bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin states modify network motifs contributing to cell-specific functions
Authors: Zhao Hongying , Liu Tingting , Liu Ling , Zhang Guanxiong , Pang Lin , Yu Fulong , Fan Huihui , Ping Yanyan , Wang Li , Xu Chaohan , Xiao Yun , Li Xia 
Published: July 2015

AbstractEpigenetic modification can affect many important biological processes, such as cell proliferation and apoptosis. It can alter chromatin conformation and contribute to gene regulation. To investigate how chromatin states associated with network motifs, we assembled chromatin state-modified regulatory networks by combining 269 ChIP-seq data and chromatin states in four cell types. We found that many chromatin states were significantly associated with network motifs, especially for feedforward loops (FFLs). These distinct chromatin state compositions contribute to different expression levels and translational control of targets in FFLs. Strikingly, the chromatin state-modified FFLs were highly cell-specific and, to a large extent, determined cell-selective functions, such as the embryonic stem cell-specific bivalent modification-related FFL with an important role in poising developmentally important genes for expression. Besides, comparisons of chromatin state-modified FFLs between cancerous/stem and primary cell lines revealed specific type of chromatin state alterations that may act together with motif structural changes cooperatively contribute to cell-to-cell functional differences. Combination of these alterations could be helpful in prioritizing candidate genes. Together, this work highlights that a dynamic epigenetic dimension can help network motifs to control cell-specific functions.
Extracellular vimentin interacts with insulin-like growth factor 1 receptor to promote axonal growth
Authors: Shigyo Michiko , Kuboyama Tomoharu , Sawai Yusuke , Tada-Umezaki Masahito , Tohda Chihiro 
Published: July 2015

AbstractVimentin, an intermediate filament protein, is generally recognised as an intracellular protein. Previously, we reported that vimentin was secreted from astrocytes and promoted axonal growth. The effect of extracellular vimentin in neurons was a new finding, but its signalling pathway was unknown. In this study, we aimed to determine the signalling mechanism of extracellular vimentin that facilitates axonal growth. We first identified insulin-like growth factor 1 receptor (IGF1R) as a receptor that is highly phosphorylated by vimentin stimulation. IGF1R blockades diminished vimentin- or IGF1-induced axonal growth in cultured cortical neurons. IGF1, IGF2 and insulin were not detected in the neuron culture medium after vimentin treatment. The combined drug affinity responsive target stability method and western blotting analysis showed that vimentin and IGF1 interacted with IGF1R directly. In addition, immunoprecipitation and western blotting analyses confirmed that recombinant IGF1R bound to vimentin. The results of a molecular dynamics simulation revealed that C-terminal residues (residue number 330-407) in vimentin are the most appropriate binding sites with IGF1R. Thus, extracellular vimentin may be a novel ligand of IGF1R that promotes axonal growth in a similar manner to IGF1. Our results provide novel findings regarding the role of extracellular vimentin and IGF1R in axonal growth.
Preliminary Characterization and In Vivo Studies of Structurally Identical 18F- and 125I-Labeled Benzyloxybenzenes for PET/SPECT Imaging of β-Amyloid Plaques
Authors: Yang Yanping , Zhang Xiaoyang , Cui Mengchao , Zhang Jinming , Guo Zhide , Li Yesen , Zhang Xianzhong , Dai Jiapei , Liu Boli 
Published: July 2015

AbstractWith the assistance of molecular docking and 3D-QSAR models established previously, structurally identical 18F- and 125I-labeled benzyloxybenzene derivatives were designed to achieve the early detection of Aβ plaques by PET/SPECT imaging. In competition binding assay, ligands 7a and 12a displayed high binding affinities to Aβ42 aggregates with Ki values of 19.5 nM and 23.9 nM, respectively. Specific plaque labeling was observed on the in vitro autoradiography of brain sections from AD patients and Tg mice. In biodistribution, [125I]7a, [18F]7a, [125I]12a and [18F]12a all exhibited high initial brain uptakes (>5% ID/g at 2 min). [125I]7a and [125I]12a cleared fast from the normal brain regions, while corresponding [18F]7a and [18F]12a showed slow washout rates. Dynamic microPET/CT and microSPECT/CT imaging data in normal ICR mice were in accordance with in vivo biodistribution results. In vivo metabolism results indicated that the different clearance profiles between the structurally identical 18F- and 125I-labeled tracers could be attributed to different biochemical characteristics of the radiometabolites. Radioiodinated benzyloxybenzene derivatives exhibited good in vivo biostability in brain. Ex vivo autoradiography further confirmed the strong in vivo Aβ labeling ability of [125I]7a. These new fluorinated and iodinated benzyloxybenzenes can develop into PET/SPECT dual imaging agents targeting Aβ plaques.
Artificial targeting of misfolded cytosolic proteins to endoplasmic reticulum as a mechanism for clearance
Authors: Liu Fen , Koepp Deanna M. , Walters Kylie J. 
Published: July 2015

