bluuebunny/crossref_metadata_2025_split huggingface dataset:
A high-throughput screen indicates gemcitabine and JAK inhibitors may be useful for treating pediatric AML
Authors: Drenberg Christina D. , Shelat Anang , Dang Jinjun , Cotton Anitria , Orwick Shelley J. , Li Mengyu , Jeon Jae Yoon , Fu Qiang , Buelow Daelynn R. , Pioso Marissa , Hu Shuiying , Inaba Hiroto , Ribeiro Raul C. , Rubnitz Jeffrey E. , Gruber Tanja A. , Guy R. Kiplin , Baker Sharyn D. 
Published: May 2019

AbstractImprovement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates <40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.
Innate lymphocyte-induced CXCR3B-mediated melanocyte apoptosis is a potential initiator of T-cell autoreactivity in vitiligo
Authors: Tulic Meri K. , Cavazza Elisa , Cheli Yann , Jacquel Arnaud , Luci Carmelo , Cardot-Leccia Nathalie , Hadhiri-Bzioueche Hanene , Abbe Patricia , Gesson Maéva , Sormani Laura , Regazzetti Claire , Beranger Guillaume E. , Lereverend Cedric , Pons Caroline , Khemis Abdallah , Ballotti Robert , Bertolotto Corine , Rocchi Stéphane , Passeron Thierry 
Published: May 2019

AbstractT-cells play a crucial role in progression of autoimmunity, including vitiligo, yet the initial steps triggering their activation and tissue damage remain unknown. Here we demonstrate increased presence of type-1 innate lymphoid cells (NK and ILC1)-producing interferon gamma (IFNγ) in the blood and in non-lesional skin of vitiligo patients. Melanocytes of vitiligo patients have strong basal expression of chemokine-receptor-3 (CXCR3) isoform B which is directly regulated by IFNγ. CXCR3B activation by CXCL10 at the surface of cultured human melanocytes induces their apoptosis. The remaining melanocytes, activated by the IFNγ production, express co-stimulatory markers which trigger T-cell proliferation and subsequent anti-melanocytic immunity. Inhibiting the CXCR3B activation prevents this apoptosis and the further activation of T cells. Our results emphasize the key role of CXCR3B in apoptosis of melanocytes and identify CXCR3B as a potential target to prevent and to treat vitiligo by acting at the early stages of melanocyte destruction.
Real-time observation of X-ray-induced intramolecular and interatomic electronic decay in CH2I2
Authors: Fukuzawa Hironobu , Takanashi Tsukasa , Kukk Edwin , Motomura Koji , Wada Shin-ichi , Nagaya Kiyonobu , Ito Yuta , Nishiyama Toshiyuki , Nicolas Christophe , Kumagai Yoshiaki , Iablonskyi Denys , Mondal Subhendu , Tachibana Tetsuya , You Daehyun , Yamada Syuhei , Sakakibara Yuta , Asa Kazuki , Sato Yuhiro , Sakai Tsukasa , Matsunami Kenji , Umemoto Takayuki , Kariyazono Kango , Kajimoto Shinji , Sotome Hikaru , Johnsson Per , Schöffler Markus S. , Kastirke Gregor , Kooser Kuno , Liu Xiao-Jing , Asavei Theodor , Neagu Liviu , Molodtsov Serguei , Ochiai Kohei , Kanno Manabu , Yamazaki Kaoru , Owada Shigeki , Ogawa Kanade , Katayama Tetsuo , Togashi Tadashi , Tono Kensuke , Yabashi Makina , Ghosh Aryya , Gokhberg Kirill , Cederbaum Lorenz S. , Kuleff Alexander I. , Fukumura Hiroshi , Kishimoto Naoki , Rudenko Artem , Miron Catalin , Kono Hirohiko , Ueda Kiyoshi 
Published: May 2019

AbstractThe increasing availability of X-ray free-electron lasers (XFELs) has catalyzed the development of single-object structural determination and of structural dynamics tracking in real-time. Disentangling the molecular-level reactions triggered by the interaction with an XFEL pulse is a fundamental step towards developing such applications. Here we report real-time observations of XFEL-induced electronic decay via short-lived transient electronic states in the diiodomethane molecule, using a femtosecond near-infrared probe laser. We determine the lifetimes of the transient states populated during the XFEL-induced Auger cascades and find that multiply charged iodine ions are issued from short-lived (∼20 fs) transient states, whereas the singly charged ones originate from significantly longer-lived states (∼100 fs). We identify the mechanisms behind these different time scales: contrary to the short-lived transient states which relax by molecular Auger decay, the long-lived ones decay by an interatomic Coulombic decay between two iodine atoms, during the molecular fragmentation.
Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly
Authors: Kang Jung-Ah , Kim Songwon , Park Minji , Park Hyun-Jin , Kim Jeong-Hyun , Park Sanghyeok , Hwang Jeong-Ryul , Kim Yong-Chul , Jun Kim Yoon , Cho Yuri , Sun Jin Mi , Park Sung-Gyoo 
Published: May 2019

