bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA vaccination protects mice against Zika virus-induced damage to the testes
Authors: Griffin Bryan D. , Muthumani Kar , Warner Bryce M. , Majer Anna , Hagan Mable , Audet Jonathan , Stein Derek R. , Ranadheera Charlene , Racine Trina , De La Vega Marc-Antoine , Piret Jocelyne , Kucas Stephanie , Tran Kaylie N. , Frost Kathy L. , De Graff Christine , Soule Geoff , Scharikow Leanne , Scott Jennifer , McTavish Gordon , Smid Valerie , Park Young K. , Maslow Joel N. , Sardesai Niranjan Y. , Kim J. Joseph , Yao Xiao-jian , Bello Alexander , Lindsay Robbin , Boivin Guy , Booth Stephanie A. , Kobasa Darwyn , Embury-Hyatt Carissa , Safronetz David , Weiner David B. , Kobinger Gary P. 
Published: June 2017

AbstractZika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented. Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm. Candidate ZIKV vaccines have shown protective efficacy in preclinical studies carried out in animal models, and several vaccines have entered clinical trials. Here, we report that administration of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) completely protects mice against ZIKV-associated damage to the testes and sperm and prevents viral persistence in the testes following challenge with a contemporary strain of ZIKV. These data suggest that DNA vaccination merits further investigation as a potential means to reduce ZIKV persistence in the male reproductive tract.
Crystal structures of U6 snRNA-specific terminal uridylyltransferase
Authors: Yamashita Seisuke , Takagi Yuko , Nagaike Takashi , Tomita Kozo 
Published: June 2017

AbstractThe terminal uridylyltransferase, TUT1, builds or repairs the 3′-oligo-uridylylated tail of U6 snRNA. The 3′-oligo-uridylylated tail is the Lsm-binding site for U4/U6 di-snRNP formation and U6 snRNA recycling for pre-mRNA splicing. Here, we report crystallographic and biochemical analyses of human TUT1, which revealed the mechanisms for the specific uridylylation of the 3′-end of U6 snRNA by TUT1. The O2 and O4 atoms of the UTP base form hydrogen bonds with the conserved His and Asn in the catalytic pocket, respectively, and TUT1 preferentially incorporates UMP onto the 3′-end of RNAs. TUT1 recognizes the entire U6 snRNA molecule by its catalytic domains, N-terminal RNA-recognition motifs and a previously unidentified C-terminal RNA-binding domain. Each domain recognizes specific regions within U6 snRNA, and the recognition is coupled with the domain movements and U6 snRNA structural changes. Hence, TUT1 functions as the U6 snRNA-specific terminal uridylyltransferase required for pre-mRNA splicing.
Indium selenide: an insight into electronic band structure and surface excitations
Authors: Politano A. , Campi D. , Cattelan M. , Ben Amara I. , Jaziri S. , Mazzotti A. , Barinov A. , Gürbulak B. , Duman S. , Agnoli S. , Caputi L. S. , Granozzi G. , Cupolillo A. 
Published: June 2017

AbstractWe have investigated the electronic response of single crystals of indium selenide by means of angle-resolved photoemission spectroscopy, electron energy loss spectroscopy and density functional theory. The loss spectrum of indium selenide shows the direct free exciton at ~1.3 eV and several other peaks, which do not exhibit dispersion with the momentum. The joint analysis of the experimental band structure and the density of states indicates that spectral features in the loss function are strictly related to single-particle transitions. These excitations cannot be considered as fully coherent plasmons and they are damped even in the optical limit, i.e. for small momenta. The comparison of the calculated symmetry-projected density of states with electron energy loss spectra enables the assignment of the spectral features to transitions between specific electronic states. Furthermore, the effects of ambient gases on the band structure and on the loss function have been probed.
Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility
Authors: Zhong Qi , Chen Xiangdong , Zhao Yan , Liu Ru , Yao Shanglong 
Published: June 2017

