bluuebunny/crossref_metadata_2025_split huggingface dataset:
AKT activation by N-cadherin regulates beta-catenin signaling and neuronal differentiation during cortical development
Authors: Zhang Jianing , Shemezis Julie R , McQuinn Erin R , Wang Jing , Sverdlov Maria , Chenn Anjen 
Published: April 2013

Abstract

Background
During cerebral cortical development, neural precursor-precursor interactions in the ventricular zone neurogenic niche coordinate signaling pathways that regulate proliferation and differentiation. Previous studies with shRNA knockdown approaches indicated that N-cadherin adhesion between cortical precursors regulates β-catenin signaling, but the underlying mechanisms remained poorly understood.

Results
Here, with conditional knockout approaches, we find further supporting evidence that N-cadherin maintains β-catenin signaling during cortical development. Using shRNA to N-cadherin and dominant negative N-cadherin overexpression in cell culture, we find that N-cadherin regulates Wnt-stimulated β-catenin signaling in a cell-autonomous fashion. Knockdown or inhibition of N-cadherin with function-blocking antibodies leads to reduced activation of the Wnt co-receptor LRP6. We also find that N-cadherin regulates β-catenin via AKT, as reduction of N-cadherin causes decreased AKT activation and reduced phosphorylation of AKT targets GSK3β and β-catenin. Inhibition of AKT signaling in neural precursors in vivo leads to reduced β-catenin-dependent transcriptional activation, increased migration from the ventricular zone, premature neuronal differentiation, and increased apoptotic cell death.

Conclusions
These results show that N-cadherin regulates β-catenin signaling through both Wnt and AKT, and suggest a previously unrecognized role for AKT in neuronal differentiation and cell survival during cortical development.
Partitioning of silver and chemical speciation of free Ag in soils amended with nanoparticles
Authors: Benoit Rachel , Wilkinson Kevin J , Sauvé Sébastien 
Published: April 2013

Abstract

Background
Knowledge about silver nanoparticles in soils is limited even if soils are a critical pathway for their environmental fate. In this paper, speciation results have been acquired using a silver ion selective electrode in three different soils.

Results
Soil organic matter and pH were the most important soil properties controlling the occurrence of silver ions in soils. In acidic soils, more free silver ions are available while in the presence of organic matter, ions were tightly bound in complexes. The evolution of the chemical speciation of the silver nanoparticles in soils was followed over six months.

Conclusion
During the first few hours, there appeared to be a strong sorption of the silver with soil ligands, whereas over time, silver ions were released, the final concentration being approximately 10 times higher than at the beginning. Ag release was associated with either the oxidation of the nanoparticles or a dissociation of adsorbed silver from the soil surfaces.
B-Raf and the inhibitors: from bench to bedside
Authors: Huang Tiangui , Karsy Michael , Zhuge Jian , Zhong Minghao , Liu Delong 
Published: April 2013

Abstract
The B-Raf protein is a key signaling molecule in the mitogen activated protein kinase (MAPK) signaling pathway and has been implicated in the pathogenesis of a variety of cancers. An important V600E mutation has been identified and can cause constitutive B-Raf activation. Recent studies have evaluated a variety of small molecule inhibitors targeting B-Raf, including PLX4032/vemurafenib, dabrafenib, LGX818, GDC0879, XL281, ARQ736, PLX3603 (RO5212054), and RAF265. Therapeutic resistance has been identified and various mechanisms described. This review also discussed the current understanding of B-Raf signaling mechanism, methods of mutation detection, treatment strategies as well as potential methods of overcoming therapeutic resistance.
Ab initio simulations of p-type porous silicon nanostructures
Authors: Landa Loustau Emilye Rosas , del Río Jesús A , Tagüeña-Martínez Julia , Sansores Luis E , Nava Rocío 
Published: April 2013

