bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term protective efficacy with a BCG-prime ID93/GLA-SE boost regimen against the hyper-virulent Mycobacterium tuberculosis strain K in a mouse model
Authors: Kwon Kee Woong , Lee Ara , Larsen Sasha E. , Baldwin Susan L. , Coler Rhea N. , Reed Steven G. , Cho Sang-Nae , Ha Sang-Jun , Shin Sung Jae 
Published: October 2019

AbstractSince ID93/GLA-SE was developed as a targeted BCG-prime booster vaccine, in the present study, we evaluated the protective efficacy of ID93/GLA-SE as a boost to a BCG-prime against the hypervirulent Mycobacterium tuberculosis (Mtb) K challenge to provide further information on the development and application of this vaccine candidate. Boosting BCG with the ID93/GLA-SE vaccine significantly reduced bacterial burden at 16 weeks post-challenge while the BCG vaccine alone did not confer significant protection against Mtb K. The pathological analysis of the lung from the challenged mice also showed the remarkably protective boosting effect of ID93/GLA-SE on BCG-immunised animals. Moreover, qualitative and quantitative analysis of the immune responses following ID93/GLA-SE-immunisation demonstrated that ID93/GLA-SE was able to elicit robust and sustained Th1-biased antigen-specific multifunctional CD4+ T-cell responses up to 16 weeks post-challenge as well as a high magnitude of an antigen-specific IgG response. Our findings demonstrate that the ID93/GLA-SE vaccine candidate given as a BCG-prime boost regimen confers a high level of long-term protection against the hypervirulent Mtb Beijing infection. These findings will provide further and more feasible validation for the potential utility of this vaccine candidate particularly in East-Asian countries, with the predominance of the Beijing genotype, after BCG vaccination.
Identification of candidate chemosensory genes of Ophraella communa LeSage (Coleoptera: Chrysomelidae) based on antennal transcriptome analysis
Authors: Ma Chao , Zhao Chenchen , Cui Shaowei , Zhang Yan , Chen Guangmei , Chen Hongsong , Wan Fanghao , Zhou Zhongshi 
Published: October 2019

AbstractAntennal olfaction plays a key role in insect survival, which mediates important behaviors like host search, mate choice, and oviposition site selection. As an oligophagous insect, olfaction is extremely important for Ophraella communa to locate host plants. However, information on the olfactory genes has been lacking in O. communa. Using next generation sequencing, we assembled the antennal transcriptome of O. communa and first reported the major chemosensory genes necessary for olfaction in this species. In this study, a total 105 candidate chemosensory genes were identified in O. communa antennae, including 25 odorant-binding proteins (OBPs), 11 chemosensory proteins (CSPs), four sensory neuron membrane proteins (SNMPs), 30 odorant receptors (ORs), 18 ionotropic receptors (IRs), and 17 gustatory receptors (GRs). We also identified full-length sequences of the highly conserved ORco and IR8a/25a family in O. communa. In addition, the expression profile of 15 ORs and four OBPs were validated by quantitative real-time polymerase chain reaction (qPCR). We found that OcomOR2/4/19 and OcomOBP19/20 had a biased expression in male antennae, and OcomOR8 had a biased expression in the female antennae. This large number of chemosensory genes handled by homology analysis and qPCR results will provide the first insights into molecular basis for the olfactory systems of O. communa as well as advance our understanding of olfactory mechanisms in Coleoptera.
Transgenic mouse models expressing human and macaque prion protein exhibit similar prion susceptibility on a strain-dependent manner
Authors: Espinosa Juan Carlos , Comoy Emmanuel E. , Marin-Moreno Alba , Aguilar-Calvo Patricia , Birling Marie-Christine , Pitarch José Luis , Deslys Jean-Philippe , Torres Juan María 
Published: October 2019

AbstractCynomolgus macaque has been used for the evaluation of the zoonotic potential of prion diseases, especially for classical-Bovine Spongiform Encephalopathy (classical-BSE) infectious agent. PrP amino acid sequence is considered to play a key role in the susceptibility to prion strains and only one amino acid change may alter this susceptibility. Macaque and human-PrP sequences have only nine amino acid differences, but the effect of these amino acid changes in the susceptibility to dissimilar prion strains is unknown. In this work, the transmissibility of a panel of different prions from several species was compared in transgenic mice expressing either macaque-PrPC (TgMac) or human-PrPC (Hu-Tg340). Similarities in the transmissibility of most prion strains were observed suggesting that macaque is an adequate model for the evaluation of human susceptibility to most of the prion strains tested. Interestingly, TgMac were more susceptible to classical-BSE strain infection than Hu-Tg340. This differential susceptibility to classical-BSE transmission should be taken into account for the interpretation of the results obtained in macaques. It could notably explain why the macaque model turned out to be so efficient (worst case model) until now to model human situation towards classical-BSE despite the limited number of animals inoculated in the laboratory experiments.
Details of the cooperative binding of piperlongumine with rat serum albumin obtained by spectroscopic and computational analyses
Authors: Povinelli Ana Paula Ribeiro , Zazeri Gabriel , de Freitas Lima Marcelo , Cornélio Marinônio Lopes 
Published: October 2019

