bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA targeted therapies
Authors: Ip Carman K. M. , Ng Patrick K. S. , Jeong Kang Jin , Shao S. H. , Ju Zhenlin , Leonard P. G. , Hua Xu , Vellano Christopher P. , Woessner Richard , Sahni Nidhi , Scott Kenneth L. , Mills Gordon B. 
Published: October 2018

AbstractActivation of platelet-derived growth factor receptor alpha (PDGFRA) by genomic aberrations contributes to tumor progression in several tumor types. In this study, we characterize 16 novel PDGFRA mutations identified from different tumor types and identify three previously uncharacterized activating mutations that promote cell survival and proliferation. PDGFRA Y288C, an extracellular domain mutation, is primarily high mannose glycosylated consistent with trapping in the endoplasmic reticulum (ER). Strikingly, PDGFRA Y288C is constitutively dimerized and phosphorylated in the absence of ligand suggesting that trapping in the ER or aberrant glycosylation is sufficient for receptor activation. Importantly, PDGFRA Y288C induces constitutive phosphorylation of Akt, ERK1/2, and STAT3. PDGFRA Y288C is resistant to PDGFR inhibitors but sensitive to PI3K/mTOR and MEK inhibitors consistent with pathway activation results. Our findings further highlight the importance of characterizing functional consequences of individual mutations for precision medicine.
Progressive divisions of multipotent neural progenitors generate late-born chandelier cells in the neocortex
Authors: Sultan Khadeejah T. , Liu Wenying Angela , Li Zhao-Lu , Shen Zhongfu , Li Zhizhong , Zhang Xin-Jun , Dean Owen , Ma Jian , Shi Song-Hai 
Published: October 2018

AbstractDiverse γ-aminobutyric acid (GABA)-ergic interneurons provide different modes of inhibition to support circuit operation in the neocortex. However, the cellular and molecular mechanisms underlying the systematic generation of assorted neocortical interneurons remain largely unclear. Here we show that NKX2.1-expressing radial glial progenitors (RGPs) in the mouse embryonic ventral telencephalon divide progressively to generate distinct groups of interneurons, which occupy the neocortex in a time-dependent, early inside-out and late outside-in, manner. Notably, the late-born chandelier cells, one of the morphologically and physiologically highly distinguishable GABAergic interneurons, arise reliably from continuously dividing RGPs that produce non-chandelier cells initially. Selective removal of Partition defective 3, an evolutionarily conserved cell polarity protein, impairs RGP asymmetric cell division, resulting in premature depletion of RGPs towards the late embryonic stages and a consequent loss of chandelier cells. These results suggest that consecutive asymmetric divisions of multipotent RGPs generate diverse neocortical interneurons in a progressive manner.
An information-theoretic framework for deciphering pleiotropic and noisy biochemical signaling
Authors: Jetka Tomasz , Nienałtowski Karol , Filippi Sarah , Stumpf Michael P. H. , Komorowski Michał 
Published: October 2018

AbstractMany components of signaling pathways are functionally pleiotropic, and signaling responses are marked with substantial cell-to-cell heterogeneity. Therefore, biochemical descriptions of signaling require quantitative support to explain how complex stimuli (inputs) are encoded in distinct activities of pathways effectors (outputs). A unique perspective of information theory cannot be fully utilized due to lack of modeling tools that account for the complexity of biochemical signaling, specifically for multiple inputs and outputs. Here, we develop a modeling framework of information theory that allows for efficient analysis of models with multiple inputs and outputs; accounts for temporal dynamics of signaling; enables analysis of how signals flow through shared network components; and is not restricted by limited variability of responses. The framework allows us to explain how identity and quantity of type I and type III interferon variants could be recognized by cells despite activating the same signaling effectors.
Magnetic field compatible circuit quantum electrodynamics with graphene Josephson junctions
Authors: Kroll J. G. , Uilhoorn W. , van der Enden K. L. , de Jong D. , Watanabe K. , Taniguchi T. , Goswami S. , Cassidy M. C. , Kouwenhoven L. P. 
Published: October 2018

