bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic enhancers supporting 1-carbon cycle affect sperm functionality: an in vitro comparative study
Authors: Gallo A. , Menezo Y. , Dale B. , Coppola G. , Dattilo M. , Tosti E. , Boni R. 
Published: July 2018

AbstractThe sperm plasma membrane is a sensitive target to oxidative stress. The most representative reactive oxygen species (ROS) scavengers in the genital tract, hypotaurine and glutathione, require, for their synthesis, cysteine whose availability is associated with the 1-carbon cycle (1-CC). Human, bovine and ascidian spermatozoa were incubated with compounds supporting the 1-CC (Vitamin B6, Methylcobalamin, 5 Methyl Tetrahydrofolate, Zinc Bisglycinate and N-acetyl-cysteine) (TRT) and compared to the effects induced solely by N-acetyl-cysteine (NAC). In control groups (CNTRL), spermatozoa were incubated with medium alone. After 90 and 180 minutes of incubation, the mitochondrial membrane potential (ΔΨM) in TRT and NAC was significantly (P < 0.01) higher than in CNTRL. At H2DCFDA evaluation, ROS production differed between species whereas, at 2-OH Ethidium, it significantly decreased in bovine TRT group. Intracellular pH (pHi) did not significantly vary in relation to treatment. In ascidian spermatozoa, the NAC supplementation decreased external pH, which in turn brought to a pHilowering. Buffering seawater with NaHCO3reversed the beneficial effects of N-acetyl-cysteine supplementation. In conclusion, both fully supporting the 1-CC and treatment with N-acetyl-cysteine alone improved kinetics, ΔΨM and ROS production in mammalian sperm demonstrating for the first time the directin vitroeffects of these compounds on sperm functionality.
Inverse-response Ca2+ indicators for optogenetic visualization of neuronal inhibition
Authors: Zhao Yufeng , Bushey Daniel , Zhao Yongxin , Schreiter Eric R. , Harrison D. Jed , Wong Allan M. , Campbell Robert E. 
Published: July 2018

AbstractWe have developed a series of yellow genetically encoded Ca2+ indicators for optical imaging (Y-GECOs) with inverted responses to Ca2+ and apparent dissociation constants (Kd′) ranging from 25 to 2400 nM. To demonstrate the utility of this affinity series of Ca2+ indicators, we expressed the four highest affinity variants (Kd′s = 25, 63, 121, and 190 nM) in the Drosophila medulla intrinsic neuron Mi1. Hyperpolarization of Mi1 by optogenetic stimulation of the laminar monopolar neuron L1 produced a decrease in intracellular Ca2+ in layers 8–10, and a corresponding increase in Y-GECO fluorescence. These experiments revealed that lower Kd′ was associated with greater increases in fluorescence, but longer delays to reach the maximum signal change due to slower off-rate kinetics.
All optical dual stage laser wakefield acceleration driven by two-color laser pulses
Authors: Pathak Vishwa Bandhu , Kim Hyung Taek , Vieira J. , Silva L. O. , Nam Chang Hee 
Published: July 2018

AbstractWe propose an all-optical dual-stage laser wakefield acceleration (LWFA), staged with co-propagating two-color laser pulses in a plasma medium, to enhance the electron bunch energy. After the depletion of the leading fundamental laser pulse that initiates self-injection and sets up the first stage particle acceleration, the subsequent second-harmonic laser pulse takes over the acceleration process and accelerates the electron bunch in the second stage over a significantly longer distance than in the first stage. In this all optical dual-stage LWFA, the electrons can gain 3 times higher energy as compared to the energy gain from the single stage LWFA driven by a single-color laser pulse with equivalent energy. Our multi-dimensional particle-in-cell simulations demonstrate that a 10-GeV electron bunch with 20-pC charge can be obtained by the two-color dual-stage LWFA using total input laser power of 0.6 PW.
Novel Nanosized Chitosan-Betulinic Acid Against Resistant Leishmania Major and First Clinical Observation of such parasite in Kidney
Authors: Zadeh Mehrizi Tahereh , Shafiee Ardestani Mehdi , Haji Molla Hoseini Mostafa , Khamesipour Ali , Mosaffa Nariman , Ramezani Amitis 
Published: July 2018

