bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diffusive tail anchorage determines velocity and force produced by kinesin-14 between crosslinked microtubules
Authors: Lüdecke Annemarie , Seidel Anja-Maria , Braun Marcus , Lansky Zdenek , Diez Stefan 
Published: June 2018

AbstractForm and function of the mitotic spindle depend on motor proteins that crosslink microtubules and move them relative to each other. Among these are kinesin-14s, such as Ncd, which interact with one microtubule via their non-processive motor domains and with another via their diffusive tail domains, the latter allowing the protein to slip along the microtubule surface. Little is known about the influence of the tail domains on the protein’s performance. Here, we show that diffusive anchorage of Ncd’s tail domains impacts velocity and force considerably. Tail domain slippage reduced velocities from 270 nm s−1 to 60 nm s−1 and forces from several piconewtons to the sub-piconewton range. These findings challenge the notion that kinesin-14 may act as an antagonizer of other crosslinking motors, such as kinesin-5, during mitosis. It rather suggests a role of kinesin-14 as a flexible element, pliantly sliding and crosslinking microtubules to facilitate remodeling of the mitotic spindle.
Non-fluorescent nanoscopic monitoring of a single trapped nanoparticle via nonlinear point sources
Authors: Yoon Seung Ju , Lee Jungmin , Han Sangyoon , Kim Chang-Kyu , Ahn Chi Won , Kim Myung-Ki , Lee Yong-Hee 
Published: June 2018

AbstractDetection of single nanoparticles or molecules has often relied on fluorescent schemes. However, fluorescence detection approaches limit the range of investigable nanoparticles or molecules. Here, we propose and demonstrate a non-fluorescent nanoscopic trapping and monitoring platform that can trap a single sub-5-nm particle and monitor it with a pair of floating nonlinear point sources. The resonant photon funnelling into an extremely small volume of ~5 × 5 × 7 nm3 through the three-dimensionally tapered 5-nm-gap plasmonic nanoantenna enables the trapping of a 4-nm CdSe/ZnS quantum dot with low intensity of a 1560-nm continuous-wave laser, and the pumping of 1560-nm femtosecond laser pulses creates strong background-free second-harmonic point illumination sources at the two vertices of the nanoantenna. Under the stable trapping conditions, intermittent but intense nonlinear optical spikes are observed on top of the second-harmonic signal plateau, which is identified as the 3.0-Hz Kramers hopping of the quantum dot trapped in the 5-nm gap.
Uncovering Cellular retinoic acid-binding protein 2 as a potential target for rheumatoid arthritis synovial hyperplasia
Authors: Mosquera Nerea , Rodriguez-Trillo Angela , Mera-Varela Antonio , Gonzalez Antonio , Conde Carmen 
Published: June 2018

AbstractRheumatoid arthritis (RA) is a systemic autoimmune disease including synovitis and synovial hyperplasia that contribute to joint destruction. Pivotal pathogenic mechanisms in this process are the dysregulated proliferation and apoptosis of fibroblast-like synoviocytes (FLS). Unfortunately, the mechanisms of FLS dysregulation are not completely elucidated. Here, we explored a new hypothesis based in the potent anti-proliferative and pro-apoptotic activity of retinoids in some types of cancer. Specifically, we investigated the role of retinoids and of the retinoic acid binding proteins, CRABP2 and FABP5, on the proliferation and apoptosis of FLS from RA by adding all-trans retinoic acid (ATRA) or silencing CRABP2 and FABP5. We showed an unconventional behaviour of RA FLS, which were relatively insensitive to ATRA. In effect, ATRA increased the resistance to apoptosis despite the high CRABP2/FABP5 ratio of RA FLS; andCRABP2suppression sensitized RA FLS to Fas-induced apoptosis. This latter effect was associated with changes in expression of kinases,ASK1up-regulation andERKdown-regulation, and increased phosphorylation of JNK. In addition, the potentiation of FLS apoptosis by CRABP2 silencing persisted in the presence of pro-inflammatory mediators, TNF e IL1β. Therefore, the results point to CRABP2 as a potential target to decrease synovial hyperplasia in RA.
Accurate and Robust Non-rigid Point Set Registration using Student’s-t Mixture Model with Prior Probability Modeling
Authors: Zhou Zhiyong , Tu Jianfei , Geng Chen , Hu Jisu , Tong Baotong , Ji Jiansong , Dai Yakang 
Published: June 2018

