bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary soy and meat proteins induce distinct physiological and gene expression changes in rats
Authors: Song Shangxin , Hooiveld Guido J. , Li Mengjie , Zhao Fan , Zhang Wei , Xu Xinglian , Muller Michael , Li Chunbao , Zhou Guanghong
Published: February 2016

This study reports on a comprehensive comparison of the effects of soy and meat proteins given at the recommended level on physiological markers of metabolic syndrome and the hepatic transcriptome. Male rats were fed semi-synthetic diets for 1 wk that differed only regarding protein source, with casein serving as reference. Body weight gain and adipose tissue mass were significantly reduced by soy but not meat proteins. The insulin resistance index was improved by soy and to a lesser extent by meat proteins. Liver triacylglycerol contents were reduced by both protein sources, which coincided with increased plasma triacylglycerol concentrations. Both soy and meat proteins changed plasma amino acid patterns. The expression of 1571 and 1369 genes were altered by soy and meat proteins respectively. Functional classification revealed that lipid, energy and amino acid metabolic pathways, as well as insulin signaling pathways were regulated differently by soy and meat proteins. Several transcriptional regulators, including NFE2L2, ATF4, Srebf1 and Rictor were identified as potential key upstream regulators. These results suggest that soy and meat proteins induce distinct physiological and gene expression responses in rats and provide novel evidence and suggestions for the health effects of different protein sources in human diets.
Continuous quantification of HER2 expression by microfluidic precision immunofluorescence estimates HER2 gene amplification in breast cancer
Authors: Dupouy Diego G. , Ciftlik Ata Tuna , Fiche Maryse , Heintze Déborah , Bisig Bettina , de Leval Laurence , Gijs Martin A. M.
Published: February 2016

Chromogenic immunohistochemistry (IHC) is omnipresent in cancer diagnosis, but has also been criticized for its technical limit in quantifying the level of protein expression on tissue sections, thus potentially masking clinically relevant data. Shifting from qualitative to quantitative, immunofluorescence (IF) has recently gained attention, yet the question of how precisely IF can quantify antigen expression remains unanswered, regarding in particular its technical limitations and applicability to multiple markers. Here we introduce microfluidic precision IF, which accurately quantifies the target expression level in a continuous scale based on microfluidic IF staining of standard tissue sections and low-complexity automated image analysis. We show that the level of HER2 protein expression, as continuously quantified using microfluidic precision IF in 25 breast cancer cases, including several cases with equivocal IHC result, can predict the number of HER2 gene copies as assessed by fluorescence in situ hybridization (FISH). Finally, we demonstrate that the working principle of this technology is not restricted to HER2 but can be extended to other biomarkers. We anticipate that our method has the potential of providing automated, fast and high-quality quantitative in situ biomarker data using low-cost immunofluorescence assays, as increasingly required in the era of individually tailored cancer therapy.
Dictyocaulus viviparus genome, variome and transcriptome elucidate lungworm biology and support future intervention
Authors: McNulty Samantha N. , Strübe Christina , Rosa Bruce A. , Martin John C. , Tyagi Rahul , Choi Young-Jun , Wang Qi , Hallsworth Pepin Kymberlie , Zhang Xu , Ozersky Philip , Wilson Richard K. , Sternberg Paul W. , Gasser Robin B. , Mitreva Makedonka
Published: February 2016

The bovine lungworm, Dictyocaulus viviparus (order Strongylida), is an important parasite of livestock that causes substantial economic and production losses worldwide. Here we report the draft genome, variome and developmental transcriptome of D. viviparus. The genome (161 Mb) is smaller than those of related bursate nematodes and encodes fewer proteins (14,171 total). In the first genome-wide assessment of genomic variation in any parasitic nematode, we found a high degree of sequence variability in proteins predicted to be involved host-parasite interactions. Next, we used extensive RNA sequence data to track gene transcription across the life cycle of D. viviparus and identified genes that might be important in nematode development and parasitism. Finally, we predicted genes that could be vital in host-parasite interactions, genes that could serve as drug targets and putative RNAi effectors with a view to developing functional genomic tools. This extensive, well-curated dataset should provide a basis for developing new anthelmintics, vaccines and improved diagnostic tests and serve as a platform for future investigations of drug resistance and epidemiology of the bovine lungworm and related nematodes.
Selective and reversible suppression of intestinal stem cell differentiation by pharmacological inhibition of BET bromodomains
Authors: Nakagawa Akifumi , Adams Curtis E. , Huang Yinshi , Hamarneh Sulaiman R. , Liu Wei , Von Alt Kate N. , Mino-Kenudson Mari , Hodin Richard A. , Lillemoe Keith D. , Fernández-del Castillo Carlos , Warshaw Andrew L. , Liss Andrew S.
Published: February 2016

