bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent roles of FT-like 9 in flowering transition under different day lengths in Brachypodium distachyon
Authors: Qin Zhengrui , Bai Yuxue , Muhammad Sajid , Wu Xia , Deng Pingchuan , Wu Jiajie , An Hailong , Wu Liang 
Published: February 2019

AbstractTiming of reproductive transition is precisely modulated by environmental cues in flowering plants. Facultative long-day plants, including Arabidopsis and temperate grasses, trigger rapid flowering in long-day conditions (LDs) and delay flowering under short-day conditions (SDs). Here, we characterize a SD-induced FLOWERING LOCUS T ortholog, FT-like 9 (FTL9), that promotes flowering in SDs but inhibits flowering in LDs in Brachypodium distachyon. Mechanistically, like photoperiod-inductive FT1, FTL9 can interact with FD1 to form a flowering activation complex (FAC), but the floral initiation efficiency of FTL9-FAC is much lower than that of FT1-FAC, thereby resulting in a positive role for FTL9 in promoting floral transition when FT1 is not expressed, but a dominant-negative role when FT1 accumulates significantly. We also find that CONSTANS 1 (CO1) can suppress FTL9 in addition to stimulate FT1 to enhance accelerated flowering under LDs. Our findings on the antagonistic functions of FTL9 under different day-length environments will contribute to understanding the multifaceted roles of FT in fine-tune modulation of photoperiodic flowering in plants.
PD-1 blockade potentiates HIV latency reversal ex vivo in CD4+ T cells from ART-suppressed individuals
Authors: Fromentin Rémi , DaFonseca Sandrina , Costiniuk Cecilia T. , El-Far Mohamed , Procopio Francesco Andrea , Hecht Frederick M. , Hoh Rebecca , Deeks Steven G. , Hazuda Daria J. , Lewin Sharon R. , Routy Jean-Pierre , Sékaly Rafick-Pierre , Chomont Nicolas 
Published: February 2019

AbstractHIV persists in latently infected CD4+ T cells during antiretroviral therapy (ART). Immune checkpoint molecules, including PD-1, are preferentially expressed at the surface of persistently infected cells. However, whether PD-1 plays a functional role in HIV latency and reservoir persistence remains unknown. Using CD4+ T cells from HIV-infected individuals, we show that the engagement of PD-1 inhibits viral production at the transcriptional level and abrogates T-cell receptor (TCR)-induced HIV reactivation in latently infected cells. Conversely, PD-1 blockade with the monoclonal antibody pembrolizumab enhances HIV production in combination with the latency reversing agent bryostatin without increasing T cell activation. Our results suggest that the administration of immune checkpoint blockers to HIV-infected individuals on ART may facilitate latency disruption.
Adenosine deaminase-1 delineates human follicular helper T cell function and is altered with HIV
Authors: Tardif Virginie , Muir Roshell , Cubas Rafael , Chakhtoura Marita , Wilkinson Peter , Metcalf Talibah , Herro Rana , Haddad Elias K. 
Published: February 2019

AbstractFollicular helper T cells (Tfh) play critical roles instructing, and initiating T-cell dependent antibody responses. The underlying mechanisms that enhance their function is therefore critical for vaccine development. Here we apply gene array analysis identifying adenosine deaminase (ADA) as a key molecule that delineates a human Tfh helper program in proliferating circulating Tfh (cTfh) cells and Germinal Centers Tfh (GC-Tfh). ADA-1 expression and enzymatic activity are increased in efficient cTfh2-17/GC-Tfh cells. Exogenous ADA-1 enhances less efficient cTfh1 and pro-follicular Tfh PD-1+ CXCR5+ cells to provide B cell help, while pharmacological inhibition of ADA-1 activity impedes cTfh2-17/GC-Tfh function and diminished antibody response. Mechanistically, ADA-1 controls the Tfh program by influencing IL6/IL-2 production, controlling CD26 extracellular expression and could balance signals through adenosine receptors. Interestingly, dysfunctional Tfh from HIV infected-individual fail to regulate the ADA pathway. Thus, ADA-1 regulates human Tfh and represents a potential target for development of vaccine strategy.
Active learning in materials science with emphasis on adaptive sampling using uncertainties for targeted design
Authors: Lookman Turab , Balachandran Prasanna V. , Xue Dezhen , Yuan Ruihao 
Published: February 2019