AbstractRegarding the antiparasitic effects of Betulinic acid (B) against Leishmaniasis, it was loaded into nanochitosan (K) for the first time in order to improve its therapeutic effects and decrease its side effects for the treatment of Leishmania major-infected Balb/c mice. Improvement the therapeutic efficacy of Bas an anti-leishmania agent through increasing the effective dose was achieved by using a novel solvent and phase separation method for K synthesis. The synthesized K with the size of 102 nm and Betulinic acid-nanochitosan (BK) with the size of 124 nm and drug loading efficiency of 93%, cellular uptake of 97.5% with the slow drug release pattern was prepared. To increase the therapeutic dose, a modified 10% acetic acid solvent was used. Thein vitroandin vivoresults showed that the nanodrug of BK was non toxic by 100% and BK20 mg/kg could completely performed the wound healing and inhibit the parasite in a large extent (P ˂ 0.001) compared to other groups. Therefore, BK could be considered as an alternative regimen for treatment of L. major.
Co-expression of Cancer Stem Cell Markers OCT4 and NANOG Predicts Poor Prognosis in Renal Cell Carcinomas
Authors: Rasti Arezoo , Mehrazma Mitra , Madjd Zahra , Abolhasani Maryam , Saeednejad Zanjani Leili , Asgari Mojgan 
Published: July 2018

AbstractMany renal cancer patients experience disease recurrence after combined treatments or immunotherapy due to permanence of cancer stem cells (CSCs). This study was conducted to evaluate the expression patterns and clinical significance of octamer-binding transcription factor 4 (OCT4) and NANOG as the key stem cell factors in renal cell carcinoma (RCC). A total of 186 RCC tissues were immunostained on a tissue microarray (TMA) for the putative CSC markers OCT4 and NANOG. Subsequently, the correlation among the expression of these markers, the clinicopathological variables and survival outcomes were determined. OCT4 and NANOG were expressed in both the nucleus and the cytoplasm of RCC cells. Coexpression of OCT4 and NANOG in renal cancer was significantly associated with RCC subtypes. A significant association was found among nuclear coexpression of OCT4 and NANOG, worse PFS in RCC, and the clear cell renal cell carcinomas (ccRCC) subtype. The OCT4-nuclear high/NANOG-nuclear high phenotype in RCC and ccRCC subtype indicated aggressive tumor behavior and predicted a worse clinical outcome, which may be a useful biomarker to identify patients at high risk of postoperative recurrence and metastasis. Cytoplasmic expression of NANOG could be considered as a novel independent prognostic predictor in patients with renal cancer.
Ectopic overexpression of Kir6.1 in the mouse heart impacts on the life expectancy
Authors: Watanabe Yasuhiro , Kishimoto Takashi , Miki Takashi , Seino Susumu , Nakaya Haruaki , Matsumoto Akio 
Published: July 2018

AbstractWe recently reported the reduced ATP-sensitive potassium (KATP) channel activities in the transgenic mouse heart overexpressing the vascular type KATP channel pore-forming subunit (Kir6.1). Although dysfunction of cardiac KATP channel has been nominated as a cause of cardiomyopathy in human, these transgenic mice looked normal as wild-type (WT) during the experiment period (~20 weeks). Extended observation period revealed unexpected deaths beginning from 30 weeks and about 50% of the transgenic mice died by 55 weeks. Surface ECG recordings from the transgenic mice at rest demonstrated the normal sinus rhythm and the regular ECG complex as well as the control WT mice except for prolonged QT interval. However, the stress ECG test with noradrenaline revealed abnormal intraventricular conduction delay and arrhythmogeneity in the transgenic mouse. Fibrotic changes in the heart tissue were remarkable in aged transgenic mice, and the cardiac fibrosis developed progressively at least from the age of 30 weeks. Gene expression analyses revealed the differentiation of cardiac fibroblasts to myofibroblasts with elevated cytokine expressions was initiated way in advance before the fibrotic changes and the upregulation of BNP in the ventricle. In sum, Kir6.1TG mice provide an electro-pathological disease concept originated from KATP channel dysfunction.
Sample size effects on the assessment of eukaryotic diversity and community structure in aquatic sediments using high-throughput sequencing
Authors: Nascimento Francisco J. A. , Lallias Delphine , Bik Holly M. , Creer Simon 
Published: July 2018

