bluuebunny/crossref_metadata_2025_split huggingface dataset:
C-Abl is not actıvated in DNA damage-induced and Tap63-mediated oocyte apoptosıs in human ovary
Authors: Bildik Gamze , Acılan Ceyda , Sahin Gizem Nur , Karahuseyinoglu Sercin , Oktem Ozgur 
Published: September 2018

AbstractThere is a controversy in literature as to whether c-Abl is crucial for the induction of TAp63-mediated apoptosis and whether that inhibition of c-Abl with imatinib, which was designed to inhibit the oncogenic kinase BCR-ABL and c-kit, protects oocytes from chemotherapy-induced apoptosis in mice. No human data are available on this issue. We therefore aimed to explore whether genomic damage induced by chemotherapy drug cisplatin activates c-Abl along with TAp63 and the inhibition of c-Abl with imatinib prevents cisplatin-induced oocyte death and follicle loss in human ovary. Exposure to cisplatin induced DNA damage, activated TAp63 and SAPK/JNK pathway, and triggered apoptosis in the oocytes and granulosa cells. However, TAp63 activation after cisplatin was not associated with any increase in the expression of c-Abl. Imatinib did not prevent cisplatin-induced apoptosis of the granulosa cells or oocytes. Moreover, treatment with this drug resulted in the formation of bizarre shaped follicles lacking oocytes and increased follicular atresia by inducing apoptosis of granulosa cells and oocytes. Similar toxic effects were observed when ovarian tissue samples were incubated with a c-kit antagonist drug anti-CD117, but not with another c-Abl tyrosine kinase inhibitor GNF-2, which lacks an inhibitory action on c-kit. Intraperitoneal administration of imatinib to the xenografted animals produced similar histomorphological abnormalities in the follicles in human ovarian grafts and did not prevent cisplatin-induced follicle loss when co-administered with cisplatin. Our findings provide, for the first time, a molecular evidence for ovarian toxicity of this drug in human. Furthermore, this study together with two previous case reports of a severely compromised ovarian response to gonadotropin stimulation and premature ovarian failure in patients, while receiving imatinib, further heighten the concerns about its potential gonadotoxicity on human ovary and urge caution in its use in young female patients.
Structural basis for broad neutralization of ebolaviruses by an antibody targeting the glycoprotein fusion loop
Authors: Janus Benjamin M. , van Dyk Nydia , Zhao Xuelian , Howell Katie A. , Soto Cinque , Aman M. Javad , Li Yuxing , Fuerst Thomas R. , Ofek Gilad 
Published: September 2018

AbstractThe severity of the 2014–2016 ebolavirus outbreak in West Africa expedited clinical development of therapeutics and vaccines though the countermeasures on hand were largely monospecific and lacked efficacy against other ebolavirus species that previously emerged. Recent studies indicate that ebolavirus glycoprotein (GP) fusion loops are targets for cross-protective antibodies. Here we report the 3.72 Å resolution crystal structure of one such cross-protective antibody, CA45, bound to the ectodomain of Ebola virus (EBOV) GP. The CA45 epitope spans multiple faces of the fusion loop stem, across both GP1 and GP2 subunits, with ~68% of residues identical across > 99.5% of known ebolavirus isolates. Extensive antibody interactions within a pan-ebolavirus small-molecule inhibitor binding cavity on GP define this cavity as a novel site of immune vulnerability. The structure elucidates broad ebolavirus neutralization through a highly conserved epitope on GP and further enables rational design and development of broadly protective vaccines and therapeutics.
Magnetized fast isochoric laser heating for efficient creation of ultra-high-energy-density states
Authors: Sakata Shohei , Lee Seungho , Morita Hiroki , Johzaki Tomoyuki , Sawada Hiroshi , Iwasa Yuki , Matsuo Kazuki , Law King Fai Farley , Yao Akira , Hata Masayasu , Sunahara Atsushi , Kojima Sadaoki , Abe Yuki , Kishimoto Hidetaka , Syuhada Aneez , Shiroto Takashi , Morace Alessio , Yogo Akifumi , Iwata Natsumi , Nakai Mitsuo , Sakagami Hitoshi , Ozaki Tetsuo , Yamanoi Kohei , Norimatsu Takayoshi , Nakata Yoshiki , Tokita Shigeki , Miyanaga Noriaki , Kawanaka Junji , Shiraga Hiroyuki , Mima Kunioki , Nishimura Hiroaki , Bailly-Grandvaux Mathieu , Santos João Jorge , Nagatomo Hideo , Azechi Hiroshi , Kodama Ryosuke , Arikawa Yasunobu , Sentoku Yasuhiko , Fujioka Shinsuke 
Published: September 2018

