bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergence of new red-shifted carbon nanotube photoluminescence based on proximal doped-site design
Authors: Shiraki Tomohiro , Shiraishi Tomonari , Juhász Gergely , Nakashima Naotoshi
Published: June 2016

Single-walled carbon nanotubes (SWNTs) show unique photoluminescence (PL) in the near-infrared (NIR) region. Here we propose a concept based on the proximal modification in local covalent functionalization of SWNTs. Quantum mechanical simulations reveal that the SWNT band gap changes specifically based on the proximal doped-site design. Thus, we synthesize newly-designed bisdiazonium molecules and conduct local fucntionalisation of SWNTs. Consequently, new red-shifted PL (E112*) from the bisdiazonium-modified SWNTs with (6, 5) chirality is recognized around 1250 nm with over ~270 nm Stokes shift from the PL of the pristine SWNTs and the PL wavelengths are shifted depending on the methylene spacer lengths of the modifiers. The present study revealed that SWNT PL modulation is enable by close-proximity-local covalent modification, which is highly important for fundamental understanding of intrinsic SWNT PL properties as well as exciton engineering–based applications including photonic devices and (bio)imaging/sensing.
Involvement of Cl−/HCO3− exchanger SLC26A3 and SLC26A6 in preimplantation embryo cleavage
Authors: Lu Yong Chao , Yang Jing , Fok Kin Lam , Ye Ying Hui , Jin Liang , Chen Zheng Yun , Zhang Xin Mei , Huang He Feng , Chan Hsiao Chang
Published: June 2016

Bicarbonate (HCO3−) is essential for preimplantation embryo development. However, the mechanism underlying the HCO3−transport into the embryo remains elusive. In the present study, we examined the possible involvement of Cl−/HCO3−exchanger in mediating HCO3−transport into the embryo. Our results showed that depletion of extracellular Cl−, even in the presence of HCO3−, suppressed embryo cleavage in a concentration-dependent manner. Cleavage-associated HCO3−-dependent events, including increase of intracellular pH, upregulation of miR-125b and downregulation of p53, also required Cl−. We further showed that Cl−/HCO3−exchanger solute carrier family 26 (SLC26) A3 and A6 were expressed at 2-cell through blastocyst stage. Blocking individual exchanger’s activity by inhibitors or gene knockdown differentially decreased embryo cleavage and inhibited HCO3−-dependent events, while inhibiting/knocking down both produced an additive effect to an extent similar to that observed when CFTR was inhibited. These results indicate the involvement of SLC26A3 and A6 in transporting HCO3−essential for embryo cleavage, possibly working in concert with CFTR through a Cl−recycling pathway. The present study sheds light into our understanding of molecular mechanisms regulating embryo cleavage by the female reproductive tract.
Present-day uplift of the western Alps
Authors: Nocquet J.-M. , Sue C. , Walpersdorf A. , Tran T. , Lenôtre N. , Vernant P. , Cushing M. , Jouanne F. , Masson F. , Baize S. , Chéry J. , van der Beek P. A.
Published: June 2016

Collisional mountain belts grow as a consequence of continental plate convergence and eventually disappear under the combined effects of gravitational collapse and erosion. Using a decade of GPS data, we show that the western Alps are currently characterized by zero horizontal velocity boundary conditions, offering the opportunity to investigate orogen evolution at the time of cessation of plate convergence. We find no significant horizontal motion within the belt, but GPS and levelling measurements independently show a regional pattern of uplift reaching ~2.5 mm/yr in the northwestern Alps. Unless a low viscosity crustal root under the northwestern Alps locally enhances the vertical response to surface unloading, the summed effects of isostatic responses to erosion and glaciation explain at most 60% of the observed uplift rates. Rock-uplift rates corrected from transient glacial isostatic adjustment contributions likely exceed erosion rates in the northwestern Alps. In the absence of active convergence, the observed surface uplift must result from deep-seated processes.
Correction: Corrigendum: Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal
Authors: Risso Davide S. , Mezzavilla Massimo , Pagani Luca , Robino Antonietta , Morini Gabriella , Tofanelli Sergio , Carrai Maura , Campa Daniele , Barale Roberto , Caradonna Fabio , Gasparini Paolo , Luiselli Donata , Wooding Stephen , Drayna Dennis
Published: June 2016

Scientific Reports 6: Article number: 25506; published online: 03 May 2016; updated: 27 June 2016. In this Article, all instances of “rs714598” should read “rs713598”.
Correction: Corrigendum: Prioritizing functional phosphorylation sites based on multiple feature integration
Authors: Xiao Qingyu , Miao Benpeng , Bi Jie , Wang Zhen , Li Yixue
Published: June 2016

Scientific Reports 6: Article number: 24735 published online: 19 April 2016; updated: 27 June 2016. The original version of this Article contained typographical errors in the Predict Functional Phosphosites website ‘http://pfp.biosino.org/pfp’ which was incorrectly given as ‘http://pfp.biosino.org/’. These errors have now been corrected in the PDF and HTML versions of the Article.
Thiazine Red+ platelet inclusions in Cerebral Blood Vessels are first signs in an Alzheimer’s Disease mouse model
Authors: Kniewallner Kathrin M. , Wenzel Daniela , Humpel Christian
Published: June 2016