AbstractUnderstanding how biodiversity changes in time and space is vital to assess the effects of environmental change on benthic ecosystems. Due to the limitations of morphological methods, there has been a rapid expansion in the application of high-throughput sequencing methods to study benthic eukaryotic communities. However, the effect of sample size and small-scale spatial variation on the assessment of benthic eukaryotic diversity is still not well understood. Here, we investigate the effect of different sample volumes in the genetic assessment of benthic metazoan and non-metazoan eukaryotic community composition. Accordingly, DNA was extracted from five different cumulative sediment volumes comprising 100% of the top 2 cm of five benthic sampling cores, and used as template for Ilumina MiSeq sequencing of 18 S rRNA amplicons. Sample volumes strongly impacted diversity metrics for both metazoans and non-metazoan eukaryotes. Beta-diversity of treatments using smaller sample volumes was significantly different from the beta-diversity of the 100% sampled area. Overall our findings indicate that sample volumes of 0.2 g (1% of the sampled area) are insufficient to account for spatial heterogeneity at small spatial scales, and that relatively large percentages of sediment core samples are needed for obtaining robust diversity measurement of both metazoan and non-metazoan eukaryotes.
Control of swarming of molecular robots
Authors: Keya Jakia Jannat , Kabir Arif Md. Rashedul , Inoue Daisuke , Sada Kazuki , Hess Henry , Kuzuya Akinori , Kakugo Akira 
Published: July 2018

AbstractRecently we demonstrated swarming of a self-propelled biomolecular motor system microtubule (MT)-kinesin where interactions among thousands of motile MTs were regulated in a highly programmable fashion by using DNA as a processor. However, precise control of this potential system is yet to be achieved to optimize the swarm behavior. In this work, we systematically controlled swarming of MTs on kinesin adhered surface by different physicochemical parameters of MT-kinesin and DNA. Tuning the length of DNA sequences swarming was precisely controlled with thermodynamic and kinetic feasibility. In addition, swarming was regulated using different concentration of DNA crosslinkers. Reversibility of swarming was further controlled by changing the concentration of strand displacement DNA signal allowing dissociation of swarm. The control over the swarm was accompanied by variable stiffness of MTs successfully, providing translational and circular motion. Moreover, the morphology of swarm was also found to be changed not only depending on the stiffness but also body length of MTs. Such detail study of precise control of swarming would provide new insights in developing a promising molecular swarm robotic system with desired functions.
Insights into the structure and dynamics of lysyl oxidase propeptide, a flexible protein with numerous partners
Authors: Vallet Sylvain D. , Miele Adriana E. , Uciechowska-Kaczmarzyk Urszula , Liwo Adam , Duclos Bertrand , Samsonov Sergey A. , Ricard-Blum Sylvie 
Published: July 2018

AbstractLysyl oxidase (LOX) catalyzes the oxidative deamination of lysine and hydroxylysine residues in collagens and elastin, which is the first step of the cross-linking of these extracellular matrix proteins. It is secreted as a proenzyme activated by bone morphogenetic protein-1, which releases the LOX catalytic domain and its bioactive N-terminal propeptide. We characterized the recombinant human propeptide by circular dichroism, dynamic light scattering, and small-angle X-ray scattering (SAXS), and showed that it is elongated, monomeric, disordered and flexible (Dmax: 11.7 nm, Rg: 3.7 nm). We generated 3D models of the propeptide by coarse-grained molecular dynamics simulations restrained by SAXS data, which were used for docking experiments. Furthermore, we have identified 17 new binding partners of the propeptide by label-free assays. They include four glycosaminoglycans (hyaluronan, chondroitin, dermatan and heparan sulfate), collagen I, cross-linking and proteolytic enzymes (lysyl oxidase-like 2, transglutaminase-2, matrix metalloproteinase-2), a proteoglycan (fibromodulin), one growth factor (Epidermal Growth Factor, EGF), and one membrane protein (tumor endothelial marker-8). This suggests new roles for the propeptide in EGF signaling pathway.
Conflict and adaptation signals in the anterior cingulate cortex and ventral tegmental area
Authors: Elston Thomas W. , Kalhan Shivam , Bilkey David K. 
Published: July 2018