AbstractFast isochoric heating of a pre-compressed plasma core with a high-intensity short-pulse laser is an attractive and alternative approach to create ultra-high-energy-density states like those found in inertial confinement fusion (ICF) ignition sparks. Laser-produced relativistic electron beam (REB) deposits a part of kinetic energy in the core, and then the heated region becomes the hot spark to trigger the ignition. However, due to the inherent large angular spread of the produced REB, only a small portion of the REB collides with the core. Here, we demonstrate a factor-of-two enhancement of laser-to-core energy coupling with the magnetized fast isochoric heating. The method employs a magnetic field of hundreds of Tesla that is applied to the transport region from the REB generation zone to the core which results in guiding the REB along the magnetic field lines to the core. This scheme may provide more efficient energy coupling compared to the conventional ICF scheme.
UBL3 modification influences protein sorting to small extracellular vesicles
Authors: Ageta Hiroshi , Ageta-Ishihara Natsumi , Hitachi Keisuke , Karayel Ozge , Onouchi Takanori , Yamaguchi Hisateru , Kahyo Tomoaki , Hatanaka Ken , Ikegami Koji , Yoshioka Yusuke , Nakamura Kenji , Kosaka Nobuyoshi , Nakatani Masashi , Uezumi Akiyoshi , Ide Tomihiko , Tsutsumi Yutaka , Sugimura Haruhiko , Kinoshita Makoto , Ochiya Takahiro , Mann Matthias , Setou Mitsutoshi , Tsuchida Kunihiro 
Published: September 2018

AbstractExosomes, a type of small extracellular vesicles (sEVs), derived from multivesicular bodies (MVBs), mediate cell-to-cell communication by transporting proteins, mRNAs, and miRNAs. However, the molecular mechanism by which proteins are sorted to sEVs is not fully understood. Here, we report that ubiquitin-like 3 (UBL3)/membrane-anchored Ub-fold protein (MUB) acts as a posttranslational modification (PTM) factor that regulates protein sorting to sEVs. We find that UBL3 modification is indispensable for sorting of UBL3 to MVBs and sEVs. We also observe a 60% reduction of total protein levels in sEVs purified from Ubl3-knockout mice compared with those from wild-type mice. By performing proteomics analysis, we find 1241 UBL3-interacting proteins, including Ras. We also show that UBL3 directly modifies Ras and oncogenic RasG12V mutant, and that UBL3 expression enhances sorting of RasG12V to sEVs via UBL3 modification. Collectively, these results indicate that PTM by UBL3 influences the sorting of proteins to sEVs.
Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume
Authors: Vojinovic Dina , Adams Hieab H. , Jian Xueqiu , Yang Qiong , Smith Albert Vernon , Bis Joshua C. , Teumer Alexander , Scholz Markus , Armstrong Nicola J. , Hofer Edith , Saba Yasaman , Luciano Michelle , Bernard Manon , Trompet Stella , Yang Jingyun , Gillespie Nathan A. , van der Lee Sven J. , Neumann Alexander , Ahmad Shahzad , Andreassen Ole A. , Ames David , Amin Najaf , Arfanakis Konstantinos , Bastin Mark E. , Becker Diane M. , Beiser Alexa S. , Beyer Frauke , Brodaty Henry , Bryan R. Nick , Bülow Robin , Dale Anders M. , De Jager Philip L. , Deary Ian J. , DeCarli Charles , Fleischman Debra A. , Gottesman Rebecca F. , van der Grond Jeroen , Gudnason Vilmundur , Harris Tamara B. , Homuth Georg , Knopman David S. , Kwok John B. , Lewis Cora E. , Li Shuo , Loeffler Markus , Lopez Oscar L. , Maillard Pauline , El Marroun Hanan , Mather Karen A. , Mosley Thomas H. , Muetzel Ryan L. , Nauck Matthias , Nyquist Paul A. , Panizzon Matthew S. , Pausova Zdenka , Psaty Bruce M. , Rice Ken , Rotter Jerome I. , Royle Natalie , Satizabal Claudia L. , Schmidt Reinhold , Schofield Peter R. , Schreiner Pamela J. , Sidney Stephen , Stott David J. , Thalamuthu Anbupalam , Uitterlinden Andre G. , Valdés Hernández Maria C. , Vernooij Meike W. , Wen Wei , White Tonya , Witte A. Veronica , Wittfeld Katharina , Wright Margaret J. , Yanek Lisa R. , Tiemeier Henning , Kremen William S. , Bennett David A. , Jukema J. Wouter , Paus Tomas , Wardlaw Joanna M. , Schmidt Helena , Sachdev Perminder S. , Villringer Arno , Grabe Hans Jörgen , Longstreth W T , van Duijn Cornelia M. , Launer Lenore J. , Seshadri Sudha , Ikram M Arfan , Fornage Myriam 
Published: September 2018

