bluuebunny/crossref_metadata_2025_split huggingface dataset:
APRIL and BAFF increase breast cancer cell stemness
Authors: Pelekanou Vasiliki , Notas George , Athanasouli Paraskevi , Alexakis Konstantinos , Kiagiadaki Fotini , Peroulis Nikolaos , Kalyvianaki Konstantina , Kampouri Errika , Polioudaki Hara , Theodoropoulos Panayiotis , Tsapis Andreas , Castanas Elias , Kampa Marilena 
Published: June 2017

AbstractRecent advances in cancer immunology revealed immune-related properties of cancer cells as novel promising therapeutic targets. The two TNF superfamily members, APRIL and BAFF even though were primarily studied in lymphocyte maturation, they have also been associated with tumor growth and aggressiveness in a number of solid tumors, including breast cancer. In the present work we studied the effect of APRIL and BAFF on epithelial to mesenchymal transition and migration of breast cancer cells, and their action on the sub-population of cancer stem cells identified by autofluorescence and ALDH activity. Their action on an number of pluripotency genes was examined and breast cancer stem cell ability to form mammospheres was also utilized. The receptor and the signaling pathway involved as well as the role of steroid hormones in their action were also investigated. Our findings show that both APRIL and BAFF increase epithelial to mesenchymal transition and migratory capacity of breast cancer cells, as well as cancer stem cell numbers, by inducing pluripotency genes such as KLF4 and NANOG. These effects are mediated by their common receptor BCMA and the JNK signaling pathway. Interestingly, androgens enhance APRIL transcription and subsequently its pluripotency effect. In conclusion, our data support the significant role of APRIL and BAFF in breast cancer disease progression and provide evidence for a new possible mechanism of therapy resistance, that could be particularly relevant in aromatase inhibitors-treated patients, were local androgen is increased.
Intrinsic adaptive value and early fate of gene duplication revealed by a bottom-up approach
Authors: Rodrigo Guillermo , Fares Mario A. 
Published: June 2017

ABSTRACTGene duplication is a major source of functional innovations and genome complexity, albeit this evolutionary process requires the preservation of duplicates in the genomes for long time. However, the population genetic mechanisms governing this preservation, especially in the critical very initial phase, have remained largely unknown. Here, we demonstrate that gene duplication confersper sea weak selective advantage in scenarios of fitness trade-offs. Through a precise quantitative description of a model system, we show that a second gene copy enhances the information transfer from the environmental signal to the phenotypic response by reducing gene expression inaccuracies derived from pervasive molecular noise and suboptimal gene regulation. We then reveal that such a phenotypic accuracy yields a selective advantage in the order of 0.1% on average, which would allow the positive selection of gene duplication in populations with moderate or large sizes. This advantage is greater at higher noise levels and intermediate concentrations of the environmental molecule, when fitness trade-offs become more evident. Moreover, we show that the genome rearrangement rates greatly condition the eventual fixation of duplicated genes, either by natural selection or by random genetic drift. Overall, our theoretical results highlight an original adaptive value for cells carrying new-born duplicates, broadly analyze the selective conditions that determine their early fates in different organisms, and reconcile population genetics with evolution by gene duplication.SIGNIFICANCEGene duplication is considered a major driver for the evolution of biological complexity. However, it is still enigmatic to what extent natural selection and genetic drift have governed this evolutionary process. This work uncovers a selective advantage for genotypes carrying duplicates, called phenotypic accuracy, widely characterized thanks to a multi-scale mathematical model coupling gene regulation with population genetics. Importantly, the integrative results presented here provide a detailed mechanistic description for the fixation of duplicates, which allows making predictions about the genome architectures, and which is relevant to understand the origins of complexity.
YASS: Yet Another Spike Sorter
Authors: Lee JinHyung , Carlson David , Shokri Hooshmand , Yao Weichi , Goetz Georges , Hagen Espen , Batty Eleanor , Chichilnisky EJ , Einevoll Gaute , Paninski Liam 
Published: June 2017