Absorptive and secretory cells of the small intestine are derived from a single population of Lgr5-expressing stem cells. While key genetic pathways required for differentiation into specific lineages have been defined, epigenetic programs contributing to this process remain poorly characterized. Members of the BET family of chromatin adaptors contain tandem bromodomains that mediate binding to acetylated lysines on target proteins to regulate gene expression. In this study, we demonstrate that mice treated with a small molecule inhibitor of BET bromodomains, CPI203, exhibit greater than 90% decrease in tuft and enteroendocrine cells in both crypts and villi of the small intestine, with no changes observed in goblet or Paneth cells. BET bromodomain inhibition did not alter the abundance of Lgr5-expressing stem cells in crypts, but rather exerted its effects on intermediate progenitors, in part through regulation of Ngn3 expression. When BET bromodomain inhibition was combined with the chemotherapeutic gemcitabine, pervasive apoptosis was observed in intestinal crypts, revealing an important role for BET bromodomain activity in intestinal homeostasis. Pharmacological targeting of BET bromodomains defines a novel pathway required for tuft and enteroendocrine differentiation and provides an important tool to further dissect the progression from stem cell to terminally differentiated secretory cell.
Human monocytes undergo functional re-programming during differentiation to dendritic cell mediated by human extravillous trophoblasts
Authors: Zhao Lei , Shao Qianqian , Zhang Yun , Zhang Lin , He Ying , Wang Lijie , Kong Beihua , Qu Xun
Published: February 2016

Maternal immune adaptation is required for a successful pregnancy to avoid rejection of the fetal–placental unit. Dendritic cells within the decidual microenvironment lock in a tolerogenic profile. However, how these tolerogenic DCs are induced and the underlying mechanisms are largely unknown. In this study, we show that human extravillous trophoblasts redirect the monocyte-to-DC transition and induce regulatory dendritic cells. DCs differentiated from blood monocytes in the presence of human extravillous trophoblast cell line HTR-8/SVneo displayed a DC-SIGN+CD14+CD1a− phenotype, similar with decidual DCs. HTR8-conditioned DCs were unable to develop a fully mature phenotype in response to LPS and altered the cytokine secretory profile significantly. Functionally, conditioned DCs poorly induced the proliferation and activation of allogeneic T cells, whereas promoted CD4+CD25+Foxp3+ Treg cells generation. Furthermore, the supernatant from DC and HTR-8/SVneo coculture system contained significant high amount of M-CSF and MCP-1. Using neutralizing antibodies, we discussed the role of M-CSF and MCP-1 during monocyte-to-DCs differentiation mediated by extravillous trophoblasts. Our data indicate that human extravillous trophoblasts play an important role in modulating the monocyte-to-DC differentiation through M-CSF and MCP-1, which facilitate the establishment of a tolerogenic microenvironment at the maternal–fetal interface.
Selective plasmon-driven catalysis for para-nitroaniline in aqueous environments
Authors: Cui Lin , Wang Peijie , Li Yuanzuo , Sun Mengtao
Published: February 2016

The plasmon-driven oxidation of amine (−NH2) groups and the reduction of nitro (−NO2) groups on a nanostructured metal surface in an aqueous environment have been reported experimentally and theoretically. The question of which process occurs first in the aqueous environment is an interesting question in the field of plasmon-related photochemistry. Para-nitroaniline (PNA), with both nitro (−NO2) and amine (−NH2) groups, is the best candidate for studying the priority of the plasmon-driven oxidation and the reduction reactions in an aqueous environment. Using surface-enhanced Raman scattering (SERS) spectroscopy, our experimental results and theoretical simulations reveal that PNA is selectively catalyzed to 4,4′-diaminoazobenzene (DAAB) through the plasmon-assisted dimerization of the nitro (−NO2) group into an azo group in an aqueous environment. This indicates that the plasmon-driven reduction of the nitro (−NO2) group clearly occurs before the oxidation of the amine (−NH2) group in an aqueous environment. The plasmon-driven reduction of PNA to DAAB is a selective surface catalytic reduced reaction in aqueous environment.
Small-molecule inhibition of PTPRZ reduces tumor growth in a rat model of glioblastoma
Authors: Fujikawa Akihiro , Nagahira Asako , Sugawara Hajime , Ishii Kentaro , Imajo Seiichi , Matsumoto Masahito , Kuboyama Kazuya , Suzuki Ryoko , Tanga Naomi , Noda Masanori , Uchiyama Susumu , Tomoo Toshiyuki , Ogata Atsuto , Masumura Makoto , Noda Masaharu
Published: February 2016

Protein tyrosine phosphatase receptor-type Z (PTPRZ) is aberrantly over-expressed in glioblastoma and a causative factor for its malignancy. However, small molecules that selectively inhibit the catalytic activity of PTPRZ have not been discovered. We herein performed an in vitro screening of a chemical library and identified SCB4380 as the first potent inhibitor for PTPRZ. The stoichiometric binding of SCB4380 to the catalytic pocket was demonstrated by biochemical and mass spectrometric analyses. We determined the crystal structure of the catalytic domain of PTPRZ and the structural basis of the binding of SCB4380 elucidated by a molecular docking method was validated by site-directed mutagenesis studies. The intracellular delivery of SCB4380 by liposome carriers inhibited PTPRZ activity in C6 glioblastoma cells and thereby suppressed their migration and proliferation in vitro and tumor growth in a rat allograft model. Therefore, selective inhibition of PTPRZ represents a promising approach for glioma therapy.
The Biosynthesis of Infrared-Emitting Quantum Dots in Allium Fistulosum
Authors: Green M. , Haigh S. J. , Lewis E. A. , Sandiford L. , Burkitt-Gray M. , Fleck R. , Vizcay-Barrena G. , Jensen L. , Mirzai H. , Curry R. J. , Dailey L.-A.
Published: February 2016

