bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma
Authors: Nikbakht Hamid , Panditharatna Eshini , Mikael Leonie G. , Li Rui , Gayden Tenzin , Osmond Matthew , Ho Cheng-Ying , Kambhampati Madhuri , Hwang Eugene I. , Faury Damien , Siu Alan , Papillon-Cavanagh Simon , Bechet Denise , Ligon Keith L. , Ellezam Benjamin , Ingram Wendy J. , Stinson Caedyn , Moore Andrew S. , Warren Katherine E. , Karamchandani Jason , Packer Roger J. , Jabado Nada , Majewski Jacek , Nazarian Javad 
Published: April 2016

AbstractDiffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M—including H3.2K27M—mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often affect the PI3K pathway. Our findings are consistent with early tumour spread outside the brainstem including the cerebrum. The spatial and temporal homogeneity of main driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships.
SCFSAP controls organ size by targeting PPD proteins for degradation in Arabidopsis thaliana
Authors: Wang Zhibiao , Li Na , Jiang Shan , Gonzalez Nathalie , Huang Xiahe , Wang Yingchun , Inzé Dirk , Li Yunhai 
Published: April 2016

AbstractControl of organ size by cell proliferation and growth is a fundamental process, but the mechanisms that determine the final size of organs are largely elusive in plants. We have previously revealed that the ubiquitin receptor DA1 regulates organ size by repressing cell proliferation in Arabidopsis. Here we report that a mutant allele of STERILE APETALA (SAP) suppresses the da1-1 mutant phenotype. We show that SAP is an F-box protein that forms part of a SKP1/Cullin/F-box E3 ubiquitin ligase complex and controls organ size by promoting the proliferation of meristemoid cells. Genetic analyses suggest that SAP may act in the same pathway with PEAPOD1 and PEAPOD2, which are negative regulators of meristemoid proliferation, to control organ size, but does so independently of DA1. Further results reveal that SAP physically associates with PEAPOD1 and PEAPOD2, and targets them for degradation. These findings define a molecular mechanism by which SAP and PEAPOD control organ size.
Calcium-sensing receptors signal constitutive macropinocytosis and facilitate the uptake of NOD2 ligands in macrophages
Authors: Canton Johnathan , Schlam Daniel , Breuer Christian , Gütschow Michael , Glogauer Michael , Grinstein Sergio 
Published: April 2016

AbstractMacropinocytosis can be induced in several cell types by stimulation with growth factors. In selected cell types, notably macrophages and dendritic cells, macropinocytosis occurs constitutively, supporting the uptake of antigens for subsequent presentation. Despite their different mode of initiation and contrasting physiological roles, it is tacitly assumed that both types of macropinocytosis are mechanistically identical. We report that constitutive macropinocytosis is stringently calcium dependent, while stimulus-induced macropinocytosis is not. Extracellular calcium is sensed by G-protein-coupled calcium-sensing receptors (CaSR) that signal macropinocytosis through Gα-, phosphatidylinositol 3-kinase and phospholipase C. These pathways promote the recruitment of exchange factors that stimulate Rac and/or Cdc42, driving actin-dependent formation of ruffles and macropinosomes. In addition, the heterologous expression of CaSR in HEK293 cells confers on them the ability to perform constitutive macropinocytosis. Finally, we show that CaSR-induced constitutive macropinocytosis facilitates the sentinel function of macrophages, promoting the efficient delivery of ligands to cytosolic pattern-recognition receptors.
Identification and characterization of histone lysine methylation modifiers in Fragaria vesca
Authors: Gu Tingting , Han Yuhui , Huang Ruirui , McAvoy Richard J. , Li Yi 
Published: April 2016