Strong evidence shows an association between cerebral vascular diseases and Alzheimer´s disease (AD). In order to study the interaction of beta-amyloid (Aβ) plaques with brain vessels, we crossbred an AD mouse model (overexpressing amyloid precursor protein with the Swedish-Dutch-Iowa mutations, APP_SweDI) with mice expressing green fluorescent protein (GFP) under the flt-1/VEGFR1 promoter in vessels (GFP_FLT1). Our data show, that only very few Aβ plaques were seen in 4-months old mice, focused in the mammillary body and in the lateral septal nucleus. The number of plaques markedly increased with age being most prominent in 12-months old mice. Thiazine Red was used to verify the plaques. Several Thiazine Red+ inclusions were found in GFP+ vessels, but only in non-perfused 4-months old mice. These inclusions were verified by Resorufin stainings possibly representing cerebral amyloid angiopathy. The inclusions were also seen in non-crossbred APP_SweDI but not in wildtype and GFP_FLT1 mice. In order to characterize these inclusions Flow Cytometry (FACS) analysis demonstrated that platelets were specifically stained by Thiazine Red+, more pronounced when aggregated. In conclusion, our data show that Thiazine Red+ inclusions representing aggregated platelets are a first pathological sign in AD before plaque development and may become important therapeutic targets in early AD.
Time-to-Progression of NSCLC from Early to Advanced Stages: An Analysis of data from SEER Registry and a Single Institute
Authors: Yuan Ping , Cao Jin Lin , Rustam Azmat , Zhang Chong , Yuan Xiao Shuai , Bao Fei Chao , Lv Wang , Hu Jian
Published: June 2016

The average time required for cancers to progress through stages can be reflected in the average age of the patients diagnosed at each stage of disease. To estimate the time it takes for non-small-cell lung cancer (NSCLC) to progress through different tumor, node and metastasis (TNM) stages and sizes, we compared the mean adjusted age of 45904 NSCLC patients with different stages and tumor sizes from Surveillance, Epidemiology and End Results (SEER) cancer registry database and our institute. Multiple-linear-regression models for age were generated adjusting for various factors. Caucasian, African-American and Asian patients with stage IA cancers were on average 0.8, 1.0 and 1.38 adjusted years younger, respectively, than those with stage IIIB cancers (p < 0.001). And these with T1a cancers were on average 0.84, 0.92 and 1.21 adjusted years younger, respectively, than patients with T3 cancers (p < 0.001). Patients with tumors measuring larger than 8 cm in diameter were on average 0.85 adjusted years older than these with tumors smaller than 1 cm (p < 0.001), with Caucasian demonstrating the shortest age span (0.79 years, P < 0.001). In conclusion, the time-to-progression of NSCLC from early to advanced stages varied among ethnicities, Caucasian patients demonstrating a more rapid progression nature of tumor than their African-American and Asian counterparts.
Planning for assisted colonization of plants in a warming world
Authors: Ferrarini Alessandro , Selvaggi Alberto , Abeli Thomas , Alatalo Juha M. , Orsenigo Simone , Gentili Rodolfo , Rossi Graziano
Published: June 2016

Assisted colonization is one way of facilitating range shifts for species that are restricted in their ability to move in response to climate change. Here we conceptualize and apply a new decision framework for modelling assisted colonization of plant species prior to in situ realization. Three questions were examined: a) Is species translocation useful in a certain area? b) where and c) how long will it be successful in the future? Applying our framework to Carex foetida in Italy at the core of its distribution and its southern edge revealed that assisted colonization could be successful in short-term (2010–2039) climate conditions, partially in medium (2040–2069) but not in long-term (2070–2099) scenarios. We show that, for some species, it is likely that assisted colonization would be successful in some portions of the recipient site under current and short-term climate conditions, but over the mid- and long-term, climate changes will make species translocation unsuccessful. The proposed decision framework can help identify species that will need different conservation actions (seed banks and/or botanical gardens) when assisted colonization is unlikely to be successful. Furthermore it has broad applicability, as it can support planning of assisted migration in mountainous areas in the face of climate change.
The insect repellent N,N-diethyl-m-toluamide (DEET) induces angiogenesis via allosteric modulation of the M3 muscarinic receptor in endothelial cells
Authors: Legeay Samuel , Clere Nicolas , Hilairet Grégory , Do Quoc-Tuan , Bernard Philippe , Quignard Jean-François , Apaire-Marchais Véronique , Lapied Bruno , Faure Sébastien
Published: June 2016

The insect repellent N,N-diethyl-m-toluamide (DEET) has been reported to inhibit AChE (acetylcholinesterase) and to possess potential carcinogenic properties with excessive vascularization. In the present paper, we demonstrate that DEET specifically stimulates endothelial cells that promote angiogenesis which increases tumor growth. DEET activates cellular processes that lead to angiogenesis including proliferation, migration and adhesion. This is associated with an enhancement of NO production and VEGF expression in endothelial cells. M3 silencing or the use of a pharmacological M3 inhibitor abrogates all of these effects which reveals that DEET-induced angiogenesis is M3 sensitive. The experiments involving calcium signals in both endothelial and HEK cells overexpressing M3 receptors, as well as binding and docking studies demonstrate that DEET acts as an allosteric modulator of the M3 receptor. In addition, DEET inhibited AChE which increased acetylcholine bioavailability and binding to M3 receptors and also strengthened proangiogenic effects by an allosteric modulation.
Prevalence and Dynamics of Ribosomal DNA Micro-heterogeneity Are Linked to Population History in Two Contrasting Yeast Species
Authors: James Stephen A. , West Claire , Davey Robert P. , Dicks Jo , Roberts Ian N.
Published: June 2016