AbstractCircuit quantum electrodynamics has proven to be a powerful tool to probe mesoscopic effects in hybrid systems and is used in several quantum computing (QC) proposals that require a transmon qubit able to operate in strong magnetic fields. To address this we integrate monolayer graphene Josephson junctions into microwave frequency superconducting circuits to create graphene based transmons. Using dispersive microwave spectroscopy we resolve graphene’s characteristic band dispersion and observe coherent electronic interference effects confirming the ballistic nature of our graphene Josephson junctions. We show that the monoatomic thickness of graphene renders the device insensitive to an applied magnetic field, allowing us to perform energy level spectroscopy of the circuit in a parallel magnetic field of 1 T, an order of magnitude higher than previous studies. These results establish graphene based superconducting circuits as a promising platform for QC and the study of mesoscopic quantum effects that appear in strong magnetic fields.
Early heme oxygenase 1 induction delays tumour initiation and enhances DNA damage repair in liver macrophages of Mdr2−/− mice
Authors: Barikbin Roja , Berkhout Laura , Bolik Julia , Schmidt-Arras Dirk , Ernst Thomas , Ittrich Harald , Adam Gerhard , Parplys Ann , Casar Christian , Krech Till , Karimi Khalil , Sass Gabriele , Tiegs Gisa 
Published: October 2018

AbstractMulti drug resistance protein 2 knockout mice (Mdr2−/−) are a mouse model of chronic liver inflammation and inflammation-induced tumour development. Here we investigated the kinetics of early heme oxygenase 1 (HO-1) induction on inflammation, tumour development, and DNA damage in Mdr2−/− mice. HO-1 was induced by intraperitoneal injection of cobalt protoporphyrin IX (CoPP) twice weekly for 9 consecutive weeks. Immediately after HO-1 induction, liver function improved and infiltration of CD4+ and CD8+ T cells was reduced. Furthermore, we observed increased p38 activation with concomitant reduction of Cyclin D1 expression in aged Mdr2−/− mice. Long-term effects of HO-1 induction included increased CD8+ T cell infiltration as well as delayed and reduced tumour growth in one-year-old animals. Unexpectedly, DNA double-strand breaks were detected predominantly in macrophages of 65-week-old Mdr2−/− mice, while DNA damage was reduced in response to early HO-1 induction in vivo and in vitro. Overall, early induction of HO-1 in Mdr2−/− mice had a beneficial short-term effect on liver function and reduced hepatic T cell accumulation. Long-term effects of early HO-1 induction were increased CD8+ T cell numbers, decreased proliferation as wells as reduced DNA damage in liver macrophages of aged animals, accompanied by delayed and reduced tumour growth.
Development of a 3D Collagen Model for the In Vitro Evaluation of Magnetic-assisted Osteogenesis
Authors: Yuan Zhiyu , Memarzadeh Kaveh , Stephen Abish S. , Allaker Robert P. , Brown Robert A. , Huang Jie 
Published: October 2018

AbstractMagnetic stimulation has been applied to bone regeneration, however, the cellular and molecular mechanisms of repair still require a better understanding. A three-dimensional (3D) collagen model was developed using plastic compression, which produces dense, cellular, mechanically strong native collagen structures. Osteoblast cells (MG-63) and magnetic iron oxide nanoparticles (IONPs) were incorporated into collagen gels to produce a range of cell-laden models. A magnetic bio-reactor to support cell growth under static magnetic fields (SMFs) was designed and fabricated by 3D printing. The influences of SMFs on cell proliferation, differentiation, extracellular matrix production, mineralisation and gene expression were evaluated. Polymerase chain reaction (PCR) further determined the effects of SMFs on the expression of runt-related transcription factor 2 (Runx2), osteonectin (ON), and bone morphogenic proteins 2 and 4 (BMP-2 and BMP-4). Results demonstrate that SMFs, IONPs and the collagen matrix can stimulate the proliferation, alkaline phosphatase production and mineralisation of MG-63 cells, by influencing matrix/cell interactions and encouraging the expression of Runx2, ON, BMP-2 and BMP-4. Therefore, the collagen model developed here not only offers a novel 3D bone model to better understand the effect of magnetic stimulation on osteogenesis, but also paves the way for further applications in tissue engineering and regenerative medicine.
Self-structuring in Zr1−xAlxN films as a function of composition and growth temperature
Authors: Ghafoor N. , Petrov I. , Holec D. , Greczynski G. , Palisaitis J. , Persson P. O. A. , Hultman L. , Birch J. 
Published: October 2018