AbstractThe diploid woodland strawberry (Fragaria vesca) is an important model for fruit crops because of several unique characteristics including the small genome size, an ethylene-independent fruit ripening process, and fruit flesh derived from receptacle tissues rather than the ovary wall which is more typical of fruiting plants. Histone methylation is an important factor in gene regulation in higher plants but little is known about its roles in fruit development. We have identified 45 SET methyltransferase, 22 JmjC demethylase and 4 LSD demethylase genes in F. vesca. The analysis of these histone modifiers in eight plant species supports the clustering of those genes into major classes consistent with their functions. We also provide evidence that whole genome duplication and dispersed duplications via retrotransposons may have played pivotal roles in the expansion of histone modifier genes in F. vesca. Furthermore, transcriptome data demonstrated that expression of some SET genes increase as the fruit develops and peaks at the turning stage. Meanwhile, we have observed that expression of those SET genes responds to cold and heat stresses. Our results indicate that regulation of histone methylation may play a critical role in fruit development as well as responses to abiotic stresses in strawberry.
On hybrid circuits exploiting thermistive properties of slime mould
Authors: Walter Xavier Alexis , Horsfield Ian , Mayne Richard , Ieropoulos Ioannis A. , Adamatzky Andrew 
Published: April 2016

AbstractSlime mould Physarum polycephalum is a single cell visible by the unaided eye. Let the slime mould span two electrodes with a single protoplasmic tube: if the tube is heated to approximately ≈40 °C, the electrical resistance of the protoplasmic tube increases from ≈3 MΩ to ≈10,000 MΩ. The organism’s resistance is not proportional nor correlated to the temperature of its environment. Slime mould can therefore not be considered as a thermistor but rather as a thermic switch. We employ the P. polycephalum thermic switch to prototype hybrid electrical analog summator, NAND gates and cascade the gates into Flip-Flop latch. Computing operations performed on this bio-hybrid computing circuitry feature high repeatability, reproducibility and comparably low propagation delays.
Strontium-90 activity concentration in soil samples from the exclusion zone of the Fukushima daiichi nuclear power plant
Authors: Sahoo Sarata Kumar , Kavasi Norbert , Sorimachi Atsuyuki , Arae Hideki , Tokonami Shinji , Mietelski Jerzy Wojciech , Łokas Edyta , Yoshida Satoshi 
Published: April 2016

AbstractThe radioactive fission product 90Sr has a long biological half-life (˜18 y) in the human body. Due to its chemical similarity to calcium it accumulates in bones and irradiates the bone marrow, causing its high radio-toxicity. Assessing 90Sr is therefore extremely important in case of a nuclear disaster. In this work 16 soil samples were collected from the exclusion zone (<30 km) of the earthquake-damaged Fukushima Daiichi nuclear power plant, to measure 90Sr activity concentration using liquid scintillation counting. 137Cs activity concentration was also measured with gamma-spectroscopy in order to investigate correlation with 90Sr. The 90Sr activity concentrations ranged from 3.0 ± 0.3 to 23.3 ± 1.5 Bq kg−1 while the 137Cs from 0.7 ± 0.1 to 110.8 ± 0.3 kBq kg−1. The fact that radioactive contamination originated from the Fukushima nuclear accident was obvious due to the presence of 134Cs. However, 90Sr contamination was not confirmed in all samples although detectable amounts of 90Sr can be expected in Japanese soils, as a background, stemming from global fallout due to the atmospheric nuclear weapon tests. Correlation analysis between 90Sr and 137Cs activity concentrations provides a potentially powerful tool to discriminate background 90Sr level from its Fukushima contribution.
Chronic cerebral hypoperfusion enhances Tau hyperphosphorylation and reduces autophagy in Alzheimer’s disease mice
Authors: Qiu Lifeng , Ng Gandi , Tan Eng King , Liao Ping , Kandiah Nagaendran , Zeng Li 
Published: April 2016

