bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics inside the cancer cell attractor reveal cell heterogeneity, limits of stability, and escape
Authors: Li Qin , Wennborg Anders , Aurell Erik , Dekel Erez , Zou Jie-Zhi , Xu Yuting , Huang Sui , Ernberg Ingemar 
Published: March 2016

SignificanceIt has been proposed, based on theory of complex gene regulatory networks, that cell types, including cancer cells, represent attractor states of the network dynamics. Here, we characterize for the first time, to our knowledge, the detailed dynamics of a cancer cell attractor at single-cell resolution. The results provide quantitative knowledge on nongenetic intercellular heterogeneity and its dynamics within an isogenic cell population of cancerous cells, affording insights at a previously unidentified level of resolution between molecular pathways and macroscopic tumor behaviors. This new dimension of characterizing tumor cells might impact design of future rational cancer therapies by taking into account the dynamic robustness and high volatility of a heterogeneous cancer cell population.
Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes
Authors: Li Xiaoheng , Wang Zhao , Jiang Zhenming , Guo Jingjing , Zhang Yuxi , Li Chenhao , Chung Jinyong , Folmer Janet , Liu June , Lian Qingquan , Ge Renshan , Zirkin Barry R. , Chen Haolin 
Published: March 2016

Significance
Leydig cells, derived from stem cells, are the primary source of testosterone in males. Testosterone deficiency has been linked to sexual dysfunction and decreased bone density, muscle mass, and cognition. Thus, the formation and maintenance of the Leydig cell population is of fundamental importance. Through the use of a unique tubule culture system, we have identified critical niche factors that control the proliferation and differentiation of the Leydig stem cells. Additionally, we report on the isolation and purification of these cells through a specific cell surface marker protein.
Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice
Authors: Matak Pavle , Matak Andrija , Moustafa Sarah , Aryal Dipendra K. , Benner Eric J. , Wetsel William , Andrews Nancy C. 
Published: March 2016

Significance
The brain requires iron for mitochondrial respiration and synthesis of myelin, neurotransmitters, and monoamine oxidases. Iron accumulates in distinct parts of the brain in patients with neurodegenerative diseases, and some have proposed that neurons die because they contain too much iron. Neuronal iron handling is not well understood. We focused on dopaminergic neurons, affected in Parkinson’s disease, and manipulated molecules involve in iron uptake and release. We showed that loss of ferroportin, which exports cellular iron, had no apparent effect. In contrast, loss of transferrin receptor, involved in iron uptake, caused neuronal iron deficiency and neurodegeneration with features similar to Parkinson’s disease. We propose that neuronal iron deficiency may contribute to neurodegeneration in human disease.
Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure
Authors: Torres Ashley M. , Matheny Jonathan B. , Keaveny Tony M. , Taylor David , Rimnac Clare M. , Hernandez Christopher J. 
Published: March 2016

Significance
Lightweight structures often use foam cores to achieve high strength and stiffness. Structures that are submitted to cyclic loading with long service lives must also resist crack propagation. We show that the foam-like regions of cancellous bone resist damage propagation by varying material heterogeneity within struts, a strategy that makes the material less susceptible to stress concentrations at the surface and enhances the ability of the structure to recover its initial shape after mechanical failure. The ability to recover deformation after failure improves long-term function of bones after a fracture. Our findings suggest a previously unidentified design strategy of man-made foams in which material heterogeneity can be used to mitigate the effect of local failure to better maintain mechanical function.
Early signaling dynamics of the epidermal growth factor receptor
Authors: Reddy Raven J. , Gajadhar Aaron S. , Swenson Eric J. , Rothenberg Daniel A. , Curran Timothy G. , White Forest M. 
Published: March 2016