AbstractChronic hepatitis B virus (HBV) infection can cause cirrhosis and hepatocellular carcinoma and is therefore a serious public health problem. Infected patients are currently treated with nucleoside/nucleotide analogs and interferon α, but this approach is not curative. Here, we screen 978 FDA-approved compounds for their ability to inhibit HBV replication in HBV-expressing HepG2.2.15 cells. We find that ciclopirox, a synthetic antifungal agent, strongly inhibits HBV replication in cells and in mice by blocking HBV capsid assembly. The crystal structure of the HBV core protein and ciclopirox complex reveals a unique binding mode at dimer-dimer interfaces. Ciclopirox synergizes with nucleoside/nucleotide analogs to prevent HBV replication in cells and in a humanized liver mouse model. Therefore, orally-administered ciclopirox may provide a novel opportunity to combat chronic HBV infection by blocking HBV capsid assembly.
TYGS is an automated high-throughput platform for state-of-the-art genome-based taxonomy
Authors: Meier-Kolthoff Jan P. , Göker Markus 
Published: May 2019

AbstractMicrobial taxonomy is increasingly influenced by genome-based computational methods. Yet such analyses can be complex and require expert knowledge. Here we introduce TYGS, the Type (Strain) Genome Server, a user-friendly high-throughput web server for genome-based prokaryote taxonomy, connected to a large, continuously growing database of genomic, taxonomic and nomenclatural information. It infers genome-scale phylogenies and state-of-the-art estimates for species and subspecies boundaries from user-defined and automatically determined closest type genome sequences. TYGS also provides comprehensive access to nomenclature, synonymy and associated taxonomic literature. Clinically important examples demonstrate how TYGS can yield new insights into microbial classification, such as evidence for a species-level separation of previously proposed subspecies ofSalmonella enterica. TYGS is an integrated approach for the classification of microbes that unlocks novel scientific approaches to microbiologists worldwide and is particularly helpful for the rapidly expanding field of genome-based taxonomic descriptions of new genera, species or subspecies.
Direct imaging of the circular chromosome in a live bacterium
Authors: Wu Fabai , Japaridze Aleksandre , Zheng Xuan , Wiktor Jakub , Kerssemakers Jacob W. J. , Dekker Cees 
Published: May 2019

AbstractAlthough the physical properties of chromosomes, including their morphology, mechanics, and dynamics are crucial for their biological function, many basic questions remain unresolved. Here we directly image the circular chromosome in live E. coli with a broadened cell shape. We find that it exhibits a torus topology with, on average, a lower-density origin of replication and an ultrathin flexible string of DNA at the terminus of replication. At the single-cell level, the torus is strikingly heterogeneous, with blob-like Mbp-size domains that undergo major dynamic rearrangements, splitting and merging at a minute timescale. Our data show a domain organization underlying the chromosome structure of E. coli, where MatP proteins induce site-specific persistent domain boundaries at Ori/Ter, while transcription regulators HU and Fis induce weaker transient domain boundaries throughout the genome. These findings provide an architectural basis for the understanding of the dynamic spatial organization of bacterial genomes in live cells.
Ultrafast multi-focus 3-D nano-fabrication based on two-photon polymerization
Authors: Geng Qiang , Wang Dien , Chen Pengfei , Chen Shih-Chi 
Published: May 2019