AbstractPiperlongumine (PPL) has presented a variety of important pharmacological activities. In recent pharmacokinetics studies in rats, this molecule reached 76.39% of bioavailability. Although PPL is present in the bloodstream, no information is found on the interaction between PPL and rat serum albumin (RSA), the most abundant protein with the function of transporting endo/exogenous molecules. In this sense, the present study elucidated the mechanism of interaction between PPL and RSA, using in conjunction spectroscopic and computational techniques. This paper shows the importance of applying inner filter correction over the entire fluorescence spectrum prior to any conclusion regarding changes in the polarity of the fluorophore microenvironment, also demonstrates the convergence of the results obtained from the treatment of fluorescence data using the area below the spectrum curve and the intensity in a single wavelength. Thermodynamic parameters revealed that PPL binds to RSA spontaneously (ΔG < 0) and the process is entropically driven. Interaction density function method (IDF) indicated that PPL accessed two cooperative sites in RSA, with moderate binding constants (2.3 × 105 M−1 and 1.3 × 105 M−1). The molecular docking described the microenvironment of the interaction sites, rich in apolar residues. The stability of the RSA-PPL complex was checked by molecular dynamics.
Neurons in the pigeon nidopallium caudolaterale, but not the corticoidea dorsolateralis, display value and effort discounting activity
Authors: Dykes Madeline , Porter Blake , Colombo Michael 
Published: October 2019

AbstractWe recorded from single neurons in two areas of the pigeon brain while birds were required to peck a stimulus indicating either a high effort task or a low effort task would follow. Upon completion of the task the birds received the same reward. We found that activity in the nidopallium caudolaterale, an area equivalent to the mammalian prefrontal cortex, was modulated by the value of the reward that would be received based on how much effort was required to obtain it. Value coding was most prominent during the presentation of the stimulus indicating a high or low effort task, and in the delay period immediately prior to carrying out the effort task. In contrast, activity in the corticoidea dorsolateralis was not modulated by value, however, population firing patterns suggest that it may be involved in associating actions with outcomes. Our findings support the view that activity in the nidopallium caudolaterale reflects value of reward as a function of effort discounting and as such may serve functions similar to the mammalian anterior cingulate cortex.
Dual growth mode of boron nitride nanotubes in high temperature pressure laser ablation
Authors: Kim Jun Hee , Cho Hyunjin , Pham Thang Viet , Hwang Jae Hun , Ahn Seokhoon , Jang Se Gyu , Lee Hunsu , Park Cheol , Kim Cheol Sang , Kim Myung Jong 
Published: October 2019

AbstractThe morphological analysis of the end of boron nitride nanotubes (BNNTs) using high-resolution transmission electron microscopy (HR-TEM) can provide valuable insight into the growth mechanism in high temperature pressure (HTP) laser ablation where the best quality of BNNT materials can be obtained so far. Two growth modes of BNNT coexisting during the synthesis process have been proposed based on HR-TEM observation and length analysis. One is the root growth mode, in which boron nitride (BN) species formed via the surface interaction between surrounding N2 molecules and boron nanodroplets incorporate into the tubular structure. Another mode called open-end growth mode means the prolongation of tube growth from the exposed BN edge surrounding the surface of boron nanodroplets which is constructed by the heterogeneous nucleation of absorbed BN radicals from the gas plume. The statistical data, the proportions of end structures and the length of BNNTs, could be fitted to two growth modes, and the open-end growth mode is found to be especially effective in producing longer nanotubes with a higher growth rate. The scientific understanding of the growth mechanism is believed to provide the control for optimized production of BNNTs.
Effects of attachment-based compassion therapy (ABCT) on brain-derived neurotrophic factor and low-grade inflammation among fibromyalgia patients: A randomized controlled trial
Authors: Montero-Marin Jesus , Andrés-Rodríguez Laura , Tops Mattie , Luciano Juan V. , Navarro-Gil Mayte , Feliu-Soler Albert , López-del-Hoyo Yolanda , Garcia-Campayo Javier 
Published: October 2019