AbstractNanostructure formation via surface-diffusion-mediated segregation of ZrN and AlN in Zr1−xAlxN films during high mobility growth conditions is investigated for 0 ≤ × ≤ 1. The large immiscibility combined with interfacial surface and strain energy balance resulted in a hard nanolabyrinthine lamellar structure with well-defined (semi) coherent c-ZrN and w-AlN domains of sub-nm to ~4 nm in 0.2 ≤ × ≤ 0.4 films, as controlled by atom mobility. For high AlN contents (x > 0.49) Al-rich ZrN domains attain wurtzite structure within fine equiaxed nanocomposite wurtzite lattice. Slow diffusion in wurtzite films points towards crystal structure dependent driving force for decomposition. The findings of unlikelihood of iso-structural decomposition in c-Zr1−xAlxN, and stability of w-Zr1−xAlxN (in large × films) is complemented with first principles calculations.
Impact of DNA extraction method and targeted 16S-rRNA hypervariable region on oral microbiota profiling
Authors: Teng Fei , Darveekaran Nair Sree Sankar , Zhu Pengfei , Li Shanshan , Huang Shi , Li Xiaolan , Xu Jian , Yang Fang 
Published: October 2018

AbstractAmplification and sequencing of 16S amplicons are widely used for profiling the structure of oral microbiota. However, it remains not clear whether and to what degree DNA extraction and targeted 16S rRNA hypervariable regions influence the analysis. Based on a mock community consisting of five oral bacterial species in equal abundance, we compared the 16S amplicon sequencing results on the Illumina MiSeq platform from six frequently employed DNA extraction procedures and three pairs of widely used 16S rRNA hypervariable primers targeting different 16S rRNA regions. Technical reproducibility of selected 16S regions was also assessed. DNA extraction method exerted considerable influence on the observed bacterial diversity while hypervariable regions had a relatively minor effect. Protocols with beads added to the enzyme-mediated DNA extraction reaction produced more accurate bacterial community structure than those without either beads or enzymes. Hypervariable regions targeting V3-V4 and V4-V5 seemed to produce more reproducible results than V1-V3. Neither sequencing batch nor change of operator affected the reproducibility of bacterial diversity profiles. Therefore, DNA extraction strategy and 16S rDNA hypervariable regions both influenced the results of oral microbiota biodiversity profiling, thus should be carefully considered in study design and data interpretation.
Differential recognition of Haemophilus influenzae whole bacterial cells and isolated lipooligosaccharides by galactose-specific lectins
Authors: Kalograiaki Ioanna , Euba Begoña , Fernández-Alonso María del Carmen , Proverbio Davide , St. Geme Joseph W. , Aastrup Teodor , Garmendia Junkal , Cañada F. Javier , Solís Dolores 
Published: October 2018

AbstractBacterial surfaces are decorated with carbohydrate structures that may serve as ligands for host receptors. Based on their ability to recognize specific sugar epitopes, plant lectins are extensively used for bacteria typing. We previously observed that the galactose-specific agglutinins from Ricinus communis (RCA) and Viscum album (VAA) exhibited differential binding to nontypeable Haemophilus influenzae (NTHi) clinical isolates, their binding being distinctly affected by truncation of the lipooligosaccharide (LOS). Here, we examined their binding to the structurally similar LOS molecules isolated from strains NTHi375 and RdKW20, using microarray binding assays, saturation transfer difference NMR, and molecular dynamics simulations. RCA bound the LOSRdKW20 glycoform displaying terminal Galβ(1,4)Glcβ, whereas VAA recognized the Galα(1,4)Galβ(1,4)Glcβ epitope in LOSNTHi375 but not in LOSRdKW20, unveiling a different presentation. Binding assays to whole bacterial cells were consistent with LOSNTHi375 serving as ligand for VAA, and also suggested recognition of the glycoprotein HMW1. Regarding RCA, comparable binding to NTHi375 and RdKW20 cells was observed. Interestingly, an increase in LOSNTHi375 abundance or expression of HMW1 in RdKW20 impaired RCA binding. Overall, the results revealed that, besides the LOS, other carbohydrate structures on the bacterial surface serve as lectin ligands, and highlighted the impact of the specific display of cell surface components on lectin binding.
Genetic background and window of exposure contribute to thyroid dysfunction promoted by low-dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice
Authors: Reale Carla , Porreca Immacolata , Russo Filomena , Marotta Maria , Roberto Luca , Russo Nicola Antonino , Carchia Emanuele , Mallardo Massimo , De Felice Mario , Ambrosino Concetta 
Published: October 2018