AbstractTwo-photon polymerization (TPP) is the most precise 3-D printing process that has been used to create many complex structures for advanced photonic and nanoscale applications. However, to date the technology still remains a laboratory tool due to its high operation cost and limited fabrication rate, i.e., serial laser scanning process. Here we present a revolutionary laser nanofabrication process based on TPP and an ultrafast random-access digital micromirror device (DMD) scanner. By exploiting binary holography, the DMD scanner can simultaneously generate and individually control one to tens of laser foci for parallel nanofabrication at 22.7 kHz. Complex 3-D trusses and woodpile structures have been fabricated via single or multi-focus processes, showing a resolution of ~500 nm. The nanofabrication system may be used for largescale nano-prototyping or creation of complex structures, e.g., overhanging structures, that cannot be easily fabricated via conventional raster-scanning-based systems, bringing significant impact to the world of nanomanufacturing.
secCl is a cys-loop ion channel necessary for the chloride conductance that mediates hormone-induced fluid secretion in Drosophila
Authors: Feingold Daniel , Knogler Laura , Starc Tanja , Drapeau Pierre , O’Donnell Michael J. , Nilson Laura A. , Dent Joseph A. 
Published: May 2019

AbstractOrganisms use circulating diuretic hormones to control water balance (osmolarity), thereby avoiding dehydration and managing excretion of waste products. The hormones act through G-protein-coupled receptors to activate second messenger systems that in turn control the permeability of secretory epithelia to ions like chloride. In insects, the chloride channel mediating the effects of diuretic hormones was unknown. Surprisingly, we find a pentameric, cys-loop chloride channel, a type of channel normally associated with neurotransmission, mediating hormone-induced transepithelial chloride conductance. This discovery is important because: 1) it describes an unexpected role for pentameric receptors in the membrane permeability of secretory epithelial cells, and 2) it suggests that neurotransmitter-gated ion channels may have evolved from channels involved in secretion.
Significant plastic accumulation on the Cocos (Keeling) Islands, Australia
Authors: Lavers J. L. , Dicks L. , Dicks M. R. , Finger A. 
Published: May 2019

AbstractFor over 60 years, our oceans have been a reservoir for exponentially increasing amounts of plastic waste. Plastic has been documented at all levels of the marine food web, from the deepest oceanic trenches to the most far-flung beaches. Here, we present data on the presence of significant quantities of plastic on the remote Cocos (Keeling) Island group, located 2,100 km off the northwest coast of Australia. From our comprehensive surveys of debris on the beach surface, buried, and beach-back vegetation, we estimate there are 414 million anthropogenic debris items, weighing 238 tonnes, currently deposited on the Cocos (Keeling) Island group. Of the identifiable items, ~25% were classified as disposable plastics, including straws, bags, and toothbrushes. Debris buried up to 10 cm below the surface is estimated to account for 93% (~383 million items) of all debris present on Cocos, the majority of which (~60%) is comprised of micro-debris (2–5 mm). In the absence of meaningful change, debris will accumulate rapidly on the world’s beaches. Small, buried items pose considerable challenges for wildlife, and volunteers charged with the task of cleaning-up, thus preventing new items from entering the ocean remains key to addressing this issue.
Long-term field comparison of multiple low-cost particulate matter sensors in an outdoor urban environment
Authors: Bulot Florentin M. J. , Johnston Steven J. , Basford Philip J. , Easton Natasha H. C. , Apetroaie-Cristea Mihaela , Foster Gavin L. , Morris Andrew K. R. , Cox Simon J. , Loxham Matthew 
Published: May 2019

AbstractExposure to ambient particulate matter (PM) air pollution is a leading risk factor for morbidity and mortality, associated with up to 8.9 million deaths/year worldwide. Measurement of personal exposure to PM is hindered by poor spatial resolution of monitoring networks. Low-cost PM sensors may improve monitoring resolution in a cost-effective manner but there are doubts regarding data reliability. PM sensor boxes were constructed using four low-cost PM micro-sensor models. Three boxes were deployed at each of two schools in Southampton, UK, for around one year and sensor performance was analysed. Comparison of sensor readings with a nearby background station showed moderate to good correlation (0.61 < r < 0.88, p < 0.0001), but indicated that low-cost sensor performance varies with different PM sources and background concentrations, and to a lesser extent relative humidity and temperature. This may have implications for their potential use in different locations. Data also indicates that these sensors can track short-lived events of pollution, especially in conjunction with wind data. We conclude that, with appropriate consideration of potential confounding factors, low-cost PM sensors may be suitable for PM monitoring where reference-standard equipment is not available or feasible, and that they may be useful in studying spatially localised airborne PM concentrations.
Improving the Micropore Capacity of Activated Carbon by Preparation under a High Magnetic Field of 10 T
Authors: Hamasaki Atom , Furuse Ayumi , Sekinuma Yuya , Fujio Kazuki , Iide Masashi , Ozeki Sumio 
Published: May 2019