AbstractFibromyalgia (FM) is a disabling syndrome characterized by chronic pain associated with fatigue. Its pathogenesis is unknown, but alterations in central sensitization, involving an imbalance of brain-derived neurotrophic factor (BDNF) and inflammatory biomarkers, appear to be implicated. The aim of this study was to evaluate the impact of attachment-based compassion therapy (ABCT) on levels of BDNF, the inflammatory markers TNF-α, IL-6, IL-10, and the C-reactive protein (CRP), analysing whether biomarkers play a mediating/moderating role in improvements in FM functional status. Thirty-four female patients with FM participated in a RCT and were assigned to ABCT or relaxation therapy. Blood extractions were conducted at baseline and post-intervention, with self-report assessments of functional status (FIQ) at baseline, post-intervention and 3-month follow-up. A pro-inflammatory composite was obtained by summing up IL-6, TNF-α and CRP normalized values. Non-parametric tests, analysis of variance and regression models were used to evaluate treatment and mediation/moderation. Compared to relaxation therapy, ABCT showed significant improvements in FIQ and decreases in BDNF, CRP, and pro-inflammatory composite. Changes in BDNF had a mediating role in FIQ. ABCT seems to reduce BDNF and appears to have anti-inflammatory effects in FM patients. Reductions in BDNF could be a mechanism of FM functional status improvement.Clinical Trial Registration:http://ClinicalTrials.gov, identifier NCT02454244. Date: May 27th, 2015.
Physiological and transcriptome analyses of photosynthesis and chlorophyll metabolism in variegated Citrus (Shiranuhi and Huangguogan) seedlings
Authors: Xiong Bo , Qiu Xia , Huang Shengjia , Wang Xiaojia , Zhang Xu , Dong Tiantian , Wang Tie , Li Sichen , Sun Guochao , Zhu Jin , Wang Zhihui 
Published: October 2019

AbstractCitrus species are among the most economically important fruit crops. Physiological characteristics and molecular mechanisms associated with de-etiolation have been partially revealed. However, little is known about the mechanisms controlling the expression and function of genes associated with photosynthesis and chlorophyll biosynthesis in variegated citrus seedlings. The lower biomass, chlorophyll contents, and photosynthetic parameter values recorded for the variegated seedlings suggested that chlorophyll biosynthesis was partially inhibited. Additionally, roots of the variegated seedlings were longer than the roots of green seedlings. We obtained 567.07 million clean reads and 85.05 Gb of RNA-sequencing data, with more than 94.19% of the reads having a quality score of Q30 (sequencing error rate = 0.1%). Furthermore, we detected 4,786 and 7,007 differentially expressed genes (DEGs) between variegated and green Shiranuhi and Huangguogan seedlings. Thirty common pathways were differentially regulated, including pathways related to photosynthesis (GO: 0015979) and the chloroplast (GO: 0009507). Photosynthesis (44 and 63 DEGs), photosynthesis-antenna proteins (14 and 29 DEGs), and flavonoid biosynthesis (16 and 29 DEGs) pathways were the most common KEGG pathways detected in two analyzed libraries. Differences in the expression patterns of PsbQ, PetF, PetB, PsaA, PsaN, PsbP, PsaF, Cluster-2274.8338 (ZIP1), Cluster-2274.38688 (PTC52), and Cluster-2274.78784 might be responsible for the variegation in citrus seedlings. We completed a physiological- and transcriptome-level comparison of the Shiranuhi and Huangguogan cultivars that differ in terms of seedling variegation. We performed mRNA-seq analyses of variegated and green Shiranuhi and Huangguogan seedlings to explore the genes and regulatory pathways involved in the inhibition of chlorophyll biosynthesis and decreases in Chl a and Chl b contents. The candidate genes described herein should be investigated in greater detail to further characterize variegated citrus seedlings.
Enzyme-free release of adhered cells from standard culture dishes using intermittent ultrasonic traveling waves
Authors: Kurashina Yuta , Imashiro Chikahiro , Hirano Makoto , Kuribara Taiki , Totani Kiichiro , Ohnuma Kiyoshi , Friend James , Takemura Kenjiro 
Published: October 2019