The development of simple routes to emissive solid-state materials is of paramount interest and in this report we describe the biosynthesis of infrared emitting quantum dots in a living plant via a mutual antagonistic reaction. Exposure of common Allium fistulosum to mercury and tellurium salts under ambient conditions resulted in the expulsion of crystalline, non-passivated HgTe quantum dots that exhibited emissive characteristics in the near-infrared spectral region, a wavelength range that is important in telecommunications and solar energy conversion.
Lanthanum and Neodymium Doped Barium Ferrite-TiO2/MCNTs/poly(3-methyl thiophene) Composites with Nest Structures: Preparation, Characterization and Electromagnetic Microwave Absorption Properties
Authors: Zhao Jie , Yu Jian , Xie Yu , Le Zhanggao , Hong Xiaowei , Ci Suqin , Chen Junhong , Qing Xiaoyan , Xie Weijie , Wen Zhenhai
Published: February 2016

We report herein the synthesis of a novel nest structured electromagnetic composite through in-situ chemical polymerization of 3-methyl thiophene (3MT) in the presence of the BaFe11.92(LaNd)0.04O19-TiO2 (BFTO) nanoparticles and MCNTs. As an absorbing material, the BFTO/MCNTs/P3MT/wax composites were prepared at various loadings of BFTO/MCNTs/P3MT (0.2:0.10:1.0 ~ 0.2:0.30:1.0) and they exhibited strong microwave absorption properties in the range of 1.0–18 GHz. When the loading of BFTO/MCNTs/P3MT is 0.2:0.30:1.0, the composite has a strongest absorbing peak at 11.04 GHz and achieves a maximum absorbing value of −21.56 dB. The absorbing peak position moves to higher frequencies with the increase of MCNTs content. The mechanism for microwave absorption of these composites has been explained in detail.
Quantitative assessment of radiation force effect at the dielectric air-liquid interface
Authors: Capeloto Otávio Augusto , Zanuto Vitor Santaella , Malacarne Luis Carlos , Baesso Mauro Luciano , Lukasievicz Gustavo Vinicius Bassi , Bialkowski Stephen Edward , Astrath Nelson Guilherme Castelli
Published: February 2016

We induce nanometer-scale surface deformation by exploiting momentum conservation of the interaction between laser light and dielectric liquids. The effect of radiation force at the air-liquid interface is quantitatively assessed for fluids with different density, viscosity and surface tension. The imparted pressure on the liquids by continuous or pulsed laser light excitation is fully described by the Helmholtz electromagnetic force density.
The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells
Authors: Sharma Dileep , Hamlet Stephen Mark , Petcu Eugen Bogdan , Ivanovski Saso
Published: February 2016

The contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This in vitro study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities. pMSC multipotency was confirmed by successful differentiation into cells of both the osteogenic and endothelial lineages, as demonstrated by positive Alizarin Red S staining and Ac-LDL uptake. pMSC differentiation in the presence of non-cytotoxic BP concentrations showed that nitrogen containing BPs had a significant inhibitory effect on cell migration and endothelial marker gene expression, as well as compromised endothelial differentiation as demonstrated using von Willebrand factor immunofluorescence staining and tube formation assay. This in vitro study demonstrated that at non-cytotoxic levels, nitrogen-containing BPs inhibit differentiation of pMSCs into cells of an endothelial lineage and affect the downstream functional capability of these cells supporting a multi-modal effect of BPs on angiogenesis as pathogenic mechanism contributing to bone healing disorders such as bisphosphonate related osteonecrosis of the jaws (BRONJ).
TGFβ3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis
Authors: Qin Xing , Yan Ming , Zhang Jianjun , Wang Xu , Shen Zongze , Lv Zhongjing , Li Zhihui , Wei Wenyi , Chen Wantao
Published: February 2016

The matrix-specific protein periostin (POSTN) is up-regulated in human cancers and associated with cancer growth, metastasis and angiogenesis. Although the stroma of cancer tissues is the main source of POSTN, it is still unclear how POSTN plays a role to facilitate the interplay between cancer cells and cancer-associated fibroblasts (CAFs) in head and neck cancer (HNC), thereby promoting tumorigenesis via modifying the tumor microenvironment. Herein, we have performed studies to investigate POSTN and its role in HNC microenvironment. Our results indicated that POSTN was significantly up-regulated in HNCs, especially in the tissues with lymph node metastasis. Moreover, POSTN was highly enriched in the stroma of cancer tissues and produced mainly by CAFs. More importantly, we have pinpointed TGF-β3 as the major upstream molecular that triggers the induction of POSTN in CAFs. As such, during the interaction between fibroblasts and cancer cells, the increased stromal POSTN induced by TGF-β3 directly accelerated the growth, migration and invasion of cancer cells. Hence, our study has provided a novel modulative role for POSTN on HNC progression and further reveals POSTN as an effective biomarker to predict metastasis as well as a potential cancer therapeutic target.
Gold nanoparticle-assisted all optical localized stimulation and monitoring of Ca2+ signaling in neurons
Authors: Lavoie-Cardinal Flavie , Salesse Charleen , Bergeron Éric , Meunier Michel , De Koninck Paul
Published: February 2016