Abstract

Abstract
The morphology of porous silicon (p-Si) depends on several parameters such as the doping type and the carriers’ concentration of the crystalline silicon substrate. The electrolytes used in the p-Si fabrication also have an important role. The final structure determines if p-Si is luminescent or suitable for photonic applications. Experimental results on p-Si produced by electrochemical etching show that although the carriers are greatly reduced by the etching process, boron atoms remain in the bulk. The study of p-type porous silicon nanostructures by means of an ab initio computational simulation might help to understand how boron atoms influence the p-Si final structure. Here, we report electronic and topological properties of ten p-type porous silicon structures as an extension of our previous paper on p-type crystalline silicon. Our results suggest that the boron atoms can not remain bonded on the porous surface but do so in the bulk. The presence of impurities changes the bond distance of their neighbors within a radius of 5 Å. The energy of the models is essentially the same for all the boron positions in the silicon backbone. The high electronic density around the boron impurity could influence the trajectory of an HF ion entering a p-Si pore during the fabrication process.
TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions
Authors: Kim Daehwan , Pertea Geo , Trapnell Cole , Pimentel Harold , Kelley Ryan , Salzberg Steven L 
Published: April 2013

AbstractTopHat is a popular spliced aligner for RNA-sequence (RNA-seq) experiments. In this paper, we describe TopHat2, which incorporates many significant enhancements to TopHat. TopHat2 can align reads of various lengths produced by the latest sequencing technologies, while allowing for variable-length indels with respect to the reference genome. In addition to de novo spliced alignment, TopHat2 can align reads across fusion breaks, which can occur after genomic translocations. TopHat2 combines the ability to identify novel splice sites with direct mapping to known transcripts, producing sensitive and accurate alignments, even for highly repetitive genomes or in the presence of pseudogenes. TopHat2 is available at http://ccb.jhu.edu/software/tophat.
Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro
Authors: Zhou Ying , Xu Huitao , Xu Wenrong , Wang Bingying , Wu Huiyi , Tao Yang , Zhang Bin , Wang Mei , Mao Fei , Yan Yongmin , Gao Shuo , Gu Hongbing , Zhu Wei , Qian Hui 
Published: April 2013

Abstract
Introduction
Administration of bone marrow mesenchymal stem cells (MSCs) or secreted microvesicles improves recovery from acute kidney injury (AKI). However, the potential roles and mechanisms are not well understood. In the current study, we focused on the protective effect of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) on cisplatin-induced nephrotoxicity in vivo and in vitro.

Methods
We constructed cisplatin-induced AKI rat models. At 24 h after treatment with cisplatin, hucMSC-ex were injected into the kidneys via the renal capsule; human lung fibroblast (HFL-1)-secreted exosomes (HFL-1-ex) were used as controls. All animals were killed at day 5 after administration of cisplatin. Renal function, histological changes, tubular apoptosis and proliferation, and degree of oxidative stress were evaluated. In vitro, rat renal tubular epithelial (NRK-52E) cells were treated with or without cisplatin and after 6 h treated with or without exosomes. Cells continued to be cultured for 24 h, and were then harvested for western blotting, apoptosis and detection of degree of oxidative stress.

Results
After administration of cisplatin, there was an increase in blood urea nitrogen (BUN) and creatinine (Cr) levels, apoptosis, necrosis of proximal kidney tubules and formation of abundant tubular protein casts and oxidative stress in rats. Cisplatin-induced AKI rats treated with hucMSC-ex, however, showed a significant reduction in all the above indexes. In vitro, treatment with cisplatin alone in NRK-52E cells resulted in an increase in the number of apoptotic cells, oxidative stress and activation of the p38 mitogen-activated protein kinase (p38MAPK) pathway followed by a rise in the expression of caspase 3, and a decrease in cell multiplication, while those results were reversed in the hucMSCs-ex-treated group. Furthermore, it was observed that hucMSC-ex promoted cell proliferation by activation of the extracellular-signal-regulated kinase (ERK)1/2 pathway.

Conclusions
The results in the present study indicate that hucMSC-ex can repair cisplatin-induced AKI in rats and NRK-52E cell injury by ameliorating oxidative stress and cell apoptosis, promoting cell proliferation in vivo and in vitro. This suggests that hucMSC-ex could be exploited as a potential therapeutic tool in cisplatin-induced nephrotoxicity.
The innate defense regulator peptides IDR-HH2, IDR-1002, and IDR-1018 modulate human neutrophil functions
Authors: Niyonsaba François , Madera Laurence , Afacan Nicole , Okumura Ko , Ogawa Hideoki , Hancock Robert E W 
Published: April 2013

