bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rescue therapy with Tanshinone IIA hinders transition of acute kidney injury to chronic kidney disease via targeting GSK3β
Authors: Jiang Chunming , Zhu Wei , Yan Xiang , Shao Qiuyuan , Xu Biao , Zhang Miao , Gong Rujun 
Published: November 2016

AbstractAcute kidney injury (AKI) remains challenging for clinical practice and poses a risk of developing progressive chronic kidney disease (CKD) with no definitive treatment available yet. Tanshinone IIA, an active ingredient of Chinese herbal Salvia miltiorrhiza, has been widely used in Asia for the remarkable organoprotective activities. Its effect on established AKI, however, remains unknown. In mice with folic acid-induced AKI, delayed treatment with Tanshinone IIA, commenced early or late after injury, diminished renal expression of kidney injury markers, reduced apoptosis and improved kidney dysfunction, concomitant with mitigated histologic signs of AKI to CKD transition, including interstitial fibrosis and tubular atrophy, and with an ameliorated inflammatory infiltration in tubulointerstitium and a favored M2-skewed macrophage polarization. Mechanistically, Tanshinone IIA blunted glycogen synthase kinase (GSK)3β overactivity and hyperactivation of its downstream mitogen-activated protein kinases that are centrally implicated in renal fibrogenesis and inflammation. Inhibition of GSK3β is likely a key mechanism mediating the therapeutic activity of Tanshinone IIA, because sodium nitroprusside, a GSK3β activator, largely offset its renoprotective effect. In confirmatory studies, rescue treatment with Tanshinone IIA likewise ameliorated ischemia/reperfusion-induced kidney destruction in mice. Our data suggest that Tanshinone IIA represents a valuable treatment that improves post-AKI kidney salvage via targeting GSK3β.
Precise identification of Dirac-like point through a finite photonic crystal square matrix
Authors: Dong Guoyan , Zhou Ji , Yang Xiulun , Meng Xiangfeng 
Published: November 2016

AbstractThe phenomena of the minimum transmittance spectrum or the maximum reflection spectrum located around the Dirac frequency have been observed to demonstrate the 1/L scaling law near the Dirac-like point through the finite ribbon structure. However, so far there is no effective way to identify the Dirac-like point accurately. In this work we provide an effective measurement method to identify the Dirac-like point accurately through a finite photonic crystal square matrix. Based on the Dirac-like dispersion achieved by the accidental degeneracy at the centre of the Brillouin zone of dielectric photonic crystal, both the simulated and experimental results demonstrate that the transmittance spectra through a finite photonic crystal square matrix not only provide the clear evidence for the existence of Dirac-like point but also can be used to identify the precise location of Dirac-like point by the characteristics of sharp cusps embedded in the extremum spectra surrounding the conical singularity.
LUC7L3/CROP inhibits replication of hepatitis B virus via suppressing enhancer II/basal core promoter activity
Authors: Li Yuan , Ito Masahiko , Sun Suofeng , Chida Takeshi , Nakashima Kenji , Suzuki Tetsuro 
Published: November 2016

AbstractThe core promoter of hepatitis B virus (HBV) genome is a critical region for transcriptional initiation of 3.5 kb, pregenome and precore RNAs and for the viral replication. Although a number of host-cell factors that potentially regulate the viral promoter activities have been identified, the molecular mechanisms of the viral gene expression, in particular, regulatory mechanisms of the transcriptional repression remain elusive. In this study, we identified LUC7 like 3 pre-mRNA splicing factor (LUC7L3, also known as hLuc7A or CROP) as a novel interacting partner of HBV enhancer II and basal core promoter (ENII/BCP), key elements within the core promoter, through the proteomic screening and found that LUC7L3 functions as a negative regulator of ENII/BCP. Gene silencing of LUC7L3 significantly increased expression of the viral genes and antigens as well as the activities of ENII/BCP and core promoter. In contrast, overexpression of LUC7L3 inhibited their activities and HBV replication. In addition, LUC7L3 possibly contributes to promotion of the splicing of 3.5 kb RNA, which may also be involved in negative regulation of the pregenome RNA level. This is the first to demonstrate the involvement of LUC7L3 in regulation of gene transcription and in viral replication.
Atomistic switch of giant magnetoresistance and spin thermopower in graphene-like nanoribbons
Authors: Zhai Ming-Xing , Wang Xue-Feng 
Published: November 2016