Light-assisted manipulation of cells to control membrane activity or intracellular signaling has become a major avenue in life sciences. However, the ability to perform subcellular light stimulation to investigate localized signaling has been limited. Here, we introduce an all optical method for the stimulation and the monitoring of localized Ca2+ signaling in neurons that takes advantage of plasmonic excitation of gold nanoparticles (AuNPs). We show with confocal microscopy that 800 nm laser pulse application onto a neuron decorated with a few AuNPs triggers a transient increase in free Ca2+, measured optically with GCaMP6s. We show that action potentials, measured electrophysiologically, can be induced with this approach. We demonstrate activation of local Ca2+ transients and Ca2+ signaling via CaMKII in dendritic domains, by illuminating a single or few functionalized AuNPs specifically targeting genetically-modified neurons. This NP-Assisted Localized Optical Stimulation (NALOS) provides a new complement to light-dependent methods for controlling neuronal activity and cell signaling.
Spatial Electron-hole Separation in a One Dimensional Hybrid Organic–Inorganic Lead Iodide
Authors: Savory Christopher N. , Palgrave Robert G. , Bronstein Hugo , Scanlon David O.
Published: February 2016

The increasing efficiency of the inorganic-organic hybrid halides has revolutionised photovoltaic research. Despite this rapid progress, the significant issues of poor stability and toxicity have yet to be suitably overcome. In this article, we use Density Functional Theory to examine (Pb2I6) · (H2DPNDI) · (H2O) · (NMP), an alternative lead-based hybrid inorganic-organic solar absorber based on a photoactive organic cation. Our results demonstrate that optical properties suitable for photovoltaic applications, in addition to spatial electron-hole separation, are possible but efficient charge transport may be a limiting factor.
Sorting nexin 10 acting as a novel regulator of macrophage polarization mediates inflammatory response in experimental mouse colitis
Authors: You Yan , Zhou Chun , Li Dong , Cao Zhong-Lian , Shen Weixing , Li Wan-Zhen , Zhang Sulin , Hu Bin , Shen Xiaoyan
Published: February 2016

In response to changes in microenvironment, macrophages polarize into functionally distinct phenotypes, playing a crucial role in the pathogenesis of inflammatory bowel disease (IBD). Here, we investigated the effects of sorting nexin 10 (SNX10), a protein involved in endosomal trafficking and osteoclast maturation, on regulation of macrophage polarization and progression of mouse colitis. Our results revealed that SNX10 deficiency increased the population of M2-type monocytes/macrophages and protected against colonic inflammation and pathological damage induced by dextran sulfate sodium (DSS). By in vitro study, we showed that deficiency of SNX10 polarized macrophages derived from mouse bone marrow or human peripheral blood mononuclear cells (PBMCs) towards an anti-inflammatory M2 phenotype, which partially reversed by SNX10 plasmid transfection. Adoptive transfer of SNX10−/− macrophages ameliorated colitis in WT mice. However, transfer of WT macrophages exacerbated colitis in SNX10−/− mice. Our data disclose a crucial role and novel function for SNX10 in macrophage polarization. Loss of SNX10 function may be a potential promising therapeutic strategy for IBD.
Efficient graphene saturable absorbers on D-shaped optical fiber for ultrashort pulse generation
Authors: Zapata J. D. , Steinberg D. , Saito L. A. M. , de Oliveira R. E. P. , Cárdenas A. M. , de Souza E. A. Thoroh
Published: February 2016

We demonstrated a method to construct high efficiency saturable absorbers based on the evanescent light field interaction of CVD monolayer graphene deposited on side-polished D-shaped optical fiber. A set of samples was fabricated with two different core-graphene distances (0 and 1 μm), covered with graphene ranging between 10 and 25 mm length. The mode-locking was achieved and the best pulse duration was 256 fs, the shortest pulse reported in the literature with CVD monolayer graphene in EDFL. As result, we find a criterion between the polarization relative extinction ratio in the samples and the pulse duration, which relates the better mode-locking performance with the higher polarization extinction ratio of the samples. This criterion also provides a better understanding of the graphene distributed saturable absorbers and their reproducible performance as optoelectronic devices for optical applications.
Functional transcription factor target discovery via compendia of binding and expression profiles
Authors: Banks Christopher J. , Joshi Anagha , Michoel Tom
Published: February 2016

Genome-wide experiments to map the DNA-binding locations of transcription-associated factors (TFs) have shown that the number of genes bound by a TF far exceeds the number of possible direct target genes. Distinguishing functional from non-functional binding is therefore a major challenge in the study of transcriptional regulation. We hypothesized that functional targets can be discovered by correlating binding and expression profiles across multiple experimental conditions. To test this hypothesis, we obtained ChIP-seq and RNA-seq data from matching cell types from the human ENCODE resource, considered promoter-proximal and distal cumulative regulatory models to map binding sites to genes and used a combination of linear and non-linear measures to correlate binding and expression data. We found that a high degree of correlation between a gene’s TF-binding and expression profiles was significantly more predictive of the gene being differentially expressed upon knockdown of that TF, compared to using binding sites in the cell type of interest only. Remarkably, TF targets predicted from correlation across a compendium of cell types were also predictive of functional targets in other cell types. Finally, correlation across a time course of ChIP-seq and RNA-seq experiments was also predictive of functional TF targets in that tissue.
Genome stability of Propionibacterium acnes: a comprehensive study of indels and homopolymeric tracts
Authors: Scholz Christian F. P. , Brüggemann Holger , Lomholt Hans B. , Tettelin Hervé , Kilian Mogens
Published: February 2016