AbstractThe integration and utilization of feedback in order to determine which decision strategy to use in different contexts is the core of executive function. The anterior cingulate cortex (ACC) is central to these processes but how feedback is made available to the ACC is unclear. To address this question, we trained rats with implants in the ACC and the ventral tegmental area (VTA), a dopaminergic brain region implicated in feedback processing, in a spatial decision reversal task with rule switching occurring approximately every 12 trials. Following a rule switch, the rats had to shift and sustain responses to the alternative side in order to obtain reward. Partial directed coherence (PDC) models of signal directionality between the ACC and VTA indicated that VTA → ACC communication (near 4 Hz) increased immediately prior to incorrect choices and during post-error decisions. This increase did not occur during correct choices. These data indicate that the VTA provides a feedback-driven, bottom-up modulating signal to the ACC which may be involved in assessing, and correcting for, decision conflict.
Hybrid cell reactor system from Escherichia coli protoplast cells and arrayed lipid bilayer chamber device
Authors: Moriizumi Yoshiki , Tabata Kazuhito V. , Watanabe Rikiya , Doura Tomohiro , Kamiya Mako , Urano Yasuteru , Noji Hiroyuki 
Published: July 2018

AbstractWe developed a novel hybrid cell reactor system via functional fusion of single Escherichia coli protoplast cells, that are deficient in cell wall and expose plasma membrane, with arrayed lipid bilayer chambers on a device in order to incorporate the full set of cytosolic and membrane constituents into the artificial chambers. We investigated gene expression activity to represent the viability of the hybrid cell reactors: over 20% of hybrid cells showed gene expression activity from plasmid or mRNA. This suggests that the hybrid cell reactors retained fundamental activity of genetic information transduction. To expand the applicability of the hybrid cell reactors, we also developed the E. coli-in-E. coli cytoplasm system as an artificial parasitism system. Over 30% of encapsulated E. coli cells exhibited normal cell division, showing that hybrid cells can accommodate and cultivate living cells. This novel artificial cell reactor technology would enable unique approaches for synthetic cell researches such as reconstruction of living cell, artificial parasitism/symbiosis system, or physical simulation to test functionality of synthetic genome.
On the use of functional responses to quantify emergent multiple predator effects
Authors: Sentis Arnaud , Boukal David S. 
Published: July 2018

AbstractNon-independent interactions among predators can have important consequences for the structure and dynamics of ecological communities by enhancing or reducing prey mortality rate through, e.g., predator facilitation or interference. The multiplicative risk model, traditionally used to detect these emergent multiple predator effects (MPEs), is biased because it assumes linear functional response (FR) and no prey depletion. To rectify these biases, two approaches based on FR modelling have recently been proposed: the direct FR approach and the population-dynamic approach. Here we compare the strengths, limitations and predictions of the three approaches using simulated data sets. We found that the predictions of the direct FR and the multiplicative risk models are very similar and underestimate predation rates when prey density is high or prey depletion is substantial. As a consequence, these two approaches often fail in detecting risk reduction. Finally, parameters estimated with the direct FR approach lack mechanistic interpretation, which limits the understanding of the mechanisms driving multiple predator interactions and potential extension of this approach to more complex food webs. We thus strongly recommend using the population-dynamic approach because it is robust, precise, and provides a scalable mechanistic framework to detect and quantify MPEs.
Chitin promotes antigen-specific Th2 cell-mediated murine asthma through induction of IL-33-mediated IL-1β production by DCs
Authors: Arae Ken , Morita Hideaki , Unno Hirotoshi , Motomura Kenichiro , Toyama Sumika , Okada Naoko , Ohno Tatsukuni , Tamari Masato , Orimo Keisuke , Mishima Yuko , Suto Hajime , Okumura Ko , Sudo Katsuko , Miyazawa Hiroshi , Taguchi Haruhiko , Saito Hirohisa , Matsumoto Kenji , Nakae Susumu 
Published: July 2018

AbstractChitin, which is a major component of house dust mites (HDM), fungi, crustaceans, etc., can activate immune cells, suggesting that it contributes to development of allergic disorders such as asthma. Although the pathophysiological sensitization route of asthmatic patients to allergens is considered via the respiratory tract, the roles of intranasally-administered chitin in development of asthma remain unclear. After ovalbumin (OVA) challenge, development of airway inflammation was profoundly exacerbated in mice sensitized with OVA in the presence of chitin. The exacerbation was dependent on IL-33, but not IL-25, thymic stromal lymphopoietin or IL-17A. Chitin enhanced IL-33-dependent IL-1β production by dendritic cells (DCs). Furthermore, chitin- and IL-33-stimulated DC-derived IL-1β promoted OVA-specific Th2 cell activation, resulting in aggravation of OVA-induced airway inflammation. These findings indicate the adjuvant activity of chitin via a new mechanism and provide important clues for development of therapeutics for allergic disorders caused by HDM, fungi and crustaceans.
Capacity for instantaneous catabolism of preferred and non-preferred carbon sources in Escherichia coli and Bacillus subtilis
Authors: Buffing Marieke F. , Link Hannes , Christodoulou Dimitris , Sauer Uwe 
Published: July 2018