AbstractThe volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = −0.59, p-value = 3.14 × 10−6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.
A scalable online tool for quantitative social network assessment reveals potentially modifiable social environmental risks
Authors: Dhand Amar , White Charles C. , Johnson Catherine , Xia Zongqi , De Jager Philip L. 
Published: September 2018

AbstractSocial networks are conduits of support, information, and health behavior flows. Existing measures of social networks used in clinical research are typically summative scales of social support or artificially truncated networks of ≤ 5 people. Here, we introduce a quantitative social network assessment tool on a secure open-source web platform, readily deployable in large-scale clinical studies. The tool maps an individual’s personal network, including specific persons, their relationships to each other, and their health habits. To demonstrate utility, we used the tool to measure the social networks of 1493 persons at risk of multiple sclerosis. We examined each person’s social network in relation to self-reported neurological disability. We found that the characteristics of persons surrounding the participant, such as negative health behaviors, were strongly associated with the individual’s functional disability. This quantitative assessment reveals the key elements of individuals’ social environments that could be targeted in clinical trials.
Structural analysis of HTL and D14 proteins reveals the basis for ligand selectivity in Striga
Authors: Xu Yuqun , Miyakawa Takuya , Nosaki Shohei , Nakamura Akira , Lyu Ying , Nakamura Hidemitsu , Ohto Umeharu , Ishida Hanako , Shimizu Toshiyuki , Asami Tadao , Tanokura Masaru 
Published: September 2018

AbstractHYPOSENSITIVE TO LIGHT (HTL) and DWARF14 (D14) mediate the perception of karrikin and strigolactone, which stimulates germination of the parasitic weed Striga. However, their role in parasitic seeds is poorly understood, and the basis for their differing responsiveness remains unclear. Here, we show that Striga hermonthica HTL proteins (ShHTLs) in ‘conserved’ and ‘intermediate’ clades are able to bind karrikin. The ‘divergent’ clade is able to hydrolyze strigolactone. Unexpectedly, we find that ShD14 is also capable of hydrolyzing strigolactone. Through comparative analysis of ShHTLs and ShD14 crystal structures, we provide insights into the basis for their selectivity. Moreover, we show that both ShD14 and divergent clade ShHTLs, but not conserved and intermediate clade ShHTLs, can interact with the putative downstream signaling component ShMAX2 in the presence of the synthetic strigolactone, rac-GR24. These findings provide insight into how strigolactone is perceived and how ligand specificity is determined.
A bioinspired multilegged soft millirobot that functions in both dry and wet conditions
Authors: Lu Haojian , Zhang Mei , Yang Yuanyuan , Huang Qiang , Fukuda Toshio , Wang Zuankai , Shen Yajing 
Published: September 2018

AbstractDeveloping untethered millirobots that can adapt to harsh environments with high locomotion efficiency is of interest for emerging applications in various industrial and biomedical settings. Despite recent success in exploiting soft materials to impart sophisticated functions which are not available in conventional rigid robotics, it remains challenging to achieve superior performances in both wet and dry conditions. Inspired by the flexible, soft, and elastic leg/foot structures of many living organisms, here we report an untethered soft millirobot decorated with multiple tapered soft feet architecture. Such robot design yields superior adaptivity to various harsh environments with ultrafast locomotion speed (>40 limb length/s), ultra-strong carrying capacity (>100 own weight), and excellent obstacle-crossing ability (stand up 90° and across obstacle >10 body height). Our work represents an important advance in the emerging area of bio-inspired robotics and will find a wide spectrum of applications.
Multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition
Authors: Lu Hongzhong , Cao Weiqiang , Liu Xiaoyun , Sui Yufei , Ouyang Liming , Xia Jianye , Huang Mingzhi , Zhuang Yingping , Zhang Siliang , Noorman Henk , Chu Ju 
Published: September 2018