AbstractSignificant individual susceptibility to intravenous anesthetic propofol exists. The etiology of individual variability in the response to propofol may be influenced by genetic polymorphisms in metabolic and functional pathways. With current pharmacogenetics and modern molecular biology technologies, it is possible to study the influence of genetic polymorphisms on susceptibility to propofol. When inducing general anesthesia with intravenous propofol, high individual susceptibility to propofol was found. Using Sequenom MassARRAY single-nucleotide polymorphism (SNP) genotyping, we identified a mutation (rs6313) in the 5HT2A gene that was correlated to individual susceptibility to propofol effect-site concentration (Cep) and onset time of propofol induction. Carriers of the minor allele (G) of 5HT2A rs6313 required less propofol (20% decrease in Cep) and less time (40% decrease in onset time) to induce anesthesia. Moreover, associations were found between the gamma-aminobutyric acid (GABA) receptor SNP rs2279020 and the SCN9A SNP rs6746030 and the susceptibility of bispectral index (BIS) after propofol-induced anesthesia. In addition, dominant mutations in GABAA1 rs2279020, GABAA2 rs11503014, and CHRM2 rs1824024 were putatively associated with cardiovascular susceptibility to propofol anesthesia. No gene-gene interactions were found through a standardized measure of linkage disequilibrium and a multifactor dimensionality reduction analysis. Our results suggest that genetic polymorphisms related to mechanisms of propofol anesthesia are involved in propofol susceptibility.
Chlorophyll derivatives enhance invertebrate red-light and ultraviolet phototaxis
Authors: Degl’Innocenti Andrea , Rossi Leonardo , Salvetti Alessandra , Marino Attilio , Meloni Gabriella , Mazzolai Barbara , Ciofani Gianni 
Published: June 2017

AbstractChlorophyll derivatives are known to enhance vision in vertebrates. They are thought to bind visual pigments (i.e., opsins apoproteins bound to retinal chromophores) directly within the retina. Consistent with previous findings in vertebrates, here we show that chlorin e6 — a chlorophyll derivative — enhances photophobicity in a flatworm (Dugesia japonica), specifically when exposed to UV radiation (λ = 405 nm) or red light (λ = 660 nm). This is the first report of chlorophyll derivatives acting as modulators of invertebrate phototaxis, and in general the first account demonstrating that they can artificially alter animal response to light at a behavioral level. Our findings show that the interaction between chlorophyll derivatives and opsins virtually concerns the vast majority of bilaterian animals, and also occurs in visual systems based on rhabdomeric (rather than ciliary) opsins.
Safety of Acupuncture: Overview of Systematic Reviews
Authors: Chan Malcolm W. C. , Wu Xin Yin , Wu Justin C. Y. , Wong Samuel Y. S. , Chung Vincent C. H. 
Published: June 2017

AbstractAcupuncture is increasingly used worldwide. It is becoming more accepted by both patients and healthcare providers. However, the current understanding of its adverse events (AEs) is fragmented. We conducted this overview to collect all systematic reviews (SRs) on the AEs of acupuncture and related therapies. MEDLINE and EMBASE were searched from inception to December 2015. Methodological quality of included reviews was assessed with a validated instrument. Evidence was narratively reported. Seventeen SRs covering various types of acupuncture were included. Methodological quality of the reviews was overall mediocre. Four major categories of AEs were identified, which are organ or tissue injuries (13 reviews, median: 36 cases, median deaths: 4), infections (11 reviews, median: 17 cases, median deaths: 0.5), local AEs or reactions (12 reviews, median: 8.5 cases, no deaths were reported), and other complications such as dizziness or syncope (11 reviews, median: 21 cases, no deaths were reported). Minor and serious AEs can occur during the use of acupuncture and related modalities, contrary to the common impression that acupuncture is harmless. Serious AEs are rare, but need significant attention as mortality can be associated with them. Referrals should consider acupuncturists’ training credibility, and patient safety should be a core part of acupuncture education.
Identification of a gene cluster for telomestatin biosynthesis and heterologous expression using a specific promoter in a clean host
Authors: Amagai Keita , Ikeda Haruo , Hashimoto Junko , Kozone Ikuko , Izumikawa Miho , Kudo Fumitaka , Eguchi Tadashi , Nakamura Takemichi , Osada Hiroyuki , Takahashi Shunji , Shin-ya Kazuo 
Published: June 2017