AbstractSpike sorting is a critical first step in extracting neural signals from large-scale electrophysiological data. This manuscript describes an efficient, reliable pipeline for spike sorting on dense multi-electrode arrays (MEAs), where neural signals appear across many electrodes and spike sorting currently represents a major computational bottleneck. We present several new techniques that make dense MEA spike sorting more robust and scalable. Our pipeline is based on an efficient multi-stage “triage-then-cluster-then-pursuit” approach that initially extracts only clean, high-quality waveforms from the electrophysiological time series by temporarily skipping noisy or “collided” events (representing two neurons firing synchronously). This is accomplished by developing a neural network detection method followed by efficient outlier triaging. The clean waveforms are then used to infer the set of neural spike waveform templates through nonparametric Bayesian clustering. Our clustering approach adapts a “coreset” approach for data reduction and uses efficient inference methods in a Dirichlet process mixture model framework to dramatically improve the scalability and reliability of the entire pipeline. The “triaged” waveforms are then finally recovered with matching-pursuit deconvolution techniques. The proposed methods improve on the state-of-the-art in terms of accuracy and stability on both real and biophysically-realistic simulated MEA data. Furthermore, the proposed pipeline is efficient, learning templates and clustering much faster than real-time for a ≃ 500-electrode dataset, using primarily a single CPU core.
Reflected Stochastic Differential Equation Models for Constrained Animal Movement
Authors: Hanks Ephraim M. , Johnson Devin S. , Hooten Mevin B. 
Published: June 2017

AbstractMovement for many animal species is constrained in space by barriers such as rivers, shore-lines, or impassable cliffs. We develop an approach for modeling animal movement constrained in space by considering a class of constrained stochastic processes, reflected stochastic differential equations. Our approach generalizes existing methods for modeling unconstrained animal movement. We present methods for simulation and inference based on augmenting the constrained movement path with a latent unconstrained path and illustrate this augmentation with a simulation example and an analysis of telemetry data from a Steller sea lion(Eumatopias jubatus)in southeast Alaska.
Feedback inhibition of Ras activity coordinates cell fusion with cell-cell contact
Authors: Merlini Laura , Khalili Bita , Dudin Omaya , Michon Laetitia , Vincenzetti Vincent , G Martin Sophie 
Published: June 2017

AbstractIn fission yeastSchizosaccharomyces pombe, pheromone signalling engages a GPCR-Ras-MAPK cascade to trigger sexual differentiation leading to gamete fusion. Cell-cell fusion necessitates local cell wall digestion, the location of which relies on an initially dynamic actin fusion focus that becomes stabilized upon local enrichment of the signalling cascade. We constructed a live-reporter of active Ras1 (Ras1-GTP), also functional inS. cerevisiae, which revealed Ras activity at polarity sites peaking on the fusion structure before fusion. Remarkably, constitutive Ras1 activation promoted fusion focus stabilization and fusion attempts irrespective of cell-cell pairing, leading to cell lysis. Ras1 activity is restricted by the GTPase activating protein (GAP) Gap1, itself recruited to sites of Ras1-GTP. While the GAP domain on its own does not suffice for this localization, its recruitment to Ras1-GTP sites is essential to block untimely fusion attempts. We conclude that negative feedback control of Ras activity restrains the MAPK signal and couples fusion with cell-cell engagement.
Inter-organ regulation ofDrosophilaintestinal stem cell proliferation by a hybrid organ boundary zone
Authors: Sawyer Jessica K. , Cohen Erez , Fox Donald T. 
Published: June 2017

SUMMARY STATEMENTGene expression at theDrosophilamidgut-hindgut boundary is a hybrid of both organs. Hybrid cells repress stem cell division, but boundary injury activates stem cell division through inter-organ JAK-STAT signaling.ABSTRACTThe molecular identities and regulation of cells at inter-organ boundaries are often unclear, despite the increasingly appreciated role of organ boundaries in disease. UsingDrosophilaas a model, here we show that a specific population of adult midgut organ boundary intestinal stem cells (OB-ISCs) is regulated by the neighboring hindgut, a developmentally distinct organ. This distinct OB-ISCs control is due to proximity to a specialized transition zone between the endodermal midgut and ectodermal hindgut that shares molecular signatures of both organs, which we term the hybrid zone (HZ). During homeostasis, proximity to the HZ restrains OB-ISC proliferation. However, injury to the adult HZ/hindgut drives up-regulation ofupaired-3cytokine and OB-ISC hyperplasia. If HZ disruption is severe, hyperplastic OB-ISCs expand across the inter-organ boundary. Our data suggest that inter-organ signaling plays an important role in controlling OB-ISCs in homeostasis and injury repair, which is likely critical in prevention of disease.
Silver microwires from treating tooth decay with silver diamine fluoride
Authors: Seto Jong , Horst Jeremy A. , Parkinson Dilworth Y. , Frachella John C. , DeRisi Joseph L. 
Published: June 2017