Despite the considerable number and taxonomic breadth of past and current genome sequencing projects, many of which necessarily encompass the ribosomal DNA, detailed information on the prevalence and evolutionary significance of sequence variation in this ubiquitous genomic region are severely lacking. Here, we attempt to address this issue in two closely related yet contrasting yeast species, the baker’s yeast Saccharomyces cerevisiae and the wild yeast Saccharomyces paradoxus. By drawing on existing datasets from the Saccharomyces Genome Resequencing Project, we identify a rich seam of ribosomal DNA sequence variation, characterising 1,068 and 970 polymorphisms in 34 S. cerevisiae and 26 S. paradoxus strains respectively. We discover the two species sets exhibit distinct mutational profiles. Furthermore, we show for the first time that unresolved rDNA sequence variation resulting from imperfect concerted evolution of the ribosomal DNA region follows a U-shaped allele frequency distribution in each species, similar to loci that evolve under non-concerted mechanisms but arising through rather different evolutionary processes. Finally, we link differences between the shapes of these allele frequency distributions to the two species’ contrasting population histories.
Characterization of genome-wide SNPs for the water flea Daphnia pulicaria generated by genotyping-by-sequencing (GBS)
Authors: Muñoz Joaquín , Chaturvedi Anurag , De Meester Luc , Weider Lawrence J.
Published: June 2016

The keystone aquatic herbivore Daphnia has been studied for more than 150 years in the context of evolution, ecology and ecotoxicology. Although it is rapidly becoming an emergent model for environmental and population genomics, there have been limited genome-wide level studies in natural populations. We report a unique resource of novel Single Nucleotide Polymorphic (SNP) markers for Daphnia pulicaria using the reduction in genomic complexity with the restriction enzymes approach, genotyping-by-sequencing. Using the genome of D. pulex as a reference, SNPs were scored for 53 clones from five natural populations that varied in lake trophic status. Our analyses resulted in 32,313 highly confident and bi-allelic SNP markers. 1,364 outlier SNPs were mapped on the annotated D. pulex genome, which identified 2,335 genes, including 565 within functional genes. Out of 885 EuKaryotic Orthologous Groups that we found from outlier SNPs, 294 were involved in three metabolic and four regulatory pathways. Bayesian-clustering analyses showed two distinct population clusters representing the possible combined effects of geography and lake trophic status. Our results provide an invaluable tool for future population genomics surveys in Daphnia targeting informative regions related to physiological processes that can be linked to the ecology of this emerging eco-responsive taxon.
Urbanization affects neophilia and risk-taking at bird-feeders
Authors: Tryjanowski Piotr , Møller Anders Pape , Morelli Federico , Biaduń Waldemar , Brauze Tomasz , Ciach Michał , Czechowski Paweł , Czyż Stanisław , Dulisz Beata , Goławski Artur , Hetmański Tomasz , Indykiewicz Piotr , Mitrus Cezary , Myczko Łukasz , Nowakowski Jacek J. , Polakowski Michał , Takacs Viktoria , Wysocki Dariusz , Zduniak Piotr
Published: June 2016

Urban environments cover vast areas with a high density of humans and their dogs and cats causing problems for exploitation of new resources by wild animals. Such resources facilitate colonization by individuals with a high level of neophilia predicting that urban animals should show more neophilia than rural conspecifics. We provided bird-feeders across urban environments in 14 Polish cities and matched nearby rural habitats, testing whether the presence of a novel item (a brightly coloured green object made out of gum with a tuft of hair) differentially delayed arrival at feeders in rural compared to urban habitats. The presence of a novel object reduced the number of great tits Parus major, but also the total number of all species of birds although differentially so in urban compared to rural areas. That was the case independent of the potentially confounding effects of temperature, population density of birds and the abundance of cats, dogs and pedestrians. The number of great tits and the total number of birds attending feeders increased in urban compared to rural areas independent of local population density of birds. This implies that urban birds have high levels of neophilia allowing them to readily exploit unpredictable resources in urban environments.
THz Acoustic Spectroscopy by using Double Quantum Wells and Ultrafast Optical Spectroscopy
Authors: Wei Fan Jun , Yeh Yu-Hsiang , Sheu Jinn-Kong , Lin Kung-Hsuan
Published: June 2016

GaN is a pivotal material for acoustic transducers and acoustic spectroscopy in the THz regime, but its THz phonon properties have not been experimentally and comprehensively studied. In this report, we demonstrate how to use double quantum wells as a THz acoustic transducer for measuring generated acoustic phonons and deriving a broadband acoustic spectrum with continuous frequencies. We experimentally investigated the sub-THz frequency dependence of acoustic attenuation (i.e., phonon mean-free paths) in GaN, in addition to its physical origins such as anharmonic scattering, defect scattering, and boundary scattering. A new upper limit of attenuation caused by anharmonic scattering, which is lower than previously reported values, was obtained. Our results should be noteworthy for THz acoustic spectroscopy and for gaining a fundamental understanding of heat conduction.
Btg2 is a Negative Regulator of Cardiomyocyte Hypertrophy through a Decrease in Cytosolic RNA
Authors: Masumura Yuki , Higo Shuichiro , Asano Yoshihiro , Kato Hisakazu , Yan Yi , Ishino Saki , Tsukamoto Osamu , Kioka Hidetaka , Hayashi Takaharu , Shintani Yasunori , Yamazaki Satoru , Minamino Tetsuo , Kitakaze Masafumi , Komuro Issei , Takashima Seiji , Sakata Yasushi
Published: June 2016