AbstractGenetic and environmental factors contribute to thyroid diseases. Although still debated, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is thought to induce thyroid dysfunction in humans and rodents. The data here reported point out the contribution of the exposure window and genetic background in mediating the low-dose TCDD effects on thyroid. Indeed, early (from E0.5 to PND30) and low-dose (0,001 μg/kg/day) TCDD exposure reduced the circulating fT4 and altered the expression of thyroid specific transcripts. The role of genetic components was estimated monitoring the same markers in Pax8+/− and Nkx2-1+/− mice, susceptible to thyroid dysfunction, exposed to 0, 1 μg/kg/day TCDD from E15.5 to PND60. Haploinsufficiency of either Pax8 or Nkx2-1 genes exacerbated the effects of the exposure impairing the thyroid enriched mRNAs in sex dependent manner. Such effect was mediated by mechanisms involving the Nkx2-1/p53/p65/IĸBα pathway in vitro and in vivo. Foetal exposure to TCDD impaired both thyroid function and genes expression while thyroid development and differentiation did not appear significantly affected. In mouse, stronger effects were related to earlier exposure or specific genetic background such as either Pax8 or Nkx2-1 haploinsufficiency, both associated to hypothyroidism in humans. Furthermore, our data underline that long exposure time are needed to model in vitro and in vivo results.
Genome-wide Identification, Classification, and Expression Pattern of Homeobox Gene Family in Brassica rapa under Various Stresses
Authors: Khan Nadeem , Hu Chun-mei , Khan Waleed Amjad , Wang Wenli , Ke Han , Huijie Dong , Zhishuo Zhang , Hou Xilin 
Published: October 2018

AbstractHomeobox (HB) genes are crucial for plant growth and development processes. They encode transcription factors and responses to various stresses, as reported by recent emerging evidence. In this study, a total of 113 BraHB genes were identified in Brassica rapa. On the basis of domain organization and phylogenetic analysis, the BraHBs were grouped into nine subclasses, in which homeobox leucine-zipper (HB LZP-III) showed the highest number of genes (28) compared to other subclasses. The BraHBs exhibited similarities in exon–intron organization and motif composition among the members of the same subclasses. The analysis revealed that HB-Knotted was more preferentially retained than any other subclass of BraHB. Furthermore, we evaluated the impact of whole-genome triplication on the evolution of BraHBs. In order to analyze the subgenomes of B. rapa, we identified 39 paralogous pairs for which synonymous substitution values were lower than 1.00 for further purifying selection. Finally, the expression patterns of BraHBs across six tissues expressed dynamic variations combined with their responses against multiple stresses. The current study provides brief information on the homeobox gene family in B. rapa. Our findings can serve as a reference for further functional analysis of BraHBs.
Rational design, synthesis, characterization and catalytic properties of high-quality low-silica hierarchical FAU- and LTA-type zeolites
Authors: Parsapur Rajesh K. , Selvam Parasuraman 
Published: October 2018

AbstractDespite the development of several synthetic strategies employing various templates as (pore) structure directing agents, the preparation of high-quality aluminum-rich hierarchical zeolites (designated as ZH) with Si/Al < 5 from its molecular precursors is still a challenge to the scientific community. For the first time, we report here, a successful synthesis methodology for the preparation of hierarchical zeolites, having FAU and LTA topologies with uniform micropores and mesopores by a rationally designed method. Here, a stable supramolecular self-assembly was achieved under the challenging synthesis conditions by tailoring the zeolitization process, viz., by a homogeneous nucleation and a multi-step crystallization. This has resulted in regular mesoporosity in FAU-type zeolites and a unique mesoporosity in LTA-type zeolites, hitherto not reported so far.
Comparative Transcriptional Profiling and Physiological Responses of Two Contrasting Oat Genotypes under Salt Stress
Authors: Wu Bin , Munkhtuya Yarvaan , Li Jianjiang , Hu Yani , Zhang Qian , Zhang Zongwen 
Published: October 2018