AbstractWe report that misfolded cytosolic proteins can be cleared from mammalian cells by directing them to endoplasmic reticulum (ER). NAT1 R64W and Parkin R42P are naturally occurring misfolded variants of cytosolic enzymes that acetylate arylamines and ubiquitinate proteins, respectively. We demonstrate that proteasome inhibition causes ER accumulation of NAT1 R64W and its ubiquitinated species and that these products are cleared from cells following inhibition release. NAT1 WT by contrast is stable and not present at ER. The R42P mutation in Parkin locates to a UBL domain that interacts with C-terminal domains. Parkin R42P full length protein is trafficked poorly to ER and stable. Interestingly, fusion of the isolated R42P UBL to NAT1 WT results in a fusion product that is trafficked robustly to ER and degraded. Thus, the misfolded UBL is apparently masked by the intramolecular interactions. We also find that artificially directing Parkin R42P to ER by fusion with the Sec61β ER-directing transmembrane domain triggers its clearance. Altogether, our results suggest that routing misfolded cytosolic proteins to ER may be an effective strategy for clearance.
Comparison of Vocal Vibration-Dose Measures for Potential-Damage Risk Criteria
Authors: Titze Ingo R. , Hunter Eric J. 
Published: July 2015

Purpose
Schoolteachers have become a benchmark population for the study of occupational voice use. A decade of vibration-dose studies on the teacher population allows a comparison to be made between specific dose measures for eventual assessment of damage risk.

Method
Vibration dosimetry is reformulated with the inclusion of collision stress. Two methods of estimating amplitude of vocal-fold vibration are compared to capture variations in vocal intensity. Energy loss from collision is added to the energy-dissipation dose. An equal-energy-dissipation criterion is defined and used on the teacher corpus as a potential-damage risk criterion.

Results
Comparison of time-, cycle-, distance-, and energy-dose calculations for 57 teachers reveals a progression in information content in the ability to capture variations in duration, speaking pitch, and vocal intensity. The energy-dissipation dose carries the greatest promise in capturing excessive tissue stress and collision but also the greatest liability, due to uncertainty in parameters. Cycle dose is least correlated with the other doses.

Conclusion
As a first guide to damage risk in excessive voice use, the equal-energy-dissipation dose criterion can be used to structure trade-off relations between loudness, adduction, and duration of speech.
Bidirectional Interference Between Speech and Nonspeech Tasks in Younger, Middle-Aged, and Older Adults
Authors: Bailey Dallin J. , Dromey Christopher 
Published: July 2015

Purpose
The purpose of this study was to examine divided attention over a large age range by looking at the effects of 3 nonspeech tasks on concurrent speech motor performance. The nonspeech tasks were designed to facilitate measurement of bidirectional interference, allowing examination of their sensitivity to speech activity. A cross-sectional design was selected to explore possible changes in divided-attention effects associated with age.

Method
Sixty healthy participants were separated into 3 groups of 20: younger (20s), middle-aged (40s), and older (60s) adults. Each participant completed a speech task (sentence repetitions) once in isolation and once concurrently with each of 3 nonspeech tasks: a semantic-decision linguistic task, a quantitative-comparison cognitive task, and a manual motor task. The nonspeech tasks were also performed in isolation.

Results
Data from speech kinematics and nonspeech task performance indicated significant task-specific divided attention interference, with divided attention affecting speech and nonspeech measures in the linguistic and cognitive conditions and affecting speech measures in the manual motor condition. There was also a significant age effect for utterance duration.