AbstractOne of the main challenges in materials discovery is efficiently exploring the vast search space for targeted properties as approaches that rely on trial-and-error are impractical. We review how methods from the information sciences enable us to accelerate the search and discovery of new materials. In particular, active learning allows us to effectively navigate the search space iteratively to identify promising candidates for guiding experiments and computations. The approach relies on the use of uncertainties and making predictions from a surrogate model together with a utility function that prioritizes the decision making process on unexplored data. We discuss several utility functions and demonstrate their use in materials science applications, impacting both experimental and computational research. We summarize by indicating generalizations to multiple properties and multifidelity data, and identify challenges, future directions and opportunities in the emerging field of materials informatics.
Enhancing hydrogen evolution on the basal plane of transition metal dichacolgenide van der Waals heterostructures
Authors: Ling Faling , Kang Wei , Jing Huirong , Zeng Wen , Chen Yankun , Liu Xiaoqing , Zhang Yixin , Qi Lin , Fang Liang , Zhou Miao 
Published: February 2019

AbstractRecent years have seen a surge in the use of low-dimensional transition metal dichacolgenides, such as MoS2, as catalysts for the electrochemical hydrogen evolution reaction. In particular, sulfur vacancies in MoS2 can activate the inert basal plane, but that requires an unrealistically high defect concentration (~9%) to achieve optimal activity. In this work, we demonstrate by first-principles calculations that assembling van der Waals heterostructures can enhance the catalytic activity of MoS2 with low concentrations of sulfur vacancies. We integrate MoS2 with various two-dimensional nanostructures, including graphene, h-BN, phosphorene, transition metal dichacolgenides, MXenes, and their derivatives, aiming to fine-tune the free energy of atomic hydrogen adsorption. Remarkably, an optimal free energy can be achieved for a low sulfur vacancy concentration of ~2.5% in the MoS2/MXene-OH heterostructure, as well as high porosity and tunability. These results demonstrate the potential of combining two-dimensional van der Waals assembly with defect engineering for efficient hydrogen production.
Low Frequency ALK Hotspots Mutations In Neuroblastoma Tumours Detected By Ultra-deep Sequencing: Implications For ALK Inhibitor Treatment
Authors: Javanmardi Niloufar , Fransson Susanne , Djos Anna , Sjöberg Rose-Marie , Nilsson Staffan , Truvé Katarina , Kogner Per , Martinsson Tommy 
Published: February 2019

AbstractThe ALK tyrosine kinase receptor is oncogenically activated in neuroblastoma. Whereas numerous ALK fusion genes have been reported in different malignancies, in neuroblastoma ALK is mainly activated through point mutations. Three hotspot residues (F1174, F1245, and R1275) account for 85% of mutant ALK seen in neuroblastoma. In a cohort of 105 Swedish neuroblastoma cases of all stages, these hotspot regions were re-sequenced (>5000X). ALK mutations were detected in 16 of 105 patients (range of variant allele fraction: 2.7–60%). Mutations at the F1174 and F1245 hotspot were observed in eleven and three cases respectively. ALK mutations were also detected at the I1171 and L1240 codons in one tumor each. No mutations were detected at R1275. Sanger sequencing could confirm ALK status for all mutated samples with variant allele fraction above 15%. Four of the samples with subclonal ALK mutation fraction below this would have gone undetected relying on Sanger sequencing only. No distinct mutation spectrum in relation to neuroblastoma tumours genomic subtypes could be detected although there was a paucity of ALK mutations among 11q-deleted tumors. As ALK mutations status opens up an excellent opportunity for application of small molecule inhibitors targeting ALK, early and sensitive detection of ALK alterations is clinically important considering its potential role in tumour progression.
Defects, Lithium Mobility and Tetravalent Dopants in the Li3NbO4 Cathode Material
Authors: Kuganathan Navaratnarajah , Kordatos Apostolos , Kelaidis Nikolaos , Chroneos Alexander 
Published: February 2019

