bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted mutagenesis in the medicinal plant Salvia miltiorrhiza
Authors: Li Bin , Cui Guanghong , Shen Guoan , Zhan Zhilai , Huang Luqi , Chen Jiachun , Qi Xiaoquan 
Published: March 2017

AbstractCRISPR/Cas9 is a powerful genome editing tool that has been extensively used in model plants and crops, such as Arabidopsis thaliana, rice, wheat, and soybean. Here, we report the use of CRISPR/Cas9 to precisely knock out the committed diterpene synthase gene (SmCPS1) involved in tanshinone biosynthesis in Salvia miltiorrhiza, a traditional Chinese medicinal herb with significant pharmacological activities, such as vasorelaxation, protection against ischemia-reperfusion injury, and antiarrhythmic effects. Three homozygous and eight chimeric mutants were obtained from 26 independent transgenic hairy root lines by Agrobacterium rhizogenes-mediated transformation. The metabolomic analysis based on LC-qTOF-MS and Q-TRAP-LC-MS/MS revealed that tanshinones, especially cryptotanshinone, tanshinone IIA and tanshinone I, are completely missing in homozygous mutants, without influencing other phenolic acid metabolites. By contrast, tanshinones are decreased but still detectable in chimeric mutants, which is similar to a previously-reported an RNAi study of SmCPS1. These results demonstrate that Agrobacterium rhizogenes- mediated transformation using CRISPR/Cas9 is a simple and efficient genome editing tool in S. miltiorrhiza, thus paving the way for large-scale genome editing in S. miltiorrhiza, which is important for pathway elucidation of secondary metabolites, quality improvement, and yield increases for this valuable traditional Chinese medicinal herb.
Genetic variation architecture of mitochondrial genome reveals the differentiation in Korean landrace and weedy rice
Authors: Tong Wei , He Qiang , Park Yong-Jin 
Published: March 2017

AbstractMitochondrial genome variations have been detected despite the overall conservation of this gene content, which has been valuable for plant population genetics and evolutionary studies. Here, we describe mitochondrial variation architecture and our performance of a phylogenetic dissection of Korean landrace and weedy rice. A total of 4,717 variations across the mitochondrial genome were identified adjunct with 10 wild rice. Genetic diversity assessment revealed that wild rice has higher nucleotide diversity than landrace and/or weedy, and landrace rice has higher diversity than weedy rice. Genetic distance was suggestive of a high level of breeding between landrace and weedy rice, and the landrace showing a closer association with wild rice than weedy rice. Population structure and principal component analyses showed no obvious difference in the genetic backgrounds of landrace and weedy rice in mitochondrial genome level. Phylogenetic, population split, and haplotype network evaluations were suggestive of independent origins of the indica and japonica varieties. The origin of weedy rice is supposed to be more likely from cultivated rice rather than from wild rice in mitochondrial genome level.
The role of indoleamine 2,3-dioxygenase-aryl hydrocarbon receptor pathway in the TLR4-induced tolerogenic phenotype in human DCs
Authors: Salazar Fabián , Awuah Dennis , Negm Ola H. , Shakib Farouk , Ghaemmaghami Amir M. 
Published: March 2017

AbstractA controlled inflammatory response is required for protection against infection, but persistent inflammation causes tissue damage. Dendritic cells (DCs) have a unique capacity to promote both inflammatory and anti-inflammatory processes. One key mechanism involved in DC-mediated immunosuppression is the expression of tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO). IDO has been implicated in diverse processes in health and disease but its role in endotoxin tolerance in human DCs is still controversial. Here we investigated the role of IDO in shaping DCs phenotype and function under endotoxin tolerance conditions. Our data show that TLR4 ligation in LPS-primed DCs, induced higher levels of both IDO isoforms together with the transcription factor aryl-hydrocarbon receptor (AhR), compared to unprimed controls. Additionally, LPS conditioning induced an anti-inflammatory phenotype in DCs - with an increase in IL-10 and higher expression of programmed death ligand (PD-L)1 and PD-L2 - which were partially dependent on IDO. Furthermore, we demonstrated that the AhR-IDO pathway was responsible for the preferential activation of non-canonical NF-κB pathway in LPS-conditioned DCs. These data provide new insight into the mechanisms of the TLR4-induced tolerogenic phenotype in human DCs, which can help the better understanding of processes involved in induction and resolution of chronic inflammation and tolerance.
Word meaning acquisition is reflected in brain potentials of isolated words
Authors: Kuipers Jan Rouke , Uminski Anastasia , Green Zoe , Hughes David , Aglietti Tommaso 
Published: March 2017

