bluuebunny/crossref_metadata_2025_split huggingface dataset:
The structural switch of nucleotide-free kinesin
Authors: Cao Luyan , Cantos-Fernandes Soraya , Gigant Benoît 
Published: February 2017

AbstractKinesin-1 is an ATP-dependent motor protein that moves towards microtubules (+)-ends. Whereas structures of isolated ADP-kinesin and of complexes with tubulin of apo-kinesin and of ATP-like-kinesin are available, structural data on apo-kinesin-1 in the absence of tubulin are still missing, leaving the role of nucleotide release in the structural cycle unsettled. Here, we identified mutations in the kinesin nucleotide-binding P-loop motif that interfere with ADP binding. These mutations destabilize the P-loop (T87A mutant) or magnesium binding (T92V), highlighting a dual mechanism for nucleotide release. The structures of these mutants in their apo form are either isomorphous to ADP-kinesin-1 or to tubulin-bound apo-kinesin-1. Remarkably, both structures are also obtained from the nucleotide-depleted wild-type protein. Our results lead to a model in which, when detached from microtubules, apo-kinesin possibly occupies the two conformations we characterized, whereas, upon microtubule binding, ADP-kinesin converts to the tubulin-bound apo-kinesin conformation and releases ADP. This conformation is primed to bind ATP and, therefore, to run through the natural nucleotide cycle of kinesin-1.
New findings of silica nanoparticles induced ER autophagy in human colon cancer cell
Authors: Wei Fujing , Wang Yimin , Luo Zewei , Li Yu , Duan Yixiang 
Published: February 2017

AbstractNanoparticle-induced autophagy has been extensively studied, however, real time information about the endoplasmic reticulum involved autophagic process (ER autophagy) induced by nanomaterials remains unknown. In this work, silica nanoparticles (SNPs) were synthesized with characteristics of low toxicity, good biocompatibility and excellent water dispersibility to treat cells. Results show that either low concentration (10 μg/mL) or high concentration (200 μg/mL) of SNPs could increase the quantity of processing from microtubule-associated protein 1-light chain 3-I (LC3-I) to the other variant of LC3 (LC3-II). Interestingly, the level of autophagy induced by the SNPs is associated with the treated time but not the concentrations of SNPs. Importantly, for the first time, SNP accumulation in ER was discovered through co-localization analysis, which incurs ER autophagy. These new findings about SNPs-induced ER autophagy could open an effective way for securely designing silica-based nanoparticles and enable us to know more about ER autophagy.
TAZ contributes to pulmonary fibrosis by activating profibrotic functions of lung fibroblasts
Authors: Noguchi Satoshi , Saito Akira , Mikami Yu , Urushiyama Hirokazu , Horie Masafumi , Matsuzaki Hirotaka , Takeshima Hideyuki , Makita Kosuke , Miyashita Naoya , Mitani Akihisa , Jo Taisuke , Yamauchi Yasuhiro , Terasaki Yasuhiro , Nagase Takahide 
Published: February 2017

AbstractTranscriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes. Nuclear translocation and activation of TAZ are regulated by multiple mechanisms, including actin cytoskeleton and mechanical forces. TAZ is involved in lung alveolarization during lung development and Taz-heterozygous mice are resistant to bleomycin-induced lung fibrosis. In this study, we explored the roles of TAZ in the pathogenesis of idiopathic pulmonary fibrosis (IPF) through histological analyses of human lung tissues and cell culture experiments. TAZ was highly expressed in the fibroblastic foci of lungs from patients with IPF. TAZ controlled myofibroblast marker expression, proliferation, migration, and matrix contraction in cultured lung fibroblasts. Importantly, actin stress fibers and nuclear accumulation of TAZ were more evident when cultured on a stiff matrix, suggesting a feedback mechanism to accelerate fibrotic responses. Gene expression profiling revealed TAZ-mediated regulation of connective tissue growth factor (CTGF) and type I collagen. Clinical relevance of TAZ-regulated gene signature was further assessed using publicly available transcriptome data. These findings suggest that TAZ is involved in the pathogenesis of IPF through multifaceted effects on lung fibroblasts.
Spatial distribution of soil organic carbon stock in Moso bamboo forests in subtropical China
Authors: Tang Xiaolu , Xia Mingpeng , Pérez-Cruzado César , Guan Fengying , Fan Shaohui 
Published: February 2017