AbstractTelomestatin, a strong telomerase inhibitor with G-quadruplex stabilizing activity, is a potential therapeutic agent for treating cancers. Difficulties in isolating telomestatin from microbial cultures and in chemical synthesis are bottlenecks impeding the wider use. Therefore, improvement in telomestatin production and structural diversification are required for further utilization and application. Here, we discovered the gene cluster responsible for telomestatin biosynthesis, and achieved production of telomestatin by heterologous expression of this cluster in the engineered Streptomyces avermitilis SUKA strain. Utilization of an optimal promoter was essential for successful production. Gene disruption studies revealed that the tlsB, tlsC, and tlsO–T genes play key roles in telomestatin biosynthesis. Moreover, exchanging TlsC core peptide sequences resulted in the production of novel telomestatin derivatives. This study sheds light on the expansion of chemical diversity of natural peptide products for drug development.
Improved efficacy of an arthropod toxin expressing fungus against insecticide-resistant malaria-vector mosquitoes
Authors: Bilgo Etienne , Lovett Brian , Fang Weiguo , Bende Niraj , King Glenn F. , Diabate Abdoulaye , St. Leger Raymond J. 
Published: June 2017

AbstractThe continued success of malaria control efforts requires the development, study and implementation of new technologies that circumvent insecticide resistance. We previously demonstrated that fungal pathogens can provide an effective delivery system for mosquitocidal or malariacidal biomolecules. Here we compared genes from arthropod predators encoding insect specific sodium, potassium and calcium channel blockers for their ability to improve the efficacy of Metarhizium against wild-caught, insecticide-resistant anophelines. Toxins expressed under control of a hemolymph-specific promoter increased fungal lethality to mosquitoes at spore dosages as low as one conidium per mosquito. One of the most potent, the EPA approved Hybrid (Ca++/K+ channel blocker), was studied for pre-lethal effects. These included reduced blood feeding behavior, with almost 100% of insects infected with ~6 spores unable to transmit malaria within 5 days post-infection, surpassing the World Health Organization threshold for successful vector control agents. Furthermore, recombinant strains co-expressing Hybrid toxin and AaIT (Na+ channel blocker) produced synergistic effects, requiring 45% fewer spores to kill half of the mosquitoes in 5 days as single toxin strains. Our results identify a repertoire of toxins with different modes of action that improve the utility of entomopathogens as a technology that is compatible with existing insecticide-based control methods.
Radioiodination of BODIPY and its application to a nuclear and optical dual functional labeling agent for proteins and peptides
Authors: Ono Masahiro , Watanabe Hiroyuki , Ikehata Yuki , Ding Ning , Yoshimura Masashi , Sano Kohei , Saji Hideo 
Published: June 2017

AbstractIn molecular imaging research, the development of multimodal imaging probes has recently attracted much attention. In the present study, we prepared radioiodinated BODIPY and applied it as a nuclear and optical dual functional labeling agent for proteins and peptides. We designed and synthesized [125I]BODIPY with a N-hydroxysuccinimide (NHS) ester, and evaluated its utility as a nuclear and fluorescent dual labeling agent for proteins and peptides. In the radioiodination reaction of BODIPY-NHS with [125I]NaI, [125I]BODIPY-NHS was obtained at a 48% radiochemical yield. When we carried out the conjugation reaction of [125I]BODIPY-NHS with bovine serum albumin (BSA) and RGD (Arg-Gly-Asp) peptide as a model protein and peptide, respectively, [125I]BODIPY-BSA and [125I]BODIPY-RGD peptide were successfully prepared at 98 and 82% radiochemical yields, respectively. Furthermore, we prepared [123I]BODIPY-trastuzumab by this conjugation reaction and successfully applied it to single photon emission computed tomography (SPECT) imaging studies using tumor-bearing mice, suggesting that radioiodinated BODIPY-NHS serves as a dual functional labeling agent for proteins and peptides. Since iodine has various radioisotopes that can be used for SPECT and positron emission tomography (PET) imaging, biological research, and radiotherapy, the radioiodinated BODIPY may be extensively applicable from basic to clinical research.
Dressmakers show enhanced stereoscopic vision
Authors: Chopin Adrien , Levi Dennis M. , Bavelier Daphné 
Published: June 2017