Significance
To date, poor temporal resolution of response measurement has obscured the complex initiation of receptor tyrosine kinase (RTK) signaling that governs cellular response to stimulation. To address this deficiency, we have performed a systems-level characterization of the phosphorylation changes that occur in the immediate period after growth factor stimulation with 10-s resolution. We treated MCF-10A cells with EGF and measured tyrosine phosphorylation levels from 0 to 80 s on hundreds of sites in the cell. Examining phosphorylation dynamics on this timescale reveals patterns that were not observable with slower sampling rates. We further explore the roles of negative and positive feedback, providing further insight into systems-level behaviors of the EGF receptor (EGFR) signaling network.
Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome
Authors: Tripathi Satyendra C. , Peters Haley L. , Taguchi Ayumu , Katayama Hiroyuki , Wang Hong , Momin Amin , Jolly Mohit Kumar , Celiktas Muge , Rodriguez-Canales Jaime , Liu Hui , Behrens Carmen , Wistuba Ignacio I. , Ben-Jacob Eshel , Levine Herbert , Molldrem Jeffrey J. , Hanash Samir M. , Ostrin Edwin J. 
Published: March 2016

Significance
The success rate of therapeutic trials that target tumor antigens is quite limited. We demonstrate for the first time to our knowledge that lung cancer cells that have undergone epithelial-to-mesenchymal transition lose immunoproteasome expression, resulting in markedly reduced antigen presentation. Reduced expression of the immunoproteasome was associated with and can predict poor outcome in non-small cell lung carcinoma (NSCLC) patients. Induction of the immunoproteasome with IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment can overcome this immune escape mechanism of mesenchymal cells by restoring functional HLA class I-bound peptides. These findings have substantial relevance for development of effective strategies to target tumor cells with inherent resistance to T cell-mediated immunotherapy.
Human DNMT1 transition state structure
Authors: Du Quan , Wang Zhen , Schramm Vern L. 
Published: March 2016

Significance
DNA methyltransferase 1 (DNMT1) is the major enzyme responsible for maintenance of DNA CpG methylation marks in human cells. The enzyme is a validated target for cancer, but current treatments are mutagenic. Knowledge of the transition state (TS) structure of DNMT1 will inform the chemical reaction mechanism and provide information for TS analog design. Here, we report the subangstrom geometric and electrostatic character of the TS for the DNMT1 methylation of hemimethylated DNA. The experimental and computational TS analysis indicates methyl transfer is the rate-limiting chemical step for the reaction. Methyl group transfer can be characterized as a loose nucleophilic substitution TS. TS analysis of DNMT1 demonstrates an approach to understand a complex epigenetic enzyme.
Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy
Authors: Palma Eleonora , Reyes-Ruiz Jorge Mauricio , Lopergolo Diego , Roseti Cristina , Bertollini Cristina , Ruffolo Gabriele , Cifelli Pierangelo , Onesti Emanuela , Limatola Cristina , Miledi Ricardo , Inghilleri Maurizio 
Published: March 2016

SignificanceAmyotrophic lateral sclerosis (ALS) is a fatal disease leading to motor neuron degeneration and progressive paralysis. Other studies have revealed defects in skeletal muscle even in the absence of motor neuron anomalies, focusing on acetylcholine receptors (AChRs) and supporting the so-called “dying-back” hypothesis. Our results indicate that the endocannabinoid palmitoylethanolamide (PEA) reduces the rundown of AChRs currents in ALS muscle and can clinically improve patients’ pulmonary function. This study strengthens the important role of muscle in ALS pathogenesis and the idea that AChRs can be therapeutic targets.
Impacts of nonstate, market-driven governance on Chilean forests
Authors: Heilmayr Robert , Lambin Eric F. 
Published: March 2016

SignificanceGlobal trade in commodities has become an important driver of environmental degradation. In response, there has been a proliferation of nonstate, market-driven governance seeking to reduce environmental degradation through interventions in the supply chain. We provide some of the first quasiexperimental evidence to show that private, market-driven policies can slow deforestation. We compare the impacts of two certification schemes and a deforestation moratorium in Chile using a factorial quasiexperimental design. Our results indicate that governance regimes with greater collaboration between environmental and industry stakeholders achieved better environmental outcomes. In contrast to many public conservation policies, we find that private governance systems can effectively target high-deforestation properties.
Spectral gap optimization of order parameters for sampling complex molecular systems
Authors: Tiwary Pratyush , Berne B. J. 
Published: March 2016