AbstractCell detachment is essential in culturing adherent cells. Trypsinization is the most popular detachment technique, even though it reduces viability due to the damage to the membrane and extracellular matrix. Avoiding such damage would improve cell culture efficiency. Here we propose an enzyme-free cell detachment method that employs the acoustic pressure, sloshing in serum-free medium from intermittent traveling wave. This method detaches 96.2% of the cells, and increases its transfer yield to 130% of conventional methods for 48 h, compared to the number of cells detached by trypsinization. We show the elimination of trypsinization reduces cell damage, improving the survival of the detached cells. Acoustic pressure applied to the cells and media sloshing from the intermittent traveling wave were identified as the most important factors leading to cell detachment. This proposed method will improve biopharmaceutical production by expediting the amplification of tissue-cultured cells through a more efficient transfer process.
Partially oxidized DJ-1 inhibits α-synuclein nucleation and remodels mature α-synuclein fibrils in vitro
Authors: Kumar Roshan , Kumar Sanjay , Hanpude Pranita , Singh Abhishek Kumar , Johari Tanu , Majumder Sushanta , Maiti Tushar Kanti 
Published: October 2019

AbstractDJ-1 is a deglycase enzyme which exhibits a redox-sensitive chaperone-like activity. The partially oxidized state of DJ-1 is active in inhibiting the aggregation of α-synuclein, a key protein associated with Parkinson’s disease. The underlying molecular mechanism behind α-synuclein aggregation inhibition remains unknown. Here we report that the partially oxidized DJ-1 possesses an adhesive surface which sequesters α-synuclein monomers and blocks the early stages of α-synuclein aggregation and also restricts the elongation of α-synuclein fibrils. DJ-1 remodels mature α-synuclein fibrils into heterogeneous toxic oligomeric species. The remodeled fibers show loose surface topology due to a decrease in elastic modulus and disrupt membrane architecture, internalize easily and induce aberrant nitric oxide release. Our results provide a mechanism by which partially oxidized DJ-1 counteracts α-synuclein aggregation at initial stages of aggregation and provide evidence of a deleterious effect of remodeled α-synuclein species generated by partially oxidized DJ-1.
VLT/SPHERE exploration of the young multiplanetary system PDS70
Authors: Mesa D. , Keppler M. , Cantalloube F. , Rodet L. , Charnay B. , Gratton R. , Langlois M. , Boccaletti A. , Bonnefoy M. , Vigan A. , Flasseur O. , Bae J. , Benisty M. , Chauvin G. , de Boer J. , Desidera S. , Henning T. , Lagrange A.-M. , Meyer M. , Milli J. , Müller A. , Pairet B. , Zurlo A. , Antoniucci S. , Baudino J.-L. , Brown Sevilla S. , Cascone E. , Cheetham A. , Claudi R. U. , Delorme P. , D’Orazi V. , Feldt M. , Hagelberg J. , Janson M. , Kral Q. , Lagadec E. , Lazzoni C. , Ligi R. , Maire A.-L. , Martinez P. , Menard F. , Meunier N. , Perrot C. , Petrus S. , Pinte C. , Rickman E. L. , Rochat S. , Rouan D. , Samland M. , Sauvage J.-F. , Schmidt T. , Udry S. , Weber L. , Wildi F. 
Published: October 2019

Context. PDS 70 is a young (5.4 Myr), nearby (~113 pc) star hosting a known transition disk with a large gap. Recent observations with SPHERE and NACO in the near-infrared (NIR) allowed us to detect a planetary mass companion, PDS 70 b, within the disk cavity. Moreover, observations in Hα with MagAO and MUSE revealed emission associated to PDS 70 b and to another new companion candidate, PDS 70 c, at a larger separation from the star. PDS 70 is the only multiple planetary system at its formation stage detected so far through direct imaging.
Aims. Our aim is to confirm the discovery of the second planet PDS 70 c using SPHERE at VLT, to further characterize its physical properties, and search for additional point sources in this young planetary system.
Methods. We re-analyzed archival SPHERE NIR observations and obtained new data in Y, J, H and K spectral bands for a total of four different epochs. The data were reduced using the data reduction and handling pipeline and the SPHERE data center. We then applied custom routines (e.g., ANDROMEDA and PACO) to subtract the starlight.
Results. We re-detect both PDS 70 b and c and confirm that PDS 70 c is gravitationally bound to the star. We estimate this second planet to be less massive than 5 MJup and with a Teff around 900 K. Also, it has a low gravity with logg between 3.0 and 3.5 dex. In addition, a third object has been identified at short separation (~0.12′′) from the star and gravitationally bound to the star. Its spectrum is however very blue, meaning that we are probably seeing stellar light reflected by dust and our analysis seems to demonstrate that it is a feature of the inner disk. We cannot however completely exclude the possibility that it is a planetary mass object enshrouded by a dust envelope. In this latter case, its mass should be of the order of a few tens of M⊕. Moreover, we propose a possible structure for the planetary system based on our data, and find that this structure cannot be stable on a long timescale.
Observational signatures of the third harmonic in a decaying kink oscillation of a coronal loop
Authors: Duckenfield T. J. , Goddard C. R. , Pascoe D. J. , Nakariakov V. M. 
Published: October 2019