We present a species-wide comparative analysis of 90 genomes of Propionibacterium acnes that represent the known diversity of the species. Our results are augmented by six high-quality genomes and a manual investigation of all gene-sized indels found in the strains. Overall, the order of genes is conserved throughout the species. A public sybil database for easy comparative analysis of the 90 genomes was established. The analysis of indels revealed a total of 66 loci of non-core genes that correlate with phylogenetic clades. No gene was strain-specific in agreement with our conclusion that the P. acnes pan-genome is closed. An exhaustive search for homopolymeric tracts (HPTs) identified a total of 54 variable-length HPTs almost exclusively of guanine/cytosines located between genes or affecting the reading frame of genes. The repeat variation was consistent with phylogenetic clades suggesting slow accumulation over time rather than active modification. By transcriptome analysis we demonstrate how an HPT variation can affect the gene expression levels. Selected cases of both indels and HPTs are described. The catalogued data and the public P. acnes Sybil database provide a solid foundation for generating hypotheses and facilitate comparative genetic analyses in future P. acnes research.
Pentiptycene-Based Luminescent Cu (II) MOF Exhibiting Selective Gas Adsorption and Unprecedentedly High-Sensitivity Detection of Nitroaromatic Compounds (NACs)
Authors: Zhang Minghui , Zhang Liangliang , Xiao Zhenyu , Zhang Qinhui , Wang Rongming , Dai Fangna , Sun Daofeng
Published: February 2016

The assembly of a fluorescent pentiptycene-based ligand with copper ion resulted in the formation of a 3D porous metal-organic framework (UPC-21) based on well-known paddlewheel SBUs. UPC-21 exhibits selective adsorption of CO2 over CH4 and N2 at 273 K and 295 K, C2H2 over CH4 at 273 K. The most significant performance of UPC-21 is its highly efficient detection of NACs such as 4-NP, 1,4-DNB, NB and 1,3-DNB with the calculated quenching constants, Ksv, being 3.097 × 106, 1.406 × 106, 4.420 × 105 and 1.498 × 105 M−1 for 4-NP, 1,4-DNB, NB, 1,3-DNB, respectively, which keeps a record on the fluorescence detection of NACs. This is the first porous Cu(II) MOF that exhibits fluorescent detection of NACs with high sensitivities.
Cerebral white matter lesions – associations with Aβ isoforms and amyloid PET
Authors: van Westen Danielle , Lindqvist Daniel , Blennow Kaj , Minthon Lennart , Nägga Katarina , Stomrud Erik , Zetterberg Henrik , Hansson Oskar
Published: February 2016

Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of β-amyloid (Aβ) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of Aβ in cerebrospinal fluid (CSF) and cortical Aβ in 831 subjects with cognitive performance ranging from normal to Alzheimer’s disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of Aβ38 and Aβ40 were consistently associated with increased WML in all subgroups, while lower levels of CSF Aβ42 were associated with WML mainly in AD. CSF Aβ38 and Aβ40 were associated with regional WML in all regions, while CSF Aβ42 was associated with temporal WML only. A composite measure of 18F-flutemetamol uptake was not associated with WML, and regional 18F-flutemetamol uptake only with temporal WML. Lacunes were not associated with Aβ isoforms nor 18F-flutemetamol uptake. Our results suggest that WML may be associated with alterations in the production or clearance of Aβ species, particularly of Aβ38 and Aβ40. However, in AD cases, Aβ42 pathology might be associated with WML, especially in the temporal lobe.
A molecular nanodevice for targeted degradation of mRNA during protein synthesis
Authors: Lee Kyung-Ho , Min Seung-Eui , Kim Haseong , Lee Seung-Goo , Kim Dong-Myung
Published: February 2016

RNase H is an endonuclease that catalyzes the cleavage of RNA. Because it only acts on RNA in RNA:DNA hybrids, RNase H can be used for targeted degradation of RNA when used in combination with antisense oligodeoxyribonucleotides (ASODNs) designed against a specific sequence of the target RNA. In this study, ASODN and RNase H were co-conjugated on magnetic nanoparticles. The resulting nanoparticles, having integrated functions of probing and processing target RNA, were able to remove target mRNA sequences more effectively than free ASODNs. The paramagnetic property of the nanoparticles also enabled timed engagement and disengagement of the RNA-degrading components in a given system, and these nanoparticles were able to be used for ON/OFF control of gene expression during cell-free protein synthesis reactions.
Plumericin inhibits proliferation of vascular smooth muscle cells by blocking STAT3 signaling via S-glutathionylation
Authors: Heiss Elke H , Liu Rongxia , Waltenberger Birgit , Khan Shafaat , Schachner Daniel , Kollmann Paul , Zimmermann Kristin , Cabaravdic Muris , Uhrin Pavel , Stuppner Hermann , Breuss Johannes M , Atanasov Atanas G , Dirsch Verena M
Published: February 2016

The etiology of atherosclerosis and restenosis involves aberrant inflammation and proliferation, rendering compounds with both anti-inflammatory and anti-mitogenic properties as promising candidates for combatting vascular diseases. A recent study identified the iridoid plumericin as a new scaffold inhibitor of the pro-inflammatory NF-κB pathway in endothelial cells. We here examined the impact of plumericin on the proliferation of primary vascular smooth muscle cells (VSMC). Plumericin inhibited serum-stimulated proliferation of rat VSMC. It arrested VSMC in the G1/G0-phase of the cell cycle accompanied by abrogated cyclin D1 expression and hindered Ser 807/811-phosphorylation of retinoblastoma protein. Transient depletion of glutathione by the electrophilic plumericin led to S-glutathionylation as well as hampered Tyr705-phosphorylation and activation of the transcription factor signal transducer and activator of transcription 3 (Stat3). Exogenous addition of glutathione markedly prevented this inhibitory effect of plumericin on Stat3. It also overcame downregulation of cyclin D1 expression and the reduction of biomass increase upon serum exposure. This study revealed an anti-proliferative property of plumericin towards VSMC which depends on plumericin’s thiol reactivity and S-glutathionylation of Stat3. Hence, plumericin, by targeting at least two culprits of vascular dysfunction –inflammation and smooth muscle cell proliferation -might become a promising electrophilic lead compound for vascular disease therapy.
Constitutive expression of a novel antimicrobial protein, Hcm1, confers resistance to both Verticillium and Fusarium wilts in cotton
Authors: Zhang Zhiyuan , Zhao Jun , Ding Lingyun , Zou Lifang , Li Yurong , Chen Gongyou , Zhang Tianzhen
Published: February 2016