AbstractCerebral hypoperfusion and impaired autophagy are two etiological factors that have been identified as being associated with the development of Alzheimer’s disease (AD). Nevertheless, the exact relationships among these pathological processes remain unknown. To elucidate the impact of cerebral hypoperfusion in AD, we created a unilateral common carotid artery occlusion (UCCAO) model by occluding the left common carotid artery in both young and old 3xTg-AD mice. Two months after occlusion, we found that ligation increases phospho-Tau (p-Tau) at Serine 199/202 in the hippocampus of 3-month-old AD mice, compared to sham-operated AD mice; whereas, there is no change in the wild type (WT) mice after ligation. Moreover, cerebral hypoperfusion led to significant increase of p-Tau in both the hippocampus and cortex of 16-month-old AD mice and WT mice. Notably, we did not detect any change in Aβ42 level in either young or old AD and WT mice after ligation. Interestingly, we observed a downregulation of LC3-II in the cortex of aged AD mice and WT mice after ligation. Our results suggest that elevated p-Tau and reduced autophagy are major cellular changes that are associated with hypoperfusion in AD. Therefore, targeting p-Tau and autophagy pathways may ameliorate hypoperfusion-induced brain damage in AD.
Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice
Authors: Zhao Lihua , Du Xinhua , Huang Kun , Zhang Tuo , Teng Zhen , Niu Wanbao , Wang Chao , Xia Guoliang 
Published: April 2016

AbstractThe size of the primordial follicle pool determines the reproductive potential of mammalian females and establishment of the pool is highly dependent on specific genes expression. However, the molecular mechanisms by which the essential genes are regulated coordinately to ensure primordial follicle assembly remain a mystery. Here, we show that the small GTPase Rac1 plays an indispensable role in controlling the formation of primordial follicles in mouse ovary. Employing fetal mouse ovary organ culture system, we demonstrate that disruption of Rac1 retarded the breakdown of germline cell cysts while Rac1 overexpression accelerated the formation of primordial follicles. In addition, in vivo inhibitor injection resulted in the formation of multi-oocyte follicles. Subsequent investigation showed that Rac1 induced nuclear import of STAT3 by physical binding. In turn, nuclear STAT3 directly activated the transcription of essential oocyte-specific genes, including Jagged1, GDF9, BMP15 and Nobox. Further, GDF9 and BMP15 regulated the translation of Notch2 via mTORC1 activation in pregranulosa cells. Overexression or addition of Jagged1, GDF9 and BMP15 not only reversed the effect of Rac1 disruption, but also accelerated primordial follicle formation via Notch2 signaling activation. Collectively, these results indicate that Rac1 plays important roles as a key regulator in follicular assembly.
Trim69 regulates zebrafish brain development by ap-1 pathway
Authors: Han Ruiqin , Wang Renxian , Zhao Qing , Han Yongqing , Zong Shudong , Miao Shiying , Song Wei , Wang Linfang 
Published: April 2016

AbstractProteins belonging to the TRIM family have been implicated in a variety of cellular processes such as apoptosis, differentiation, neurogenesis, muscular physiology and innate immune responses. Trim69, previously identified as a novel gene cloned from a human testis cDNA library, has a homologous gene in zebrafish and this study focused on investigating the function of trim69 in zebrafish neurogenesis. Trim69 was found to be expressed in zebrafish embryo brain at the early stages. Knockdown of trim69 led to deformed brain development, obvious signs of apoptosis present in the head and decreased expression of neuronal differentiation and stem cell markers. This phenotype was rescued upon co-injection of human mRNA together along with the trim69 knockdown. Results of this study also showed an interaction between TRIM69 and c-Jun in human cells and upon TRIM69 knock down c-Jun expression subsequently increased, whereas the over-expression of TRIM69 led to the down-regulation of c-Jun. Additionally, knockdown both c-Jun and trim69 can rescue the deformed brain, evident cellular apoptosis in the head and decreased expression of neuronal differentiation and stem cell markers. Overall, our results support a role for trim69 in the development of the zebrafish brain through ap-1 pathway.
Surface energetics and protein-protein interactions: analysis and mechanistic implications
Authors: Peri Claudio , Morra Giulia , Colombo Giorgio 
Published: April 2016