Aims. An observation of a coronal loop standing kink mode is analysed to search for higher harmonics, aiming to reveal the relation between different harmonics’ quality factors.
Methods. Observations of a coronal loop were taken by the Atmospheric Imaging Assembly (AIA) of the Solar Dynamics Observatory (SDO). The loop’s axis was tracked at many spatial positions along the loop to generate time series data.
Results. The distribution of spectral power of the oscillatory transverse displacements throughout the loop reveals the presence of two harmonics, a fundamental at a period of ∼8 min and its third harmonic at ∼2.6 min. The node of the third harmonic is seen at approximately a third of the way along the length of the loop, and cross correlations between the oscillatory motion on opposing sides of the node show a change in phase behaviour. The ratio of periods P1/3P3 was found to be ∼0.87, indicating a non-uniform distribution of kink speed through the loop. The quality factor for the fundamental mode of oscillation was measured to be ∼3.4. The quality factor of the third harmonic was measured for each spatial location and, where data was reliable, yielded a value of ∼3.6. For all locations, the quality factors for the two harmonics were found to agree within error as expected from 1d resonant absorption theory. This is the first time a measurement of the signal quality for a higher harmonic of a kink oscillation has been reported with spatially resolved data.
Anti-Tumor Activity and Safety of Multikinase Inhibitors in
Advanced and/or Metastatic Thyroid Cancer: A Systematic Review
and Network Meta-Analysis of Randomized Controlled Trials
Authors: Tsoli Marina , Alexandraki Krystallenia I. , Spei Maria-Eleni , Kaltsas Gregory A. , Daskalakis Kosmas 
Published: October 2019

AbstractMany trials have demonstrated prime antitumor activity of novel, small molecule
multikinase inhibitors (MKIs) in advanced and/or metastatic thyroid
cancer (TC). In this work, the PubMed, EMBASE, Cochrane Central Register of
Controlled Trials, Web of Science, SCOPUS, and clinicaltrials.gov databases were
searched. Quality/risk of bias were assessed using GRADE criteria.
Randomized clinical trials (RCTs) comparing two or more systemic therapies in
patients with advanced and/or metastatic thyroid cancer were assessed. A
total of 1347 articles and 548 clinical trials in clinicaltrials.gov were
screened. We included seven relevant RCTs comprising 1934 unique patients
assigned to different MKIs. Two separate network meta-analyses included four
RCTs in radioiodine refractory well-differentiated thyroid cancer (RR-WDTC) and
three RCTs in medullary thyroid cancer (MTC), respectively; all with a low risk
of bias. We identified three therapies for RR-WDTC: sorafenib [disease control
rate (DCR) odds ratio (OR): 0.11 (95% CI: 0.03–0.40);
progression-free survival (PFS) hazard ratio (HR): 1.99 (95% CI:
1.62–2.46)], vandetanib [DCR_OR:0.26 (95% CI:
0.06–1.24); PFS_HR: 0.99 (95% CI: 0.82–1.20)] and
lenvatinib [DCR_OR: 0.26 (95% CI: 0.05–1.33); PFS_HR: 0.99
(95% CI: 0.81–1.22)]; and the following therapies for MTC:
vandetanib 300 mg [objective response rate (ORR)_OR: 3.31 (95%
CI: 0.68–16.22); vandetanib 150 mg ORR_OR: 0.60 (95% CI:
0.16–2.33)]; and cabozantinib [ORR_OR: 85.32 (95% CI:
5.22–1395.15)]. Serious side effect (SE) analysis per
organ/system demonstrated a varying MKI SE profile across both RR-WDTC
and MTC diagnoses, more commonly involving metabolic/nutritional
disorders [OR: 2.07 [95% CI: 0.82–5.18)] and gastrointestinal SE
[OR: 1.63 (95% CI: 1.0–2.66)]. This network meta-analysis on
advanced and/or metastatic TC points towards a higher efficacy of
lenvatinib in RR-WDTC. The included MKIs exhibit a varying SE profile across
different organs/systems favoring a patient-tailored approach with the
anticipated toxicities guiding clinicians’ decisions.