AbstractSalinity is one of the major abiotic factors that affect productivity in oat. Here, we report a comparison of the transcriptomes of two hexaploid oat cultivars, ‘Hanyou-5’ and ‘Huazao-2’, which differ with respect to salt tolerance, in seedlings exposed to salt stress. Analysis of the assembled unigenes from the osmotically stressed and control libraries of ‘Hanyou-5’ and ‘Huazao-2’ showed that the expression of 21.92% (36,462/166,326) of the assembled unigenes was differentially regulated in the two cultivars after different durations of salt stress. Bioinformatics analysis showed that the main functional categories enriched in these DEGs were “metabolic process”, “response to stresses”, “plant hormone signal transduction”, “MAPK signalling”, “oxidative phosphorylation”, and the plant-pathogen interaction pathway. Some regulatory genes, such as those encoding MYB, WRKY, bHLH, and zinc finger proteins, were also found to be differentially expressed under salt stress. Physiological measurements also detected significant differences in the activities of POD (76.24 ± 1.07 Vs 81.53 ± 1.47 U/g FW) in the two genotypes in response to osmotic stress. Furthermore, differential expression of 18 of these genes was successfully validated using RNA-seq and qRT-PCR analyses. A number of stress-responsive genes were identified in both cultivars, and candidate genes with potential roles in the adaptation to salinity were proposed.
Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib
Authors: Karademir Betul , Sari Gulce , Jannuzzi Ayse Tarbin , Musunuri Sravani , Wicher Grzegorz , Grune Tilman , Mi Jia , Hacioglu-Bay Husniye , Forsberg-Nilsson Karin , Bergquist Jonas , Jung Tobias 
Published: October 2018

AbstractThe proteasomal system is responsible for the turnover of damaged proteins. Because of its important functions in oncogenesis, inhibiting the proteasomal system is a promising therapeutic approach for cancer treatment. Bortezomib (BTZ) is the first proteasome inhibitor approved by FDA for clinical applications. However neuropathic side effects are dose limiting for BTZ as many other chemotherapeutic agents. Therefore second-generation proteasome inhibitors have been developed including carfilzomib (CFZ). Aim of the present work was investigating the mechanisms of peripheral neuropathy triggered by the proteasome inhibitor BTZ and comparing the pathways affected by BTZ and CFZ, respectively. Neural stem cells, isolated from the cortex of E14 mouse embryos, were treated with BTZ and CFZ and mass spectrometry was used to compare the global protein pool of treated cells. BTZ was shown to cause more severe cytoskeletal damage, which is crucial in neural cell integrity. Excessive protein carbonylation and actin filament destabilization were also detected following BTZ treatment that was lower following CFZ treatment. Our data on cytoskeletal proteins, chaperone system, and protein oxidation may explain the milder neurotoxic effects of CFZ in clinical applications.
Step Sizes and Rate Constants of Single-headed Cytoplasmic Dynein Measured with Optical Tweezers
Authors: Kinoshita Yoshimi , Kambara Taketoshi , Nishikawa Kaori , Kaya Motoshi , Higuchi Hideo 
Published: October 2018

AbstractA power stroke of dynein is thought to be responsible for the stepping of dimeric dynein. However, the actual size of the displacement driven by a power stroke has not been directly measured. Here, the displacements of single-headed cytoplasmic dynein were measured by optical tweezers. The mean displacement of dynein interacting with microtubule was ~8 nm at 100 µM ATP, and decreased sigmoidally with a decrease in the ATP concentration. The ATP dependence of the mean displacement was explained by a model that some dynein molecules bind to microtubule in pre-stroke conformation and generate 8-nm displacement, while others bind in the post-stroke one and detach without producing a power stroke. Biochemical assays showed that the binding affinity of the post-stroke dynein to a microtubule was ~5 times higher than that of pre-stroke dynein, and the dissociation rate was ~4 times lower. Taking account of these rates, we conclude that the displacement driven by a power stroke is 8.3 nm. A working model of dimeric dynein driven by the 8-nm power stroke was proposed.
Valence band behaviour of zirconium oxide, Photoelectron and Auger spectroscopy study
Authors: Azdad Zakaria , Marot Laurent , Moser Lucas , Steiner Roland , Meyer Ernst 
Published: October 2018

AbstractIn this study X-ray Photoelectron Spectroscopy and Ultraviolet Photoelectron Spectroscopy were combined to investigate the effect of oxygen incorporation on the valence band behaviour of ZrOx. The Auger transitions involving valence bands are found to mimic the self-folded density of state measured using Ultraviolet Photoelectron Spectroscopy. The valence band once constructed in a sub-oxide form, stays at a fixed energy position despite the change in the stoichiometry. This behaviour is found to be useful in setting a reference for X-ray Photoelectron Spectroscopy charge correction. The results of the charged corrected spectra were compared to other methods and found to be in great agreement. Finally, a correlation between the core-level binding energy and the structural property of ZrOxis given.