Under hypertrophic stimulation, cardiomyocytes enter a hypermetabolic state and accelerate biomass accumulation. Although the molecular pathways that regulate protein levels are well-studied, the functional implications of RNA accumulation and its regulatory mechanisms in cardiomyocytes remain elusive. Here, we have elucidated the quantitative kinetics of RNA in cardiomyocytes through single cell imaging and c-Myc (Myc)-mediated hypermetabolic analytical model using cultured cardiomyocytes. Nascent RNA labeling combined with single cell imaging demonstrated that Myc protein significantly increased the amount of global RNA production per cardiomyocyte. Chromatin immunoprecipitation with high-throughput sequencing clarified that overexpressed Myc bound to a specific set of genes and recruits RNA polymerase II. Among these genes, we identified Btg2 as a novel target of Myc. Btg2 overexpression significantly reduced cardiomyocyte surface area. Conversely, shRNA-mediated knockdown of Btg2 accelerated adrenergic stimulus-induced hypertrophy. Using mass spectrometry analysis, we determined that Btg2 binds a series of proteins that comprise mRNA deadenylation complexes. Intriguingly, Btg2 specifically suppresses cytosolic, but not nuclear, RNA levels. Btg2 knockdown further enhances cytosolic RNA accumulation in cardiomyocytes under adrenergic stimulation, suggesting that Btg2 negatively regulates reactive hypertrophy by negatively regulating RNA accumulation. Our findings provide insight into the functional significance of the mechanisms regulating RNA levels in cardiomyocytes.
Highly pathogenic avian influenza H5N1 virus delays apoptotic responses via activation of STAT3
Authors: Hui Kenrie P. Y. , Li Hung Sing , Cheung Man Chun , Chan Renee W. Y. , Yuen Kit M. , Mok Chris K. P. , Nicholls John M. , Peiris J. S. Malik , Chan Michael C. W.
Published: June 2016

Highly pathogenic avian influenza (HPAI) H5N1 virus continues to pose pandemic threat, but there is a lack of understanding of its pathogenesis. We compared the apoptotic responses triggered by HPAI H5N1 and low pathogenic H1N1 viruses using physiologically relevant respiratory epithelial cells. We demonstrated that H5N1 viruses delayed apoptosis in primary human bronchial and alveolar epithelial cells (AECs) compared to H1N1 virus. Both caspase-8 and -9 were activated by H5N1 and H1N1 viruses in AECs, while H5N1 differentially up-regulated TRAIL. H5N1-induced apoptosis was reduced by TRAIL receptor silencing. More importantly, STAT3 knock-down increased apoptosis by H5N1 infection suggesting that H5N1 virus delays apoptosis through activation of STAT3. Taken together, we demonstrate that STAT3 is involved in H5N1-delayed apoptosis compared to H1N1. Since delay in apoptosis prolongs the duration of virus replication and production of pro-inflammatory cytokines and TRAIL from H5N1-infected cells, which contribute to orchestrate cytokine storm and tissue damage, our results suggest that STAT3 may play a previously unsuspected role in H5N1 pathogenesis.
Ecological Responses to Extreme Flooding Events: A Case Study with a Reintroduced Bird
Authors: Soriano-Redondo Andrea , Bearhop Stuart , Cleasby Ian R. , Lock Leigh , Votier Stephen C. , Hilton Geoff M.
Published: June 2016

In recent years numerous studies have documented the effects of a changing climate on the world’s biodiversity. Although extreme weather events are predicted to increase in frequency and intensity and are challenging to organisms, there are few quantitative observations on the survival, behaviour and energy expenditure of animals during such events. We provide the first data on activity and energy expenditure of birds, Eurasian cranes Grus grus, during the winter of 2013–14, which saw the most severe floods in SW England in over 200 years. We fitted 23 cranes with telemetry devices and used remote sensing data to model flood dynamics during three consecutive winters (2012–2015). Our results show that during the acute phase of the 2013–14 floods, potential feeding areas decreased dramatically and cranes restricted their activity to a small partially unflooded area. They also increased energy expenditure (+15%) as they increased their foraging activity and reduced resting time. Survival did not decline in 2013–14, indicating that even though extreme climatic events strongly affected time-energy budgets, behavioural plasticity alleviated any potential impact on fitness. However under climate change scenarios such challenges may not be sustainable over longer periods and potentially could increase species vulnerability.
Integrative analyses shed new light on human ribosomal protein gene regulation
Authors: Li Xin , Zheng Yiyu , Hu Haiyan , Li Xiaoman
Published: June 2016

Ribosomal protein genes (RPGs) are important house-keeping genes that are well-known for their coordinated expression. Previous studies on RPGs are largely limited to their promoter regions. Recent high-throughput studies provide an unprecedented opportunity to study how human RPGs are transcriptionally modulated and how such transcriptional regulation may contribute to the coordinate gene expression in various tissues and cell types. By analyzing the DNase I hypersensitive sites under 349 experimental conditions, we predicted 217 RPG regulatory regions in the human genome. More than 86.6% of these computationally predicted regulatory regions were partially corroborated by independent experimental measurements. Motif analyses on these predicted regulatory regions identified 31 DNA motifs, including 57.1% of experimentally validated motifs in literature that regulate RPGs. Interestingly, we observed that the majority of the predicted motifs were shared by the predicted distal and proximal regulatory regions of the same RPGs, a likely general mechanism for enhancer-promoter interactions. We also found that RPGs may be differently regulated in different cells, indicating that condition-specific RPG regulatory regions still need to be discovered and investigated. Our study advances the understanding of how RPGs are coordinately modulated, which sheds light to the general principles of gene transcriptional regulation in mammals.
Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging
Authors: Wang Rui-Hong , Zhao Tingrui , Cui Kairong , Hu Gangqing , Chen Qiang , Chen Weiping , Wang Xin-Wei , Soto-Gutierrez Alejandro , Zhao Keji , Deng Chu-Xia
Published: June 2016

Sirtuin 1 (SIRT1) is involved in both aging and circadian-clock regulation, yet the link between the two processes in relation to SIRT1 function is not clear. Using Sirt1-deficient mice, we found that Sirt1 and Period 2 (Per2) constitute a reciprocal negative regulation loop that plays important roles in modulating hepatic circadian rhythmicity and aging. Sirt1-deficient mice exhibited profound premature aging and enhanced acetylation of histone H4 on lysine16 (H4K16) in the promoter of Per2, the latter of which leads to its overexpression; in turn, Per2 suppresses Sirt1 transcription through binding to the Sirt1 promoter at the Clock/Bmal1 site. This negative reciprocal relationship between SIRT1 and PER2 was also observed in human hepatocytes. We further demonstrated that the absence of Sirt1 or the ectopic overexpression of Per2 in the liver resulted in a dysregulated pace of the circadian rhythm. The similar circadian rhythm was also observed in aged wild type mice. The interplay between Sirt1 and Per2 modulates aging gene expression and circadian-clock maintenance.
Stress-induced nuclear translocation of CDK5 suppresses neuronal death by downregulating ERK activation via VRK3 phosphorylation
Authors: Song Haengjin , Kim Wanil , Choi Jung-Hyun , Kim Sung-Hoon , Lee Dohyun , Park Choon-Ho , Kim Sangjune , Kim Do-Yeon , Kim Kyong-Tai
Published: June 2016