AbstractMoso bamboo (Phyllostachys heterocycla (Carr.) Mitford cv. Pubescens) is an important timber substitute in China. Site specific stand management requires an accurate estimate of soil organic carbon (SOC) stock for maintaining stand productivity and understanding global carbon cycling. This study compared ordinary kriging (OK) and inverse distance weighting (IDW) approaches to study the spatial distribution of SOC stock within 0–60 cm using 111 soil samples in Moso bamboo forests in subtropical China. Similar spatial patterns but different spatial distribution ranges of SOC stock from OK and IDW highlighted the necessity to apply different approaches to obtain accurate and consistent results of SOC stock distribution. Different spatial patterns of SOC stock suggested the use of different fertilization treatments in Moso bamboo forests across the study area. SOC pool within 0–60 cm was 6.46 and 6.22 Tg for OK and IDW; results which were lower than that of conventional approach (CA, 7.41 Tg). CA is not recommended unless coordinates of the sampling locations are missing and the spatial patterns of SOC stock are not required. OK is recommended for the uneven distribution of sampling locations. Our results can improve methodology selection for investigating spatial distribution of SOC stock in Moso bamboo forests.
Cigarette smoke attenuates phagocytic ability of macrophages through down-regulating Milk fat globule-EGF factor 8 (MFG-E8) expressions
Authors: Wang Yueqin , Luo Guangwei , Chen Jie , Jiang Rui , Zhu Jianhua , Hu Na , Huang Wei , Cheng Guilian , Jia Min , Su Bingtao , Zhang Nian , Cui Tianpen 
Published: February 2017

AbstractChronic obstructive pulmonary disease (COPD) is one of the most common inflammatory diseases resulting from habitual smoking. Impaired clearance of apoptotic cell by airway macrophages contributes to lung inflammation. Milk fat globule-EGF factor 8 (MFG-E8), as a link between apoptotic cells and phagocytes, facilitates clearance of apoptotic cells and attenuates inflammation. We sought to investigate altered expression and potential role of MFG-E8 in COPD. In this study, apoptosis was increased and the level of MFG-E8 was decreased while HMGB1 expression was increased in lung tissues of CS-exposed mice. Compared with CS-exposed WT mice, more apoptotic cells were accumulated in lung tissues of CS-exposed MFG-E8 deficiency mice. Exposure of a range of macrophages to cigarette smoke extract (CSE) resulted in decreased MFG-E8 expression. Administration of rmMFG-E8 ameliorated phagocytic ability of RAW264.7 cells and suppressed inflammatory response induced by CS-exposure. 10% CSE stimulation suppressed Rac1 membrane localization in RAW264.7 cells which was restored by administration of rmMFG-E8. MFG-E8 deficiency diminished uptake of apoptotic thymocytes by peritoneal macrophages upon CSE exposure. Overall, the findings in current work provide a novel target for diagnosing and treating COPD.
SUMO regulates the activity of Smoothened and Costal-2 in Drosophila Hedgehog signaling
Authors: Zhang Jie , Liu Yajuan , Jiang Kai , Jia Jianhang 
Published: February 2017

AbstractIn Hedgehog (Hh) signaling, the GPCR-family protein Smoothened (Smo) acts as a signal transducer that is regulated by phosphorylation and ubiquitination, which ultimately change the cell surface accumulation of Smo. However, it is not clear whether Smo is regulated by other post-translational modifications, such as sumoylation. Here, we demonstrate that knockdown of the small ubiquitin-related modifier (SUMO) pathway components Ubc9 (a SUMO-conjugating enzyme E2), PIAS (a SUMO-protein ligase E3), and Smt3 (the SUMO isoform in Drosophila) by RNAi prevents Smo accumulation and alters Smo activity in the wing. We further show that Hh-induced-sumoylation stabilizes Smo, whereas desumoylation by Ulp1 destabilizes Smo in a phosphorylation independent manner. Mechanistically, we discover that excessive Krz, the Drosophila β-arrestin 2, inhibits Smo sumoylation and prevents Smo accumulation through Krz regulatory domain. Krz likely facilitates the interaction between Smo and Ulp1 because knockdown of Krz by RNAi attenuates Smo-Ulp1 interaction. Finally, we provide evidence that Cos2 is also sumoylated, which counteracts its inhibitory role on Smo accumulation in the wing. Taken together, we have uncovered a novel mechanism for Smo activation by sumoylation that is regulated by Hh and Smo interacting proteins.
Does Naming Therapy Make Ordering in a Restaurant Easier? Dynamics of Co-Occurring Change in Cognitive-Linguistic and Functional Communication Skills in Aphasia
Authors: Meier Erin L. , Johnson Jeffrey P. , Villard Sarah , Kiran Swathi 
Published: February 2017

Purpose
This study was conducted to investigate the static and dynamic relationships between impairment-level cognitive-linguistic abilities and activity-level functional communication skills in persons with aphasia (PWA).