Conclusions
The results increase what is known about bidirectional interference between speech and other concurrent tasks as well as age effects on speech motor control.
Active control strategy based on vector‐proportion integration controller for proton exchange membrane fuel cell grid‐connected system
Authors: Li Qi , Chen Weirong , Liu Zhixiang , Zhou Guohua , Ma Lei 
Published: July 2015

Considering the influence of slow response characteristic of a high‐power proton exchange membrane fuel cell (PEMFC) on a grid‐connected system adequately, a 150 kW PEMFC grid‐connected system, including a PEMFC power unit based on a Ballard Stack Modules‐FCvelocity™ HD6 is developed in this study. Moreover, then an active control strategy with vector‐proportion integration controller is proposed to regulate the cascade system actively and improve the performance of compensating low‐order harmonics. The comparisons with conventional active/reactive power (PQ) control are carried out to verify the validity of the proposed method under different conditional tests. The results demonstrate that the proposed strategy can not only track the grid power demand quickly, but also prevent the unsteady phenomena which are aroused by PQ control method from the relatively slow response of high‐power PEMFC power unit. Furthermore, the total harmonic distortion of grid‐connected current is measured by means of the criterion of IEEE Std1547‐2003 and the result of fast Fourier transform analysis testifies that the proposed strategy can decrease the total harmonic content of currents better. Therefore, this proposed method will be an optional effective technique for the design of advanced high‐power PEMFC grid‐connected control system.
Union Rate and Complications in Spine Fusion with Recombinant Human Bone Morphogenetic Protein-7: Systematic Review and Meta-Analysis
Authors: Vavken Julia , Vavken Patrick , Mameghani Alexander , Schaeren Stefan 
Published: July 2015

Study Design Systematic review and meta-analysis. Objective The objective of this meta-analysis was to evaluate the current best evidence to assess effectiveness and safety of recombinant human bone morphogenetic protein-7 (rhBMP-7) as a biological stimulant in spine fusion. Methods Studies were included if they reported on outcomes after spine fusion with rhBMP-7. The data was synthesized using Mantel-Haenszel pooled risk ratios (RRs) with 95% confidence intervals (CIs). Main end points were union rate, overall complications, postoperative back and leg pain, revision rates, and new-onset cancer. Results Our search produced 796 studies, 6 of which were eligible for inclusion. These studies report on a total of 442 patients (328 experimental, 114 controls) with a mean age of 59 ± 11 years. Our analysis showed no statistically significant differences in union rates (RR 0.97, 95% CI 0.84 to 1.11, p = 0.247), overall complications (RR 0.92, 95% CI 0.71 to 1.20, p = 0.545), postoperative back and leg pain (RR 1.03, 95% CI 0.48 to 2.19, p = 0.941), or revision rate (RR 0.81, 95% CI 0.47 to 1.40, p = 0.449). There was a mathematical indicator of increased tumor rates, but with only one case, the clinical meaningfulness of this finding is questionable. Conclusion We were not able to find data in support of the use of rhBMP-7 for spine fusion. We found no evidence for increased complication or revision rates with rhBMP-7. On the other hand, we also found no evidence in support of improved union rates.
Coupling of diversification and pH adaptation during the evolution of terrestrial Thaumarchaeota
Authors: Gubry-Rangin Cécile , Kratsch Christina , Williams Tom A. , McHardy Alice C. , Embley T. Martin , Prosser James I. , Macqueen Daniel J. 
Published: July 2015

Significance
The link between species diversification and adaptation has long interested biologists working on multicellular eukaryotes, but remains poorly understood in prokaryotes, in which diversity is much greater. We tested the hypothesis that diversification is associated with environmental adaptation in Thaumarchaeota, an ancient and abundant microbial group and key player in the global nitrogen cycle. We provide evidence that the Thaumarchaeota underwent a major radiation event hundreds of millions of years ago that coincided with a major period of pH adaptation. Subsequently, these microbes have maintained high rates of diversification, potentially because of the high rate at which new terrestrial niches arise. This study provides a framework for comparing dynamics of evolutionary processes across the tree of life.
Energy flow and functional compensation in Great Basin small mammals under natural and anthropogenic environmental change
Authors: Terry Rebecca C. , Rowe Rebecca J. 
Published: July 2015