Although extracellular signal-related kinase 1/2 (ERK 1/2) activity is generally associated with cell survival, prolonged ERK activation induced by oxidative stress also mediates neuronal cell death. Here we report that oxidative stress-induced cyclin-dependent kinase 5 (CDK5) activation stimulates neuroprotective signaling via phosphorylation of vaccinia-related kinase 3 (VRK3) at Ser 108. The binding of vaccinia H1-related (VHR) phosphatase to phosphorylated VRK3 increased its affinity for phospho-ERK and subsequently downregulated ERK activation. Overexpression of VRK3 protected human neuroblastoma SH-SY5Y cells against hydrogen peroxide (H2O2)-induced apoptosis. However the CDK5 was unable to phosphorylate mutant VRK3, and thus the mutant forms of VRK3 could not attenuate apoptotic process. Suppression of CDK5 activity results in increase of ERK activation and elevation of proapoptotic protein Bak expression in mouse cortical neurons. Results from VRK3-deficient neurons were further confirmed the role of VRK3 phosphorylation in H2O2-evoked ERK regulation. Importantly, we showed an association between phospho-VRK3 levels and the progression of human Alzheimer’s disease (AD) and Parkinson’s disease (PD). Together our work reveals endogenous protective mechanism against oxidative stress-induced neuronal cell death and suggest VRK3 as a potential therapeutic target in neurodegenerative diseases.
DDX3 Represses Stemness by Epigenetically Modulating Tumor-suppressive miRNAs in Hepatocellular Carcinoma
Authors: Li Hao-Kang , Mai Ru-Tsun , Huang Hsien-Da , Chou Chih-Hung , Chang Yi-An , Chang Yao-Wen , You Li-Ru , Chen Chun-Ming , Lee Yan-Hwa Wu
Published: June 2016

Studies indicate that the presence of cancer stem cells (CSCs) is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, the functional role of DDX3 in regulation of hepatic CSCs was investigated. Our results demonstrated that reduced DDX3 expression was not only inversely associated with tumor grade, but also predicted poor prognosis of HCC patients. Knockdown of DDX3 in HCC cell line HepG2 induced stemness gene signature followed by occurrence of self-renewal, chemoreisistance, EMT, migration as well as CSC expansion and most importantly, DDX3 knockdown promotes tumorigenesis. Moreover, we found positive correlations between DDX3 level and expressions of tumor-suppressive miR-200b, miR-200c, miR-122 and miR-145, but not miR-10b and miR-519a, implying their involvement in DDX3 knockdown-induced CSC phenotypes. In addition, DDX3 reduction promoted up-regulation of DNA methyltransferase 3A (DNMT3A), while neither DNMT3B nor DNMT1 expression was affected. Enriched DNMT3A binding along with hypermethylation on promoters of these tumor-suppressive miRNAs reflected their transcriptional repressions in DDX3-knockdown cells. Furthermore, individual restoration of these tumor-suppressive miRNAs represses DDX3 knockdown-induced CSC phenotypes. In conclusion, our study suggested that DDX3 prevents generation of CSCs through epigenetically regulating a subset of tumor-suppressive miRNAs expressions, which strengthens tumor suppressor role of DDX3 in HCC.
Quantitative analysis of co-oligomer formation by amyloid-beta peptide isoforms
Authors: Iljina Marija , Garcia Gonzalo A. , Dear Alexander J. , Flint Jennie , Narayan Priyanka , Michaels Thomas C. T. , Dobson Christopher M. , Frenkel Daan , Knowles Tuomas P. J. , Klenerman David
Published: June 2016

Multiple isoforms of aggregation-prone proteins are present under physiological conditions and have the propensity to assemble into co-oligomers with different properties from self-oligomers, but this process has not been quantitatively studied to date. We have investigated the amyloid-β (Aβ) peptide, associated with Alzheimer’s disease, and the aggregation of its two major isoforms, Aβ40 and Aβ42, using a statistical mechanical modelling approach in combination with in vitro single-molecule fluorescence measurements. We find that at low concentrations of Aβ, corresponding to its physiological abundance, there is little free energy penalty in forming co-oligomers, suggesting that the formation of both self-oligomers and co-oligomers is possible under these conditions. Our model is used to predict the oligomer concentration and size at physiological concentrations of Aβ and suggests the mechanisms by which the ratio of Aβ42 to Aβ40 can affect cell toxicity. An increased ratio of Aβ42 to Aβ40 raises the fraction of oligomers containing Aβ42, which can increase the hydrophobicity of the oligomers and thus promote deleterious binding to the cell membrane and increase neuronal damage. Our results suggest that co-oligomers are a common form of aggregate when Aβ isoforms are present in solution and may potentially play a significant role in Alzheimer’s disease.
RETRACTED ARTICLE: High Expression of RIOK2 and NOB1 Predict Human Non-small Cell Lung Cancer Outcomes
Authors: Liu Kun , Chen Hong-Lin , Wang Shuo , Gu Ming-Ming , Chen Xin-Ming , Zhang Shuang-Long , Yu Kang-Jun , You Qing-Sheng
Published: June 2016