Method

In Experiment 1, a battery of standardized assessments was administered to a group of PWA (
N
= 72) to examine associations between cognitive-linguistic ability and functional communication at a single time point. In Experiment 2, impairment-based treatment was administered to a subset of PWA from Experiment 1 (
n
= 39) in order to examine associations between change in cognitive-linguistic ability and change in function and associations at a single time point.

Results
In both experiments, numerous significant associations were found between scores on tests of cognitive-linguistic ability and a test of functional communication at a single time point. In Experiment 2, significant treatment-induced gains were seen on both types of measures in participants with more severe aphasia, yet cognitive-linguistic change scores were not significantly correlated with functional communication change scores.

Conclusions
At a single time point, cognitive-linguistic and functional communication abilities are associated in PWA. However, although changes on standardized assessments reflecting improvements in both types of skills can occur following an impairment-based therapy, these changes may not be significantly associated with each other.
Executive Function in Preschoolers with Primary Language Impairment
Authors: Yang Hui-Chun , Gray Shelley 
Published: February 2017

Purpose
The purpose of this study was to evaluate whether preschoolers with primary language impairment (PLI) show deficits in executive function (EF) compared with their peers with typical development (TD) when inhibition, updating, and mental-set shifting are examined using both linguistically based and visually based tasks.

Method
Twenty-two 4- and 5-year-old preschoolers with PLI and 30 preschoolers with TD completed 2 sets of computerized EF tasks: 3 that were linguistically based and 3 that were visually based. This permitted us to test the hypothesis that poor performance on EF tasks in preschoolers with PLI results from impaired language rather than impaired EF.

Results
The PLI group scored significantly lower than the TD group on linguistically and visually based updating tasks and mental-set shifting tasks. The PLI and TD groups did not differ significantly for accuracy or response time on linguistically and visually based inhibition tasks.

Conclusion
Results suggest that preschool-age children with PLI have domain-general EF deficits in updating and mental-set shifting but not inhibition deficits, as measured by our tasks.
ALMA hints at the existence of an unseen reservoir of diffuse molecular gas in the Galactic bulge
Authors: Gerin M. , Liszt H. 
Published: February 2017

Aims. We aim to understand the unexpected presence of mm-wave molecular absorption at −200 km s-1<v<−140 km s-1 in a direction that is well away from regions of the Galactic bulge where CO emission at such velocities is prominent.
Methods. We compared 89 GHz Cycle 2 ALMA absorption spectra of HCO+, HCN, and HNC toward the extragalactic continuum source B1741-312 at l = −2.14°, b = −1.00° with existing CO, H I, and dust emission and absorption measurements. We placed the atomic and molecular gas in the bulge and disk using circular and non-circular galactic kinematics, deriving N(H I) from a combination of 21 cm emission and absorption and we derive N(H2) from scaling of the HCO+ absorption. We then inverted the variation of near-IR reddening E(J−K) with distance modulus and scale E(J−K) to a total gas column density N(H) that may be compared to N(H I) and N(H2).
Results. At galactocentric radii Rgal> 1.5 kpc, conventional measures such as the standard CO-H2 conversion factor and locally observed N(HCO+)/N(H2) ratio separately imply that H I and H2 contribute about equally to N(H), and the gas-derived N(H) values are in broad agreement with those derived from E(J−K). Within the Galactic bulge at Rgal< 1.5 kpc, H I contributes less than 10% of the material inferred from E(J−K), so that the molecular absorption detected here is needed to understand the extinction.
Bleeding Scores for the Diagnosis of von Willebrand Disease
Authors: Bowman Mackenzie , James Paula 
Published: February 2017

AbstractObtaining a personal history of bleeding is a critical component to the diagnosis of von Willebrand disease (VWD). The collection of this information can be challenging for physicians, however, as the reporting and interpretation of bleeding symptoms is subjective. The need for more precise quantification of bleeding symptoms was recognized and the Vicenza Bleeding Questionnaire was developed in 2005. This questionnaire collects data regarding the presence and severity of bleeding symptoms and generates a bleeding score by summing the severity of all symptoms reported by a patient. Several subsequent bleeding assessment tools (BATs) have been developed based from this original questionnaire and there has been a surge in the use of BATs in various clinical settings for the diagnosis and evaluation of VWD. This review will discuss the evolution of BATs over the past decade, as well as their use and validation in various settings for the diagnosis and evaluation of VWD. Additionally, we will discuss the clinical utility of BATs, the limitations of these tools, and future directions.
“Is, ought, should”—scientists’ role in discourse on the ethical and social implications of science and technology
Authors: Mehlich Jan 
Published: February 2017