AbstractLearning a new concept and corresponding word typically involves repeated exposure to the word in the same or a similar context until the link crystallizes in long term memory. Although electrophysiological indices of the result of learning are well documented, there is currently no measure of the process of conceptually-mediated learning itself. Here, we recorded event-related brain potentials from participants who read unfamiliar words presented in isolation followed by a definition that either explained the meaning of the word or was a true, but uninformative statement. Self-reported word knowledge ratings increased for those words that were followed by meaningful definitions and were correlated with a decrease in ERP amplitude of a late frontal negativity (LFN) elicited by the isolated word. Importantly, the rate of LFN amplitude change predicted post-hoc learning outcome measures. Therefore, the LFN is real-time measure that is not under conscious control and which reflects conceptually-mediated learning. We propose that the LFN provides for the first time the opportunity to assess learning during study.
The Expanding Family of Natural Anion Channelrhodopsins Reveals Large Variations in Kinetics, Conductance, and Spectral Sensitivity
Authors: Govorunova Elena G. , Sineshchekov Oleg A. , Rodarte Elsa M. , Janz Roger , Morelle Olivier , Melkonian Michael , Wong Gane K.-S. , Spudich John L. 
Published: March 2017

AbstractNatural anion channelrhodopsins (ACRs) discovered in the cryptophyte alga Guillardia theta generate large hyperpolarizing currents at membrane potentials above the Nernst equilibrium potential for Cl− and thus can be used as efficient inhibitory tools for optogenetics. We have identified and characterized new ACR homologs in different cryptophyte species, showing that all of them are anion-selective, and thus expanded this protein family to 20 functionally confirmed members. Sequence comparison of natural ACRs and engineered Cl−-conducting mutants of cation channelrhodopsins (CCRs) showed radical differences in their anion selectivity filters. In particular, the Glu90 residue in channelrhodopsin 2, which needed to be mutated to a neutral or alkaline residue to confer anion selectivity to CCRs, is nevertheless conserved in all of the ACRs identified. The new ACRs showed a large variation of the amplitude, kinetics, and spectral sensitivity of their photocurrents. A notable variant, designated “ZipACR”, is particularly promising for inhibitory optogenetics because of its combination of larger current amplitudes than those of previously reported ACRs and an unprecedentedly fast conductance cycle (current half-decay time 2–4 ms depending on voltage). ZipACR expressed in cultured mouse hippocampal neurons enabled precise photoinhibition of individual spikes in trains of up to 50 Hz frequency.
V2O5 encapsulated MWCNTs in 2D surface architecture: Complete solid-state bendable highly stabilized energy efficient supercapacitor device
Authors: Pandit Bidhan , Dubal Deepak P. , Gómez-Romero Pedro , Kale Bharat B. , Sankapal Babasaheb R. 
Published: March 2017

AbstractA simple and scalable approach has been reported for V2O5 encapsulation over interconnected multi-walled carbon nanotubes (MWCNTs) network using chemical bath deposition method. Chemically synthesized V2O5/MWCNTs electrode exhibited excellent charge-discharge capability with extraordinary cycling retention of 93% over 4000 cycles in liquid-electrolyte. Electrochemical investigations have been performed to evaluate the origin of capacitive behavior from dual contribution of surface-controlled and diffusion-controlled charge components. Furthermore, a complete flexible solid-state, flexible symmetric supercapacitor (FSS-SSC) device was assembled with V2O5/MWCNTs electrodes which yield remarkable values of specific power and energy densities along with enhanced cyclic stability over liquid configuration. As a practical demonstration, the constructed device was used to lit the ‘VNIT’ acronym assembled using 21 LED’s.
Hydraulic forces contribute to left ventricular diastolic filling
Authors: Maksuti Elira , Carlsson Marcus , Arheden Håkan , Kovács Sándor J. , Broomé Michael , Ugander Martin 
Published: March 2017