Fusarium and Verticillium wilts, two of the most important diseases in cotton, pose serious threats to cotton production. Here we introduced a novel antimicrobial proteinHcm1, which comprisedharpin protein fromXanthomonas oryzaepv.oryzicola(Xoc), and the chimeric protein, cecropin A-melittin, into cotton. The transgenic cotton lines with stableHcm1expression showed a higher resistance to Verticillium and Fusarium wilts both in greenhouse and field trials compared to controls.Hcm1enabled the transgenic cotton to produced a microscopic hypersensitive response (micro-HR), reactive oxygen species (ROS) burst, and caused the activation of pathogenesis-related (PR) genes in response to biotic stress, indicating that the transgenic cotton was in a primed state and ready to protect the host from pathogenic infection. Simultaneously, Hcm1 protein inhibited the growth ofVerticillium dahliae(V. dahliae) andFusarium oxysporum(F. oxysporum)in vitro. The spread of fungal biomass was also inhibitedin vivosince theV. dahliaebiomass was decreased dramatically in transgenic cotton plants after inoculation withV. dahliae. Together, these results demonstrate thatHcm1could activate innate immunity and inhibit the growth ofV. dahliaeandF. oxysporumto protect cotton against Verticillium and Fusarium wilts.
Spin-orbit torque in Pt/CoNiCo/Pt symmetric devices
Authors: Yang Meiyin , Cai Kaiming , Ju Hailang , Edmonds Kevin William , Yang Guang , Liu Shuai , Li Baohe , Zhang Bao , Sheng Yu , Wang Shouguo , Ji Yang , Wang Kaiyou
Published: February 2016

Current induced magnetization switching by spin-orbit torques offers an energy-efficient means of writing information in heavy metal/ferromagnet (FM) multilayer systems. The relative contributions of field-like torques and damping-like torques to the magnetization switching induced by the electrical current are still under debate. Here, we describe a device based on a symmetric Pt/FM/Pt structure, in which we demonstrate a strong damping-like torque from the spin Hall effect and unmeasurable field-like torque from Rashba effect. The spin-orbit effective fields due to the spin Hall effect were investigated quantitatively and were found to be consistent with the switching effective fields after accounting for the switching current reduction due to thermal fluctuations from the current pulse. A non-linear dependence of deterministic switching of average Mz on the in-plane magnetic field was revealed, which could be explained and understood by micromagnetic simulation.
Human Frataxin Folds Via an Intermediate State. Role of the C-Terminal Region
Authors: Faraj Santiago E. , González-Lebrero Rodolfo M. , Roman Ernesto A. , Santos Javier
Published: February 2016

The aim of this study is to investigate the folding reaction of human frataxin, whose deficiency causes the neurodegenerative disease Friedreich’s Ataxia (FRDA). The characterization of different conformational states would provide knowledge about how frataxin can be stabilized without altering its functionality. Wild-type human frataxin and a set of mutants, including two highly destabilized FRDA-associated variants were studied by urea-induced folding/unfolding in a rapid mixing device and followed by circular dichroism. The analysis clearly indicates the existence of an intermediate state (I) in the folding route with significant secondary structure content but relatively low compactness, compared with the native ensemble. However, at high NaCl concentrations I-state gains substantial compaction and the unfolding barrier is strongly affected, revealing the importance of electrostatics in the folding mechanism. The role of the C-terminal region (CTR), the key determinant of frataxin stability, was also studied. Simulations consistently with experiments revealed that this stretch is essentially unstructured, in the most compact transition state ensemble (TSE2). The complete truncation of the CTR drastically destabilizes the native state without altering TSE2. Results presented here shed light on the folding mechanism of frataxin, opening the possibility of mutating it to generate hyperstable variants without altering their folding kinetics.
Tracing amino acid exchange during host-pathogen interaction by combined stable-isotope time-resolved Raman spectral imaging
Authors: Naemat Abida , Elsheikha Hany M. , Boitor Radu A. , Notingher Ioan
Published: February 2016