AbstractWe demonstrate that the giant magnetoresistance can be switched off (on) in even- (odd-) width zigzag graphene-like nanoribbons by an atomistic gate potential or edge disorder inside the domain wall in the antiparallel (ap) magnetic configuration. A strong magneto-thermopower effect is also predicted that the spin thermopower can be greatly enhanced in the ap configuration while the charge thermopower remains low. The results extracted from the tight-binding model agree well with those obtained by first-principles simulations for edge doped graphene nanoribbons. Analytical expressions in the simplest case are obtained to facilitate qualitative analyses in general contexts.
Glycation potentiates neurodegeneration in models of Huntington’s disease
Authors: Vicente Miranda Hugo , Gomes Marcos António , Branco-Santos Joana , Breda Carlo , Lázaro Diana F. , Lopes Luísa Vaqueiro , Herrera Federico , Giorgini Flaviano , Outeiro Tiago Fleming 
Published: November 2016

AbstractProtein glycation is an age-dependent posttranslational modification associated with several neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. By modifying amino-groups, glycation interferes with folding of proteins, increasing their aggregation potential. Here, we studied the effect of pharmacological and genetic manipulation of glycation on huntingtin (HTT), the causative protein in Huntington’s disease (HD). We observed that glycation increased the aggregation of mutant HTT exon 1 fragments associated with HD (HTT72Q and HTT103Q) in yeast and mammalian cell models. We found that glycation impairs HTT clearance thereby promoting its intracellular accumulation and aggregation. Interestingly, under these conditions autophagy increased and the levels of mutant HTT released to the culture medium decreased. Furthermore, increased glycation enhanced HTT toxicity in human cells and neurodegeneration in fruit flies, impairing eclosion and decreasing life span. Overall, our study provides evidence that glycation modulates HTT exon-1 aggregation and toxicity, and suggests it may constitute a novel target for therapeutic intervention in HD.
Size Switchable Supramolecular Nanoparticle Based on Azobenzene Derivative within Anionic Pillar[5]arene
Authors: Zhang Cai-Cai , Li Sheng-Hua , Zhang Cui-Fang , Liu Yu 
Published: November 2016

AbstractA photo/thermal-switchable supramolecular nanoparticles assembly has been constructed based on an inclusion complex between anionic pillar[5]arene 2C-WP5A and azobenzene derivative Azo-py-OMe (G). The novel anionic pillar[5]arene-based host-guest inclusion complexation was investigated by the 1H NMR titration, 2D ROESY and isothermal titration microcalorimetry (ITC) showing high association constant (Ka) of (2.60 ± 0.06) × 104 M−1 with 1:1 binding stoichiometry. Furthermore, the supramolecular nanoparticles assembly can be conveniently obtained from G and a small amount of 2C-WP5A in aqueous solution, which was so-called “host induced aggregating (HIA)”. The size and morphology of the supramolecular nanoparticles assembly were characterized by TEM and DLS. As a result of the photo/thermal-isomerization of G included in the cavity of 2C-WP5A, the size of these nanoparticles could reversibly change from ~800 nm to ~250 nm, which could switch the solution of this assembly from turbid to clear.
Development and Characterization of Lecithin-based Self-assembling Mixed Polymeric Micellar (saMPMs) Drug Delivery Systems for Curcumin
Authors: Chen Ling-Chun , Chen Yin-Chen , Su Chia-Yu , Wong Wan-Ping , Sheu Ming-Thau , Ho Hsiu-O 
Published: November 2016

