bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic tensile forces drive collective cell migration through three-dimensional extracellular matrices
Authors: Gjorevski Nikolce , S. Piotrowski Alexandra , Varner Victor D. , Nelson Celeste M. 
Published: July 2015

AbstractCollective cell migration drives tissue remodeling during development, wound repair and metastatic invasion. The physical mechanisms by which cells move cohesively through dense three-dimensional (3D) extracellular matrix (ECM) remain incompletely understood. Here, we show directly that migration of multicellular cohorts through collagenous matrices occurs via a dynamic pulling mechanism, the nature of which had only been inferred previously in 3D. Tensile forces increase at the invasive front of cohorts, serving a physical, propelling role as well as a regulatory one by conditioning the cells and matrix for further extension. These forces elicit mechanosensitive signaling within the leading edge and align the ECM, creating microtracks conducive to further migration. Moreover, cell movements are highly correlated and in phase with ECM deformations. Migrating cohorts use spatially localized, long-range forces and consequent matrix alignment to navigate through the ECM. These results suggest biophysical forces are critical for 3D collective migration.
Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells
Authors: Jones Anna J , Gokhale Paul J , Allison Thomas F , Sampson Barry , Athwal Sharan , Grant Simon , Andrews Peter W , Allen Nicholas D , Patrick Case C 
Published: July 2015

AbstractMaternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular ‘bystander signalling’ both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development.
Ultra-high-resolution 3D imaging of atherosclerosis in mice with synchrotron differential phase contrast: a proof of concept study
Authors: Bonanno Gabriele , Coppo Simone , Modregger Peter , Pellegrin Maxime , Stuber Annina , Stampanoni Marco , Mazzolai Lucia , Stuber Matthias , van Heeswijk Ruud B. 
Published: July 2015

AbstractThe goal of this study was to investigate the performance of 3D synchrotron differential phase contrast (DPC) imaging for the visualization of both macroscopic and microscopic aspects of atherosclerosis in the mouse vasculature ex vivo. The hearts and aortas of 2 atherosclerotic and 2 wild-type control mice were scanned with DPC imaging with an isotropic resolution of 15 μm. The coronary artery vessel walls were segmented in the DPC datasets to assess their thickness and histological staining was performed at the level of atherosclerotic plaques. The DPC imaging allowed for the visualization of complex structures such as the coronary arteries and their branches, the thin fibrous cap of atherosclerotic plaques as well as the chordae tendineae. The coronary vessel wall thickness ranged from 37.4 ± 5.6 μm in proximal coronary arteries to 13.6 ± 3.3 μm in distal branches. No consistent differences in coronary vessel wall thickness were detected between the wild-type and atherosclerotic hearts in this proof-of-concept study, although the standard deviation in the atherosclerotic mice was higher in most segments, consistent with the observation of occasional focal vessel wall thickening. Overall, DPC imaging of the cardiovascular system of the mice allowed for a simultaneous detailed 3D morphological assessment of both large structures and microscopic details.
T2D and Depression Risk Gene Proteasome Modulator 9 is Linked to Insomnia
Authors: Hao Han , Haas Michael J. , Wu Rongling , Gragnoli Claudia 
Published: July 2015

AbstractInsomnia increases type-2 diabetes (T2D) risk. The 12q24 locus is linked to T2D, depression, bipolar disorder and anxiety. At the 12q24 locus, the Proteasome-Modulator 9 (PSMD9) single nucleotide polymorphisms (SNPs) rs74421874 [intervening sequence (IVS) 3+nt460-G>A], rs3825172 (IVS3+nt437-C>T) and rs14259 (E197G-A>G) are linked to: T2D, depression, anxiety, maturity-onset-diabetes-of the young 3/MODY3, obesity, waist circumference, hypertension, hypercholesterolemia, T2D-macrovascular disease, T2D-microvascular disease, T2D-neuropathy, T2D-carpal-tunnel syndrome, T2D-nephropathy, T2D-retinopathy and non-diabetic retinopathy. PSMD9 SNP rs1043307/rs14259 (E197G-A>G) plays a role in anti-depressant therapy response, depression and schizophrenia. We aimed at determining PSMD9 rs74421874/rs3825172/rs14259 SNPs potential linkage to primary insomnia and sleep hours in T2D families. We recruited 200 Italian T2D families phenotyping them for primary insomnia and sleep hours per night. PSMD9-T2D-risk SNPs rs74421874/rs3825172 and rs1043307/rs14259 were tested for linkage with insomnia and sleep hours. Non-parametric-linkage analysis, linkage-disequilibrium-model analysis, single-SNP analysis, cluster-based-parametric analysis, quantitative-trait and variant-component analysis were performed using Merlin software. To validate data, 1000 replicates were executed for the significant non-parametric data. PSMD9 rs74421874 (IVS3+nt460-G>A), rs3825172 (IVS3+nt437-C>T) and rs1043307/rs14259 (E197G-A>G) SNPs are linked to insomnia in our Italian families.
Differential and coherent processing patterns from small RNAs
Authors: Pundhir Sachin , Gorodkin Jan 
Published: July 2015