AbstractThe influence of an applied magnetic field on the formation of carbon materials from coal tar pitch is investigated. Under an applied magnetic field, crystallites in a mesophase resembling liquid crystals are magnetically oriented during the carbonization process. Compared with that under a nonmagnetic field, carbonized coal tar pitch under a strong magnetic field of 10 T, generated by a superconducting magnet, has a highly oriented structure of carbon crystallites. The orientation of samples prepared under 2 T, which can easily be supplied by an electromagnet, was insufficient. Activation by potassium hydroxide is effective for affording a precursor for activated carbon. The activated carbon obtained under a strong magnetic field has a unique adsorption ability, which arises from its increase in relative surface area and total pore volume compared with those of an activated carbon sample prepared from a precursor produced under zero magnetic field. The precursor carbonized under a magnetic field of 10 T contains a larger number of crystallites than that carbonized under a 0-T magnetic field, which leads to high-performance activated carbon.
Pharmaceutically modified subtilisins withstand acidic conditions and effectively degrade gluten in vivo
Authors: Darwish Ghassan , Helmerhorst Eva J. , Schuppan Detlef , Oppenheim Frank G. , Wei Guoxian 
Published: May 2019

AbstractDetoxification of gluten immunogenic epitopes is a promising strategy for the treatment of celiac disease. Our previous studies have shown that these epitopes can be degraded in vitro by subtilisin enzymes derived from Rothia mucilaginosa, a natural microbial colonizer of the oral cavity. The challenge is that the enzyme is not optimally active under acidic conditions as encountered in the stomach. We therefore aimed to protect and maintain subtilisin-A enzyme activity by exploring two pharmaceutical modification techniques: PEGylation and Polylactic glycolic acid (PLGA) microencapsulation. PEGylation of subtilisin-A (Sub-A) was performed by attaching methoxypolyethylene glycol (mPEG, 5 kDa). The PEGylation protected subtilisin-A from autolysis at neutral pH. The PEGylated Sub-A (Sub-A-mPEG) was further encapsulated by PLGA. The microencapsulated Sub-A-mPEG-PLGA showed significantly increased protection against acid exposure in vitro. In vivo, gluten immunogenic epitopes were decreased by 60% in the stomach of mice fed with chow containing Sub-A-mPEG-PLGA (0.2 mg Sub-A/g chow) (n = 9) compared to 31.9% in mice fed with chow containing unmodified Sub-A (n = 9). These results show that the developed pharmaceutical modification can protect Sub-A from auto-digestion as well as from acid inactivation, thus rendering the enzyme more effective for applications in vivo.
Imaging local brain activity of multiple freely moving mice sharing the same environment
Authors: Inagaki Shigenori , Agetsuma Masakazu , Ohara Shinya , Iijima Toshio , Yokota Hideo , Wazawa Tetsuichi , Arai Yoshiyuki , Nagai Takeharu 
Published: May 2019

AbstractElectrophysiological field potential dynamics have been widely used to investigate brain functions and related psychiatric disorders. Considering recent demand for its applicability to freely moving subjects, especially for animals in a group and socially interacting with each other, here we propose a new method based on a bioluminescent voltage indicator LOTUS-V. Using our fiber-free recording method based on the LOTUS-V, we succeeded in capturing dynamic change of brain activity in freely moving mice. Because LOTUS-V is the ratiometric indicator, motion and head-angle artifacts were not significantly detected. Taking advantage of our method as a fiber-free system, we further succeeded in simultaneously recording from multiple independently-locomotive mice that were freely interacting with one another. Importantly, this enabled us to find that the primary visual cortex, a center of visual processing, was activated during the interaction of mice. This methodology may further facilitate a wide range of studies in neurobiology and psychiatry.
A lasered mouse model of retinal degeneration displays progressive outer retinal pathology providing insights into early geographic atrophy
Authors: Ibbett Paul , Goverdhan Srinivas V. , Pipi Elena , Chouhan Joe K. , Keeling Eloise , Angus Elizabeth M. , Scott Jenny A. , Gatherer Maureen , Page Anton , Teeling Jessica L. , Lotery Andrew J. , Arjuna Ratnayaka J. 
Published: May 2019