AbstractSelf-assembling mixed polymeric micelles (saMPMs) were developed for overcoming major obstacles of poor bioavailability (BA) associated with curcumin delivery. Lecithin added was functioned to enlarge the hydrophobic core of MPMs providing greater solubilization capacity. Amphiphilic polymers (sodium deoxycholate [NaDOC], TPGS, CREMOPHOR, or a PLURONIC series) were examined for potentially self-assembling to form MPMs (saMPMs) with the addition of lecithin. Particle size, size distribution, encapsulation efficacy (E.E.), and drug loading (D.L.) of the mixed micelles were optimally studied for their influences on the physical stability and release of encapsulated drugs. Overall, curcumin:lecithin:NaDOC and curcumin:lecithin:PLURONIC P123 in ratios of 2:1:5 and 5:2:20, respectively, were optimally obtained with a particle size of < 200 nm, an E.E. of >80%, and a D.L. of >10%. The formulated system efficiently stabilized curcumin in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C and delayed the in vitro curcumin release. In vivo results further demonstrated that the slow release of curcumin from micelles and prolonged duration increased the curcumin BA followed oral and intravenous administrations in rats. Thus, lecithin-based saMPMs represent an effective curcumin delivery system, and enhancing BA of curcumin can enable its wide applications for treating human disorders.
A biodiversity hotspot losing its top predator: The challenge of jaguar conservation in the Atlantic Forest of South America
Authors: Paviolo Agustin , De Angelo Carlos , Ferraz Katia M. P. M. B. , Morato Ronaldo G. , Martinez Pardo Julia , Srbek-Araujo Ana C. , Beisiegel Beatriz de Mello , Lima Fernando , Sana Denis , Xavier da Silva Marina , Velázquez Myriam C. , Cullen Laury , Crawshaw Jr Peter , Jorge María Luisa S. P. , Galetti Pedro M. , Di Bitetti Mario S. , de Paula Rogerio Cunha , Eizirik Eduardo , Aide T. Mitchell , Cruz Paula , Perilli Miriam L. L. , Souza Andiara S. M. C. , Quiroga Verónica , Nakano Eduardo , Ramírez Pinto Fredy , Fernández Sixto , Costa Sebastian , Moraes Jr Edsel A. , Azevedo Fernando 
Published: November 2016

AbstractThe jaguar is the top predator of the Atlantic Forest (AF), which is a highly threatened biodiversity hotspot that occurs in Brazil, Paraguay and Argentina. By combining data sets from 14 research groups across the region, we determine the population status of the jaguar and propose a spatial prioritization for conservation actions. About 85% of the jaguar’s habitat in the AF has been lost and only 7% remains in good condition. Jaguars persist in around 2.8% of the region, and live in very low densities in most of the areas. The population of jaguars in the AF is probably lower than 300 individuals scattered in small sub-populations. We identified seven Jaguar Conservation Units (JCUs) and seven potential JCUs, and only three of these areas may have ≥50 individuals. A connectivity analysis shows that most of the JCUs are isolated. Habitat loss and fragmentation were the major causes for jaguar decline, but human induced mortality is the main threat for the remaining population. We classified areas according to their contribution to jaguar conservation and we recommend management actions for each of them. The methodology in this study could be used for conservation planning of other carnivore species.
Two PTP receptors mediate CSPG inhibition by convergent and divergent signaling pathways in neurons
Authors: Ohtake Yosuke , Wong Daniella , Abdul-Muneer P. M. , Selzer Michael E. , Li Shuxin 
Published: November 2016

AbstractReceptor protein tyrosine phosphatase σ (PTPσ) and its subfamily member LAR act as transmembrane receptors that mediate growth inhibition of chondroitin sulfate proteoglycans (CSPGs). Inhibition of either receptor increases axon growth into and beyond scar tissues after CNS injury. However, it is unclear why neurons express two similar CSPG receptors, nor whether they use the same or different intracellular pathways. We have now studied the signaling pathways of these two receptors using N2A cells and primary neurons derived from knockout mice. We demonstrate that both receptors share certain signaling pathways (RhoA, Akt and Erk), but also use distinct signals to mediate CSPG actions. Activation of PTPσ by CSPGs selectively inactivated CRMP2, APC, S6 kinase and CREB. By contrast LAR activation inactivated PKCζ, cofilin and LKB1. For the first time, we propose a model of the signaling pathways downstream of these two CSPG receptors. We also demonstrate that deleting both receptors exhibits additive enhancement of axon growth in adult neuronal cultures in vitro. Our findings elucidate the novel downstream pathways of CSPGs and suggest potential synergy of blocking their two PTP receptors.
ELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions
Authors: Sharma Krishna Rakesh , Heckler Karl , Stoll Sandra J. , Hillebrands Jan-Luuk , Kynast Katharina , Herpel Esther , Porubsky Stefan , Elger Marlies , Hadaschik Boris , Bieback Karen , Hammes Hans-Peter , Nawroth Peter P. , Kroll Jens 
Published: November 2016