Significance
Small mammals play a critical role in the maintenance of desert ecosystems. Using Quaternary fossils from the Great Basin, we show that energy flow through a small mammal community during today’s heightened climate warming differs from that experienced during natural rapid warming in the past. This discrepancy highlights a modern breakdown in energetic compensation among functional groups, and stresses the importance of novel anthropogenic impacts, such as the replacement of shrublands by invasive annual grasses introduced to North American deserts more than a century ago. Use of the fossil record to untangle the effects of climate and anthropogenic habitat change on ecosystem function today is thus critical for understanding how ecosystems will respond to future environmental change.
Predicting the onset of period-doubling bifurcations in noisy cardiac systems
Authors: Quail Thomas , Shrier Alvin , Glass Leon 
Published: July 2015

Significance
Predicting the onset of transitions in the qualitative dynamics of complex systems remains a challenging problem, with relevance in diverse fields. This study focuses on the development of early warning signals that can predict the onset of alternating cardiac rhythms. We treat cardiac cells with a potassium channel blocker, which induces the initiation of alternating rhythms. Based on these experiments, we develop a quantitative measure that can detect how far the system is from the transition. Our results suggest that it is possible to predict the onset of potentially dangerous alternating rhythms in the heart.
Cysteine cathepsins are essential in lysosomal degradation of α-synuclein
Authors: McGlinchey Ryan P. , Lee Jennifer C. 
Published: July 2015

Significance
Identifying factors that regulate the degradation of α-synuclein, the protein at the center of Parkinson’s disease etiology, is vital in designing therapeutic strategies. This study provides new mechanistic insights into α-synuclein clearance in the lysosome, a cellular site for proteolysis by using purified mouse lysosomes and purified lysosomal proteases. Cathepsins B and L are identified to be vital through peptide mapping by mass spectrometry. Importantly, cathepsin L degrades α-synuclein amyloid fibrils, materials associated with neurodegeneration, and, thus, changes in its activity or levels could provide a promising avenue for intervention. Additional results on the stimulatory effect of anionic phospholipids on cathepsin activity suggest that changes in lipid metabolism may also contribute to lysosomal dysfunction leading to pathogenesis.
Vaccine-elicited antibody that neutralizes H5N1 influenza and variants binds the receptor site and polymorphic sites
Authors: Winarski Katie L. , Thornburg Natalie J. , Yu Yingchun , Sapparapu Gopal , Crowe James. E. , Spiller Benjamin W. 
Published: July 2015

Significance
A small number of mutations to the viral hemagglutinin are sufficient to permit aerosol transmission, in a ferret model of human infection, of highly pathogenic avian H5N1 influenza A viruses. Here, we show how an antibody (H5.3) against hemagglutinin 5 (H5) recognizes both WT and variant H5 proteins. H5.3 retains germ-line characteristics, most remarkably a conformationally flexible combining site, consistent with an antibody that has not been through multiple cycles of affinity maturation. Many antibodies against H5 are lightly mutated and may arise from naive B cells, explaining the low antigenicity of H5N1 vaccines relative to seasonal influenza vaccines and supporting the idea that multiple exposures are necessary to develop a strong immune response to H5N1 strains.
Three-dimensional model of surfactant replacement therapy
Authors: Filoche Marcel , Tai Cheng-Feng , Grotberg James B. 
Published: July 2015

Significance
To our knowledge, this paper presents the first structural model of surfactant replacement therapy (SRT), the delivery of liquid bolus surfactant mixtures into the lung airways. SRT has succeeded in premature neonates with surfactant deficiency but mostly failed in adults with acute respiratory distress syndrome, which claims ∼74,500 lives annually in the United States at a 39% mortality rate. Our model incorporates the fluid mechanics of the liquid bolus propagating through a branching airway tree with gravity effects. It reveals well-mixed distributions in the neonatal lung, but poorly mixed, highly nonlinear distribution features in adult lungs. The model suggests adult SRT failures are likely due to inadequate delivery, while providing a rational basis for successful protocols.
Self-control forecasts better psychosocial outcomes but faster epigenetic aging in low-SES youth
Authors: Miller Gregory E. , Yu Tianyi , Chen Edith , Brody Gene H. 
Published: July 2015