AbstractThe defect processes of oxides such as self-diffusion impact their performance in electrochemical devices such as batteries and solid oxide fuel cells. The performance of lithium ion batteries can be improved by increasing the Li-ion diffusion. In that respect Li3NbO4 is identified as a positive electrode material for rechargeable lithium ion batteries. Here, we employ static atomistic scale simulations to examine the defect properties, doping behaviour and lithium ion migration paths in Li3NbO4. The present calculations show a correct reproduction of experimentally observed crystal structure of Li3NbO4. The Li-Nb anti-site defect is found to be the dominant intrinsic defect process suggesting that a small concentration of Li on Nb sites and Nb on Li sites is present. Vacancy assisted long range lithium diffusion paths were examined and our calculations reveal that the lowest activation energy (1.13 eV) migration path is two dimensional forming a zig-zag shape. Subvalent doping by Ge on the Nb site is thermodynamically favourable process and a potential strategy to incorporate extra Li in the form of Li interstitial in Li3NbO4. The results presented herein can motivate further experimental work for the development of Li3NbO4 based batteries.
Molecular modelling evaluation of exon 18 His845_Asn848delinsPro PDGFRα mutation in a metastatic GIST patient responding to imatinib
Authors: Nannini Margherita , Tarantino Giuseppe , Indio Valentina , Ravegnini Gloria , Astolfi Annalisa , Urbini Milena , De Leo Antonio , Santini Donatella , Ceccarelli Claudio , Gruppioni Elisa , Altimari Annalisa , Castellucci Paolo , Fanti Stefano , Di Scioscio Valerio , Saponara Maristella , Gatto Lidia , Pession Andrea , Martelli Pier Luigi , Casadio Rita , Pantaleo Maria Abbondanza 
Published: February 2019

AbstractPlatelet-Derived Growth Factor Receptor Alpha (PDGFRA) mutations occur in approximately 5–7% of gastrointestinal stromal tumours (GIST). Over half of all PDGFRA mutations are represented by the substitution at position 842 in the A-loop of an aspartic acid (D) with a valine (V), recognized as D842V, conferring primary resistance to imatinib in vitro and in clinical observations due to the conformation of the kinase domain, which negatively affects imatinib binding. The lack of interaction between imatinib and the D842V PDGFRA mutated model has been established and widely confirmed in vivo. However, for the other PDGFRA mutations, the correlation between pre-clinical and clinical data is still unclear. An in silico evaluation of the p.His845_Asn848delinsPro mutation involving exon 18 of PDGFRA in a metastatic GIST patient responding to first-line imatinib has been provided. Docking analyses were performed, and the ligand-receptor interactions were evaluated with the jCE algorithm for structural alignment. The docking simulation and structural superimposition analysis show that PDGFRA p.His845_Asn848delinsPro stabilizes the imatinib binding site with the residues that are conserved in KIT. The in vivo evidence that PDGFRA p.His845_Asn848delinsPro is sensitive to imatinib was confirmed by the molecular modelling, which may represent a reliable tool for the prediction of clinical outcomes and treatment selection in GIST, especially for rare mutations.
Lambda bacteriophage nanoparticles displaying GP2, a HER2/neu derived peptide, induce prophylactic and therapeutic activities against TUBO tumor model in mice
Authors: Razazan Atefeh , Nicastro Jessica , Slavcev Roderick , Barati Nastaran , Arab Atefeh , Mosaffa Fatemeh , Jaafari Mahmoud Reza , Behravan Javad 
Published: February 2019

AbstractGenerating a protective and long-lasting immune response is the primary goal in the expanding field of immunotherapeutic research. In current study we designed an immunogenic bacteriophage- based vaccine to induce a cytotoxic T lymphocyte activity against a mice tumor model over-expressing HER2/neu. Bacteriophage λ displaying a HER2/neu derived peptide GP2 was constructed and used as an anti-cancer vaccine in a BALB/c mouse xenograft tumor model. The results of our study indicated that phage nanoparticles displaying GP2 as a fused peptide to the gpD phage capsid protein induced a robust CTL response. Furthermore, the chimeric phage nanoparticles protected mice against HER2/neu-positive tumor challenge in both prophylactic and therapeutic settings. In conclusion, we propose that λ phage nanoparticles decorated with GP2 peptide merit further investigation for the development of peptide-based vaccines against HER2/neu overexpressing tumors.
The effect of Robertsonian translocations on the intranuclear positioning of NORs (nucleolar organizing regions) in human sperm cells
Authors: Wiland Ewa , Olszewska Marta , Huleyuk Nataliya , Chernykh Vyacheslav B. , Kurpisz Maciej 
Published: February 2019