AbstractMyocardial active relaxation and restoring forces are known determinants of left ventricular (LV) diastolic function. We hypothesize the existence of an additional mechanism involved in LV filling, namely, a hydraulic force contributing to the longitudinal motion of the atrioventricular (AV) plane. A prerequisite for the presence of a net hydraulic force during diastole is that the atrial short-axis area (ASA) is smaller than the ventricular short-axis area (VSA). We aimed (a) to illustrate this mechanism in an analogous physical model, (b) to measure the ASA and VSA throughout the cardiac cycle in healthy volunteers using cardiovascular magnetic resonance imaging, and (c) to calculate the magnitude of the hydraulic force. The physical model illustrated that the anatomical difference between ASA and VSA provides the basis for generating a hydraulic force during diastole. In volunteers, VSA was greater than ASA during 75–100% of diastole. The hydraulic force was estimated to be 10–60% of the peak driving force of LV filling (1–3 N vs 5–10 N). Hydraulic forces are a consequence of left heart anatomy and aid LV diastolic filling. These findings suggest that the relationship between ASA and VSA, and the associated hydraulic force, should be considered when characterizing diastolic function and dysfunction.
Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro
Authors: Tamaddon M. , Burrows M. , Ferreira S. A. , Dazzi F. , Apperley J. F. , Bradshaw A. , Brand D. D. , Czernuszka J. , Gentleman E. 
Published: March 2017

AbstractOsteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS – which was released from scaffolds quickly – significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.
Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis
Authors: Medina-Rodríguez Eva María , Bribián Ana , Boyd Amanda , Palomo Valle , Pastor Jesús , Lagares Alfonso , Gil Carmen , Martínez Ana , Williams Anna , de Castro Fernando 
Published: March 2017

AbstractMultiple Sclerosis (MS) is a neurodegenerative disease where immune-driven demyelination occurs with inefficient remyelination, but therapies are limited, especially those to enhance repair. Here, we show that the dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, VP3.15, a heterocyclic small molecule with good pharmacokinetic properties and safety profile, improves in vivo remyelination in mouse and increases both adult mouse and adult human oligodendrocyte progenitor cell (OPC) differentiation, in addition to its immune regulatory action. The dual inhibition is synergistic, as increasing intracellular levels of cAMP by cyclic nucleotide PDE inhibition both suppresses the immune response and increases remyelination, and in addition, inhibition of GSK3 limits experimental autoimmune encephalomyelitis in mice. This combination of an advantageous effect on the immune response and an enhancement of repair, plus demonstration of its activity on adult human OPCs, leads us to propose dual PDE7-GSK3 inhibition, and specifically VP3.15, as a neuroprotective and neuroreparative disease-modifying treatment for MS.
Cryptic diversity in Tranzscheliella spp. (Ustilaginales) is driven by host switches
Authors: Li Ying-Ming , Shivas Roger G. , Cai Lei 
Published: March 2017

AbstractSpecies of Tranzscheliella have been reported as pathogens of more than 30 genera of grasses (Poaceae). In this study, a combined morphological and molecular phylogenetic approach was used to examine 33 specimens provisionally identified as belonging to the T. hypodytes species complex. The phylogenetic analysis resolved several well-supported clades that corresponded to known and novel species of Tranzscheliella. Four new species are described and illustrated. In addition, a new combination in Tranzscheliella is proposed for Sorosporium reverdattoanum. Cophylogenetic analyses assessed by distance-based and event-cost based methods, indicated host switches are likely the prominent force driving speciation in Tranzscheliella.
PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology
Authors: Sweeney Amanda M. , Fleming Kelsey E. , McCauley John P. , Rodriguez Marvin F. , Martin Elliot T. , Sousa Alioscka A. , Leapman Richard D. , Scimemi Annalisa 
Published: March 2017