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. However, there is a shortage of suitable diagnostic markers for early stages of NSCLC and therapeutic targets are limited. Right open reading frame (Rio) kinase 2 (RIOK2) and Nin one binding (NOB1) protein are important accessory factors in ribosome assembly and are highly expressed in malignant tumours; moreover, they interact with each other. However, the RIOK2 expression profile and its clinical significance as well as NOB1’s mechanism in NSCLC remain unknown. In this study, NSCLC cell lines and 15 NSCLC tumour tissues (paired with adjacent normal lung tissues) were collected for a real-time quantitative PCR (RT-qPCR) analysis. In addition, 153 NSCLC cases and 27 normal lung tissues were used in an immunohistochemical analysis to evaluate the RIOK2 and NOB1 expression profiles, their clinicopathological factors in NSCLC and their correlations with prognoses. RIOK2 and NOB1 were highly expressed in NSCLC cells and tissues and their expression profiles were significantly associated with the Tumour Node Metastasis (TNM) clinical stage, lymph node metastasis and differentiation. RIOK2 expression was correlated with NOB1. The results suggested that simultaneously determining the expression of RIOK2 and NOB1 will improve the diagnostic rate in early stages of NSCLC. Moreover, RIOK2 and NOB1 might be potential targets for NSCLC therapy.
Ndk, a novel host-responsive regulator, negatively regulates bacterial virulence through quorum sensing in Pseudomonas aeruginosa
Authors: Yu Hua , Xiong Junzhi , Zhang Rong , Hu Xiaomei , Qiu Jing , Zhang Di , Xu Xiaohui , Xin Rong , He Xiaomei , Xie Wei , Sheng Halei , Chen Qian , Zhang Le , Rao Xiancai , Zhang Kebin
Published: June 2016

Pathogenic bacteria could adjust gene expression to enable their survival in the distinct host environment. However, the mechanism by which bacteria adapt to the host environment is not well described. In this study, we demonstrated that nucleoside diphosphate kinase (Ndk) of Pseudomonas aeruginosa is critical for adjusting the bacterial virulence determinants during infection. Ndk expression was down-regulated in the pulmonary alveoli of a mouse model of acute pneumonia. Knockout of ndk up-regulated transcription factor ExsA-mediated T3S regulon expression and decreased exoproduct-related gene expression through the inhibition of the quorum sensing hierarchy. Moreover, in vitro and in vivo studies demonstrated that the ndk mutant exhibits enhanced cytotoxicity and host pathogenicity by increasing T3SS proteins. Taken together, our data reveal that ndk is a critical novel host-responsive gene required for coordinating P. aeruginosa virulence upon acute infection.
Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicits neutralizing antibodies against JEV and hepatitis C virus
Authors: Saga Ryohei , Fujimoto Akira , Watanabe Noriyuki , Matsuda Mami , Hasegawa Makoto , Watashi Koichi , Aizaki Hideki , Nakamura Noriko , Tajima Shigeru , Takasaki Tomohiko , Konishi Eiji , Kato Takanobu , Kohara Michinori , Takeyama Haruko , Wakita Takaji , Suzuki Ryosuke
Published: June 2016

Directly acting antivirals recently have become available for the treatment of hepatitis C virus (HCV) infection, but there is no prophylactic vaccine for HCV. In the present study, we took advantage of the properties of Japanese encephalitis virus (JEV) to develop antigens for use in a HCV vaccine. Notably, the surface-exposed JEV envelope protein is tolerant of inserted foreign epitopes, permitting display of novel antigens. We identified 3 positions that permitted insertion of the HCV E2 neutralization epitope recognized by HCV1 antibody. JEV subviral particles (SVP) containing HCV-neutralization epitope (SVP-E2) were purified from culture supernatant by gel chromatography. Sera from mice immunized with SVP-E2 inhibited infection by JEV and by trans-complemented HCV particles (HCVtcp) derived from multi-genotypic viruses, whereas sera from mice immunized with synthetic E2 peptides did not show any neutralizing activity. Furthermore, sera from mice immunized with SVP-E2 neutralized HCVtcp with N415K escape mutation in E2. As with the SVP-E2 epitope-displaying particles, JEV SVPs with HCV E1 epitope also elicited neutralizing antibodies against HCV. Thus, this novel platform harboring foreign epitopes on the surface of the particle may facilitate the development of a bivalent vaccine against JEV and other pathogens.
Evidence of extensive non-allelic gene conversion among LTR elements in the human genome
Authors: Trombetta Beniamino , Fantini Gloria , D’Atanasio Eugenia , Sellitto Daniele , Cruciani Fulvio
Published: June 2016

Long Terminal Repeats (LTRs) are nearly identical DNA sequences found at either end of Human Endogenous Retroviruses (HERVs). The high sequence similarity that exists among different LTRs suggests they could be substrate of ectopic gene conversion events. To understand the extent to which gene conversion occurs and to gain new insights into the evolutionary history of these elements in humans, we performed an intra-species phylogenetic study of 52 LTRs on different unrelated Y chromosomes. From this analysis, we obtained direct evidence that demonstrates the occurrence of ectopic gene conversion in several LTRs, with donor sequences located on both sex chromosomes and autosomes. We also found that some of these elements are characterized by an extremely high density of polymorphisms, showing one of the highest nucleotide diversities in the human genome, as well as a complex patchwork of sequences derived from different LTRs. Finally, we highlighted the limits of current short-read NGS studies in the analysis of genetic diversity of the LTRs in the human genome. In conclusion, our comparative re-sequencing analysis revealed that ectopic gene conversion is a common event in the evolution of LTR elements, suggesting complex genetic links among LTRs from different chromosomes.
Hybrid-Actuating Macrophage-Based Microrobots for Active Cancer Therapy
Authors: Han Jiwon , Zhen Jin , Du Nguyen Van , Go Gwangjun , Choi Youngjin , Ko Seong Young , Park Jong-Oh , Park Sukho
Published: June 2016