AbstractPost-transcriptional processing events related to short RNAs are often reflected in their read profile patterns emerging from high-throughput sequencing data. MicroRNA arm switching across different tissues is a well-known example of what we define as differential processing. Here, short RNAs from the nine cell lines of the ENCODE project, irrespective of their annotation status, were analyzed for genomic loci representing differential or coherent processing. We observed differential processing predominantly in RNAs annotated as miRNA, snoRNA or tRNA. Four out of five known cases of differentially processed miRNAs that were in the input dataset were recovered and several novel cases were discovered. In contrast to differential processing, coherent processing is observed widespread in both annotated and unannotated regions. While the annotated loci predominantly consist of ~24nt short RNAs, the unannotated loci comparatively consist of ~17nt short RNAs. Furthermore, these ~17nt short RNAs are significantly enriched for overlap to transcription start sites and DNase I hypersensitive sites (p-value < 0.01) that are characteristic features of transcription initiation RNAs. We discuss how the computational pipeline developed in this study has the potential to be applied to other forms of RNA-seq data for further transcriptome-wide studies of differential and coherent processing.
Radiofrequency treatment alters cancer cell phenotype
Authors: Ware Matthew J. , Tinger Sophia , Colbert Kevin L. , Corr Stuart J. , Rees Paul , Koshkina Nadezhda , Curley Steven , Summers H. D. , Godin Biana 
Published: July 2015

AbstractThe importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.
Curved singular beams for three-dimensional particle manipulation
Authors: Zhao Juanying , Chremmos Ioannis D. , Song Daohong , Christodoulides Demetrios N. , Efremidis Nikolaos K. , Chen Zhigang 
Published: July 2015

AbstractFor decades, singular beams carrying angular momentum have been a topic of considerable interest. Their intriguing applications are ubiquitous in a variety of fields, ranging from optical manipulation to photon entanglement and from microscopy and coronagraphy to free-space communications, detection of rotating black holes and even relativistic electrons and strong-field physics. In most applications, however, singular beams travel naturally along a straight line, expanding during linear propagation or breaking up in nonlinear media. Here, we design and demonstrate diffraction-resisting singular beams that travel along arbitrary trajectories in space. These curved beams not only maintain an invariant dark “hole” in the center but also preserve their angular momentum, exhibiting combined features of optical vortex, Bessel and Airy beams. Furthermore, we observe three-dimensional spiraling of microparticles driven by such fine-shaped dynamical beams. Our findings may open up new avenues for shaped light in various applications.
Cutting improves the productivity of lucerne-rich stands used in the revegetation of degraded arable land in a semi-arid environment
Authors: Yuan Zi-Qiang , Yu Kai-Liang , Wang Bin-Xian , Zhang Wang-Yun , Zhang Xu-Long , Siddique Kadambot H. M. , Stefanova Katia , Turner Neil C. , Li Feng-Min 
Published: July 2015

AbstractUnderstanding the relationships between vegetative and environmental variables is important for revegetation and ecosystem management on the Loess Plateau, China. Lucerne (Medicago sativa L.) has been widely used in the region to improve revegetation, soil and water conservation and to enhance livestock production. However, there is little information on how environmental factors influence long-term succession in lucerne-rich vegetation. Our objective was to identify the main environmental variables controlling the succession process in lucerne-rich vegetation such that native species are not suppressed after sowing on the Loess Plateau. Vegetation and soil surveys were performed in 31 lucerne fields (three lucerne fields without any management from 2003–2013 and 28 fields containing 11-year-old lucerne with one cutting each year). Time after planting was the most important factor affecting plant species succession. Cutting significantly affected revegetation characteristics, such as aboveground biomass, plant density and diversity. Soil moisture content, soil organic carbon, soil available phosphorus and slope aspect were key environmental factors affecting plant species composition and aboveground biomass, density and diversity. Long-term cutting can cause self-thinning in lucerne, maintain the stability of lucerne production and slow its degradation. For effective management of lucerne fields, phosphate fertilizer should be applied and cutting performed.
Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment
Authors: Quintana D S , Westlye L T , Rustan Ø G , Tesli N , Poppy C L , Smevik H , Tesli M , Røine M , Mahmoud R A , Smerud K T , Djupesland P G , Andreassen O A 
Published: July 2015