AbstractUnderstanding protein-protein interactions (PPI) at the molecular level is a fundamental task in the design of new drugs, the prediction of protein function and the clarification of the mechanisms of (dis)regulation of biochemical pathways. In this study, we use a novel computational approach to investigate the energetics of aminoacid networks located on the surface of proteins, isolated and in complex with their respective partners. Interestingly, the analysis of individual proteins identifies patches of surface residues that, when mapped on the structure of their respective complexes, reveal regions of residue-pair couplings that extend across the binding interfaces, forming continuous motifs. An enhanced effect is visible across the proteins of the dataset forming larger quaternary assemblies. The method indicates the presence of energetic signatures in the isolated proteins that are retained in the bound form, which we hypothesize to determine binding orientation upon complex formation. We propose our method, BLUEPRINT, as a complement to different approaches ranging from the ab-initio characterization of PPIs, to protein-protein docking algorithms, for the physico-chemical and functional investigation of protein-protein interactions.
Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia
Authors: Brehme Marc , Koschmieder Steffen , Montazeri Maryam , Copland Mhairi , Oehler Vivian G. , Radich Jerald P. , Brümmendorf Tim H. , Schuppert Andreas 
Published: April 2016

AbstractModelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis.
Insights into the adaptive response of the plant-pathogenic oomycete Phytophthora capsici to the fungicide flumorph
Authors: Pang Zhili , Chen Lei , Mu Wenjun , Liu Li , Liu Xili 
Published: April 2016

AbstractPhytophthora capsici is an important oomycete plant pathogen that causes significant losses worldwide. The carboxylic acid amide fungicide flumorph has shown excellent activity against oomycete plant pathogens. Despite its potential, there remains concern that the sexual reproduction of oomycete pathogens, which results in genetic recombination, could result in the rapid development of resistance to flumorph. The current study utilized an iTRAQ (isobaric tags for relative and absolute quantitation) based method to compare differences between the proteome of the parental P. capsici isolate PCAS1 and its sexual progeny S2-838, which exhibits significant resistance to flumorph. A total of 2396 individual proteins were identified, of these, 181 were considered to be associated with the adaptive response of P. capsici to flumorph. The subsequent bioinformatic analysis revealed that the adaptive response of P. capsici to flumorph was complex and regulated by multiple mechanisms, including utilising carbohydrate from the host environment to compensate for the cell wall stress induced by flumorph, a shift in energy generation, decreased amino acids biosynthesis, and elevated levels of proteins associated with the pathogen’s response to stimulus and transmembrane transport. Moreover, the results of the study provided crucial data that could provide the basis for early monitoring of flumorph resistance in field populations of P. capsici.
Transverse spin relaxation and diffusion-constant measurements of spin-polarized 129Xe nuclei in the presence of a magnetic field gradient
Authors: Liu Xiaohu , Chen Chang , Qu Tianliang , Yang Kaiyong , Luo Hui 
Published: April 2016

AbstractThe presence of a magnetic field gradient in a sample cell containing spin-polarized 129Xe atoms will cause an increased relaxation rate. We measured the transverse spin relaxation time of 129Xe verse the applied magnetic field gradient and the cell temperature. We then compared the different transverse spin relaxation behavior of dual isotopes of xenon (129Xe and 131Xe) due to magnetic field gradient in the same cell. The experiment results show the residual magnetic field gradient can be measured and compensated by applying a negative magnetic gradient in the sample cell. The transverse spin relaxation time of 129Xe could be increased 2–7 times longer when applying an appropriate magnetic field gradient. The experiment results can also be used to determine the diffusion constant of 129Xe in H2 and N2 to be 0.4 ± 0.26 cm2/sec and 0.12 ± 0.02 cm2/sec. The results are close with theoretical calculation.
Immunization with a novel Clostridium perfringens epsilon toxin mutant rETXY196E-C confers strong protection in mice
Authors: Yao Wenwu , Kang Jingjing , Kang Lin , Gao Shan , Yang Hao , Ji Bin , Li Ping , Liu Jing , Xin Wenwen , Wang Jinglin 
Published: April 2016