ABSTRACT
Although HDPs were originally hypothesized to act as antimicrobial agents, they also have been shown to broadly modulate the immune response through the activation of different cell types. We recently developed a series of novel, synthetic peptides, termed IDRs, which are conceptually based on a natural HDP, bovine bactenecin. We showed that IDR-1 and IDR-1002 protect the host against bacterial infections through the induction of chemokines. The objective of this study was to investigate the effects of the IDRs on various functions of human neutrophils. Here, we demonstrated that IDR-HH2, IDR-1002, and IDR-1018 modulated the expression of neutrophil adhesion and activation markers. Moreover, these IDRs enhanced neutrophil adhesion to endothelial cells in a β2 integrin-dependent manner and induced neutrophil migration and chemokine production. The IDR peptides also increased the release of the neutrophil-generated HDPs (antimicrobial), human α-defensins, and LL-37 and augmented neutrophil-mediated killing of Escherichia coli. Notably, the IDRs significantly suppressed LPS-mediated neutrophil degranulation, the release of ROS, and the production of the inflammatory cytokines TNF-α and IL-10, consistent with their ability to dampen inflammation. As evidenced by the inhibitory effects of MAPK-specific inhibitors, IDRs activated the MAPK pathway that was required for chemokine production. In conclusion, our study provides novel evidence regarding the contribution of the IDR peptides to the innate immune response through the modulation of neutrophil functions. The results described here may aid in the development of IDRs as novel, anti-infective and immunomodulatory agents.
Cuba Calls: African American Tourism, Race, and the Cuban Revolution, 1959–1961
Authors: Benson Devyn Spence 
Published: April 2013

Abstract
This essay explores the role that conversations about race and racism played in forming a partnership between an African American public relations firm and the Cuban National Tourist Institute (INIT) in 1960, just one year after Fidel Castro’s victory over Fulgencio Batista. The article highlights how Cuban revolutionary leaders, Afro-Cubans, and African Americans exploited temporary transnational relationships to fight local battles. Claiming that the Cuban Revolution had eliminated racial discrimination, INIT invited world champion boxer Joe Louis and 50 other African Americans to the island in January 1960 to experience “first class treatment — as first class citizens.” This move benefited Cuban revolutionary leaders by encouraging new tourism as the number of mainstream white American travelers to the island declined. The business venture also allowed African Americans to compare racial violence in the US South to the supposed integrated racial paradise in Cuba and foreshadowed future visits by black radicals, including NAACP leader Robert F. Williams. The politics expressed by Cuban newspapers and travel brochures, however, did not always fit with the lived experiences of Afro-Cubans. This essay uncovers how Afro-Cubans threatened national discourses by invoking revolutionary promises to denounce continued racial segregation in the very facilities promoted to African American tourists. Ultimately, ideas about race did not just cross borders between Cuba and the United States in 1960. Rather, they constituted and constructed those borders as Afro-Cubans used government claims to reposition themselves within the new revolutionary state.
Modulation of T cell signaling by the actin cytoskeleton
Authors: Yu Yan , Smoligovets Alexander A. , Groves Jay T. 
Published: April 2013

SummaryThe actin cytoskeleton provides a dynamic framework to support membrane organization and cellular signaling events. The importance of actin in T cell function has long been recognized to go well beyond the maintenance of cell morphology and transport of proteins. Over the past several years, our understanding of actin in T cell activation has expanded tremendously, in part owing to the development of methods and techniques to probe the complex interplay between actin and T cell signaling. On the one hand, biochemical methods have led to the identification of many key cytoskeleton regulators and new signaling pathways, whereas, on the other, the combination of advanced imaging techniques and physical characterization tools has allowed the spatiotemporal investigation of actin in T cell signaling. All those studies have made a profound impact on our understanding of the actin cytoskeleton in T cell activation. Many previous reviews have focused on the biochemical aspects of the actin cytoskeleton. However, here we will summarize recent studies from a biophysical perspective to explain the mechanistic role of actin in modulating T cell activation. We will discuss how actin modulates T cell activation on multiple time and length scales. Specifically, we will reveal the distinct roles of the actin filaments in facilitating TCR triggering, orchestrating ‘signalosome’ assembly and transport, and establishing protein spatial organization in the immunological synapse.
Autophagy and microtubules – new story, old players
Authors: Mackeh Rafah , Perdiz Daniel , Lorin Séverine , Codogno Patrice , Poüs Christian 
Published: April 2013