Using macrophage recruitment in tumors, we develop active, transportable, cancer theragnostic macrophage-based microrobots as vector to deliver therapeutic agents to tumor regions. The macrophage-based microrobots contain docetaxel (DTX)-loaded poly-lactic-co-glycolic-acid (PLGA) nanoparticles (NPs) for chemotherapy and Fe3O4 magnetic NPs (MNPs) for active targeting using an electromagnetic actuation (EMA) system. And, the macrophage-based microrobots are synthesized through the phagocytosis of the drug NPs and MNPs in the macrophages. The anticancer effects of the microrobots on tumor cell lines (CT-26 and 4T1) are evaluated in vitro by cytotoxic assay. In addition, the active tumor targeting by the EMA system and macrophage recruitment, and the chemotherapeutic effect of the microrobots are evaluated using three-dimensional (3D) tumor spheroids. The microrobots exhibited clear cytotoxicity toward tumor cells, with a low survivability rate (<50%). The 3D tumor spheroid assay showed that the microrobots demonstrated hybrid actuation through active tumor targeting by the EMA system and infiltration into the tumor spheroid by macrophage recruitment, resulting in tumor cell death caused by the delivered antitumor drug. Thus, the active, transportable, macrophage-based theragnostic microrobots can be considered to be biocompatible vectors for cancer therapy.
New insights into salvianolic acid A action: Regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways ameliorates HFD-induced NAFLD in rats
Authors: Ding Chunchun , Zhao Yan , Shi Xue , Zhang Ning , Zu Guo , Li Zhenlu , Zhou Junjun , Gao Dongyan , Lv Li , Tian Xiaofeng , Yao Jihong
Published: June 2016

Salvianolic acid A (SalA), one of the most efficacious polyphenol compounds extracted from Radix Salvia miltiorrhiza (Danshen), has been shown to possess many potential pharmacological activities. This study aimed to investigate whether SalA has hepatoprotective effects against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and to further explore the mechanism underlying this process. SalA treatment significantly attenuated HFD-induced obesity and liver injury and markedly decreased lipid accumulation in HFD-fed rat livers. Moreover, SalA treatment ameliorated HFD-induced hepatic inflammation and oxidative stress by decreasing hepatotoxic levels of cytokines, suppressing the overproduction of reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) and preventing the decreased expression of superoxide dismutase (SOD). Importantly, SalA reversed the HFD- or palmitic acid (PA)-induced activation of the NLRP3 inflammasome, the nuclear translocation of ChREBP and the up-regulation of FAS and these effects were accompanied by TXNIP down-regulation. However, TXNIP siRNA treatment partially abrogated the above-mentioned effects of SalA in PA-treated HepG2 cells. Together, our results demonstrated, for the first time, that SalA protects against HFD-induced NAFLD by ameliorating hepatic lipid accumulation and inflammation and these protective effects may partially due to regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways.
Transverse writing of three-dimensional tubular optical waveguides in glass with a slit-shaped femtosecond laser beam
Authors: Liao Yang , Qi Jia , Wang Peng , Chu Wei , Wang Zhaohui , Qiao Lingling , Cheng Ya
Published: June 2016

We report on fabrication of tubular optical waveguides buried in ZBLAN glass based on transverse femtosecond laser direct writing. Irradiation in ZBLAN with focused femtosecond laser pulses leads to decrease of refractive index in the modified region. Tubular optical waveguides of variable mode areas are fabricated by forming the four sides of the cladding with slit-shaped femtosecond laser pulses, ensuring single mode waveguiding with a mode field dimension as small as ~4 μm.
DJ-1 deficiency impairs glutamate uptake into astrocytes via the regulation of flotillin-1 and caveolin-1 expression
Authors: Kim Jin-Mo , Cha Seon-Heui , Choi Yu Ree , Jou Ilo , Joe Eun-Hye , Park Sang Myun
Published: June 2016

Parkinson’s disease (PD) is a common chronic and progressive neurodegenerative disorder. Although the cause of PD is still poorly understood, mutations in many genes including SNCA, parkin, PINK1, LRRK2, and DJ-1 have been identified in the familial forms of PD. It was recently proposed that alterations in lipid rafts may cause the neurodegeneration shown in PD. Here, we observe that DJ-1 deficiency decreased the expression of flotillin-1 (flot-1) and caveolin-1 (cav-1), the main protein components of lipid rafts, in primary astrocytes and MEF cells. As a mechanism, DJ-1 regulated flot-1 stability by direct interaction, however, decreased cav-1 expression may not be a direct effect of DJ-1, but rather as a result of decreased flot-1 expression. Dysregulation of flot-1 and cav-1 by DJ-1 deficiency caused an alteration in the cellular cholesterol level, membrane fluidity, and alteration in lipid rafts-dependent endocytosis. Moreover, DJ-1 deficiency impaired glutamate uptake into astrocytes, a major function of astrocytes in the maintenance of CNS homeostasis, by altering EAAT2 expression. This study will be helpful to understand the role of DJ-1 in the pathogenesis of PD, and the modulation of lipid rafts through the regulation of flot-1 or cav-1 may be a novel therapeutic target for PD.
Structural and functional characterization of the CAP domain of pathogen-related yeast 1 (Pry1) protein
Authors: Darwiche Rabih , Kelleher Alan , Hudspeth Elissa M. , Schneiter Roger , Asojo Oluwatoyin A.
Published: June 2016

