bluuebunny/crossref_metadata_2025_split huggingface dataset:
The POU4F2/Brn-3b transcription factor is required for the hypertrophic response to angiotensin II in the heart
Authors: Mele Laura , Maskell Lauren J. , Stuckey Daniel J. , Clark James E. , Heads Richard J. , Budhram-Mahadeo Vishwanie S. 
Published: August 2019

AbstractAdult hearts respond to increased workload such as prolonged stress or injury, by undergoing hypertrophic growth. During this process, the early adaptive responses are important for maintaining cardiac output whereas at later stages, pathological responses such as cardiomyocyte apoptosis and fibrosis cause adverse remodelling, that can progress to heart failure. Yet the factors that control transition from adaptive responses to pathological remodelling in the heart are not well understood. Here we describe the POU4F2/Brn-3b transcription factor (TF) as a novel regulator of adaptive hypertrophic responses in adult hearts since Brn-3b mRNA and protein are increased in angiotensin-II (AngII) treated mouse hearts with concomitant hypertrophic changes [increased heart weight:body weight (HW:BW) ratio]. These effects occur specifically in cardiomyocytes because Brn-3b expression is increased in AngII-treated primary cultures of neonatal rat ventricular myocytes (NRVM) or foetal heart-derived H9c2 cells, which undergo characteristic sarcomeric re-organisation seen in hypertrophic myocytes and express hypertrophic markers, ANP/βMHC. The Brn-3b promoter is activated by known hypertrophic signalling pathways e.g. p42/p44 mitogen-activated protein kinase (MAPK/ERK1/2) or calcineurin (via NFAT). Brn-3b target genes, e.g. cyclin D1, GLUT4 and Bax, are increased at different stages following AngII treatment, supporting distinct roles in cardiac responses to stress. Furthermore, hearts from male Brn-3b KO mutant mice display contractile dysfunction at baseline but also attenuated hypertrophic responses to AngII treatment. Hearts from AngII-treated male Brn-3b KO mice develop further contractile dysfunction linked to extensive fibrosis/remodelling. Moreover, known Brn-3b target genes, e.g. GLUT4, are reduced in AngII-treated Brn-3b KO hearts, suggesting that Brn-3b and its target genes are important in driving adaptive hypertrophic responses in stressed heart.
PTPσ inhibitors promote hematopoietic stem cell regeneration
Authors: Zhang Yurun , Roos Martina , Himburg Heather , Termini Christina M. , Quarmyne Mamle , Li Michelle , Zhao Liman , Kan Jenny , Fang Tiancheng , Yan Xiao , Pohl Katherine , Diers Emelyne , Jin Gim Hyo , Damoiseaux Robert , Whitelegge Julian , McBride William , Jung Michael E. , Chute John P. 
Published: August 2019

AbstractReceptor type protein tyrosine phosphatase-sigma (PTPσ) is primarily expressed by adult neurons and regulates neural regeneration. We recently discovered that PTPσ is also expressed by hematopoietic stem cells (HSCs). Here, we describe small molecule inhibitors of PTPσ that promote HSC regeneration in vivo. Systemic administration of the PTPσ inhibitor, DJ001, or its analog, to irradiated mice promotes HSC regeneration, accelerates hematologic recovery, and improves survival. Similarly, DJ001 administration accelerates hematologic recovery in mice treated with 5-fluorouracil chemotherapy. DJ001 displays high specificity for PTPσ and antagonizes PTPσ via unique non-competitive, allosteric binding. Mechanistically, DJ001 suppresses radiation-induced HSC apoptosis via activation of the RhoGTPase, RAC1, and induction of BCL-XL. Furthermore, treatment of irradiated human HSCs with DJ001 promotes the regeneration of human HSCs capable of multilineage in vivo repopulation. These studies demonstrate the therapeutic potential of selective, small-molecule PTPσ inhibitors for human hematopoietic regeneration.
The complex of ferric-enterobactin with its transporter from Pseudomonas aeruginosa suggests a two-site model
Authors: Moynié Lucile , Milenkovic Stefan , Mislin Gaëtan L. A. , Gasser Véronique , Malloci Giuliano , Baco Etienne , McCaughan Rory P. , Page Malcolm G. P. , Schalk Isabelle J. , Ceccarelli Matteo , Naismith James H. 
Published: August 2019