SignificanceMolecular-dynamics (MD) simulations have become a versatile tool for exploration of complex molecular systems. However, they are limited in the timescales that can be reached. Thus, over the years, a suite of enhanced-sampling algorithms have been proposed that assist MD to transcend the timescale limitation, with diverse applications across physical and life sciences. A continuing grand challenge in the success of many such sampling methods pertains to a judicious choice of order parameters. In this work, we propose a new method for designing order parameters that minimizes the role played by human intuition and makes the progress significantly more automated than before. We expect this algorithm to be of great use in furthering the success of enhanced sampling.
Redox regulation of ascorbate and glutathione by a chloroplastic dehydroascorbate reductase is required for high-light stress tolerance in Arabidopsis
Authors: Noshi Masahiro , Hatanaka Risa , Tanabe Noriaki , Terai Yusuke , Maruta Takanori , Shigeoka Shigeru 
Published: March 2016

Abstract
Chloroplasts are a significant site for reactive oxygen species production under illumination and, thus, possess a well-organized antioxidant system involving ascorbate. Ascorbate recycling occurs in different manners in this system, including a dehydroascorbate reductase (DHAR) reaction. We herein investigated the physiological significance of DHAR3 in photo-oxidative stress tolerance in Arabidopsis. GFP-fused DHAR3 protein was targeted to chloroplasts in Arabidopsis leaves. A DHAR3 knockout mutant exhibited sensitivity to high light (HL). Under HL, the ascorbate redox states were similar in mutant and wild-type plants, while total ascorbate content was significantly lower in the mutant, suggesting that DHAR3 contributes, at least to some extent, to ascorbate recycling. Activation of monodehydroascorbate reductase occurred in dhar3 mutant, which might compensate for the lack of DHAR3. Interestingly, glutathione oxidation was consistently inhibited in dhar3 mutant. These findings indicate that DHAR3 regulates both ascorbate and glutathione redox states to acclimate to HL.
“How Do You Want to be Wise?”: The Influence of the Progymnasmata on Ælfrīc’s Colloquy
Authors: Loveridge Jordan 
Published: March 2016

ABSTRACT
This essay analyzes the tenth-century pedagogical text Ælfrīc’s Colloquy as an instance of Anglo-Saxon rhetorical instruction in the spirit of the Greco-Roman progymnasmata. Through a comparison of the text with classical sources such as Priscian’s adaptations of Hermogenes and Isidore’s Etymologies, this essay concludes that Ælfrīc knew of the progymnasmata and that these exercises served as the basis for rhetorical instruction that emphasized Benedictine ideals of communal concord through trained speaking and writing. Drawing on the commonplace of the three estates, the Colloquy demonstrated the ideal role of rhetoric in Anglo-Saxon society while modeling traditional progymnasmata exercises such as fable composition, impersonations, and comparisons.
A (Hetero)Topology of Rhetoric and Obama’s African Dreams
Authors: Chirindo Kundai 
Published: March 2016

ABSTRACT
The emplacements of rhetoric are manifold and the inquiries into the topologies of rhetoric are ways of understanding developments in rhetorical theory. To these ends, I contrast in this article the invocations of place in rhetorical theory old and new. In this long view, the spatiality of rhetoric appears to be multifaceted. I show that in Greco-Roman rhetorical theory, spatiality is topical, figured metaphorically and literally, and functions as a precedent condition for rhetoric. I argue that modern/postmodern theories differ from traditional theories of rhetoric not because they rely more or less on the materiality or immateriality of place, but because of their orientations to place as heterotopic, that is, as fluid and contingent. I then offer an account of how heterotopic rhetoric challenges orders of knowledge allowing for ever-new articulations through a close reading of Barack Obama’s Dreams from my Father. The heterotopology of rhetoric proposed here expands understandings of the heuristic function of place. The essay considers the implications heterotopic place holds for identity and subjectivity.
The Role of Aldosterone in Obesity-Related Hypertension
Authors: Kawarazaki Wakako , Fujita Toshiro 
Published: March 2016