AbstractOxygen limitation is regarded as a useful strategy to improve enzyme production by mycelial fungus like Aspergillus niger. However, the intracellular metabolic response of A. niger to oxygen limitation is still obscure. To address this, the metabolism of A. niger was studied using multi-omics integrated analysis based on the latest GEMs (genome-scale metabolic model), including metabolomics, fluxomics and transcriptomics. Upon sharp reduction of the oxygen supply, A. niger metabolism shifted to higher redox level status, as well as lower energy supply, down-regulation of genes for fatty acid synthesis and a rapid decrease of the specific growth rate. The gene expression of the glyoxylate bypass was activated, which was consistent with flux analysis using the A. niger GEMs iHL1210. The increasing flux of the glyoxylate bypass was assumed to reduce the NADH formation from TCA cycle and benefit maintenance of the cellular redox balance under hypoxic conditions. In addition, the relative fluxes of the EMP pathway were increased, which possibly relieved the energy demand for cell metabolism. The above multi-omics integrative analysis provided new insights on metabolic regulatory mechanisms of A. niger associated with enzyme production under oxygen-limited condition, which will benefit systematic design and optimization of the A. niger microbial cell factory.
Methylation deregulation of miRNA promoters identifies miR124-2 as a survival biomarker in Breast Cancer in very young women
Authors: Oltra Sara S. , Peña-Chilet Maria , Vidal-Tomas Victoria , Flower Kirsty , Martinez María Teresa , Alonso Elisa , Burgues Octavio , Lluch Ana , Flanagan James M. , Ribas Gloria 
Published: September 2018

AbstractMiRNAs are part of the epigenetic machinery, and are also epigenetically modified by DNA methylation. MiRNAs regulate expression of different genes, so any alteration in their methylation status may affect their expression. We aimed to identify methylation differences in miRNA encoding genes in breast cancer affecting women under 35 years old (BCVY), in order to identify potential biomarkers in these patients. In Illumina Infinium MethylationEPIC BeadChip samples (metEPICVal), we analysed the methylation of 9,961 CpG site regulators of miRNA-encoding genes present in the array. We identified 193 differentially methylated CpG sites in BCVY (p-value < 0.05 and methylation differences ±0.1) that regulated 83 unique miRNA encoding genes. We validated 10 CpG sites using two independent datasets based on Infinium Human Methylation 450k array. We tested gene expression of miRNAs with differential methylation in BCVY in a meta-analysis using The Cancer Genome Atlas (TCGA), Clariom D and Affymetrix datasets. Five miRNAs (miR-9, miR-124-2, miR-184, miR-551b and miR-196a-1) were differently expressed (FDRp-value < 0.01). Finally, only miR-124-2 shows a significantly different gene expression by quantitative real-time PCR. MiR-124-hypomethylation presents significantly better survival rates for older patients as opposed to the worse prognosis observed in BCVY, identifying it as a potential specific survival biomarker in BCVY.
Mutagenic assessment of chemotherapy and Smac mimetic drugs in cells with defective DNA damage response pathways
Authors: Miles Mark A. , Hawkins Christine J. 
Published: September 2018

AbstractDNA damaging therapies can spur the formation of therapy-related cancers, due to mis-repair of lesions they create in non-cancerous cells. This risk may be amplified in patients with impaired DNA damage responses. We disabled key DNA damage response pathways using genetic and pharmacological approaches, and assessed the impact of these deficiencies on the mutagenicity of chemotherapy drugs or the “Smac mimetic” GDC-0152, which kills tumor cells by targeting XIAP, cIAP1 and 2. Doxorubicin and cisplatin provoked mutations in more surviving cells deficient in ATM, p53 or the homologous recombination effector RAD51 than in wild type cells, but suppressing non-homologous end joining (NHEJ) by disabling DNA-PKcs prevented chemotherapy-induced mutagenesis. Vincristine-induced mutagenesis required p53 and DNA-PKcs but was not affected by ATM status, consistent with it provoking ATM-independent p53-mediated activation of caspases and CAD, which creates DNA lesions in surviving cells that could be mis-repaired by NHEJ. Encouragingly, GDC-0152 failed to stimulate mutations in cells with proficient or defective DNA damage response pathways. This study highlights the elevated oncogenic risk associated with treating DNA repair-deficient patients with genotoxic anti-cancer therapies, and suggests a potential advantage for Smac mimetic drugs over traditional therapies: a reduced risk of therapy-related cancers.
Molecular fingerprinting of nanoparticles in complex media with non-contact photoacoustics: beyond the light scattering limit
Authors: Pelivanov Ivan , Petrova Elena , Yoon Soon Joon , Qian Zhaoxia , Guye Kathryn , O’Donnell Matthew 
Published: September 2018