This study investigates the temporal and spatial interchange of the aromatic amino acid phenylalanine (Phe) between human retinal pigment epithelial cell line (ARPE-19) and tachyzoites of the apicomplexan protozoan parasite Toxoplasma gondii (T. gondii). Stable isotope labelling by amino acids in cell culture (SILAC) is combined with Raman micro-spectroscopy to selectively monitor the incorporation of deuterium-labelled Phe into proteins in individual live tachyzoites. Our results show a very rapid uptake of l-Phe(D8) by the intracellular growing parasite. T. gondii tachyzoites are capable of extracting l-Phe(D8) from host cells as soon as it invades the cell. l-Phe(D8) from the host cell completely replaces the l-Phe within T. gondii tachyzoites 7–9 hours after infection. A quantitative model based on Raman spectra allowed an estimation of the exchange rate of Phe as 0.5–1.6 × 104 molecules/s. On the other hand, extracellular tachyzoites were not able to consume l-Phe(D8) after 24 hours of infection. These findings further our understanding of the amino acid trafficking between host cells and this strictly intracellular parasite. In particular, this study highlights new aspects of the metabolism of amino acid Phe operative during the interaction between T. gondii and its host cell.
Using a Machine Learning Approach to Predict Outcomes after Radiosurgery for Cerebral Arteriovenous Malformations
Authors: Oermann Eric Karl , Rubinsteyn Alex , Ding Dale , Mascitelli Justin , Starke Robert M. , Bederson Joshua B. , Kano Hideyuki , Lunsford L. Dade , Sheehan Jason P. , Hammerbacher Jeffrey , Kondziolka Douglas
Published: February 2016

Predictions of patient outcomes after a given therapy are fundamental to medical practice. We employ a machine learning approach towards predicting the outcomes after stereotactic radiosurgery for cerebral arteriovenous malformations (AVMs). Using three prospective databases, a machine learning approach of feature engineering and model optimization was implemented to create the most accurate predictor of AVM outcomes. Existing prognostic systems were scored for purposes of comparison. The final predictor was secondarily validated on an independent site’s dataset not utilized for initial construction. Out of 1,810 patients, 1,674 to 1,291 patients depending upon time threshold, with 23 features were included for analysis and divided into training and validation sets. The best predictor had an average area under the curve (AUC) of 0.71 compared to existing clinical systems of 0.63 across all time points. On the heldout dataset, the predictor had an accuracy of around 0.74 at across all time thresholds with a specificity and sensitivity of 62% and 85% respectively. This machine learning approach was able to provide the best possible predictions of AVM radiosurgery outcomes of any method to date, identify a novel radiobiological feature (3D surface dose), and demonstrate a paradigm for further development of prognostic tools in medical care.
Comparative genomic and functional analysis reveal conservation of plant growth promoting traits in Paenibacillus polymyxa and its closely related species
Authors: Xie Jianbo , Shi Haowen , Du Zhenglin , Wang Tianshu , Liu Xiaomeng , Chen Sanfeng
Published: February 2016

Paenibacillus polymyxa has widely been studied as a model of plant-growth promoting rhizobacteria (PGPR). Here, the genome sequences of 9 P. polymyxa strains, together with 26 other sequenced Paenibacillus spp., were comparatively studied. Phylogenetic analysis of the concatenated 244 single-copy core genes suggests that the 9 P. polymyxa strains and 5 other Paenibacillus spp., isolated from diverse geographic regions and ecological niches, formed a closely related clade (here it is called Poly-clade). Analysis of single nucleotide polymorphisms (SNPs) reveals local diversification of the 14 Poly-clade genomes. SNPs were not evenly distributed throughout the 14 genomes and the regions with high SNP density contain the genes related to secondary metabolism, including genes coding for polyketide. Recombination played an important role in the genetic diversity of this clade, although the rate of recombination was clearly lower than mutation. Some genes relevant to plant-growth promoting traits, i.e. phosphate solubilization and IAA production, are well conserved, while some genes relevant to nitrogen fixation and antibiotics synthesis are evolved with diversity in this Poly-clade. This study reveals that both P. polymyxa and its closely related species have plant growth promoting traits and they have great potential uses in agriculture and horticulture as PGPR.
Next-generation sequencing-based molecular diagnosis of 12 inherited retinal disease probands of Uyghur ethnicity
Authors: Tajiguli Abulikemu , Xu Mingchu , Fu Qing , Yiming Rouzimaimaiti , Wang Keqing , Li Yumei , Eblimit Aiden , Sui Ruifang , Chen Rui , Aisa Haji Akber
Published: February 2016

Inherited retinal disease (IRD) is a category of genetic disorders affecting retina. Understanding the molecular basis of IRD is vital for clinical and genetic classification of patients. Uyghur people is an isolated ethnic group mainly residing in northwestern China with genetic admixture from Europeans and East Asians. The genetic etiology of IRD in this specific population still remains unknown. Here, by next-generation sequencing (NGS), we screened mutations in over 200 known retinal disease genes in a cohort of 12 unrelated Uyghur IRD probands. Out of the 12 probands, six are solved with high confidence, two with low confidence, while the remaining four are unsolved. We identified known disease-causing alleles in this cohort that suggest ancient Uyghur migration and also discovered eight novel disease-associated variants. Our results showed NGS-based mutation screening as a reliable approach for molecular diagnosis. In addition, this approach can also be applied to reveal the genetic history of a specific ethnic group.
Sonar sound groups and increased terminal buzz duration reflect task complexity in hunting bats
Authors: Hulgard Katrine , Ratcliffe John M.
Published: February 2016

More difficult tasks are generally regarded as such because they demand greater attention. Echolocators provide rare insight into this relationship because biosonar signals can be monitored. Here we show that bats produce longer terminal buzzes and more sonar sound groups during their approach to prey under presumably more difficult conditions. Specifically, we found Daubenton’s bats,Myotis daubentonii, produced longer buzzes when aerial-hawking versus water-trawling prey, but that bats taking revolving air- and water-borne prey produced more sonar sound groups than did the bats when taking stationary prey. Buzz duration and sonar sound groups have been suggested to be independent means by which bats attend to would-be targets and other objects of interest. We suggest that for attacking bats both should be considered as indicators of task difficulty and that the buzz is, essentially, an extended sonar sound group.
Metabolic/Proteomic Signature Defines Two Glioblastoma Subtypes With Different Clinical Outcome
Authors: Marziali G. , Signore M. , Buccarelli M. , Grande S. , Palma A. , Biffoni M. , Rosi A. , D’Alessandris Q.G. , Martini M. , Larocca L. M. , De Maria R. , Pallini R. , Ricci-Vitiani L.
Published: February 2016