Abstract
Obese subjects often have hypertension and related cardiovascular and renal diseases, and this has become a serious worldwide health problem. In obese subjects, impaired renal-pressure natriuresis causes sodium retention, leading to the development of salt-sensitive hypertension. Physical compression of the kidneys by visceral fat and activation of the sympathetic nervous system, renin–angiotensin systems (RAS), and aldosterone/mineralocorticoid receptor (MR) system are involved in this mechanism. Obese subjects often exhibit hyperaldosteronism, with increased salt sensitivity of blood pressure (BP). Adipose tissue excretes aldosterone-releasing factors, thereby stimulating aldosterone secretion independently of the systemic RAS, and aldosterone/MR activation plays a key role in the development of hypertension and organ damage in obesity. In obese subjects, both salt sensitivity of BP, enhanced by obesity-related metabolic disorders including aldosterone excess, and increased dietary sodium intake are closely related to the incidence of hypertension. Some salt sensitivity-related gene variants affect the risk of obesity, and together with salt intake, its combination is possibly associated with the development of hypertension in obese subjects. With high salt levels common in modern diets, salt restriction and weight control are undoubtedly important. However, not only MR blockade but also new diagnostic modalities and therapies targeting and modifying genes that are related to salt sensitivity, obesity, or RAS regulation are expected to prevent obesity and obesity-related hypertension.
Detection and removal of spatial bias in multiwell assays
Authors: Lachmann Alexander , Giorgi Federico M. , Alvarez Mariano J. , Califano Andrea 
Published: March 2016

Abstract
Motivation: Multiplex readout assays are now increasingly being performed using microfluidic automation in multiwell format. For instance, the Library of Integrated Network-based Cellular Signatures (LINCS) has produced gene expression measurements for tens of thousands of distinct cell perturbations using a 384-well plate format. This dataset is by far the largest 384-well gene expression measurement assay ever performed. We investigated the gene expression profiles of a million samples from the LINCS dataset and found that the vast majority (96%) of the tested plates were affected by a significant 2D spatial bias.
Results: Using a novel algorithm combining spatial autocorrelation detection and principal component analysis, we could remove most of the spatial bias from the LINCS dataset and show in parallel a dramatic improvement of similarity between biological replicates assayed in different plates. The proposed methodology is fully general and can be applied to any highly multiplexed assay performed in multiwell format.
Contact: ac2248@columbia.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Information, Misallocation, and Aggregate Productivity
*
Authors: David Joel M. , Hopenhayn Hugo A. , Venkateswaran Venky 
Published: March 2016

Abstract
We propose a theory linking imperfect information to resource misallocation and hence to aggregate productivity and output. In our setup, firms look to a variety of noisy information sources when making input decisions. We devise a novel empirical strategy that uses a combination of firm-level production and stock market data to pin down the information structure in the economy. Even when only capital is chosen under imperfect information, applying this methodology to data from the United States, China, and India reveals substantial losses in productivity and output due to the informational friction. Our estimates for these losses range from 7% to 10% for productivity and 10% to 14% for output in China and India, and are smaller, though still significant, in the United States. Losses are substantially higher when labor decisions are also made under imperfect information. We find that firms turn primarily to internal sources for information; learning from financial markets contributes little, even in the United States.
Colonization of Barley by the Broad-Host Hemibiotrophic Pathogen Phytophthora palmivora Uncovers a Leaf Development–Dependent Involvement of Mlo
Authors: Le Fevre Ruth , O’Boyle Bridget , Moscou Matthew J. , Schornack Sebastian 
Published: March 2016

The discovery of barley Mlo demonstrated that filamentous pathogens rely on plant genes to achieve entry and lifecycle completion in barley leaves. While having a dramatic effect on foliar pathogens, it is unclear whether overlapping or distinct mechanisms affect filamentous pathogen infection of roots. To remove the bias connected with using different pathogens to understand colonization mechanisms in different tissues, we have utilized the aggressive hemibiotrophic oomycete pathogen Phytophthora palmivora. P. palmivora colonizes root as well as leaf tissues of barley (Hordeum vulgare). The infection is characterized by a transient biotrophy phase with formation of haustoria. Barley accessions varied in degree of susceptibility, with some accessions fully resistant to leaf infection. Notably, there was no overall correlation between degree of susceptibility in roots compared with leaves, suggesting that variation in different genes influences host susceptibility above and below ground. In addition, a developmental gradient influenced infection, with more extensive colonization observed in mature leaf sectors. The mlo5 mutation attenuates P. palmivora infection but only in young leaf tissues. The barley–P. palmivora interaction represents a simple system to identify and compare genetic components governing quantitative colonization in diverse barley tissue types. [Formula: see text] Copyright © 2016 The Author(s). This is an open access article distributed under the CC BY Attribution 4.0 International license .
The Memory Quilt
Authors: Flanagan Patricia , DeMetro Nancy 
Published: March 2016