AbstractA new accurate and robust non-rigid point set registration method, named DSMM, is proposed for non-rigid point set registration in the presence of significant amounts of missing correspondences and outliers. The key idea of this algorithm is to consider the relationship between the point sets as random variables and model the prior probabilities via Dirichlet distribution. We assign the various prior probabilities of each point to its correspondences in the Student’s-t mixture model. We later incorporate the local spatial representation of the point sets by representing the posterior probabilities in a linear smoothing filter and get closed-form mixture proportions, leading to a computationally efficient registration algorithm comparing to other Student’s-t mixture model based methods. Finally, by introducing the hidden random variables in the Bayesian framework, we propose a general mixture model family for generalizing the mixture-model-based point set registration, where the existing methods can be considered as members of the proposed family. We evaluate DSMM and other state-of-the-art finite mixture models based point set registration algorithms on both artificial point set and various 2D and 3D point sets, where DSMM demonstrates its statistical accuracy and robustness, outperforming the competing algorithms.
Glucocorticoids suppress Wnt16 expression in osteoblasts in vitro and in vivo
Authors: Hildebrandt Susanne , Baschant Ulrike , Thiele Sylvia , Tuckermann Jan , Hofbauer Lorenz C. , Rauner Martina 
Published: June 2018

AbstractGlucocorticoid-induced osteoporosis is a frequent complication of systemic glucocorticoid (GC) therapy and mainly characterized by suppressed osteoblast activity. Wnt16 derived from osteogenic cells is a key determinant of bone mass. Here, we assessed whether GC suppress bone formation via inhibiting Wnt16 expression. GC treatment with dexamethasone (DEX) decreased Wnt16 mRNA levels in murine bone marrow stromal cells (mBMSCs) time- and dose-dependently. Similarly, Wnt16 expression was also suppressed after DEX treatment in calvarial organ cultures. Consistently, mice receiving GC-containing slow-release prednisolone pellets showed lower skeletal Wnt16 mRNA levels and bone mineral density than placebo-treated mice. The suppression of Wnt16 by GCs was GC-receptor-dependent as co-treatment of mBMSCs with DEX and the GR antagonist RU-486 abrogated the GC-mediated suppression of Wnt16. Likewise, DEX failed to suppress Wnt16 expression in GR knockout-mBMSCs. In addition, Wnt16 mRNA levels were unaltered in bone tissue of GC-treated GR dimerization-defective GRdim mice, suggesting that GCs suppress Wnt16 via direct DNA-binding mechanisms. Consistently, DEX treatment reduced Wnt16 promoter activity in MC3T3-E1 cells. Finally, recombinant Wnt16 restored DEX-induced suppression of bone formation in mouse calvaria. Thus, this study identifies Wnt16 as a novel target of GC action in GC-induced suppression of bone formation.
Automated 3D segmentation of methyl isocyanate-exposed rat trachea using an ultra-thin, fully fiber optic optical coherence endoscopic probe
Authors: Miao Yusi , Jing Joseph C. , Desai Vineet , Mahon Sari B. , Brenner Matthew , Veress Livia A. , White Carl W. , Chen Zhongping 
Published: June 2018

AbstractDevelopment of effective rescue countermeasures for toxic inhalational industrial chemicals, such as methyl isocyanate (MIC), has been an emerging interest. Nonetheless, current methods for studying toxin-induced airway injuries are limited by cost, labor time, or accuracy, and only provide indirect or localized information. Optical Coherence Tomography (OCT) endoscopic probes have previously been used to visualize the 3-D airway structure. However, gathering such information in small animal models, such as rat airways after toxic gas exposure, remains a challenge due to the required probe size necessary for accessing the small, narrow, and partially obstructed tracheas. In this study, we have designed a 0.4 mm miniature endoscopic probe and investigated the structural changes in rat trachea after MIC inhalation. An automated 3D segmentation algorithm was implemented so that anatomical changes, such as tracheal lumen volume and cross-sectional areas, could be quantified. The tracheal region of rats exposed to MIC by inhalation showed significant airway narrowing, especially within the upper trachea, as a result of epithelial detachment and extravascular coagulation within the airway. This imaging and automated reconstruction technique is capable of rapid and minimally-invasive identification of airway obstruction. This method can be applied to large-scale quantitative analysis of in vivo animal models.
Understanding the effects of Cr doping in rutile TiO2 by DFT calculations and X-ray spectroscopy
Authors: Vásquez G. Cristian , Maestre David , Cremades Ana , Ramírez-Castellanos Julio , Magnano Elena , Nappini Silvia , Karazhanov Smagul Zh. 
Published: June 2018