AbstractDespite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered’ nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.
Perceptions of the solarium ban in Australia: ‘Fake it, don't bake it’
Authors: Prichard Ivanka , Dobbinson Suzanne , Wilson Carlene , Hutchinson Amanda D. , Rayner Joanne , Makin Jen 
Published: July 2015

Issue addressedThe causal link between ultraviolet radiation from solarium use and skin cancer is well established. In 2012 and 2013, state governments across Australia announced plans to ban commercial solarium use from 31 December 2014. The present study examined the responses of solarium and non‐solarium users to the ban on commercial solariums in Australia.MethodsParticipants (n = 488; 388 females, 100 males; mean age = 26.02, s.d. = 9.95) completed an online questionnaire during the summer prior to the ban relating to solarium usage and their opinions about the ban.ResultsOverall, 49% (n = 237) of participants were aware of the impending ban; 17% (n = 83) had used a solarium at some point in their life. The response to the solarium ban was positive; however, some current solarium users intended post‐ban to use privately owned sunbeds and or spend a greater amount of time sun‐tanning.ConclusionsThese findings indicate a high level of public support for the solarium ban, which has removed a risky source of ultraviolet radiation in Australia.
Unique double-ring structure of the peroxisomal Pex1/Pex6 ATPase complex revealed by cryo-electron microscopy
Authors: Blok Neil B. , Tan Dongyan , Wang Ray Yu-Ruei , Penczek Pawel A. , Baker David , DiMaio Frank , Rapoport Tom A. , Walz Thomas 
Published: July 2015

Significance
Pex1 and Pex6 are members of the AAA family of ATPases, which contain two ATPase domains in a single polypeptide chain and form hexameric double rings. These two Pex proteins are involved in the biogenesis of peroxisomes, and mutations in them frequently cause diseases. Here, we determined structures of the Pex1/Pex6 complex by cryo-electron microscopy. Novel computational modeling methods allowed placement of Pex1/Pex6 domains into subnanometer density maps. Our results show that the peroxisomal Pex1/Pex6 ATPases form a unique double-ring structure in which the two proteins alternate around the ring. Our data shed light on the mechanism and function of this ATPase and suggest a role in peroxisomal protein import similar to that of p97 in ER-associated protein degradation.
The spliceosome assembly factor GEMIN2 attenuates the effects of temperature on alternative splicing and circadian rhythms
Authors: Schlaen Rubén Gustavo , Mancini Estefanía , Sanchez Sabrina Elena , Perez-Santángelo Soledad , Rugnone Matías L. , Simpson Craig G. , Brown John W. S. , Zhang Xu , Chernomoretz Ariel , Yanovsky Marcelo J. 
Published: July 2015

Significance
RNA processing, an important step in the regulation of gene expression, is mediated by proteins and RNA molecules that are highly sensitive to variations in temperature conditions. Most organisms do not control their own body temperature. Therefore, molecular mechanisms must have evolved that ensure that biological processes are robust to temperature changes. Here we identify a protein that buffers the effect of temperature on biological timing by enhancing the assembly of the spliceosome, a large ribonucleoprotein complex involved in RNA processing in organisms ranging from yeast to humans, and thereby controlling the alternative splicing of clock genes.
Human anti-nucleolin recombinant immunoagent for cancer therapy
Authors: Palmieri Dario , Richmond Timothy , Piovan Claudia , Sheetz Tyler , Zanesi Nicola , Troise Fulvia , James Cindy , Wernicke Dorothee , Nyei Fata , Gordon Timothy J. , Consiglio Jessica , Salvatore Francesco , Coppola Vincenzo , Pichiorri Flavia , De Lorenzo Claudia , Croce Carlo M. 
Published: July 2015

Significance
Because of its selective expression on the surface of a variety of different cancer cells, but not on their normal counterparts, nucleolin (NCL) represents an attractive target for antineoplastic treatments. However, previously described NCL-targeting molecules, although promising, still suffer from intrinsic limitations. Here, we describe the identification of the first fully human anti-NCL immune-based agent displaying antineoplastic activity against solid tumors, both in vitro and in vivo. This molecule could represent the prototype of a novel class of NCL-targeting drugs with enormous clinical potential as tools for the diagnosis and therapy of a wide range of human cancers.
A computational perspective on autism
Authors: Rosenberg Ari , Patterson Jaclyn Sky , Angelaki Dora E. 
Published: July 2015