AbstractThe G-protein coupled, protease-activated receptor 1 (PAR1) is a membrane protein expressed in astrocytes. Fine astrocytic processes are in tight contact with neurons and blood vessels and shape excitatory synaptic transmission due to their abundant expression of glutamate transporters. PAR1 is proteolytically-activated by bloodstream serine proteases also involved in the formation of blood clots. PAR1 activation has been suggested to play a key role in pathological states like thrombosis, hemostasis and inflammation. What remains unclear is whether PAR1 activation also regulates glutamate uptake in astrocytes and how this shapes excitatory synaptic transmission among neurons. Here we show that, in the mouse hippocampus, PAR1 activation induces a rapid structural re-organization of the neuropil surrounding glutamatergic synapses, which is associated with faster clearance of synaptically-released glutamate from the extracellular space. This effect can be recapitulated using realistic 3D Monte Carlo reaction-diffusion simulations, based on axial scanning transmission electron microscopy (STEM) tomography reconstructions of excitatory synapses. The faster glutamate clearance induced by PAR1 activation leads to short- and long-term changes in excitatory synaptic transmission. Together, these findings identify PAR1 as an important regulator of glutamatergic signaling in the hippocampus and a possible target molecule to limit brain damage during hemorrhagic stroke.
Multimodal discrimination of immune cells using a combination of Raman spectroscopy and digital holographic microscopy
Authors: McReynolds Naomi , Cooke Fiona G. M. , Chen Mingzhou , Powis Simon J. , Dholakia Kishan 
Published: March 2017

AbstractThe ability to identify and characterise individual cells of the immune system under label-free conditions would be a significant advantage in biomedical and clinical studies where untouched and unmodified cells are required. We present a multi-modal system capable of simultaneously acquiring both single point Raman spectra and digital holographic images of single cells. We use this combined approach to identify and discriminate between immune cell populations CD4+ T cells, B cells and monocytes. We investigate several approaches to interpret the phase images including signal intensity histograms and texture analysis. Both modalities are independently able to discriminate between cell subsets and dual-modality may therefore be used a means for validation. We demonstrate here sensitivities achieved in the range of 86.8% to 100%, and specificities in the range of 85.4% to 100%. Additionally each modality provides information not available from the other providing both a molecular and a morphological signature of each cell.
Multi-mode of Four and Six Wave Parametric Amplified Process
Authors: Zhu Dayu , Yang Yiheng , Zhang Da , Liu Ruizhou , Ma Danmeng , Li Changbiao , Zhang Yanpeng 
Published: March 2017

AbstractMultiple quantum modes in correlated fields are essential for future quantum information processing and quantum computing. Here we report the generation of multi-mode phenomenon through parametric amplified four- and six-wave mixing processes in a rubidium atomic ensemble. The multi-mode properties in both frequency and spatial domains are studied. On one hand, the multi-mode behavior is dominantly controlled by the intensity of external dressing effect, or nonlinear phase shift through internal dressing effect, in frequency domain; on the other hand, the multi-mode behavior is visually demonstrated from the images of the biphoton fields directly, in spatial domain. Besides, the correlation of the two output fields is also demonstrated in both domains. Our approach supports efficient applications for scalable quantum correlated imaging.
McMYB12 Transcription Factors Co-regulate Proanthocyanidin and Anthocyanin Biosynthesis in Malus Crabapple
Authors: Tian Ji , Zhang Jie , Han Zhen-yun , Song Ting-ting , Li Jin-yan , Wang Ya-ru , Yao Yun-cong 
Published: March 2017