AbstractSilver diamine fluoride (SDF) is a brush-on treatment for tooth decay that stops 81% of cavitated caries lesions (dental cavities). Before this innovation, caries was treatable only with operative approaches (dental fillings). SDF-treated lesions harden and become resistant to further decay. We hypothesized that the hardening is due to reaction with silver, rather than classic fluoride-mediated remineralization, because infected dentin is not amenable to remineralization. Using synchrotron microCT with 1.3 μm resolution, we observe filamentous densities up to 500 μm in length and 0.25-7.0 μm in diameter, formedin situby applying SDF to caries lesions. We show that these “microwires” fill voids in the lesion caused by disease, and permeate through surrounding dentinal tubules. Using spectroscopy, we confirm that the chemical composition of the observed microwires is predominantly silver. To our knowledge, this represents the first structural microscale observations resulting from clinical SDF treatment. These novel observations hint at mechanistic explanations for the first clinical method to harden carious dentin besides remineralization. We hypothesize that SDF may not only achieve its antimicrobial functions by biochemical interactions, but also through its inherent ability to integrate into dentin.
t-Darpp is an elongated monomer that binds to calcium and is phosphorylated by cyclin-dependent kinases 1 and 5
Authors: Momand Jamil , Magdziarz Patrycja , Feng You , Jiang Dianlu , Parga Elizabeth , Celis Arianna , Denny Erin , Wang Xiaoying , Phillips Martin L. , Monterroso Estuardo , Kane Susan E. , Zhou Feimeng 
Published: June 2017

ABSTRACTt-Darpp is a protein encoded by the PPP1R1B gene and is expressed in breast, colon, esophageal, gastric, and prostate cancers, as well as in normal adult brain striatal cells. Overexpression of t-Darpp in cultured cells leads to increased protein kinase A activity and increased phosphorylation of AKT (protein kinase B). In HER2+ breast cancer cells t-Darpp confers resistance to the chemotherapeutic agent trastuzumab. To shed light on t-Darpp function, we studied its secondary structure, oligomerization status, metal-binding properties, and phosphorylation by cyclin dependent kinases 1 and 5. t-Darpp exhibits 12% alpha helix, 29% beta strand, 24% beta turn and 35% random coil structures. t-Darpp binds to calcium, but not to other metals commonly found in biological systems. The T39 site, critical for t-Darpp activation of the AKT signaling pathway, is a substrate for phosphorylation by cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 5 (CDK5). Gel filtration chromatography, sedimentation equilibrium analysis, blue native gel electrophoresis, and glutaraldehyde-mediated crosslinking experiments demonstrate that the majority of t-Darpp exists as a monomer, but forms low levels (< 3%) of hetero-oligomers with its longer isoform Darpp-32. t-Darpp has a large Stokes radius of 4.4 nm relative to its mass of 19 kDa, indicating that it has an elongated structure.
TheDrosophilaFormin Fhod Nucleates Actin Filaments
Authors: Patel Aanand A. , Oztug Durer Zeynep A. , van Loon Aaron P. , Quinlan Margot E. 
Published: June 2017

ABSTRACTFormins are a conserved group of proteins that nucleate and processively elongate actin filaments. Among them, the formin homology domain-containing protein (FHOD) family of formins contributes to contractility of striated muscle and cell motility in several contexts. However, the mechanisms by which they carry out these functions remain poorly understood. Unlike other formins, mammalian FHOD1 and FHOD3 do not accelerate actin assemblyin vitro, and have instead been suggested to act as barbed end cappers or bundlers. Here, we show that purifiedDrosophilaFhod, in contrast with the mammalian homologues, potently accelerates actin assembly by nucleation. We found that Fhod binds tightly to barbed ends, where it slows elongation in the absence of profilin and allows elongation in the presence of profilin. Fhod protects barbed ends from capping protein, but dissociates from barbed ends relatively quickly. Finally, we used cosedimentation assays to determine that Fhod binds the sides of actin filaments and bundles filaments. This work establishes that Fhod shares the capacity of other formins to nucleate and bundle actin filaments, but is notably less effective at processively elongating barbed ends.
Hockey India league: remnants of India’s long lost glory
Authors: Rishi Bikramjit , Sabnis Neil , Bagchi Sayani 
Published: June 2017

Subject area
Marketing management, Sports marketing.