AbstractEpsilon toxin (ETX) is produced by toxinotypes B and D ofClostridium perfringens. It can induce lethal enterotoxemia in domestic animals, mainly in sheep, goats and cattle, causing serious economic losses to global animal husbandry. In this study, a novel and stable epsilon toxin mutant rETXY196E-C, obtained by substituting the 196th tyrosine (Y196) with glutamic acid (E) and introducing of 23 amino acids long C-terminal peptide, was determined as a promising recombinant vaccine candidate against enterotoxemia. After the third vaccination, the antibody titers against recombinant wild type (rETX) could reach 1:105in each immunized group, and the mice were completely protected from 100 × LD50(50% lethal dose) of rETX challenge. The mice in 15 μg subcutaneously immunized group fully survived at the dose of 500 × LD50of rETX challenge and 80% of mice survived at 180 μg (1000 × LD50) of rETX administration.In vitro, immune sera from 15 μg subcutaneously immunized group could completely protect MDCK cells from 16 × CT50(50% lethal dose of cells) of rETX challenge and protect against 10 × LD50dose (1.8 μg) of rETX challenge in mice. These data suggest that recombinant protein rETXY196E-C is a potential vaccine candidate for future applied researches.
High Color-Purity Green, Orange, and Red Light-Emitting Diodes Based on Chemically Functionalized Graphene Quantum Dots
Authors: Kwon Woosung , Kim Young-Hoon , Kim Ji-Hee , Lee Taehyung , Do Sungan , Park Yoonsang , Jeong Mun Seok , Lee Tae-Woo , Rhee Shi-Woo 
Published: April 2016

AbstractChemically derived graphene quantum dots (GQDs) to date have showed very broad emission linewidth due to many kinds of chemical bondings with different energy levels, which significantly degrades the color purity and color tunability. Here, we show that use of aniline derivatives to chemically functionalize GQDs generates new extrinsic energy levels that lead to photoluminescence of very narrow linewidths. We use transient absorption and time-resolved photoluminescence spectroscopies to study the electronic structures and related electronic transitions of our GQDs, which reveals that their underlying carrier dynamics is strongly related to the chemical properties of aniline derivatives. Using these functionalized GQDs as lumophores, we fabricate light-emitting didoes (LEDs) that exhibit green, orange, and red electroluminescence that has high color purity. The maximum current efficiency of 3.47 cd A−1 and external quantum efficiency of 1.28% are recorded with our LEDs; these are the highest values ever reported for LEDs based on carbon-nanoparticle phosphors. This functionalization of GQDs with aniline derivatives represents a new method to fabricate LEDs that produce natural color.
Antiferromagnetic Spin Wave Field-Effect Transistor
Authors: Cheng Ran , Daniels Matthew W. , Zhu Jian-Gang , Xiao Di 
Published: April 2016

AbstractIn a collinear antiferromagnet with easy-axis anisotropy, symmetry dictates that the spin wave modes must be doubly degenerate. Theses two modes, distinguished by their opposite polarization and available only in antiferromagnets, give rise to a novel degree of freedom to encode and process information. We show that the spin wave polarization can be manipulated by an electric field induced Dzyaloshinskii-Moriya interaction and magnetic anisotropy. We propose a prototype spin wave field-effect transistor which realizes a gate-tunable magnonic analog of the Faraday effect and demonstrate its application in THz signal modulation. Our findings open up the exciting possibility of digital data processing utilizing antiferromagnetic spin waves and enable the direct projection of optical computing concepts onto the mesoscopic scale.