The production, crystal structure and functional characterization of the C-terminal cysteine-rich secretory protein/antigen 5/pathogenesis related-1 (CAP) domain of pathogen-related yeast protein-1 (Pry1) from Saccharomyces cerevisiae is presented. The CAP domain of Pry1 (Pry1CAP) is functional in vivo as its expression restores cholesterol export to yeast mutants lacking endogenous Pry1 and Pry2. Recombinant Pry1CAP forms dimers in solution, is sufficient for in vitro cholesterol binding and has comparable binding properties as full-length Pry1. Two crystal structures of Pry1CAP are reported, one with Mg2+ coordinated to the conserved CAP tetrad (His208, Glu215, Glu233 and His250) in spacegroup I41 and the other without divalent cations in spacegroup P6122. The latter structure contains four 1,4-dioxane molecules from the crystallization solution, one of which sits in the cholesterol binding site. Both structures reveal that the divalent cation and cholesterol binding sites are connected upon dimerization, providing a structural basis for the observed Mg2+-dependent sterol binding by Pry1.
A coordination driven self-assembled Pd6L8 nanoball catalyses copper and phosphine-free Sonogashira coupling reaction in both homogeneous and heterogeneous formats
Authors: Pradhan Subhashis , Dutta Subhadip , John Rohith P.
Published: June 2016

A self-assembled Pd6L8 nanocage catalysed copper free Sonogashira reaction under mild and aerobic conditions, at 100 ppm catalyst loading in aqueous medium in the homogeneous phase, and at 500 ppm in the heterogeneous phase.
Cy5/BHQ dye–quencher pairs in fluorogenic qPCR probes: effects of charge and hydrophobicity
Authors: Farzan Valentina M. , Aparin Ilya O. , Veselova Olga A. , Podkolzin Alexander T. , Shipulin German A. , Korshun Vladimir A. , Zatsepin Timofei S.
Published: June 2016

For the first time we used a CuAAC click reaction for the synthesis of cyanine labeled qPCR probes.
Role of nucleation mechanism on the size dependent morphology of organic aerosol
Authors: Altaf Muhammad Bilal , Zuend Andreas , Freedman Miriam Arak
Published: June 2016

The size dependent morphology of PEG-400/ammonium sulfate aerosol originates from an activated process during phase separation by nucleation and growth.
On the existence of intramolecular one-electron Be–Be bonds
Authors: Brea Oriana , Mó Otilia , Yáñez Manuel , Alkorta Ibon , Elguero José
Published: June 2016

The electron attachment to 1,8-diBeX-naphthalene derivatives leads to rather stable radical anions through the formation of one-electron Be–Be bonds.
The different roles of a cationic gold(i) complex in catalysing hydroarylation of alkynes and alkenes with a heterocycle
Authors: Mehrabi Tahmineh , Ariafard Alireza
Published: June 2016

Hydroarylation of alkenes is promoted by a proton released by interaction of a cationic gold complex with an acidic species.
Dual electrically and thermally responsive broadband reflectors based on polymer network stabilized chiral nematic liquid crystals: the role of crosslink density
Authors: Khandelwal Hitesh , Timmermans Gilles H. , Debije Michael G. , Schenning Albertus P. H. J.
Published: June 2016

An adjustable broadband reflector based on a polymer stabilized chiral nematic liquid crystal has been fabricated.
Peripheral ligands as electron storage reservoirs and their role in enhancement of photocatalytic hydrogen generation
Authors: Pan Qing , Freitag Leon , Kowacs Tanja , Falgenhauer Jane C. , Korterik Jeroen P. , Schlettwein Derck , Browne Wesley R. , Pryce Mary T. , Rau Sven , González Leticia , Vos Johannes G. , Huijser Annemarie
Published: June 2016

The contrasting early-time photodynamics of two related Ru/Pt photocatalysts are reported.
35Cl solid-state NMR spectroscopy of HCl pharmaceuticals and their polymorphs in bulk and dosage forms
Authors: Namespetra Andrew M. , Hirsh David A. , Hildebrand Marcel P. , Sandre Anthony R. , Hamaed Hiyam , Rawson Jeremy M. , Schurko Robert W.
Published: June 2016

Herein, we demonstrate the use of 35Cl SSNMR for the structural fingerprinting of HCl salts of pharmaceuticals in both bulk and dosage forms.
Isn't the space-charge potential in ceria-based solid electrolytes largely overestimated?
Authors: Kim Sangtae
Published: June 2016

The height of the potential barrier at the grain boundary in concentrated ceria solid solutions found in the literature is largely overestimated.
Does the Dirac cone of germanene exist on metal substrates?
Authors: Wang Yangyang , Li Jingzhen , Xiong Junhua , Pan Yuanyuan , Ye Meng , Guo Ying , Zhang Han , Quhe Ruge , Lu Jing
Published: June 2016

The contrast of the band structures of silicene and germanene on the metal substrates. The Dirac cone of germanene is identifiable.
Molecular mechanics of the cooperative adsorption of a Pro-Hyp-Gly tripeptide on a hydroxylated rutile TiO2(110) surface mediated by calcium ions
Authors: Zheng Ting , Wu Chunya , Chen Mingjun , Zhang Yu , Cummings Peter T.
Published: June 2016

Calcium ions play an cooperative role during peptide adsorption on the hydroxylated rutile TiO2(110) surface and the molecular mechanics was studied.
Switchable polarization in an unzipped graphene oxide monolayer
Authors: Noor-A-Alam Mohammad , Shin Young-Han
Published: June 2016

Unzipped graphene oxide monolayers have polar configurations that are more stable than the flat ones, when the unit cell is doubled along the y axis, the antiferroelectric-like non-polar configuration is more stable than the polar one.
Catalytic activity of Pt38 in the oxygen reduction reaction from first-principles simulations
Authors: Sementa Luca , Andreussi Oliviero , Goddard III William A. , Fortunelli Alessandro
Published: June 2016

Mechanism of OHads/Pt38 diffusion via transient hydronium species in first-principles molecular dynamics simulations.