AbstractThe effects of Cr on local environment and electronic structure of rutile TiO2 are studied combining theoretical and experimental approaches. Neutral and negatively charged substitutional Cr impurities CrTi0 and CrTi1− as well as Cr-oxygen vacancy complex 2CrTi + VO are studied by the density functional theory (DFT) within the generalized gradient approximation (GGA) of Perdew-Burke-Ernzerhof (PBE) functional. Experimental results based on X-Ray absorption spectroscopy (XAS) and X-Ray photoelectron spectroscopy (XPS) performed on Cr doped TiO2 at the Synchrotron facility were compared to the theoretical results. It is shown that the electrons of the oxygen vacancy tend to be localized at the t2g states of the Cr ions in order to reach the stable oxidation state of Cr3+. Effects of Cr on crystal field (CF) and structural distortions in the rutile TiO2 cell were analyzed by the DFT calculations and XAS spectra revealing that the CF and tetragonal distortions in TiO2 are very sensitive to the concentration of Cr.
The Dynamic Changes in the Storage of the Danjiangkou Reservoir and the Influence of the South-North Water Transfer Project
Authors: Liu Hai , Yin Jie , Feng Lian 
Published: June 2018

AbstractDanjiangkou Reservoir is water source of Middle Route Project of the South-to-North Water Diversion (SNWD) Project, research on the dynamic changes in the water storage within the Danjiangkou Reservoir constitutes an important guide for reservoir water volume management practices. A practical method for estimating the water storage and its dynamics was proposed in this study based on inundated areas from Moderate Resolution Imaging Spectroradiometer (MODIS) observations between 2000 and 2016. The results show that the mean Danjiangkou Reservoir water storage was 10.548 billion m3 year−1. Significant seasonal changes (ρ < 0.01 in t-test) were observed with annual minima (~9.610 billion m3) occurring between February to July and annual maxima (~11.514 billion m3) occurring from August to the following January. Based on the monthly changes in the probability of the water supply, the guaranteed rate of water supply in the second half year (July–December) was higher than that during the first half year (January–June). The water supply in May was greatly deficient. In addition, the full guaranteed rate of the water supply over the past 17 years only accounted for 17.6%. Therefore, reservoir management practices should reduce the water released prior to May and reserve enough water according to the demands of water receiving areas to improve the efficiency of water resource utilization.
Characterization of a novel MYO3A missense mutation associated with a dominant form of late onset hearing loss
Authors: Dantas Vitor G. L. , Raval Manmeet H. , Ballesteros Angela , Cui Runjia , Gunther Laura K. , Yamamoto Guilherme L. , Alves Leandro Ucela , Bueno André Silva , Lezirovitz Karina , Pirana Sulene , Mendes Beatriz C. A. , Yengo Christopher M. , Kachar Bechara , Mingroni-Netto Regina C. 
Published: June 2018

AbstractWhole-exome sequencing of samples from affected members of two unrelated families with late-onset non-syndromic hearing loss revealed a novel mutation (c.2090 T > G; NM_017433) in MYO3A. The mutation was confirmed in 36 affected individuals, showing autosomal dominant inheritance. The mutation alters a single residue (L697W or p.Leu697Trp) in the motor domain of the stereocilia protein MYO3A, leading to a reduction in ATPase activity, motility, and an increase in actin affinity. MYO3A-L697W showed reduced filopodial actin protrusion initiation in COS7 cells, and a predominant tipward accumulation at filopodia and stereocilia when coexpressed with wild-type MYO3A and espin-1, an actin-regulatory MYO3A cargo. The combined higher actin affinity and duty ratio of the mutant myosin cause increased retention time at stereocilia tips, resulting in the displacement of the wild-type MYO3A protein, which may impact cargo transport, stereocilia length, and mechanotransduction. The dominant negative effect of the altered myosin function explains the dominant inheritance of deafness.
Novel interaction between Alzheimer’s disease-related protein presenilin 1 and glutamate transporter 1
Authors: Zoltowska Katarzyna Marta , Maesako Masato , Meier Joshua , Berezovska Oksana 
Published: June 2018