AbstractOptical instruments can probe physical systems even to the level of individual molecules. In particular, every molecule, solution, and structure such as a living cell has a unique absorption spectrum representing a molecular fingerprint. This spectrum can help identify a particular molecule from others or quantify its concentration; however, scattering limits molecular fingerprinting within a complex compound and must be overcome. Here, we present a new, non-contact photoacoustic (PA)-based method that can almost completely remove the influence of background light scattering on absorption measurements in heterogeneous highly scattering solutions and, furthermore, separate the intrinsic absorption of nanoscale objects from their scattering. In particular, we measure pure absorption spectra for solutions of gold nanorods (GNRs) as an example of a plasmonic agent and show that these spectra differ from the extinction measured with conventional UV-VIS spectrophotometry. Finally, we show how the original GNR absorption changes when nanoparticles are internalized by cells.
Direct RNA Sequencing of the Coding Complete Influenza A Virus Genome
Authors: Keller Matthew W. , Rambo-Martin Benjamin L. , Wilson Malania M. , Ridenour Callie A. , Shepard Samuel S. , Stark Thomas J. , Neuhaus Elizabeth B. , Dugan Vivien G. , Wentworth David E. , Barnes John R. 
Published: September 2018

AbstractFor the first time, a coding complete genome of an RNA virus has been sequenced in its original form. Previously, RNA was sequenced by the chemical degradation of radiolabeled RNA, a difficult method that produced only short sequences. Instead, RNA has usually been sequenced indirectly by copying it into cDNA, which is often amplified to dsDNA by PCR and subsequently analyzed using a variety of DNA sequencing methods. We designed an adapter to short highly conserved termini of the influenza A virus genome to target the (-) sense RNA into a protein nanopore on the Oxford Nanopore MinION sequencing platform. Utilizing this method with total RNA extracted from the allantoic fluid of influenza rA/Puerto Rico/8/1934 (H1N1) virus infected chicken eggs (EID50 6.8 × 109), we demonstrate successful sequencing of the coding complete influenza A virus genome with 100% nucleotide coverage, 99% consensus identity, and 99% of reads mapped to influenza A virus. By utilizing the same methodology one can redesign the adapter in order to expand the targets to include viral mRNA and (+) sense cRNA, which are essential to the viral life cycle, or other pathogens. This approach also has the potential to identify and quantify splice variants and base modifications, which are not practically measurable with current methods.
Direct IR Absorption Spectra of Propargyl Cation Isolated in Solid Argon
Authors: Chin Chih-Hao , Lin Meng-Yeh , Huang Tzu-Ping , Wu Pei-Zhen , Wu Yu-Jong 
Published: September 2018

AbstractThe direct infrared (IR) absorption spectra of propargyl cations were recorded. These cations were generated via the electron bombardment of a propyne/Ar matrix sample during matrix deposition. Secondary photolysis with selected ultraviolet (UV) light was used for grouping the observed bands of various products. The band assignment of the propargyl cation in solid Ar was performed according by referring to the previous infrared photodissociation (IRPD) and velocity-map imaging photoelectron (VMI-PE) data, and via theoretical predictions of the anharmonic vibrational wavenumbers, band intensities, and deuterium-substituted isotopic ratios. Almost all the IR active bands with an observable intensity were recorded and the ν11 mode was reported for the first time.
Group-based rewiring rules of binary opinion competition dynamics
Authors: Jin Cheng , Yin Chunji , Jin Xiaogang , Min Yong , Li Yixiao , Chen Nuole , Huang Jiaxuan 
Published: September 2018

AbstractThe dynamics of competing opinions on networks has attracted multi-disciplinary research. Most modelling approaches assume uniform or heterogeneous behaviour among all individuals, while the role of distinctive group behaviour is rarely addressed. Here, we consider competition occurring between two opinion groups with bound rewiring rules, i.e., opinion-preferred rewiring, degree-preferred rewiring and random rewiring. When two opinions share a balanced initial proportion, opinion-preferred rewiring is superior to the other rules under low rewiring rates, and coexistence occurs under high rewiring rates. For unbalanced proportions, the best response rule for the minority/majority is unfixed, and this depends on the initial proportion and rewiring frequency. Furthermore, we find evolution processes for all competing cases belong to two categories. Evolution Category I shows an obvious correlation between opinion proportions and the density of discordant edges (connecting nodes with different opinions), and these trends can be effectively described by numerical approximations. However, for Evolution Category II, no such correlation exists for individuals or linking pairs, and an analysis of local structures reveals the emergence of large numbers of open triads with the same opinions, denoting group prevalence. This work broadens the understanding of opinion competition and inspires exploring group strategies employed in social dynamic systems.