AbstractOnly a few studies have described sperm chromosome intranuclear positioning changes in men with reproductive failure and an incorrect somatic karyotype. We studied the influence of Robertsonian translocations on the acrocentric chromosome positioning in human sperm cells. The basis of the analysis was the localization of NORs (nucleolar organizing regions) in sperm nuclei from three Robertsonian translocation carriers, namely, rob(13;22), rob(13;15) and rob(13;14), with a known meiotic segregation pattern. All three carriers presented with a similar percentage of genetically normal sperm cells (i.e., approximately 40%). To visualize NORs, we performed 2D-FISH with directly labelled probes. We used the linear and radial topologies of the nucleus to analyse the NORs distribution. We found an affected positioning of NORs in each case of the Robertsonian translocations. Moreover, the NORs tended to group, most often in two clusters. Both in Robertsonian carriers and control sperm cells, NORs mostly colocalized in the medial areas of the nuclei. In the case of the Roberstonian carriers, NORs were mostly concentrated in the peripheral part of the medial area, in contrast to control sperm cells in which the distribution was more dispersed towards the internal area.
Extracellular and intracellular small-molecule galectin-3 inhibitors
Authors: Stegmayr John , Zetterberg Fredrik , Carlsson Michael C. , Huang Xiaoli , Sharma Gunjan , Kahl-Knutson Barbro , Schambye Hans , Nilsson Ulf J. , Oredsson Stina , Leffler Hakon 
Published: February 2019

AbstractGalectin-3 is a carbohydrate binding protein which has important roles in cancer and immunity. Potent galectin-3 inhibitors have been synthesized, for experimental purposes and potential clinical use. As galectin-3 is implicated in both intra- and extracellular activities, permeability of galectin-3 inhibitors is an important parameter determining biological effects. We compared the cellular uptake of galectin-3 inhibitors and their potency in the intracellular or extracellular space. The inhibitors differed in their polar surface area (PSA), but had similar affinities for galectin-3. Using a well-established permeability assay, we confirmed that the uptake was significantly higher for the inhibitor with the lowest PSA, as expected. To analyze intracellular activity of the inhibitors, we developed a novel assay based on galectin-3 accumulation around damaged intracellular vesicles. The results show striking differences between the inhibitors intracellular potency, correlating with their PSAs. To test extracellular activity of the inhibitors, we analyzed their potency to block binding of galectin-3 to cell surfaces. All inhibitors were equally able to block galectin-3 binding to cells and this was proportional to their affinity for galectin-3. These inhibitors may serve as useful tools in exploring biological roles of galectin-3 and may further our understanding of intracellular versus extracellular roles of galectin-3.
Long-term effects of different planting patterns on greenhouse soil micromorphological features in the North China Plain
Authors: Liu Zhe , Han Jichang , Sun Zenghui , Chen Tianqing , Hou Yin , Lei Na , Dong Qiguang , He Jing , Lu Yizhong 
Published: February 2019

AbstractSoil structure represents a basis for soil water retention and fertiliser availability. Here, we performed a micromorphological analysis of thin soil sections to evaluate the effects of 10 years of organic planting (OPP), pollution-free planting (PFP), and conventional planting (CPP) on greenhouse soil structure in the North China Plain. We also analysed soil bulk density, soil organic matter (SOM), and wet aggregate stability. The CPP soil microstructure included weakly separated angular block or plate forms and weak development of soil pores (fissured or simply accumulated pores) with the highest bulk density (1.33 g cm−3) and lowest SOM (26.76 g kg−1). Unlike CPP, the OPP soil microstructure was characterised by highly separated granular and aggregated structures and an abundance of plant and animal remains. OPP was associated with the highest total porosity (55.4%), lowest bulk density (1.17 g cm−3), and highest SOM (54.81 g kg−1) in the soil surface layer. OPP also improved the ventilation pore content (proportion of pores >0.1 mm, 44.09%). OPP aggregates showed different hierarchies of crumb microstructure and higher mean weight diameter and geometric mean diameter values than did CPP. These results confirm the benefits of long-term OPP for soil structure and quality in the greenhouse.
Effect of iron overload from multi walled carbon nanotubes on neutrophil-like differentiated HL-60 cells
Authors: Tabei Yosuke , Fukui Hiroko , Nishioka Ayako , Hagiwara Yuji , Sato Kei , Yoneda Tadashi , Koyama Tamami , Horie Masanori 
Published: February 2019