Glioblastoma (GBM) is one of the deadliest human cancers. Because of the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and therapeutic strategies based on biologically and clinically relevant subclassification systems. Analyzing a collection of seventeen patient-derived glioblastoma stem-like cells (GSCs) by gene expression profiling, NMR spectroscopy and signal transduction pathway activation, we identified two GSC clusters, one characterized by a pro-neural-like phenotype and the other showing a mesenchymal-like phenotype. Evaluating the levels of proteins differentially expressed by the two GSC clusters in the TCGA GBM sample collection, we found that SRC activation is associated with a GBM subgroup showing better prognosis whereas activation of RPS6, an effector of mTOR pathway, identifies a subgroup with a worse prognosis. The two clusters are also differentiated by NMR spectroscopy profiles suggesting a potential prognostic stratification based on metabolic evaluation. Our data show that the metabolic/proteomic profile of GSCs is informative of the genomic/proteomic GBM landscape, which differs among tumor subtypes and is associated with clinical outcome.
Attenuation of ligand-induced activation of angiotensin II type 1 receptor signaling by the type 2 receptor via protein kinase C
Authors: Inuzuka Takayuki , Fujioka Yoichiro , Tsuda Masumi , Fujioka Mari , Satoh Aya O. , Horiuchi Kosui , Nishide Shinya , Nanbo Asuka , Tanaka Shinya , Ohba Yusuke
Published: February 2016

Angiotensin II (AII) type 2 receptor (AT2R) negatively regulates type 1 receptor (AT1R) signaling. However, the precise molecular mechanism of AT2R-mediated AT1R inhibition remains poorly understood. Here, we characterized the local and functional interaction of AT2R with AT1R. AT2R colocalized and formed a complex with AT1R at the plasma membrane, even in the absence of AII. Upon AII stimulation, the spatial arrangement of the complex was modulated, as confirmed by Förster resonance energy transfer (FRET) analysis, followed by AT2R internalization along with AT1R. AT2R internalization was specifically observed only in the presence of AT1R; AT2R alone could not be internalized. The AT1R-specific inhibitor losartan completely inhibited both the conformational change and the internalization of AT2R with AT1R, whereas the AT2R-specific inhibitor PD123319 partially hindered these phenomena, demonstrating that the activation of both receptors was indispensable for these effects. In addition, treatment with the protein kinase C (PKC) inhibitors inhibited the ligand-dependent accumulation of AT2R but not that of AT1R in the endosomes. A mutation in the putative phosphorylation sites of AT2R also abrogated the co-internalization of ATR2 with AT1R and the inhibitory effect of ATR2 on AT1R. These data suggest that AT2R inhibits ligand-induced AT1R signaling through the PKC-dependent pathway.
Plasticity of intrinsic excitability in mature granule cells of the dentate gyrus
Authors: Lopez-Rojas Jeffrey , Heine Martin , Kreutz Michael R.
Published: February 2016

The dentate gyrus is the main entry gate for cortical input to the hippocampus and one of the few brain areas where adult neurogenesis occurs. Several studies have shown that it is relatively difficult to induce synaptic plasticity in mature but not in newborn dentate granule cells. In the present work we have systematically addressed how classical protocols to induce synaptic plasticity affect action potential firing and intrinsic excitability in mature granule cells. We found that stimulation paradigms considered to be relevant for learning processes consistently modified the probability to generate action potentials in response to a given synaptic input in mature cells, in some paradigms even without any modification of synaptic strength. Collectively the results suggest that plasticity of intrinsic dendritic excitability has a lower induction-threshold than synaptic plasticity in mature granule cells and that this form of plasticity might be an important mechanism by which mature granule cells contribute to hippocampal function.
NATpipe: an integrative pipeline for systematical discovery of natural antisense transcripts (NATs) and phase-distributed nat-siRNAs from de novo assembled transcriptomes
Authors: Yu Dongliang , Meng Yijun , Zuo Ziwei , Xue Jie , Wang Huizhong
Published: February 2016

Nat-siRNAs (small interfering RNAs originated from natural antisense transcripts) are a class of functional small RNA (sRNA) species discovered in both plants and animals. These siRNAs are highly enriched within the annealed regions of the NAT (natural antisense transcript) pairs. To date, great research efforts have been taken for systematical identification of the NATs in various organisms. However, developing a freely available and easy-to-use program for NAT prediction is strongly demanded by researchers. Here, we proposed an integrative pipeline named NATpipe for systematical discovery of NATs from de novo assembled transcriptomes. By utilizing sRNA sequencing data, the pipeline also allowed users to search for phase-distributed nat-siRNAs within the perfectly annealed regions of the NAT pairs. Additionally, more reliable nat-siRNA loci could be identified based on degradome sequencing data. A case study on the non-model plant Dendrobium officinale was performed to illustrate the utility of NATpipe. Finally, we hope that NATpipe would be a useful tool for NAT prediction, nat-siRNA discovery, and related functional studies. NATpipe is available at www.bioinfolab.cn/NATpipe/NATpipe.zip.