AbstractThe flavonoid compounds, proanthocyanidins (PAs), protect plants from biotic stresses, contribute to the taste of many fruits, and are beneficial to human health in the form of dietary antioxidants. In this study, we functionally characterized two Malus crabapple R2R3-MYB transcription factors, McMYB12a and McMYB12b, which co-regulate PAs and anthocyanin biosynthesis. McMYB12a was shown to be mainly responsible for upregulating the expression of anthocyanin biosynthetic genes by binding to their promoters, but to be only partially responsible for regulating PAs biosynthetic genes. In contrast, McMYB12b showed preferential binding to the promoters of PAs biosynthetic genes. Overexpression of McMYB12a and McMYB12b in tobacco (Nicotiana tabacum) altered the expression of flavonoid biosynthetic genes and promoted the accumulation of PAs and anthocyanins in tobacco petals. Conversely, transient silencing their expression in crabapple plants, using a conserved gene region, resulted in reduced PAs and anthocyanin production a green leaf phenotype. Meanwhile, transient overexpression of the two genes and silenced McMYB12s in apple (Malus domestica) fruit had a similar effect as overexpression in tobacco and silenced in crabapple. This study reveals a new mechanism for the coordinated regulation of PAs and anthocyanin accumulation in crabapple leaves, which depends on an auto-regulatory balance involving McMYB12a and McMYB12b expression.
bta-miR-23a involves in adipogenesis of progenitor cells derived from fetal bovine skeletal muscle
Authors: Guan Long , Hu Xin , Liu Li , Xing Yishen , Zhou Zhengkui , Liang Xingwei , Yang Qiyuan , Jin Shengyun , Bao Jinshan , Gao Huijiang , Du Min , Li Junya , Zhang Lupei 
Published: March 2017

AbstractIntramuscular fat deposition or marbling is essential for high quality beef. The molecular mechanism of adipogenesis in skeletal muscle remains largely unknown. In this study, we isolated Platelet-derived growth factor receptor α (PDGFRα) positive progenitor cells from fetal bovine skeletal muscle and induced into adipocytes. Using miRNAome sequencing, we revealed that bta-miR-23a was an adipogenic miRNA mediating bovine adipogenesis in skeletal muscle. The expression of bta-miR-23a was down-regulated during differentiation of PDGFRα+ progenitor cells. Forced expression of bta-miR-23a mimics reduced lipid accumulation and inhibited the key adipogenic transcription factor peroxisome proliferative activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα). Whereas down-regulation of bta-miR-23a by its inhibitors increased lipid accumulation and expression of C/EBPα, PPARγ and fatty acid-binding protein 4 (FABP4). Target prediction analysis revealed that ZNF423 was a potential target of bta-miR-23a. Dual-luciferase reporter assay revealed that bta-miR-23a directly targeted the 3′-UTR of ZNF423. Together, our data showed that bta-miR-23a orchestrates early intramuscular adipogeneic commitment as an anti-adipogenic regulator which acts by targeting ZNF423.
The genome of Leishmania adleri from a mammalian host highlights chromosome fission in Sauroleishmania
Authors: Coughlan Simone , Mulhair Peter , Sanders Mandy , Schonian Gabriele , Cotton James A. , Downing Tim 
Published: March 2017

AbstractControl of pathogens arising from humans, livestock and wild animals can be enhanced by genome-based investigation. Phylogenetically classifying and optimal construction of these genomes using short sequence reads are key to this process. We examined the mammal-infecting unicellular parasite Leishmania adleri belonging to the lizard-infecting Sauroleishmania subgenus. L. adleri has been associated with cutaneous disease in humans, but can be asymptomatic in wild animals. We sequenced, assembled and investigated the L. adleri genome isolated from an asymptomatic Ethiopian rodent (MARV/ET/75/HO174) and verified it as L. adleri by comparison with other Sauroleishmania species. Chromosome-level scaffolding was achieved by combining reference-guided with de novo assembly followed by extensive improvement steps to produce a final draft genome with contiguity comparable with other references. L. tarentolae and L. major genome annotation was transferred and these gene models were manually verified and improved. This first high-quality draft Leishmania adleri reference genome is also the first Sauroleishmania genome from a non-reptilian host. Comparison of the L. adleri HO174 genome with those of L. tarentolae Parrot-TarII and lizard-infecting L. adleri RLAT/KE/1957/SKINK-7 showed extensive gene amplifications, pervasive aneuploidy, and fission of chromosomes 30 and 36. There was little genetic differentiation between L. adleri extracted from mammals and reptiles, highlighting challenges for leishmaniasis surveillance.