AbstractMaking the right choice for nutrient consumption in an ever-changing environment is a key factor for evolutionary success of bacteria. Here we investigate the regulatory mechanisms that enable dynamic adaptation between non-preferred and preferred carbon sources for the model Gram-negative and -positive species Escherichia coli and Bacillus subtilis, respectively. We focus on the ability for instantaneous catabolism of a gluconeogenic carbon source upon growth on a glycolytic carbon source and vice versa. By following isotopic tracer dynamics on a 1–2 minute scale, we show that flux reversal from the preferred glucose to non-preferred pyruvate as the sole carbon source is primarily transcriptionally regulated. In the opposite direction, however, E. coli can reverse its flux instantaneously by means of allosteric regulation, whereas in B. subtilis this flux reversal is transcriptionally regulated. Upon removal of transcriptional regulation, B. subtilis assumes the ability of instantaneous glucose catabolism. Using an approach that combines quantitative metabolomics and kinetic modelling, we then identify the additionally necessary key metabolite-enzyme interactions that implement the instantaneous flux reversal in the transcriptionally deregulated B. subtilis, and validate the most relevant allosteric interactions.
Cell type discrimination based on image features of molecular component distribution
Authors: Germond Arno , Ichimura Taro , Chiu Liang-da , Fujita Katsumasa , Watanabe Tomonobu M. , Fujita Hideaki 
Published: July 2018

AbstractMachine learning-based cell classifiers use cell images to automate cell-type discrimination, which is increasingly becoming beneficial in biological studies and biomedical applications. Brightfield or fluorescence images are generally employed as the classifier input variables. We propose to use Raman spectral images and a method to extract features from these spatial patterns and explore the value of this information for cell discrimination. Raman images provide information regarding distribution of chemical compounds of the considered biological entity. Since each spectral wavelength can be used to reconstruct the distribution of a given compound, spectral images provide multiple channels of information, each representing a different pattern, in contrast to brightfield and fluorescence images. Using a dataset of single living cells, we demonstrate that the spatial information can be ranked by a Fisher discriminant score, and that the top-ranked features can accurately classify cell types. This method is compared with the conventional Raman spectral analysis. We also propose to combine the information from whole spectral analyses and selected spatial features and show that this yields higher classification accuracy. This method provides the basis for a novel and systematic analysis of cell-type investigation using Raman spectral imaging, which may benefit several studies and biomedical applications.
Main and interactive effects of physical activity, fitness and body mass in the prevention of cancer from the Copenhagen Male Study
Authors: Nunez Carlos , Clausen Johan , Jensen Magnus Thorsten , Holtermann Andreas , Gyntelberg Finn , Bauman Adrian 
Published: July 2018

AbstractLittle knowledge exists about the role of cardiorespiratory fitness (CRF) or its interaction with excess adiposity determined by body mass index (BMI) in cancer prevention. A total of 5,128 middle-aged men, without a history of cancer at baseline in 1970–71, were examined for subsequent incidence and mortality of several cancer types. Participants’ data were linked with cancer registration and mortality data to March 2017. During 47 years of follow-up, a total of 1,920 incident cases and 1,638 cancer-related deaths were ascertained. BMI, particularly obesity, was associated with (i) incidence and (ii) mortality from respiratory/thoracic cancers; and (iii) all cancer-cause mortality. The respective adjusted hazard ratios (HRs) were: (i) 0.51 (95%CI:0.32–0.79), (ii) 0.48 (95%CI:0.30–0.75) and (iii) 0.73 (95%CI:0.59–0.89) when compared obese men (BMI ≥30 kg/m2) to men with healthy-BMI (<25 kg/m2). Increasing CRF was inversely associated with incidence and mortality of respiratory/thoracic cancers, HRs 0.78 (95%CI:0.67–0.90) and 0.73 (95%CI:0.63–0.84) respectively; and all cancer-cause incidence 0.92 (95%CI:0.86–0.98) and mortality 0.85 (95%CI:0.79–0.91). Physical activity (PA) was not associated with most outcomes. We found no evidence of interactions between CRF or PA and BMI on cancer risk. This evidence suggests that midlife CRF is associated with lowered risk of cancer incidence and mortality with no evidence of cancer risk modification by BMI.