AbstractNeuronal hyperactivity is one of the earliest events observed in Alzheimer’s disease (AD). Moreover, alterations in the expression of glutamate transporters have been reported to exacerbate amyloid pathology and cognitive deficits in transgenic AD mouse models. However, the molecular links between these pathophysiological changes remain largely unknown. Here, we report novel interaction between presenilin 1 (PS1), the catalytic component of the amyloid precursor protein-processing enzyme, γ-secretase, and a major glutamate transporter-1 (GLT-1). Our data demonstrate that the interaction occurs between PS1 and GLT-1 expressed at their endogenous levels in vivo and in vitro, takes place in both neurons and astrocytes, and is independent of the PS1 autoproteolysis and γ-secretase activity. This intriguing discovery may shed light on the molecular crosstalk between the proteins linked to the maintenance of glutamate homeostasis and Aβ pathology.
Carriage of critically important antimicrobial resistant bacteria and zoonotic parasites amongst camp dogs in remote Western Australian indigenous communities
Authors: Rusdi Bertha , Laird Tanya , Abraham Rebecca , Ash Amanda , Robertson Ian D. , Mukerji Shewli , Coombs Geoffrey W. , Abraham Sam , O’Dea Mark A. 
Published: June 2018

AbstractCamp dogs in indigenous communities in the Western Australian Kimberley Region, share the domestic environment with humans and have the potential to act as carriers of, and sentinels for, a wide range of zoonotic agents, including intestinal parasites and antimicrobial resistant bacteria. In this study, we investigated the carriage of extended-spectrum-cephalosporin-resistant (ESC-resistant) Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA) and species of hookworm and Giardia among camp dogs in remote Western Australian Aboriginal communities. A total of 141 canine faecal samples and 156 nasal swabs were collected from dogs in four communities of the Western Australian Kimberley region. Overall, ESC-resistant E. coli was detected in 16.7% of faecal samples and MRSA was isolated from 2.6% of nasal swabs. Of most significance was the presence of the community-associated Panton-Valentine leucocidin (PVL)-positive MRSA ST93 and ST5 clones and ESC-resistant E. coli ST38 and ST131. The most prevalent zoonotic intestinal parasite infection was Ancylostoma caninum (66%). The prevalence of Giardia was 12.1%, with the main genotypes of Giardia detected being dog specific assemblages C and D, which are unlikely to cause disease in humans.
Discovery of pancreastatin inhibitor PSTi8 for the treatment of insulin resistance and diabetes: studies in rodent models of diabetes mellitus
Authors: Hossain Zakir , Valicherla Guru R. , Gupta Anand P. , Syed Anees A. , Riyazuddin Mohammed , Chandra Sharat , Siddiqi Mohammad I. , Gayen Jiaur R. 
Published: June 2018

AbstractPancreastatin (PST) is an endogenous peptide which regulates glucose and lipid metabolism in liver and adipose tissues. In type 2 diabetic patients, PST level is high and plays a crucial role in the negative regulation of insulin sensitivity. Novel therapeutic agents are needed to treat the diabetes and insulin resistance (IR) against the PST action. In this regard, we have investigated the PST inhibitor peptide-8 (PSTi8) action against diabetogenic PST. PSTi8 rescued PST-induced IR in HepG2 and 3T3L1 cells. PSTi8 increases the GLUT4 translocation to cell surface to promote glucose uptake in L6-GLUT4myc cells. PSTi8 treatment showed an increase in insulin sensitivity in db/db, high fat and fructose fed streptozotocin (STZ) induced IR mice. PSTi8 improved the glucose homeostasis which is comparable to metformin in diabetic mice, characterized by elevated glucose clearance, enhanced glycogenesis, enhanced glycolysis and reduced gluconeogenesis. PST and PSTi8 both were docked to the GRP78 inhibitor binding site in protein-protein docking, GRP78 expression and its ATPase activity studies. The mechanism of action of PSTi8 may be mediated by activating IRS1/2-phosphatidylinositol-3-kinase-AKT (FoxO1, Srebp-1c) signaling pathway. The discovery of PSTi8 provides a promising therapeutic agent for the treatment of metabolic diseases mainly diabetes.
Snail knockdown reverses stemness and inhibits tumour growth in ovarian cancer
Authors: Hojo N. , Huisken A. L. , Wang H. , Chirshev E. , Kim N. S. , Nguyen S. M. , Campos H. , Glackin C. A. , Ioffe Y. J. , Unternaehrer J. J. 
Published: June 2018