Summary
Both at a basal level and after induction (especially in response to nutrient starvation), the function of autophagy is to allow cells to degrade and recycle damaged organelles, proteins and other biological constituents. Here, we focus on the role microtubules have in autophagosome formation, autophagosome transport across the cytoplasm and in the formation of autolysosomes. Recent insights into the exact relationship between autophagy and microtubules now point to the importance of microtubule dynamics, tubulin post-translational modifications and microtubule motors in the autophagy process. Such factors regulate signaling pathways that converge to stimulate autophagosome formation. They also orchestrate the movements of pre-autophagosomal structures and autophagosomes or more globally organize and localize immature and mature autophagosomes and lysosomes. Most of the factors that now appear to link microtubules to autophagosome formation or to autophagosome dynamics and fate were identified initially without the notion that sequestration, recruitment and/or interaction with microtubules contribute to their function. Spatial and temporal coordination of many stages in the life of autophagosomes thus underlines the integrative role of microtubules and progressively reveals hidden parts of the autophagy machinery.
Organ Preservation for Adenoid Cystic Carcinoma of the Larynx
Authors: Misiukiewicz Krzysztof J. , Camille Nadia , Tishler Roy , Haddad Robert , Limaye Sewanti , Posner Marshall 
Published: April 2013

Abstract

Objectives.
Two cases of adenoid cystic carcinoma (ACC) of the larynx were treated with chemoradiotherapy (CRT) for organ preservation. We reviewed case series and current literature to contrast the potential role of primary CRT as an organ-sparing modality with standard laryngectomy and radiotherapy in patients with laryngeal ACC.

Methods.
Two treatment-naïve patients with laryngeal ACC treated at Dana-Farber Cancer Institute between 2002 and 2007 were identified. Both patients were offered standard laryngectomy followed by adjuvant radiotherapy or organ-sparing treatment modality.

Results.
Both patients were males, aged 57 and 73. The patients completed a course of combined chemoradiotherapy with weekly carboplatin and paclitaxel and 7–8 weeks of radiotherapy to a total dose of 6,600 and 7,000 cGy over 50 and 57 days, respectively. There were no treatment breaks or delays because of toxicity. The major toxicities reported by both patients, as anticipated, were Grade 3 mucositis, desquamative dermatitis, and severe dysphagia, all of which resolved. Both patients are alive with local regional control and functional larynx; one at 112+ months with pulmonary metastases at 54 months, and the other disease free at 60+ months.

Conclusions.
Definitive chemoradiation with weekly carboplatin and paclitaxel may be a potential alternative to the current standard of surgery and radiation for patients with locally advanced laryngeal ACC who request an organ-sparing approach. In this group of patients, salvage laryngectomy may be reserved for those who are locally recurrent or chemoradiotherapy resistant. Although CRT provided long-term local regional control in our two patients, there are evident limitations in obtaining evidence for a determination of treatment of rare diseases. This report provides support for following an organ preservation plan in selected patients.
Targeted Therapies in Neuroendocrine Tumors (NET): Clinical Trial Challenges and Lessons Learned
Authors: Yao James C. , Lagunes Diane Reidy , Kulke Matthew H. 
Published: April 2013

Abstract
In the past 3 years, we have witnessed the completion of four randomized phase III studies in neuroendocrine tumors and the approval of two new drugs, everolimus and sunitinib, for the treatment of patients with well-differentiated pancreatic neuroendocrine tumors. These studies demonstrate a shift from case series and single-arm studies toward prospective, randomized controlled clinical trials and evidence-based therapy in the neuroendocrine tumor field. However, the clinical development of these agents also highlights the potential challenges awaiting other new drugs in this area. Herein, we discuss the strengths and weaknesses of the most recent phase II and phase III neuroendocrine tumor studies and discuss how limitations inherent in current trial design can lead to potential pitfalls. We also discuss how trial design can be improved, with the hope of increasing the number of drugs successfully developed to treat patients with neuroendocrine tumors.
The European Medicines Agency Review of Pixantrone for the Treatment of Adult Patients With Multiply Relapsed or Refractory Aggressive Non-Hodgkin's B-Cell Lymphomas: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use
Authors: Péan Elias , Flores Beatriz , Hudson Ian , Sjöberg Jan , Dunder Kristina , Salmonson Tomas , Gisselbrecht Christian , Laane Edward , Pignatti Francesco 
Published: April 2013