AbstractBacteria use small molecules called siderophores to scavenge iron. Siderophore-Fe3+complexes are recognised by outer-membrane transporters and imported into the periplasm in a process dependent on the inner-membrane protein TonB. The siderophore enterobactin is secreted by members of the family Enterobacteriaceae, but many other bacteria includingPseudomonasspecies can use it. Here, we show that thePseudomonastransporter PfeA recognises enterobactin using extracellular loops distant from the pore. The relevance of this site is supported by in vivo and in vitro analyses. We suggest there is a second binding site deeper inside the structure and propose that correlated changes in hydrogen bonds link binding-induced structural re-arrangements to the structural adjustment of the periplasmic TonB-binding motif.
Harmonious genetic combinations rewire regulatory networks and flip gene essentiality
Authors: New Aaron M. , Lehner Ben 
Published: August 2019

AbstractWe lack an understanding of how the full range of genetic variants that occur in individuals can interact. To address this shortcoming, here we combine diverse mutations between genes in a model regulatory network, the galactose (GAL) switch of budding yeast. The effects of thousands of pairs of mutations fall into a limited number of phenotypic classes. While these effects are mostly predictable using simple rules that capture the ‘stereotypical’ genetic interactions of the network, some double mutants have unexpected outcomes including constituting alternative functional switches. Each of these ‘harmonious’ genetic combinations exhibits altered dependency on other regulatory genes. These cases illustrate how both pairwise and higher epistasis determines gene essentiality and how combinations of mutations rewire regulatory networks. Together, our results provide an overview of how broad spectra of mutations interact, how these interactions can be predicted, and how diverse genetic solutions can achieve ‘wild-type’ phenotypic behavior.
Challenging the point neuron dogma: FS basket cells as 2-stage nonlinear integrators
Authors: Tzilivaki Alexandra , Kastellakis George , Poirazi Panayiota 
Published: August 2019

AbstractInterneurons are critical for the proper functioning of neural circuits. While often morphologically complex, their dendrites have been ignored for decades, treating them as linear point neurons. Exciting new findings reveal complex, non-linear dendritic computations that call for a new theory of interneuron arithmetic. Using detailed biophysical models, we predict that dendrites of FS basket cells in both hippocampus and prefrontal cortex come in two flavors: supralinear, supporting local sodium spikes within large-volume branches and sublinear, in small-volume branches. Synaptic activation of varying sets of these dendrites leads to somatic firing variability that cannot be fully explained by the point neuron reduction. Instead, a 2-stage artificial neural network (ANN), with sub- and supralinear hidden nodes, captures most of the variance. Reduced neuronal circuit modeling suggest that this bi-modal, 2-stage integration in FS basket cells confers substantial resource savings in memory encoding as well as the linking of memories across time.
A meta-analysis of genome-wide association studies identifies multiple longevity genes
Authors: Deelen Joris , Evans Daniel S. , Arking Dan E. , Tesi Niccolò , Nygaard Marianne , Liu Xiaomin , Wojczynski Mary K. , Biggs Mary L. , van der Spek Ashley , Atzmon Gil , Ware Erin B. , Sarnowski Chloé , Smith Albert V. , Seppälä Ilkka , Cordell Heather J. , Dose Janina , Amin Najaf , Arnold Alice M. , Ayers Kristin L. , Barzilai Nir , Becker Elizabeth J. , Beekman Marian , Blanché Hélène , Christensen Kaare , Christiansen Lene , Collerton Joanna C. , Cubaynes Sarah , Cummings Steven R. , Davies Karen , Debrabant Birgit , Deleuze Jean-François , Duncan Rachel , Faul Jessica D. , Franceschi Claudio , Galan Pilar , Gudnason Vilmundur , Harris Tamara B. , Huisman Martijn , Hurme Mikko A. , Jagger Carol , Jansen Iris , Jylhä Marja , Kähönen Mika , Karasik David , Kardia Sharon L. R. , Kingston Andrew , Kirkwood Thomas B. L. , Launer Lenore J. , Lehtimäki Terho , Lieb Wolfgang , Lyytikäinen Leo-Pekka , Martin-Ruiz Carmen , Min Junxia , Nebel Almut , Newman Anne B. , Nie Chao , Nohr Ellen A. , Orwoll Eric S. , Perls Thomas T. , Province Michael A. , Psaty Bruce M. , Raitakari Olli T. , Reinders Marcel J. T. , Robine Jean-Marie , Rotter Jerome I. , Sebastiani Paola , Smith Jennifer , Sørensen Thorkild I. A. , Taylor Kent D. , Uitterlinden André G. , van der Flier Wiesje , van der Lee Sven J. , van Duijn Cornelia M. , van Heemst Diana , Vaupel James W. , Weir David , Ye Kenny , Zeng Yi , Zheng Wanlin , Holstege Henne , Kiel Douglas P. , Lunetta Kathryn L. , Slagboom P. Eline , Murabito Joanne M. 
Published: August 2019