AbstractTo develop effective therapies for advanced high grade serous ovarian cancer (HGSOC), understanding mechanisms of recurrence and metastasis is necessary. In this study, we define the epithelial/mesenchymal status of cell lines that accurately model HGSOC, and evaluate the therapeutic potential of targeting Snai1 (Snail), a master regulator of the epithelial/mesenchymal transition (EMT) in vitro and in vivo. The ratio of Snail to E-cadherin (S/E index) at RNA and protein levels was correlated with mesenchymal morphology in four cell lines. The cell lines with high S/E index (OVCAR8 and COV318) showed more CSC-like, motile, and chemoresistant phenotypes than those with low S/E index (OVSAHO and Kuramochi). We tested the role of Snail in regulation of malignant phenotypes including stemness, cell motility, and chemotherapy resistance: shRNA-mediated knockdown of Snail reversed these malignant phenotypes. Interestingly, the expression of let-7 tumour suppressor miRNA was upregulated in Snail knockdown cells. Furthermore, knockdown of Snail decreased tumour burden in an orthotopic xenograft mouse model. We conclude that Snail is important in controlling HGSOC malignant phenotypes and suggest that the Snail/Let-7 axis may be an attractive target for HGSOC treatment.
Times series analysis of age-specific tuberculosis at a rapid developing region in China, 2011–2016
Authors: Zhu Minmin , Han Guiyuan , Takiff Howard Eugene , Wang Jian , Ma Jianping , Zhang Min , Liu Shengyuan 
Published: June 2018

AbstractThe city of Shenzhen has recently experienced extraordinary economic growth accompanied by a huge internal migrant influx. We investigated the local dynamics of tuberculosis (TB) epidemiology in the Nanshan District of Shenzhen to provide insights for TB control strategies for this district and other rapidly developing regions in China. We analyzed the age-specific incidence and number of TB cases in the Nanshan District from 2011 to 2016. Over all, the age-standardized incidence of TB decreased at an annual rate of 3.4%. The incidence was lowest amongst the age group 0–14 and showed no increase in this group over the six-year period (P = 0.587). The fastest decreasing incidence was among the 15–24 age group, with a yearly decrease of 13.3% (β = 0.867, P < 0.001). In contrast, the TB incidence increased in the age groups 45–54, 55–54, and especially in those aged ≥65, whose yearly increase was 13.1% (β = 1.131, P < 0.001). The peak time of TB case presentation was in April, May, and June for all age groups, except in August for the 45–54 cohort. In the rapidly developing Nanshan District, TB control policies targeted to those aged 45 years and older should be considered. The presentation of TB cases appears to peak in the spring months.
Post-stroke kinematic analysis in rats reveals similar reaching abnormalities as humans
Authors: Balbinot Gustavo , Schuch Clarissa Pedrini , Jeffers Matthew S. , McDonald Matthew W. , Livingston-Thomas Jessica M. , Corbett Dale 
Published: June 2018

AbstractA coordinated pattern of multi-muscle activation is essential to produce efficient reaching trajectories. Disruption of these coordinated activation patterns, termed synergies, is evident following stroke and results in reaching deficits; however, preclinical investigation of this phenomenon has been largely ignored. Furthermore, traditional outcome measures of post-stroke performance seldom distinguish between impairment restitution and compensatory movement strategies. We sought to address this by using kinematic analysis to characterize reaching movements and kinematic synergies of rats performing the Montoya staircase task, before and after ischemic stroke. Synergy was defined as the simultaneous movement of the wrist and other proximal forelimb joints (i.e. shoulder, elbow) during reaching. Following stroke, rats exhibited less individuation between joints, moving the affected limb more as a unit. Moreover, abnormal flexor synergy characterized by concurrent elbow flexion, shoulder adduction, and external rotation was evident. These abnormalities ultimately led to inefficient and unstable reaching trajectories, and decreased reaching performance (pellets retrieved). The observed reaching abnormalities in this preclinical stroke model are similar to those classically observed in humans. This highlights the potential of kinematic analysis to better align preclinical and clinical outcome measures, which is essential for developing future rehabilitation strategies following stroke.
Honeybees show adaptive reactions to ethanol exposure
Authors: Miler Krzysztof , Kuszewska Karolina , Privalova Valeriya , Woyciechowski Michal 
Published: June 2018

AbstractThe honeybee is being developed as a simple invertebrate model for alcohol-related studies. To date, several effects of ethanol consumption have been demonstrated in honeybees, but the tolerance effect, one of the hallmarks of alcohol overuse, has never been shown. Here, we confirm our hypothesis that the response to ethanol (in terms of motor impairment) is lower in bees that have previously experienced intoxication than in bees encountering ethanol for the first time, indicating that the chronic tolerance effect occurs in honeybees. Furthermore, we investigated the basis of this effect and found that it likely results from conditioned compensatory responses to cues associated with ethanol delivery. Our findings significantly improve our understanding of the suitability of honeybees as models for alcoholism-related research and underline the first and foremost function of all conditioned reactions – their adaptive value.