Study level/applicability
The case is targeted at students of postgraduate and undergraduate programmes in business administration, specialising in marketing management/sports marketing.

Case overview
The Hockey India League (HIL) failed to make its mark. After the grand success of the Indian Premier League in India, there were hopes afloat for the HIL to follow suit. However, while the Pro Kabaddi League and the Premier Badminton League received much appreciation from a devout audience, the HIL did not quite live up to its expectations. With its evident failure for two consecutive seasons, investor sentiments were at an all-time low and most stakeholders wanted to back out. The future of the HIL now hangs in the balance, with the uncertainty of whether it should be shut down or given one more chance.

Expected learning outcomes
The participants are required to understand the Indian sports environment and the factors that play a major role in making a sport not only popular but also lucrative from the point of view of the investors. They will be called upon to improvise on the existing format of a sport, making it more attractive to the audience. Through such an exercise, they will understand how strategic changes to basic game formats can impact its success or failure. The case will encourage participants to think about viable business models for the revival of different types of sport.

Supplementary materials
Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 8: Marketing.
Recognition cascade and metabolite transfer in a marine bacteria‐phytoplankton model system
Authors: Durham Bryndan P. , Dearth Stephen P. , Sharma Shalabh , Amin Shady A. , Smith Christa B. , Campagna Shawn R. , Armbrust E. Virginia , Moran Mary Ann 
Published: June 2017

SummaryThe trophic linkage between marine bacteria and phytoplankton in the surface ocean is a key step in the global carbon cycle, with almost half of marine primary production transformed by heterotrophic bacterioplankton within hours to weeks of fixation. Early studies conceptualized this link as the passive addition and removal of organic compounds from a shared seawater reservoir. Here, we analysed transcript and intracellular metabolite patterns in a two‐member model system and found that the presence of a heterotrophic bacterium induced a potential recognition cascade in a marine phytoplankton species that parallels better‐understood vascular plant response systems. Bacterium Ruegeria pomeroyi DSS‐3 triggered differential expression of >80 genes in diatom Thalassiosira pseudonana CCMP1335 that are homologs to those used by plants to recognize external stimuli, including proteins putatively involved in leucine‐rich repeat recognition activity, second messenger production and protein kinase cascades. Co‐cultured diatoms also downregulated lipid biosynthesis genes and upregulated chitin metabolism genes. From differential expression of bacterial transporter systems, we hypothesize that nine diatom metabolites supported the majority of bacterial growth, among them sulfonates, sugar derivatives and organic nitrogen compounds. Similar recognition responses and metabolic linkages as observed in this model system may influence carbon transformations by ocean plankton.
Pseudomonas protegens Pf‐5 favours self‐produced siderophore over free‐loading in interspecies competition for iron
Authors: Sexton D. Joseph , Glover Rochelle C. , Loper Joyce E. , Schuster Martin 
Published: June 2017

SummaryMany microorganisms compete for extracellular iron using strain‐specific chelators known as siderophores. The ferric‐siderophore complex limits local access to iron because import requires a suitable cognate receptor. Interestingly, many species carry receptors that enable ‘cross‐feeding’ on heterologous siderophores made by neighboring organisms, although little is known about how this ubiquitous behaviour is regulated. Here, we investigated the soil bacterium Pseudomonas protegens Pf‐5, a strain remarkable for its ability to use dozens of heterologous siderophores. We characterized the expression of six pyoverdine‐type (PVD) siderophore receptors in response to their cognate PVD. In general, we found expression is tightly regulated to reflect availability of their cognate PVD. In contrast, Pf‐5 continues to secrete its own primary siderophore, PVDPf‐5, despite the capability and opportunity to cross‐feed. We demonstrate that this strategy is beneficial in co‐culture with a competing PVDPAO1‐producer, P. aeruginosa PAO1. Although Pf‐5 can cross‐feed on PVDPAO1, production of PVDPf‐5 is required to maintain a competitive advantage. We attribute this to an antagonistic effect of PVDPf‐5 on the growth of PAO1, presumably through limiting access to iron. Our results demonstrate the benefits of excluding competitors out‐weigh the incentives associated with a free‐loader lifestyle for Pf‐5.
Control of virulence gene transcription by indirect readout in Vibrio cholerae and Salmonella enterica serovar Typhimurium
Authors: Dorman Charles J. , Dorman Matthew J. 
Published: June 2017