Significance
Autism is a pervasive disorder that broadly impacts perceptual, cognitive, social, and motor functioning. Across individuals, the disorder manifests with a large degree of phenotypic diversity. Here, we propose that autism symptomatology reflects alterations in neural computation. Using neural network simulations, we show that a reduction in the amount of inhibition occurring through a computation called divisive normalization can account for perceptual consequences reported in autism, as well as proposed changes in the extent to which past experience influences the interpretation of current sensory information in individuals with the disorder. A computational perspective can help bridge our understandings of the genetic/molecular basis of autism and its behavioral characteristics, providing insights into the disorder and possible courses of treatment.
Forecasting for Recreational Fisheries Management: What's the Catch?
Authors: Farmer Nicholas A. , Froeschke John T. 
Published: July 2015

Abstract
The Magnuson–Stevens Fishery Conservation and Management Reauthorization Act of 2006 required regional fishery management councils to implement annual catch limits (ACLs) for nearly all stocks under U.S. federal management. Since 2011, the number of stocks requiring ACLs (and monitoring) has increased nearly 10-fold, with strict accountability measures requiring either in-season quota closures or shortening of subsequent seasons to avoid ACL overages. Robust forecasts of landings can also provide a projected baseline for evaluation of proposed management alternatives. We compared generalized linear models (GLMs), generalized additive models (GAMs), and seasonal autoregressive integrated moving average (SARIMA) models in terms of fit, accuracy, and ability to forecast landings of four representative fish stocks that support recreational fisheries in the southeastern United States. All models were useful in developing reliable forecasts to inform management. The GAMs provided the best fit to the observed data; however, the modeling approaches of the SARIMA model and GLM provided the best forecasts for most scenarios. The SARIMA model and GLM also provided the best predictions of the seasonal trend in landings, a desirable feature for in-season quota monitoring. The SARIMA model was more sensitive and the GLM was less sensitive to recent trends, providing a useful “bookend” for forecasts. The time span of input data affected forecast accuracy from all model types considered. This study suggests multiple forecasting models should be investigated and performance metrics carefully selected and evaluated, as no single model is likely to perform best for all stocks of interest.
Received December 18, 2014; accepted April 20, 2015
Intravenous Iron Therapy in Patients with Idiopathic Pulmonary Arterial Hypertension and Iron Deficiency
Authors: Ruiter Gerrina , Manders Emmy , Happé Chris M. , Schalij Ingrid , Groepenhoff Herman , Howard Luke S. , Wilkins Martin R. , Bogaard Harm J. , Westerhof Nico , van der Laarse Willem J. , de Man Frances S. , Anton Vonk‐Noordegraaf 
Published: July 2015

In patients with idiopathic pulmonary arterial hypertension (iPAH), iron deficiency is common and has been associated with reduced exercise capacity and worse survival. Previous studies have shown beneficial effects of intravenous iron administration. In this study, we investigated the use of intravenous iron therapy in iron‐deficient iPAH patients in terms of safety and effects on exercise capacity, and we studied whether altered exercise capacity resulted from changes in right ventricular (RV) function and skeletal muscle oxygen handling. Fifteen patients with iPAH and iron deficiency were included. Patients underwent a 6‐minute walk test, cardiopulmonary exercise tests, cardiac magnetic resonance imaging, and a quadriceps muscle biopsy and completed a quality‐of‐life questionnaire before and 12 weeks after receiving a high dose of intravenous iron. The primary end point, 6‐minute walk distance, was not significantly changed after 12 weeks (409 ± 110 m before vs. 428 ± 94 m after; P = 0.07). Secondary end points showed that intravenous iron administration was well tolerated and increased body iron stores in all patients. In addition, exercise endurance time (P < 0.001) and aerobic capacity (P < 0.001) increased significantly after iron therapy. This coincided with improved oxygen handling in quadriceps muscle cells, although cardiac function at rest and maximal were unchanged. Furthermore, iron treatment was associated with improved quality of life (P < 0.05). In conclusion, intravenous iron therapy in iron‐deficient iPAH patients improves exercise endurance capacity. This could not be explained by improved RV function; however, increased quadriceps muscle oxygen handling may play a role. (Trial registration: ClinicalTrials.gov identifier NCT01288651)