AbstractThe ability to estimate the distance of objects from one’s self and from each other is fundamental to a variety of behaviours from grasping objects to navigating. The main cue to distance, stereopsis, relies on the slight offsets between the images derived from our left and right eyes, also termed disparities. Here we ask whether the precision of stereopsis varies with professional experience with precise manual tasks. We measured stereo-acuities of dressmakers and non-dressmakers for both absolute and relative disparities. We used a stereoscope and a computerized test removing monocular cues. We also measured vergence noise and bias using the Nonius line technique. We demonstrate that dressmakers’ stereoscopic acuities are better than those of non-dressmakers, for both absolute and relative disparities. In contrast, vergence noise and bias were comparable in the two groups. Two non-exclusive mechanisms may be at the source of the group difference we document: (i) self-selection or the fact that stereo-vision is functionally important to become a dressmaker, and (ii) plasticity, or the fact that training on demanding stereovision tasks improves stereo-acuity.
Targeted sequencing of both DNA strands barcoded and captured individually by RNA probes to identify genome-wide ultra-rare mutations
Authors: Wang Qing , Wang Xu , Tang Pheobe S. , O’leary Grace M. , Zhang Ming 
Published: June 2017

AbstractNext Generation Sequencing (NGS) has been widely implemented in biological research and has made a profound impact on patient care. One of the essential NGS applications is to identify disease-causing sequence variants, where high coverage and accuracy are needed. Here, we reported a novel NGS pipeline, termed a Sequencing System of Digitalized Barcode Encrypted Single-stranded Library from Extremely Low (quality and quantity) DNA Input with Probe-based DNA Enrichment by RNA probes targeting DNA duplex (DEEPER-Seq). This method combines an ultra-sensitive single-stranded library construction with barcoding error correction, termed DEEPER-Library; and a DNA capture approach using RNA probes targeting both DNA strands, termed DEEPER-Capture. DEEPER-Seq can create NGS libraries from as little as 20 pg DNA with PCR error correcting capabilities, and capture target sequences at an average ratio of 29.2% by targeting both DNA strands simultaneously with an over 98.6% coverage. Our method tags and sequences each of the two strands of a DNA duplex independently and only scores mutations that are found at the same position in both strands, which allows us to identify mutations with allelic fractions down to 0.03% in a whole exome sequencing (WES) study with a background error rate of one artificial error per 4.8 × 109 nucleotides.
Discovery of a novel conformational equilibrium in urokinase-type plasminogen activator
Authors: Kromann-Hansen Tobias , Louise Lange Eva , Peter Sørensen Hans , Hassanzadeh-Ghassabeh Gholamreza , Huang Mingdong , Jensen Jan K. , Muyldermans Serge , Declerck Paul J. , Komives Elizabeth A. , Andreasen Peter A. 
Published: June 2017

AbstractAlthough trypsin-like serine proteases have flexible surface-exposed loops and are known to adopt higher and lower activity conformations, structural determinants for the different conformations have remained largely obscure. The trypsin-like serine protease, urokinase-type plasminogen activator (uPA), is central in tissue remodeling processes and also strongly implicated in tumor metastasis. We solved five X-ray crystal structures of murine uPA (muPA) in the absence and presence of allosteric molecules and/or substrate-like molecules. The structure of unbound muPA revealed an unsuspected non-chymotrypsin-like protease conformation in which two β-strands in the core of the protease domain undergoes a major antiparallel-to-parallel conformational transition. We next isolated two anti-muPA nanobodies; an active-site binding nanobody and an allosteric nanobody. Crystal structures of the muPA:nanobody complexes and hydrogen-deuterium exchange mass spectrometry revealed molecular insights about molecular factors controlling the antiparallel-to-parallel equilibrium in muPA. Together with muPA activity assays, the data provide valuable insights into regulatory mechanisms and conformational flexibility of uPA and trypsin-like serine proteases in general.
Targeted next-generation sequencing of the 16S-23S rRNA region for culture-independent bacterial identification - increased discrimination of closely related species
Authors: Sabat Artur J. , van Zanten Evert , Akkerboom Viktoria , Wisselink Guido , van Slochteren Kees , de Boer Richard F. , Hendrix Ron , Friedrich Alexander W. , Rossen John W. A. , Kooistra-Smid Anna M. D. 
Published: June 2017