Significance
Most childhood outcomes pattern by socioeconomic status (SES). Children from low-SES families complete less education, have worse health, and are convicted of more crimes. To ameliorate these disparities, policymakers are incorporating character-skills training into school curricula and social services. Among other goals, these programs attempt to improve self-control, or the ability to resist temptations that interfere with long-term aspirations. However, data suggest that self-control has unforeseen consequences for the health of low-SES youth. Here, we follow 292 African American teenagers as they transition into adulthood. Among low-SES youth, self-control forecasted better psychosocial outcomes, including less depression, substance use, and aggression. However, it also forecasted more rapid immune cell aging, highlighting the potential health costs of successful adjustment for disadvantaged youth.
Alleviation of off-target effects from vector-encoded shRNAs via codelivered RNA decoys
Authors: Mockenhaupt Stefan , Grosse Stefanie , Rupp Daniel , Bartenschlager Ralf , Grimm Dirk 
Published: July 2015

Significance
Induction of RNAi through shRNA expression holds great potential for biomedical research. Ideal shRNAs exhibit high specificity, potency, and safety, but options for rationally designing such shRNAs remain limited. One ensuing concern is unintended perturbation of gene expression by shRNA sense or antisense strands (off-targeting). Here, we report a novel solution that specifically counteracts adverse activity of shRNA sense strands via their sequestration by tough decoy RNAs (TuDs). Using hepatitis C virus as a clinically relevant example, we demonstrate how TuD coexpression from an Adeno-associated viral (AAV) gene therapy vector concurrently decreases shRNA off-targeting and enhances on-target inhibition. The versatility of TuDs and AAVs makes our new strategy useful for improving specificity and safety of a wide array of RNAi experiments.
Glucose-dependent acetylation of Rictor promotes targeted cancer therapy resistance
Authors: Masui Kenta , Tanaka Kazuhiro , Ikegami Shiro , Villa Genaro R. , Yang Huijun , Yong William H. , Cloughesy Timothy F. , Yamagata Kanato , Arai Nobutaka , Cavenee Webster K. , Mischel Paul S. 
Published: July 2015

Significance
Cancer cells reprogram their metabolism in response to growth factor receptor mutations. However, the effect of altered nutrient levels on oncogenic signaling and therapeutic response is not well understood. We demonstrate that glucose or acetate, two abundant “fuel” sources in the brain, promote epidermal growth factor receptor vIII (EGFRvIII)-dependent signaling through activation of mechanistic target of rapamycin complex 2 (mTORC2) by acetylation of its core component Rictor. This activity is mediated through elevated levels of acetyl-CoA. A surprising implication of this study is that glucose or acetate can contribute to targeted therapy resistance by maintaining signaling through downstream components of the growth factor receptor signaling cascade.
Effective charges and virial pressure of concentrated macroion solutions
Authors: Boon Niels , Guerrero-García Guillermo Ivan , van Roij René , Olvera de la Cruz Monica 
Published: July 2015

Significance
Colloids constitute the basic components of many everyday products and are integrated into the fabric of modern society. Understanding their assembly is key for nanotechnological and biotechnological advances. At the single-particle level, colloids commonly possess electric charge. Consequently, the structure to which they conform is strongly influenced by electrostatic interactions. In solution, these interactions are modified by the presence of ions. We have developed a model for computing the corresponding effective electrostatic interactions as well as the osmotic pressure. Our model extends the applicability of Derjaguin−Landau−Verwey−Overbeek theory to dense systems in which many-body effects are crucial. This will allow previously impossible, mesoscale studies of colloidal assembly to be performed analytically or by simulation with implicit ions models.
Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1
Authors: Sekiyama Naotaka , Arthanari Haribabu , Papadopoulos Evangelos , Rodriguez-Mias Ricard A. , Wagner Gerhard , Léger-Abraham Mélissa 
Published: July 2015

Significance
Translation initiation governs many cellular processes, including cell proliferation, growth, and development. Central to this process is the translation initiation factor 4E (eIF4E), which recruits the small ribosomal subunit to the 5′ end of the mRNA through its interaction with the scaffold protein eIF4G. The eIF4E/eIF4G interaction is highly regulated by competitive binding of 4E-binding proteins (4E-BPs), which are at a convergence point of signaling pathways and act as tumor suppressors. The recently discovered eIF4E/eIF4G interaction inhibitor 1 (4EGI-1) dissociates eIF4G but enhances 4E-BP1 binding and has antitumor activity. Here, we elucidate the mechanism for the dual activity of 4EGI-1—it dissociates eIF4G from eIF4E but stabilizes the binding of 4E-BP1.