AbstractHuman longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
An alternative framework for fluorescence correlation spectroscopy
Authors: Jazani Sina , Sgouralis Ioannis , Shafraz Omer M. , Levitus Marcia , Sivasankar Sanjeevi , Pressé Steve 
Published: August 2019

AbstractFluorescence correlation spectroscopy (FCS), is a widely used tool routinely exploited for in vivo and in vitro applications. While FCS provides estimates of dynamical quantities, such as diffusion coefficients, it demands high signal to noise ratios and long time traces, typically in the minute range. In principle, the same information can be extracted from microseconds to seconds long time traces; however, an appropriate analysis method is missing. To overcome these limitations, we adapt novel tools inspired by Bayesian non-parametrics, which starts from the direct analysis of the observed photon counts. With this approach, we are able to analyze time traces, which are too short to be analyzed by existing methods, including FCS. Our new analysis extends the capability of single molecule fluorescence confocal microscopy approaches to probe processes several orders of magnitude faster and permits a reduction of photo-toxic effects on living samples induced by long periods of light exposure.
A CRISPR-Cas12a-derived biosensing platform for the highly sensitive detection of diverse small molecules
Authors: Liang Mindong , Li Zilong , Wang Weishan , Liu Jiakun , Liu Leshi , Zhu Guoliang , Karthik Loganathan , Wang Man , Wang Ke-Feng , Wang Zhong , Yu Jing , Shuai Yuting , Yu Jiaming , Zhang Lu , Yang Zhiheng , Li Chuan , Zhang Qian , Shi Tong , Zhou Liming , Xie Feng , Dai Huanqin , Liu Xueting , Zhang Jingyu , Liu Guang , Zhuo Ying , Zhang Buchang , Liu Chenli , Li Shanshan , Xia Xuekui , Tong Yaojun , Liu Yanwen , Alterovitz Gil , Tan Gao-Yi , Zhang Li-Xin 
Published: August 2019

AbstractBesides genome editing, CRISPR-Cas12a has recently been used for DNA detection applications with attomolar sensitivity but, to our knowledge, it has not been used for the detection of small molecules. Bacterial allosteric transcription factors (aTFs) have evolved to sense and respond sensitively to a variety of small molecules to benefit bacterial survival. By combining the single-stranded DNA cleavage ability of CRISPR-Cas12a and the competitive binding activities of aTFs for small molecules and double-stranded DNA, here we develop a simple, supersensitive, fast and high-throughput platform for the detection of small molecules, designated CaT-SMelor (CRISPR-Cas12a- and aTF-mediated small molecule detector). CaT-SMelor is successfully evaluated by detecting nanomolar levels of various small molecules, including uric acid and p-hydroxybenzoic acid among their structurally similar analogues. We also demonstrate that our CaT-SMelor directly measured the uric acid concentration in clinical human blood samples, indicating a great potential of CaT-SMelor in the detection of small molecules.
An anaerobic bacterium host system for heterologous expression of natural product biosynthetic gene clusters
Authors: Hao Tingting , Xie Zhoujie , Wang Min , Liu Liwei , Zhang Yuwei , Wang Weicang , Zhang Zhao , Zhao Xuejin , Li Pengwei , Guo Zhengyan , Gao Shushan , Lou Chunbo , Zhang Guodong , Merritt Justin , Horsman Geoff P. , Chen Yihua 
Published: August 2019

AbstractAnaerobic bacteria represent an overlooked rich source of biological and chemical diversity. Due to the challenge of cultivation and genetic intractability, assessing the capability of their biosynthetic gene clusters (BGCs) for secondary metabolite production requires an efficient heterologous expression system. However, this kind of host system is still unavailable. Here, we use the facultative anaerobe Streptococcus mutans UA159 as a heterologous host for the expression of BGCs from anaerobic bacteria. A natural competence based large DNA fragment cloning (NabLC) technique was developed, which can move DNA fragments up to 40-kb directly and integrate a 73.7-kb BGC to the genome of S. mutans UA159 via three rounds of NabLC cloning. Using this system, we identify an anti-infiltration compound, mutanocyclin, from undefined BGCs from human oral bacteria. We anticipate this host system will be useful for heterologous expression of BGCs from anaerobic bacteria.
Linear discriminant analysis based predator-prey analysis of hot electron effects on the X-pinch plasma produced K-shell Aluminum spectra
Authors: Yilmaz Mehmet Fatih , Danisman Yusuf , Larour Jean , Arantchouk Leonid 
Published: August 2019