AbstractThe extent to which technology impacts society and its development has sharpened worldwide awareness of the importance of accompanying technological progress with an advanced reflection on the ethical and social implications of this process. Constructive approaches such as Technology Assessment (TA), Responsible Research and Innovation (RRI), or lately, “Open Science, Open Innovation, Open to the World”, attempt to integrate ethical and social considerations into the pathways of progress from the roots upwards. Scientists, as important enactors in scientific progress and technological innovation, are asked to participate in the discourse on ethical and social implications of their work, but find it challenging to define their role in it. This comment attempts to motivate scientists to be “responsible” and “engaged” by shedding light on their expected contributions to making constructive S&T discourse more sustainable.
Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
Authors: Vivekananda Umesh , Novak Pavel , Bello Oscar D. , Korchev Yuri E. , Krishnakumar Shyam S. , Volynski Kirill E. , Kullmann Dimitri M. 
Published: February 2017

Significance
Synaptic transmission depends on all-or-none action potentials. However, subthreshold membrane potential fluctuations at the cell body spread passively along the axon and affect the shape of presynaptic action potentials, calcium influx, and neurotransmitter release. Here we apply a superresolution method to identify small presynaptic terminals for patch clamp. Subthreshold modulation of action potentials is abolished by a mutation in the potassium channel Kv1.1 associated with the neurological channelopathy episodic ataxia type 1. Surprisingly, pharmacological or genetic ablation of Kv1.1 fails to prevent subthreshold modulation. Kv1.1 deletion and mutation have distinct effects on the composition and voltage sensitivity of presynaptic channels and consequently on modulation of neurotransmitter release.
Spatial and temporal dynamics of superspreading events in the 2014–2015 West Africa Ebola epidemic
Authors: Lau Max S. Y. , Dalziel Benjamin Douglas , Funk Sebastian , McClelland Amanda , Tiffany Amanda , Riley Steven , Metcalf C. Jessica E. , Grenfell Bryan T. 
Published: February 2017

SignificanceFor many infections, some infected individuals transmit to disproportionately more susceptibles than others, a phenomenon referred to as “superspreading.” Understanding superspreading can facilitate devising individually targeted control measures, which may outperform population-level measures. Superspreading has been described for a recent Ebola virus (EBOV) outbreak, but systematic characterizations of its spatiotemporal dynamics are still lacking. We introduce a statistical framework that allows us to identify core characteristics of EBOV superspreading. We find that the epidemic was largely driven and sustained by superspreadings that are ubiquitous throughout the outbreak and that age is an important demographic predictor for superspreading. Our results highlight the importance of control measures targeted at potential superspreaders and enhance understanding of causes and consequences of superspreading for EBOV.
Spontaneous mirror-symmetry breaking induces inverse energy cascade in 3D active fluids
Authors: Słomka Jonasz , Dunkel Jörn 
Published: February 2017

SignificanceTurbulence provides an important mechanism for energy redistribution and mixing in interstellar gases, planetary atmospheres, and the oceans. Classical turbulence theory suggests for ordinary 3D fluids or gases, such as water or air, that larger vortices can transform into smaller ones but not vice versa, thus limiting energy transfer from smaller to larger scales. Our calculations predict that bacterial suspensions and other pattern-forming active fluids can deviate from this paradigm by creating turbulent flow structures that spontaneously break mirror symmetry. These results imply that the collective dynamics of swimming microorganisms can enhance fluid mixing more strongly than previously thought.
Disruption of quercetin metabolism by fungicide affects energy production in honey bees (Apis mellifera)
Authors: Mao Wenfu , Schuler Mary A. , Berenbaum May R. 
Published: February 2017

