice core and long-term ecological time series collected in the Southern California Bight), we demonstrate the ability to identify different time-delayed interactions, distinguish between synchrony induced by strong unidirectional-forcing and true bidirectional causality and resolve transitive causal chains.
Determination of the hyperfine magnetic field in magnetic carbon-based materials: DFT calculations and NMR experiments
Authors: Freitas Jair C. C. , Scopel Wanderlã L. , Paz Wendel S. , Bernardes Leandro V. , Cunha-Filho Francisco E. , Speglich Carlos , Araújo-Moreira Fernando M. , Pelc Damjan , Cvitanić Tonči , Požek Miroslav 
Published: October 2015

AbstractThe prospect of carbon-based magnetic materials is of immense fundamental and practical importance and information on atomic-scale features is required for a better understanding of the mechanisms leading to carbon magnetism. Here we report the first direct detection of the microscopic magnetic field produced at 13C nuclei in a ferromagnetic carbon material by zero-field nuclear magnetic resonance (NMR). Electronic structure calculations carried out in nanosized model systems with different classes of structural defects show a similar range of magnetic field values (18–21 T) for all investigated systems, in agreement with the NMR experiments. Our results are strong evidence of the intrinsic nature of defect-induced magnetism in magnetic carbons and establish the magnitude of the hyperfine magnetic field created in the neighbourhood of the defects that lead to magnetic order in these materials.
Identification of Id1 as a downstream effector for arsenic-promoted angiogenesis via PI3K/Akt, NF-κB and NOS signaling
Authors: Tsai Chun-Hao , Yang Ming-Hui , Hung Amos C. , Wu Shou-Cheng , Chiu Wen-Chin , Hou Ming-Feng , Tyan Yu-Chang , Wang Yun-Ming , Yuan Shyng-Shiou F. 
Published: October 2015

Abstract
Exposure to arsenic is known to be a risk factor for various types of cancer. Apart from its carcinogenic activity, arsenic also shows promoting effects on angiogenesis, a crucial process for tumor growth. Yet, the mechanism underlying arsenic-induced angiogenesis is not fully understood. In this study, we aimed at investigating the involvement of inhibitor of DNA binding 1 (Id1) and the associated signal molecules in the arsenic-mediated angiogenesis. Our initial screening revealed that treatment with low concentrations of arsenic (0.5–1 μM) led to multiple cellular responses, including enhanced endothelial cell viability and angiogenic activity as well as increased protein expression of Id1. The arsenic-induced angiogenesis was suppressed in the Id1-knocked down cells compared to that in control cells. Furthermore, arsenic-induced Id1 expression and angiogenic activity were regulated by PI3K/Akt, NF-κB, and nitric oxide synthase (NOS) signaling. In summary, our current data demonstrate for the first time that Id1 mediates the arsenic-promoted angiogenesis, and Id1 may be regarded as an antiangiogenesis target for treatment of arsenic-associated cancer.
HIGH-RESOLUTION HYBRID SIMULATIONS OF KINETIC PLASMA TURBULENCE AT PROTON SCALES
Authors: Franci Luca , Landi Simone , Matteini Lorenzo , Verdini Andrea , Hellinger Petr 
Published: October 2015

ABSTRACT
We investigate properties of plasma turbulence from magnetohydrodynamic (MHD) to sub-ion scales by means of two-dimensional, high-resolution hybrid particle-in-cell simulations. We impose an initial ambient magnetic field perpendicular to the simulation box, and we add a spectrum of large-scale magnetic and kinetic fluctuations with energy equipartition and vanishing correlation. Once the turbulence is fully developed, we observe an MHD inertial range, where the spectra of the perpendicular magnetic field and the perpendicular proton bulk velocity fluctuations exhibit power-law scaling with spectral indices of

and

respectively. This behavior is extended over a full decade in wavevectors and is very stable in time. A transition is observed around proton scales. At sub-ion scales, both spectra steepen, with the former still following a power law with a spectral index of

A

slope is observed in the density and parallel magnetic fluctuations, highlighting the presence of compressive effects at kinetic scales. The spectrum of the perpendicular electric fluctuations follows that of the proton bulk velocity at MHD scales, and flattens at small scales. All these features, which we carefully tested against variations of many parameters, are in good agreement with solar wind observations. The turbulent cascade leads to on overall proton energization with similar heating rates in the parallel and perpendicular directions. While the parallel proton heating is found to be independent on the resistivity, the number of particles per cell, and the resolution employed, the perpendicular proton temperature strongly depends on these parameters.
Building Economic Models Corresponding to the Real World
Authors: Huffaker Ray 
Published: October 2015

AbstractIncreasingly, there are calls to audit models used in public policy for how accurately they portray the reality facing policy makers. Although models cannot be logically verified as accurate representations of reality, past work concludes that modelers can reasonably demonstrate the degree of correspondence. How to establish real‐world correspondence remains an open question. This paper outlines a framework of pre‐modeling data diagnostics to provide evidence of correspondence. The scheme—based on Nonlinear Time Series Analysis—provides a rigorous benchmark for specification and testing of policy models that reduces the likelihood that a misspecified model is discredited by an unanticipated crisis.
The Risk Attitudes of U.S. Farmers
Authors: Roe Brian E. 
Published: October 2015

AbstractI compare the distribution of risk attitudes of farm owners in the United States to nonfarm business owners and the general population using a measure of risk tolerance collected from national surveys. I find that farmers are significantly more tolerant of risk than the general population, though they are significantly less tolerant of risk than nonfarm business owners. Once demographic differences are controlled, farm and nonfarm business owners are more similar in their risk attitudes and both groups remain significantly more risk tolerant than the general population. First‐generation farmers display greater risk tolerance than farmers who inherit operations from family members, as do farmers who have just begun operating a farm; neither pattern emerges among nonfarm business owners. The most risk tolerant farmers are young and male with larger operations, higher incomes, less formal education and close proximity to metropolitan centers. Among farmers, those with less diversified operations and those with specialty enterprises are more risk tolerant than other types of farmers. Crop farmers are less risk tolerant than fruit and vegetable farmers or farmers with specialty enterprises, while farmers who receive government payments or buy enterprise insurance are not significantly different in risk tolerance from farmers who eschew such opportunities. These findings stimulate questions about how farm programs and the distinct challenges of entry in the production agriculture sector shape the underlying distribution of key farmer characteristics such as risk tolerance.