AbstractEngulfment and cell motility 1 (ELMO1) functions as a guanine exchange factor for Rac1 and was recently found to protect endothelial cells from apoptosis. Genome wide association studies suggest that polymorphisms within human elmo1 act as a potential contributing factor for the development of diabetic nephropathy. Yet, the function of ELMO1 with respect to the glomerulus and how this protein contributes to renal pathology was unknown. Thus, this study aimed to identify the role played by ELMO1 in renal development in zebrafish, under hyperglycaemic conditions, and in diabetic nephropathy patients. In zebrafish, hyperglycaemia did not alter renal ELMO1 expression. However, hyperglycaemia leads to pathophysiological and functional alterations within the pronephros, which could be rescued via ELMO1 overexpression. Zebrafish ELMO1 crispants exhibited a renal pathophysiology due to increased apoptosis which could be rescued by the inhibition of apoptosis. In human samples, immunohistochemical staining of ELMO1 in nondiabetic, diabetic and polycystic kidneys localized ELMO1 in glomerular podocytes and in the tubules. However, ELMO1 was not specifically or distinctly regulated under either one of the disease conditions. Collectively, these results highlight ELMO1 as an important factor for glomerular protection and renal cell survival via decreasing apoptosis, especially under diabetic conditions.
Fatal Community-acquired Pneumonia in Children Caused by Re-emergent Human Adenovirus 7d Associated with Higher Severity of Illness and Fatality Rate
Authors: Yu Zhiwu , Zeng Zhiwei , Zhang Jing , Pan Yuxian , Chen Manjun , Guo Yonghui , Yu Nan , Chodosh James , Fu Ning , Che Xiaoyan , Zhang Qiwei 
Published: November 2016

AbstractHuman adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), such as community-acquired pneumonia. HAdV-7d, a re-emergent genomic variant, has been recently reported in Asia and the United States after a several-decade absence. However, whether HAdV-7d is associated with higher severity than other types is currently unclear. In this study, the clinical and epidemiological investigation showed that fever, cough, and sore throat were the three most common respiratory symptoms of HAdV infections. HAdV-7 caused longer duration of fever, higher morbidity of tachypnea/dyspnea, pleural effusion, diarrhea, hepatosplenomegaly, consciousness alteration, as well as higher rates of pneumonia, mechanical ventilation and higher fatality rate (28.6%) than other types, particularly HAdV-3 and HAdV-2. The genomes of seven HAdV-7d isolates from mild, severe, and fatal cases were sequenced and highly similar with each other. Surprisingly, two isolates (2011, 2012) had 100% identical genomes with an earlier strain from a fatal ARD outbreak in China (2009), which elucidates the virus origin and confirms the unexpected HAdV genomic conservation and stability. Phylogenetic analysis indicated that L1 52/55-kDa DNA packaging protein may be associated with the higher severity of illness and fatality rate of HAdV-7. Clinicians need to be aware of HAdVs in children with ARD.
Deletion of Neurotrophin Signaling through the Glucocorticoid Receptor Pathway Causes Tau Neuropathology
Authors: Arango-Lievano Margarita , Peguet Camille , Catteau Matthias , Parmentier Marie-Laure , Wu Synphen , Chao Moses V , Ginsberg Stephen D. , Jeanneteau Freddy 
Published: November 2016

AbstractGlucocorticoid resistance is a risk factor for Alzheimer’s disease (AD). Molecular and cellular mechanisms of glucocorticoid resistance in the brain have remained unknown and are potential therapeutic targets. Phosphorylation of glucocorticoid receptors (GR) by brain-derived neurotrophic factor (BDNF) signaling integrates both pathways for remodeling synaptic structure and plasticity. The goal of this study is to test the role of the BDNF-dependent pathway on glucocorticoid signaling in a mouse model of glucocorticoid resistance. We report that deletion of GR phosphorylation at BDNF-responding sites and downstream signaling via the MAPK-phosphatase DUSP1 triggers tau phosphorylation and dendritic spine atrophy in mouse cortex. In human cortex, DUSP1 protein expression correlates with tau phosphorylation, synaptic defects and cognitive decline in subjects diagnosed with AD. These findings provide evidence for a causal role of BDNF-dependent GR signaling in tau neuropathology and indicate that DUSP1 is a potential target for therapeutic interventions.
Analysis of Microarray Data on Gene Expression and Methylation to Identify Long Non-coding RNAs in Non-small Cell Lung Cancer
Authors: Feng Nannan , Ching Travers , Wang Yu , Liu Ben , Lin Hongyan , Shi Oumin , Zhang Xiaohong , Zheng Min , Zheng Xin , Gao Ming , Zheng Zhi-jie , Yu Herbert , Garmire Lana , Qian Biyun 
Published: November 2016