Learning Objectives
Describe the efficacy profile of pixantrone in patients with relapsed or refractory NHL. Identify the most frequent toxicities associated with pixantrone treatment.
Pore-Scale Evaluation of Polymers Displacing Viscous Oil—Computational-Fluid-Dynamics Simulation of Micromodel Experiments
Authors: Clemens Torsten , Tsikouris Kostas , Buchgraber Markus , Castanier Louis , Kovscek Anthony 
Published: April 2013

Summary
The recovery of viscous oil can be significantly improved by injecting polymer solutions. The processes leading to increased oil production occur on a large scale—improving vertical and areal sweep efficiency—but they begin on a microscale.
Micromodels with realistic pore geometries have been created. These micromodels were saturated with viscous oil, and the displacement of the oil by water and polymer solutions was investigated experimentally. Polymer injection reduced fingering compared with water injection and increased sweep efficiency accordingly.
The micromodel pore-network geometry was digitized with scanning electron microscopy (SEM). The digitized model was used to perform computational-fluid-dynamics (CFD) simulation of the displacement processes.
The displacement efficiencies and displacement patterns of the CFD simulations with water, polymer solutions, and polymer solutions after water breakthrough at the outlet end to displace oil were very similar to the results of the micromodel experiments.
Then, the CFD simulations were used to investigate the displacement at the pore scale. Water injection leads to the creation of fingers along slightly more-permeable flow paths. The number and length of the fingers decrease if polymer solution is injected. Even for polymer injection after water breakthrough, the fingering is reduced, polymer solutions are diverted into less-favorable flow paths, and sweep efficiency is increased.
CFD simulations can also be used to look into non-Newtonian fluid behavior at the pore scale. The polymers injected in the micromodel experiments exhibited shear-thinning behavior. On a pore scale, CFD simulations showed that the shear stress and viscosity of the polymer solutions accordingly are significantly lower in the pore throats than in the pores. Thus, the displacement efficiency of the polymer solutions is affected by the shear-thinning behavior.
The CFD simulations are in remarkable agreement with the micromodel experiments and can be used to quantify the displacement processes at pore scale.
Editorial
Authors: Kloppenborg John 
Published: April 2013

"Comparison," wrote Jonathan Z. Smith, "is a disciplined exaggeration in the service of knowledge .... [It] provides the means by which we're-vision' phenomena as our data in order to solve our theoretical problems" (Drudgery Divine [Chicago: University of Chicago Press, 1990], p. 52, emphasis in original). Smith's words should perhaps be taken as an invitation to biblical scholars to take possession of their own discourse in a way that they have not done hitherto.
Bering Glacier and Bagley Ice Valley surge 2011: crevasse classification as an approach to map deformation stages and surge progression
Authors: Herzfeld Ute C. , McDonald Brian , Weltman Alexander 
Published: April 2013

AbstractThe dynamics of a surge is manifested in the crevasse patterns: literally, deformation state frozen in ice. This basic observation is utilized as the concept of an automated approach to map and analyze deformation stages and progression of surge kinematics. The classification method allows imagery to be used as geophysical data and is applied to aerial observations (photographic and video imagery, GPS data) collected in September 2011 during the surge of the Bering Glacier–Bagley Ice Valley system, Alaska, USA. As the third dimension that complements two-dimensional imagery, ice-surface elevation is observed using aerial laser altimetry. The classification method builds on concepts from signal processing, geostatistical data analysis and neural networks. Steps include calculation of generalized directional vario functions from image data and composition into feature vectors. The vario function operates as an information filter that retains spatial characteristics at an intermediate scale that captures crevasse spacing, anisotropy and other generalized roughness properties. Association of feature vectors to crevasse classes and hence deformation types employs a connectionist algorithm. In general, the connectionist–geostatistical classification allows the mapping of kinematic changes in crevassed glaciers.Dedicated to the memory of Austin Post