AbstractIn this study, Linear Discriminant Analysis (LDA) is applied to investigate the electron beam effects on the X-pinch produced K-shell Aluminum plasma. The radiating plasma is produced by the explosion of two 25-μm Al wires on a compact L-C (40 kV, 200 kA and 200 ns) generator, and the time integrated spectra are recorded using de Broglie spectrographs. The ion and electron oscillations of K-shell Al plasma are extracted using LDA of spectral database of non-LTE K-shell Al model. A three dimensional representation of LDA shows that the presence of electron beam exhibits outward spirals of Langmuir turbulence and the center region of the spirals recieves lower electron temperatures of 50–100 eV. These spirals then are modeled by logistic growth of predator-prey model. This modeling suggests that the ions (LD1: most dominant eigenvector of LDA) and electrons (LD2: second most dominant eigenvector of LDA) represent the predators and preys, respectively. Besides, addition of electron beams transforms evanescent oscillations to the standing ones.
An on-board 2G HTS magnets system with cooling-power-free and persistent-current operation for ultrahigh speed superconducting maglevs
Authors: Dong Fangliang , Huang Zhen , Hao Luning , Xu Xiaoyong , Jin Zhijian , Shao Nan 
Published: August 2019

AbstractIntroduction of superconductor to magnetic levitation (maglev) trains greatly enhances the performances compared to those of normal conductor maglevs, e.g. from 430 km/h of the Transrapid (in Shanghai) to 603 km/h of the L0 Series in Japan. However, one of the important constraints on development of superconducting maglevs is limited wireless feeding power for on-board superconducting magnets and cryogenic cooling. In this paper, a persistent-current superconducting magnets system with solid nitrogen (SN2) cooling preservation is proposed for liberation of its demanding on-board power feeding requirement. The magnets are optimally designed with no-insulation technique guaranteeing a safe operation with magnetic field over 0.8 T. Lasting time of persistent current (at 96.5% magnetic field retained) and SN2 cooling preservation (up to 40 K) is all >9 h, covering a maglev traveling distance of >5400 km at average designed speed of >600 km/h. The magnets have anti-vibration ability of 15 g (147 m/s2) up to 350 Hz, which has covered the vibratory motion range in maglevs. This work is intended to provide a reference for superconducting maglev developments.
Nanoemulsions Enhance in vitro Transpapillary Diffusion of Model Fluorescent Dye Nile Red
Authors: Kurtz Samantha L. , Lawson Louise B. 
Published: August 2019

AbstractWhile the feasibility of transpapillary drug delivery has previously been established, localized transport via the mammary ducts may be improved with tailored drug delivery formulations. The objective of this study was to investigate the impact of nanoemulsion encapsulation on transpapillary delivery in vitro. Nanoemulsion formulations composed of isopropyl myristate and Tween 80 encapsulating a fluorescent dye were applied topically on porcine nipples using a Franz diffusion cell. A combination of dye extraction and fluorescence image analysis was used to quantify the total amount of dye retained within the nipple and to characterize the penetration routes. After diffusion for 6 hours, the amount of dye deposited in the nipple was proportional to the formulation’s water concentration. The 90% water formulation deposited significantly more dye via both the stratum corneum and mammary ducts, while the 80% and 70% water formulations moderately increased ductal penetration, but minimally altered stratum corneum penetration as compared to the control solution. Similar trends were found after diffusion for 48 hours; however, the overall impact was diminished, likely due to the nanoemulsion’s topical instability. This study indicates that drug delivery vehicles, nanoemulsions specifically, enhance delivery of encapsulated molecules via the stratum corneum and mammary ducts in a formulation-dependent basis.
An integrated transcriptomic analysis of autism spectrum disorder
Authors: He Yi , Zhou Yuan , Ma Wei , Wang Juan 
Published: August 2019