AbstractThe aim of this study was to develop an easy-to-use culture-free diagnostic method based on next generation sequencing (NGS) of PCR amplification products encompassing whole 16S-23S rRNA region to improve the resolution of bacterial species identification. To determine the resolution of the new method 67 isolates were subjected to four identification methods: Sanger sequencing of the 16S rRNA gene; NGS of the 16S-23S rRNA region using MiSeq (Illumina) sequencer; Microflex MS (Bruker) and VITEK MS (bioMérieux). To evaluate the performance of this new method when applied directly on clinical samples, we conducted a proof of principle study with 60 urine samples from patients suspected of urinary tract infections (UTIs), 23 BacT/ALERT (bioMérieux) positive blood culture bottles and 21 clinical orthopedic samples. The resolution power of NGS of the 16S-23S rRNA region was superior to other tested identification methods. Furthermore, the new method correctly identified pathogens established as the cause of UTIs and blood stream infections with conventional culture. NGS of the 16S-23S rRNA region also showed increased detection of bacterial microorganisms in clinical samples from orthopedic patients. Therefore, we conclude that our method has the potential to increase diagnostic yield for detection of bacterial pathogenic species compared to current methods.
Giant Magnetic Band Gap in the Rashba-Split Surface State of Vanadium-Doped BiTeI: A Combined Photoemission and Ab Initio Study
Authors: Klimovskikh I. I. , Shikin A. M. , Otrokov M. M. , Ernst A. , Rusinov I. P. , Tereshchenko O. E. , Golyashov V. A. , Sánchez-Barriga J. , Varykhalov A. Yu. , Rader O. , Kokh K. A. , Chulkov E. V. 
Published: June 2017

AbstractOne of the most promising platforms for spintronics and topological quantum computation is the two-dimensional electron gas (2DEG) with strong spin-orbit interaction and out-of-plane ferromagnetism. In proximity to an s-wave superconductor, such 2DEG may be driven into a topologically non-trivial superconducting phase, predicted to support zero-energy Majorana fermion modes. Using angle-resolved photoemission spectroscopy and ab initio calculations, we study the 2DEG at the surface of the vanadium-doped polar semiconductor with a giant Rashba-type splitting, BiTeI. We show that the vanadium-induced magnetization in the 2DEG breaks time-reversal symmetry, lifting Kramers degeneracy of the Rashba-split surface state at the Brillouin zone center via formation of a huge gap of about 90 meV. As a result, the constant energy contour inside the gap consists of only one circle with spin-momentum locking. These findings reveal a great potential of the magnetically-doped semiconductors with a giant Rashba-type splitting for realization of novel states of matter.
Beta sitosterol and Daucosterol (phytosterols identified in Grewia tiliaefolia) perturbs cell cycle and induces apoptotic cell death in A549 cells
Authors: Rajavel Tamilselvam , Mohankumar Ramar , Archunan Govindaraju , Ruckmani Kandasamy , Devi Kasi Pandima 
Published: June 2017

AbstractLung cancer is the leading cause of cancer related deaths both in developed and developing countries. Since majority of the existing therapeutic methods harms both normal and malignant cells, a viable alternative is to switch into safe and beneficial traditional medicinal plants. Hence the present study was framed to identify selective anti-lung cancer agents from the medicinal plant Grewia tiliaefolia (GT). Cell viability experiments showed that benzene extract of GT (BGT) leaf effectively inhibited the growth of A549 cells, while being non-toxic to normal human lung L132 and PBMC cells. Ames and comet assays demonstrated that BGT is of non-mutagenic and non-genotoxic nature in untransformed cells. The hematological and histopathological profiles of the in vivo acute and sub-acute toxicity studies demonstrated that BGT is safe and tolerable. Importantly, western blot analysis and Annexin V-FITC staining confirmed that BGT promotes mitochondrial dependent apoptotic cell death in A549 cells by arresting cell cycle at G2/M phase. Bio-assay guided fractionation revealed the presence of phytosteols (β-sitosterol and daucosterol) which significantly inhibited the growth of A549 cells both alone and in combination. This study warrants that these phytosterols in alone or in combination can be considered as safe and potential drug candidates for lung cancer treatment.