SignificanceThe western honey bee,Apis mellifera, provides essential crop pollination services, but for 10 years, US beekeepers have experienced substantial colony losses. Although insecticides have been implicated in these losses, triazole fungicides affect bees by inhibiting cytochrome P450 monooxygenases that detoxify insecticides. These enzymes also detoxify phytochemicals, including the flavonol quercetin, in their nectar- and pollen-based diet. RNA-Seq analysis of bee larvae consuming quercetin revealed that it down-regulates multiple mitochondrion-related nuclear genes involved in energy production. Bees consuming quercetin together with the triazole myclobutanil produce less thoracic ATP and thus less energy for flight muscles. Therefore, agricultural use of triazole fungicides in combination with insecticides can potentially harm bees by compromising their capacity to extract sufficient energy from their natural diet.
Galectin-3 directs antimicrobial guanylate binding proteins to vacuoles furnished with bacterial secretion systems
Authors: Feeley Eric M. , Pilla-Moffett Danielle M. , Zwack Erin E. , Piro Anthony S. , Finethy Ryan , Kolb Joseph P. , Martinez Jennifer , Brodsky Igor E. , Coers Jörn 
Published: February 2017

Significance
To combat infections with bacterial pathogens that reside and replicate inside specialized intracellular vacuoles, the innate immune system must be able to distinguish these pathogen-containing vacuoles (PVs) from endogenous vesicles. Here, we demonstrate that the host can detect the presence of bacterial secretion systems as hallmarks of PVs. The insertion of bacterial protein secretion pores destabilizes vesicular membranes, allowing host carbohydrate-binding proteins to access the sugar-decorated luminal side of vacuolar membranes. We show that a specific carbohydrate-binding protein recruits members of a family of antimicrobial GTPases to PVs. Our findings reveal how host cells deliver antimicrobial defenses specifically to intracellular vesicles occupied by pathogens.
Optimizing virtual reality for all users through gaze-contingent and adaptive focus displays
Authors: Padmanaban Nitish , Konrad Robert , Stramer Tal , Cooper Emily A. , Wetzstein Gordon 
Published: February 2017

Significance
Wearable displays are becoming increasingly important, but the accessibility, visual comfort, and quality of current generation devices are limited. We study optocomputational display modes and show their potential to improve experiences for users across ages and with common refractive errors. With the presented studies and technologies, we lay the foundations of next generation computational near-eye displays that can be used by everyone.
Genetic regulatory signatures underlying islet gene expression and type 2 diabetes
Authors: Varshney Arushi , Scott Laura J. , Welch Ryan P. , Erdos Michael R. , Chines Peter S. , Narisu Narisu , Albanus Ricardo D’O. , Orchard Peter , Wolford Brooke N. , Kursawe Romy , Vadlamudi Swarooparani , Cannon Maren E. , Didion John P. , Hensley John , Kirilusha Anthony ,   NISC Comparative Sequencing Program, Bonnycastle Lori L. , Taylor D. Leland , Watanabe Richard , Mohlke Karen L. , Boehnke Michael , Collins Francis S. , Parker Stephen C. J. , Stitzel Michael L. , Barnabas Beatrice B. , Bouffard Gerard G. , Brooks Shelise Y. , Coleman Holly , Dekhtyar Lyudmila , Guan Xiaobin , Han Joel , Ho Shi-ling , Legaspi Richelle , Maduro Quino L. , Masiello Catherine A. , McDowell Jennifer C. , Montemayor Casandra , Mullikin James C. , Park Morgan , Riebow Nancy L. , Rosarda Jessica , Schandler Karen , Schmidt Brian , Sison Christina , Smith Raymond , Stantripop Sirintorn , Thomas James W. , Thomas Pamela J. , Vemulapalli Meghana , Young Alice C. 
Published: February 2017

Significance
The majority of genetic variants associated with type 2 diabetes (T2D) are located outside of genes in noncoding regions that may regulate gene expression in disease-relevant tissues, like pancreatic islets. Here, we present the largest integrated analysis to date of high-resolution, high-throughput human islet molecular profiling data to characterize the genome (DNA), epigenome (DNA packaging), and transcriptome (gene expression). We find that T2D genetic variants are enriched in regions of the genome where transcription Regulatory Factor X (RFX) is predicted to bind in an islet-specific manner. Genetic variants that increase T2D risk are predicted to disrupt RFX binding, providing a molecular mechanism to explain how the genome can influence the epigenome, modulating gene expression and ultimately T2D risk.
p53 regulates the cardiac transcriptome
Authors: Mak Tak W. , Hauck Ludger , Grothe Daniela , Billia Filio 
Published: February 2017

Significance
The tumor suppressor Trp53 (p53) is a gene that regulates the expression of many genes. However, the role of p53 in the heart has not been well characterized. This work documents the important role for p53 in the heart as a master regulator of the cardiac transcriptome. The contribution of p53 to the maintenance of cardiac tissue homeostasis is complex under physiological conditions.