AbstractTo identify what long non-coding RNAs (lncRNAs) are involved in non-small cell lung cancer (NSCLC), we analyzed microarray data on gene expression and methylation. Gene expression chip and HumanMethylation450BeadChip were used to interrogate genome-wide expression and methylation in tumor samples. Differential expression and methylation were analyzed through comparing tumors with adjacent non-tumor tissues. LncRNAs expressed differentially and correlated with coding genes and DNA methylation were validated in additional tumor samples using RT-qPCR and pyrosequencing. In vitro experiments were performed to evaluate lncRNA’s effects on tumor cells. We identified 8,500 lncRNAs expressed differentially between tumor and non-tumor tissues, of which 1,504 were correlated with mRNA expression. Two of the lncRNAs, LOC146880 and ENST00000439577, were positively correlated with expression of two cancer-related genes, KPNA2 and RCC2, respectively. High expression of LOC146880 and ENST00000439577 were also associated with poor survival. Analysis of lncRNA expression in relation to DNA methylation showed that LOC146880 expression was down-regulated by DNA methylation in its promoter. Lowering the expression of LOC146880 or ENST00000439577 in tumor cells could inhibit cell proliferation, invasion and migration. Analysis of microarray data on gene expression and methylation allows us to identify two lncRNAs, LOC146880 and ENST00000439577, which may promote the progression of NSCLC.
Nitrogen-induced metabolic changes and molecular determinants of carbon allocation in Dunaliella tertiolecta
Authors: Tan Kenneth Wei Min , Lin Huixin , Shen Hui , Lee Yuan Kun 
Published: November 2016

AbstractCertain species of microalgae are natural accumulators of lipids, while others are more inclined to store starch. However, what governs the preference to store lipids or starch is not well understood. In this study, the microalga Dunaliella tertiolecta was used as a model to study the global gene expression profile regulating starch accumulation in microalgae. D. tertiolecta, when depleted of nitrogen, produced only 1% of dry cell weight (DCW) in neutral lipids, while starch was rapidly accumulated up to 46% DCW. The increased in starch content was accompanied by a coordinated overexpression of genes shunting carbon towards starch synthesis, a response not seen in the oleaginous microalgae Nannochloropsis oceanica, Chlamydomonas reinhardtii or Chlorella vulgaris. Genes in the central carbon metabolism pathways, particularly those of the tricarboxylic acid cycle, were also simultaneously upregulated, indicating a robust interchange of carbon skeletons for anabolic and catabolic processes. In contrast, fatty acid and triacylglycerol synthesis genes were downregulated or unchanged, suggesting that lipids are not a preferred form of storage in these cells. This study reveals the transcriptomic influence behind storage reserve allocation in D. tertiolecta and provides valuable insights into the possible manipulation of genes for engineering microorganisms to synthesize products of interest.
The phosphorylated form of FTY720 activates PP2A, represses inflammation and is devoid of S1P agonism in A549 lung epithelial cells
Authors: Rahman Md. Mostafizur , Prünte Laura , Lebender Leonard F. , Patel Brijeshkumar S. , Gelissen Ingrid , Hansbro Philip M. , Morris Jonathan C. , Clark Andrew R. , Verrills Nicole M. , Ammit Alaina J. 
Published: November 2016

AbstractProtein phosphatase 2A (PP2A) activity can be enhanced pharmacologically by PP2A-activating drugs (PADs). The sphingosine analog FTY720 is the best known PAD and we have shown that FTY720 represses production of pro-inflammatory cytokines responsible for respiratory disease pathogenesis. Whether its phosphorylated form, FTY720-P, also enhances PP2A activity independently of the sphingosine 1-phosphate (S1P) pathway was unknown. Herein, we show that FTY720-P enhances TNF-induced PP2A phosphatase activity and significantly represses TNF-induced interleukin 6 (IL-6) and IL-8 mRNA expression and protein secretion from A549 lung epithelial cells. Comparing FTY720 and FTY720-P with S1P, we show that unlike S1P, the sphingosine analogs do not induce cytokine production on their own. In fact, FTY720 and FTY720-P significantly repress S1P-induced IL-6 and IL-8 production. We then examined their impact on expression of cyclooxygenase 2 (COX-2) and resultant prostaglandin E2 (PGE2) production. S1P did not increase production of this pro-inflammatory enzyme because COX-2 mRNA gene expression is NF-κB-dependent, and unlike TNF, S1P did not activate NF-κB. However, TNF-induced COX-2 mRNA expression and PGE2 secretion is repressed by FTY720 and FTY720-P. Hence, FTY720-P enhances PP2A activity and that PADs can repress production of pro-inflammatory cytokines and enzymes in A549 lung epithelial cells in a manner devoid of S1P agonism.