AbstractEarly stages of geographic atrophy (GA) age-related macular degeneration is characterised by the demise of photoreceptors, which precedes the loss of underlying retinal pigment epithelial (RPE) cells. Sight-loss due to GA has no effective treatment; reflecting both the complexity of the disease and the lack of suitable animal models for testing potential therapies. We report the development and characterisation of a laser-induced mouse model with early GA-like pathology. Retinas were lasered at adjacent sites using a 810 nm laser (1.9 J/spot), resulting in the development of confluent, hypopigmented central lesions with well-defined borders. Optical Coherence Tomography over 2-months showed progressive obliteration of photoreceptors with hyper-reflective outer plexiform and RPE/Bruch’s membrane (BrM) layers within lesions, but an unaffected inner retina. Light/electron microscopy after 3-months revealed lesions without photoreceptors, leaving the outer plexiform layer apposed to the RPE. We observed outer segment debris, hypo/hyperpigmented RPE, abnormal apical-basal RPE surfaces and BrM thickening. Lesions had wedge-shaped margins, extended zones of damage, activated Müller cells, microglial recruitment and functional retinal deficits. mRNA studies showed complement and inflammasome activation, microglial/macrophage phagocytosis and oxidative stress providing mechanistic insights into GA. We propose this mouse model as an attractive tool for early GA studies and drug-discovery.
Structural and dynamic studies reveal that the Ala-rich region of ataxin-7 initiates α-helix formation of the polyQ tract but suppresses its aggregation
Authors: Hong Jun-Ye , Wang Dong-Dong , Xue Wei , Yue Hong-Wei , Yang Hui , Jiang Lei-Lei , Wang Wen-Ning , Hu Hong-Yu 
Published: May 2019

AbstractAtaxin-7 (Atx7) is a disease-related protein associated with the pathogenesis of spinocerebellar ataxia 7, while its polyglutamine (polyQ) tract in N-terminus is the causative source of aggregation and proteinopathy. We investigated the structure, dynamics and aggregation properties of the N-terminal 62-residue fragment of Atx7 (Atx7-N) by biochemical and biophysical approaches. The results showed that the normal Atx7-N with a tract of 10 glutamines (10Q) overall adopts a flexible and disordered structure, but it may contain a short or small population of helical structure in solution. PolyQ expansion increases the α-helical propensity of the polyQ tract and consequently enhances its transformation into β-sheet structures during amyloid aggregation. An alanine-rich region (ARR) just ahead of the polyQ tract forms a local and relatively stable α-helix. The ARR α-helix can initiate and stabilize helical formation of the following polyQ tract, but it may suppress aggregation of the polyQ-expanded Atx7-N both in vitro and in cell. Thus, the preceding ARR segment in Atx7-N may influence the dynamic structure and aggregation property of the polyQ tract and even determine the threshold of the pathogenic polyQ lengths. This study may gain structural and dynamic insights into amyloid aggregation of Atx7 and help us further understand the Atx7 proteinopathy based on polyQ expansion.
Antarctic Streptomyces fildesensis So13.3 strain as a promising source for antimicrobials discovery
Authors: Núñez-Montero Kattia , Lamilla Claudio , Abanto Michel , Maruyama Fumito , Jorquera Milko A. , Santos Andrés , Martinez-Urtaza Jaime , Barrientos Leticia 
Published: May 2019

AbstractAntarctic have been suggested as an attractive source for antibiotics discovery and members of Streptomyces genus have historically been studied as natural producers of antimicrobial metabolites. Nonetheless, our knowledge on antibiotic-producing Streptomyces from Antarctic is very limited. In this study, the antimicrobial activity of organic extracts from Antarctic Streptomyces strains was evaluated by disk diffusion assays and minimum inhibitory concentration. The strain Streptomyces sp. So13.3 showed the greatest antibiotic activity (MIC = 15.6 μg/mL) against Gram-positive bacteria and growth reduction of Gram‒negative pathogens. The bioactive fraction in the crude extract was revealed by TLC‒bioautography at Rf = 0.78 with molecular weight between 148 and 624 m/z detected by LC-ESI-MS/MS. The strain So13.3 was taxonomically affiliated as Streptomyces fildesensis. Whole genome sequencing and analysis suggested a 9.47 Mb genome size with 42 predicted biosynthetic gene clusters (BGCs) and 56 putative clusters representing a 22% of total genome content. Interestingly, a large number of them (11 of 42 BGCs and 40 of 56 putative BGCs), did not show similarities with other known BGCs. Our results highlight the potential of the Antarctic Streptomyces strains as a promising source of novel antimicrobials, particularly the strain Streptomyces fildesensis So13.3, which first draft genome is reported in this work.