ABSTRACT:
Nursing students' learning of adult and pediatric palliative care is a daunting experience. An effective initial teaching strategy using a Memory Quilt activity can improve nursing students' interpersonal and communication skills and help prepare them for end-of-life caring. These skills help students meet patient and family needs, as they transition to care settings.
Finding our Place
Authors: Astle Barbara , Gibson Deborah 
Published: March 2016

ABSTRACT:
At the onset, the unfamiliarity of faith integration for nurse educators working within a faith-based university can be challenging. Two nurse educators describe the process they took to learn and navigate faith integration, while teaching undergraduate nursing students. Over the course of one year, various approaches toward faith integration with students were implemented, leading to an authentic relational interconnectedness.
The Software Crisis of Synthetic Biology
Authors: Valverde Sergi , Porcar Manuel , Peretó Juli , Solé Ricard V. 
Published: March 2016

AbstractIn fifteen years, Synthetic Biology (SB) has moved from proof-of-concept designs to several flagship achievements. Standardisation efforts are still under way, basic engineering concepts such as modularity and orthogonality are still controversial in biology, and making predictions from computer models is still unreliable. A deep characterization in the pattern of re-use of biological blocks in SB has not been attempted to date. We have compared the topological organisation of two different technological networks, one associated to a standard, large-scale software repository and the second provided by the Registry of Standard Biological Parts (RSBP). Our results strongly suggest that software engineering, and not industrial engineering, is the closest complex system to SB. In both cases, combining standard or quasi-standard components assembly with tinkering may not be at odds with success.
Cdk activity drives senescence from G2 phase
Authors: Müllers Erik , Silva Cascales Helena , Macurek Libor , Lindqvist Arne 
Published: March 2016

AbstractIn response to DNA damage a cell can be forced to permanently exit the cell cycle and become senescent. Senescence provides an early barrier against tumor development by preventing proliferation of cells with damaged DNA. By studying single cells, we show that Cdk activity is retained after DNA damage until terminal cell cycle exit. The low level of Cdk activity not only allows cell cycle progression, but also forces cell cycle exit at a decision point in G2 phase. We find that Cdk activity stimulates p21 production, leading to nuclear sequestration of Cyclin B1, subsequent APC/CCdh1-dependent degradation of mitotic inducers and induction of senescence. We suggest that the same activity that triggers mitosis in an unperturbed cell cycle drives senescence in the presence of DNA damage, ensuring a robust response when most needed.
Zika Virus: Endemic Versus Epidemic Dynamics and Implications for Disease Spread in the Americas
Authors: Bewick Sharon , Fagan William F. , Calabrese Justin , Agusto Folashade 
Published: March 2016

AbstractSince being introduced into Brazil in 2014, Zika virus (ZIKV) has spread explosively across Central and South America. Although the symptoms of ZIKV are generally mild, recent evidence suggests a relationship between prenatal exposure to ZIKV and microcephaly. This has led to widespread panic, including travel alerts and warnings to avoid pregnancy. Because ZIKV is an emerging disease, response efforts are complicated by limited understanding of disease dynamics. To this end, we develop a novel state- and class-structured compartment model for ZIKV. Our model shows that the risk of prenatal ZIKV exposure should decrease dramatically following the initial wave of disease, reaching almost undetectable levels in endemic systems. Our model also suggests that, depending on ZIVK transmission levels in the Americas, efforts to reduce ZIKV prenatal exposures through mosquito management and avoidance may have minimal benefit, and may even result in increased risk of microcephaly in later years of an outbreak.