AbstractMulti walled carbon nanotubes (MWCNTs) are one of the most intensively explored nanomaterials because of their unique physical and chemical properties. Due to the widespread use of MWCNTs, it is important to investigate their effects on human health. The precise mechanism of MWCNT toxicity has not been fully elucidated. The present study was designed to examine the mechanisms of MWCNT toxicity toward human promyelocytic leukemia HL-60 cells. First, we found that MWCNTs decreased the viability of neutrophil-like differentiated HL-60 cells but not undifferentiated HL-60 cells. Because neutrophil-like differentiated HL-60 cells exhibit enhanced phagocytic activity, the cytotoxicity of MWCNTs is dependent on the intracellularly localized MWCNTs. Next, we revealed that the cytotoxicity of MWCNTs is correlated with the intracellular accumulation of iron that is released from the engulfed MWCNTs in an acidic lysosomal environment. The intracellular accumulation of iron was repressed by treatment with cytochalasin D, a phagocytosis inhibitor. In addition, our results indicated that iron overload enhanced the release of interleukin-8 (IL-8), a chemokine that activates neutrophils, and subsequently elevated intracellular calcium concentration ([Ca2+]i). Finally, we found that the sustained [Ca2+]ielevation resulted in the loss of mitochondrial membrane potential and the increase of caspase-3 activity, thereby inducing apoptotic cell death. These findings suggest that the iron overload caused by engulfed MWCNTs results in the increase of IL-8 production and the elevation of [Ca2+]i, thereby activating the mitochondria-mediated apoptotic pathway.
Aurora A controls CD8+ T cell cytotoxic activity and antiviral response
Authors: Bustos-Morán Eugenio , Blas-Rus Noelia , Alcaraz-Serna Ana , Iborra Salvador , González-Martínez José , Malumbres Marcos , Sánchez-Madrid Francisco 
Published: February 2019

AbstractAurora A is a serine/threonine kinase whose role in cell cycle progression and tumour generation has been widely studied. Recent work has revealed an unexpected function for Aurora A during CD4+ T cell activation and, also, in graft versus host disease development. However, it remains unknown whether Aurora A is involved in CD8+ T cell effector function and in cytotoxic T lymphocyte-mediated antiviral response. Here, we show that Aurora A chemical inhibition leads to an impairment of both the peptide-specific cytotoxicity and the degranulation activity of CD8+ T cells. This finding was similarly proven for both mice and human CD8+ CTL activity. As a result of Aurora A blockade, we detected a reduction in the expression induced by T cell activation of genes classically related to the effector function of cytotoxic T lymphocytes such as granzyme B or perforin1. Finally, we have found that Aurora A is necessary for CD8+ T cell-mediated antiviral response, in an in vivo model of vaccinia virus infection. Thus, we can conclude that Aurora A activity is, indeed, needed for the proper effector function of cytotoxic T lymphocytes and for their activity against viral threats.
Delayed Captopril Administration Mitigates Hematopoietic Injury in a Murine Model of Total Body Irradiation
Authors: McCart Elizabeth A. , Lee Young H. , Jha Jyoti , Mungunsukh Ognoon , Rittase W. Bradley , Summers Thomas A. , Muir Jeannie , Day Regina M. 
Published: February 2019

AbstractThe increasing potential for accidental radiation exposure from either nuclear accidents or terrorist activities has escalated the need for radiation countermeasure development. We previously showed that a 30-day course of high-dose captopril, an ACE inhibitor, initiated 1–4 h after total body irradiation (TBI), improved Hematopoietic Acute Radiation Syndrome (H-ARS) and increased survival in mice. However, because of the time likely required for the deployment of a stockpiled radiation countermeasure to a radiation mass casualty site, there is a need for therapies that can be administered 24–48 hours after initial exposure. Using C57BL/6 mice exposed to an LD50-80/30 of 60Co TBI (7.75–7.9 Gy, 0.615 Gy/min), we show that low-dose captopril administration, initiated as late as 48 h post-TBI and continued for 14 days, significantly enhanced overall survival similarly to high-dose, rapid administration. Captopril treatment did not affect radiation-induced cell cycle arrest genes or the immediate loss of hematopoietic precursors. Reduced mortality was associated with the recovery of bone marrow cellularity and mature blood cell recovery at 21–30 days post-irradiation. Captopril reduced radiation-induced cytokines EPO, G-CSF, and SAA in the plasma. Finally, delayed captopril administration mitigated brain micro-hemorrhage at 21 days post-irradiation. These data indicate that low dose captopril administered as late as 48 h post-TBI for only two weeks improves survival that is associated with hematopoietic recovery and reduced inflammatory response. These data suggest that captopril may be an ideal countermeasure to mitigate H-ARS following accidental radiation exposure.