SummaryIndirect readout mechanisms of transcription control rely on the recognition of DNA shape by transcription factors (TFs). TFs may also employ a direct readout mechanism that involves the reading of the base sequence in the DNA major groove at the binding site. TFs with winged helix–turn–helix (wHTH) motifs use an alpha helix to read the base sequence in the major groove while inserting a beta sheet ‘wing’ into the adjacent minor groove. Such wHTH proteins are important regulators of virulence gene transcription in many pathogens; they also control housekeeping genes. This article considers the cases of the non‐invasive Gram‐negative pathogen Vibrio cholerae and the invasive pathogen Salmonella enterica serovar Typhimurium. Both possess clusters of A + T‐rich horizontally acquired virulence genes that are silenced by the nucleoid‐associated protein H‐NS and regulated positively or negatively by wHTH TFs: for example, ToxR and LeuO in V. cholerae; HilA, LeuO, SlyA and OmpR in S. Typhimurium. Because of their relatively relaxed base sequence requirements for target recognition, indirect readout mechanisms have the potential to engage regulatory proteins with many more targets than might be the case using direct readout, making indirect readout an important, yet often ignored, contributor to the expression of pathogenic phenotypes.
Bupropion Overdose Resulted in a Pharmacobezoar in a Fatal Bupropion (Wellbutrin®) Sustained‐release Overdose: Postmortem Distribution of Bupropion and its Major Metabolites
Authors: Schmit Gregory , De Boosere Evy , Vanhaebost Jessica , Capron Arnaud 
Published: June 2017

AbstractBupropion (BUP) overdose commonly causes generalized seizures and central nervous system depression. The case of a 28‐year‐old woman who died from a massive lethal overdose with sustained‐release bupropion (Wellbutrin® 300 mg) is herein presented. The autopsy revealed the presence of a pharmacobezoar consisting of at least 40 tablets in the stomach. Determination of bupropion and its active metabolites (hydroxybupropion, threobupropion, erythrobupropion) was achieved by a liquid chromatographic mass spectrometry (LC‐MS/MS) method. Postmortem concentrations for bupropion, hydroxybupropion, threobupropion, and erythrobupropion were obtained in intracranial blood, urine, bile, liver, kidney, and vitreous humor. In this case, intracranial blood level of the parent drug was 1.9 mg/L. Threobupropion was the most abundant metabolite in both blood and urine, 59.3 and 890.6 mg/L. Tissue distribution showed the highest concentration in the liver, 12.3 mg/kg. The 0.8 bupropion concentration ratio vitreous/blood suggested that vitreous could be a valuable specimen for toxicological analysis should postmortem blood be unavailable.
A Two‐Year Study of Δ 9 Tetrahydrocannabinol Concentrations in Drivers; Part 2: Physiological Signs on Drug Recognition Expert (DRE) and non‐DRE Examinations,,
Authors: Declues Kari , Perez Shelli , Figueroa Ariana 
Published: June 2017

AbstractWhole blood samples were examined for ∆9‐Tetrahydrocannabinol (THC) over 2 years in drivers suspected of driving under the influence. Part one of the study examined the link between [THC] and performance on field sobriety tests. This portion examined objective signs, eye examinations and physiological indicators; and their relationship to the presence of THC. Several objective signs were excellent indicators of the presence of THC: red eyes (94%), droopy eyelids (85.6%), affected speech (87.6%), tongue coating (96.2%), and odor of marijuana (82.4%). About 63.6% of THC positive subjects had dialted pupils (room light). THC positive subjects had either rebound dilation or hippus in 88.8% of cases. Pulse and blood pressure (BP) were evaluated to determine any correlation with [THC]. An increased pulse rate correlated well to the presence of THC (88.5%), but not [THC]. BP did not correlate to [THC] and was also a poor indicator of THC in the blood (50% high).