AbstractAutism spectrum disorder (ASD) is not a single disease but a set of disorders. To find clues of ASD pathogenesis in transcriptomic data, we performed an integrated transcriptomic analysis of ASD. After screening based on several standards in Gene Expression Omnibus (GEO) database, we obtained 11 series of transcriptomic data of different human tissues of ASD patients and healthy controls. Multidimensional scaling analysis revealed that datasets from the same tissue had bigger similarity than from different tissues. Functional enrichment analysis demonstrated that differential expressed genes were significantly enriched in inflammation/immune response, mitochondrion-related function and oxidative phosphorylation. Interestingly, genes enriched in inflammation/immune response were up-regulated in the brain tissues and down-regulated in the blood. In addition, drug prediction provided several compounds which might reverse gene expression profiles of ASD patients. And we also replicated the methods and criteria of transcriptomic analysis with datasets of ASD animal models and healthy controls, the results from animal models consolidated the results of transcriptomic analysis of ASD human tissues. In general, the results of our study may provide researchers a new sight of understanding the etiology of ASD and clinicians the possibilities of developing medical therapies.
Discrete image recovery via stochastic resonance in optically induced photonic lattices
Authors: Zhang Yongbin , Liu Hongjun , Huang Nan , Wang Zhaolu 
Published: August 2019

AbstractWe demonstrate numerically the discrete image recovery via stochastic resonance in optically induced photonic lattices. The underlying signals are regularly reinforced at the expense of scattering noise with the interplay of the periodic potentials and the self-focusing nonlinearity. We founded that the energy redistribution tends to be periodic and the signal reinforcement is promoted with the help of periodic potentials. The lattice intensity levels, applied voltages, and correlation lengths are important parameters to influence the recovery effects. The dynamic nonlinear evolution including intensity and power spectrum is modeled according to the two-dimensional quasi-particle motion model. Our results suggest a potential technology to detect the noisy images.
The undeveloped properties of GABA neurons in the ventral tegmental area promote energy intake for growth in juvenile rats
Authors: Maejima Yuko , Yokota Shoko , Horita Shoichiro , Shimomura Kenju 
Published: August 2019

AbstractJuvenile animals show higher energy intake (EI) per body weight (BW) to meet the energy requirements for growth. However, the underlying mechanisms that induce high EI/BW in juvenile animals remain unknown. The EI from a control diet (CD) and high fat diet (HFD), as well as BW changes were compared between juvenile (3 weeks old) and adult (8 weeks old) rats. BW gain and EI were increased in the HFD-fed adult rats compared to the CD-fed adult rats. However, in the juvenile rats, there were no differences in BW gain and EI between the CD-fed and HFD-fed groups. The locomotor activity was significantly increased in HFD group compared with the CD group in juvenile, but not in adult rats. Gamma-aminobutyric acid (GABA) neurons in the VTA were found to remain undeveloped with less GABAergic input into dopamine neurons in the juvenile rats. The deletion of the VTA GABA neurons in the adult rats significantly increased CD consumption, but showed almost no change in HFD consumption. These data suggest that undeveloped properties of VTA GABA neurons in juvenile rats can promote higher EI regardless of high or less palatable feeding, and contribute to growth promotion.
Synthesis of MgAC-Fe3O4/TiO2 hybrid nanocomposites via sol-gel chemistry for water treatment by photo-Fenton and photocatalytic reactions
Authors: Bui Vu Khac Hoang , Park Duckshin , Pham Tuyet Nhung , An Yejin , Choi Jin Seok , Lee Hyun Uk , Kwon Oh-Hyeok , Moon Ju-Young , Kim Ki-Tae , Lee Young-Chul 
Published: August 2019

AbstractMgAC-Fe3O4/TiO2hybrid nanocomposites were synthesized in different ratios of MgAC-Fe3O4and TiO2precursor. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray fluorescence spectrometry (XRF), electron spin resonance spectrometry (ESR), Brunauer-Emmett-Teller (BET), photoluminescence (PL), and UV photoelectron spectroscopy (UPS) were used to characterize the nanocomposites. The increase of MgAC-Fe3O4, in the hybrid nanocomposites’ core-shell structure, led to the decrease of anatase TiO2peaks, thus reducing the photo-Fenton and photocatalytic activities. According to the obtained data, MgAC-Fe3O4[0.05 g]/TiO2showed the best photo-Fenton and photocatalytic activities, having removed ~93% of MB (photo-Fenton reaction) and ~80% of phenol (photocatalytic reaction) after 20 and 80 mins, respectively. On the pilot scale (30 L), MgAC-Fe3O4[0.05 g]/TiO2was completely removed after 27 and 30 hours by the photo-Fenton and photocatalytic activities, respectively. The synergistic effect gained from the combined photo-Fenton and photocatalytic activities of Fe3O4and TiO2, respectively, was credited for the performances of the MgAC-Fe3O4/TiO2hybrid nanocomposites.