bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells
Authors: Kozono Shingo , Lin Yu-Min , Seo Hyuk-Soo , Pinch Benika , Lian Xiaolan , Qiu Chenxi , Herbert Megan K. , Chen Chun-Hau , Tan Li , Gao Ziang Jeff , Massefski Walter , Doctor Zainab M. , Jackson Brian P. , Chen Yuanzhong , Dhe-Paganon Sirano , Lu Kun Ping , Zhou Xiao Zhen 
Published: July 2018

AbstractArsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination safely cures fatal acute promyelocytic leukemia, but their mechanisms of action and efficacy are not fully understood. ATRA inhibits leukemia, breast, and liver cancer by targeting isomerase Pin1, a master regulator of oncogenic signaling networks. Here we show that ATO targets Pin1 and cooperates with ATRA to exert potent anticancer activity. ATO inhibits and degrades Pin1, and suppresses its oncogenic function by noncovalent binding to Pin1’s active site. ATRA increases cellular ATO uptake through upregulating aquaporin-9. ATO and ATRA, at clinically safe doses, cooperatively ablate Pin1 to block numerous cancer-driving pathways and inhibit the growth of triple-negative breast cancer cells and tumor-initiating cells in cell and animal models including patient-derived orthotopic xenografts, like Pin1 knockout, which is substantiated by comprehensive protein and microRNA analyses. Thus, synergistic targeting of Pin1 by ATO and ATRA offers an attractive approach to combating breast and other cancers.
Directed evolution of CRISPR-Cas9 to increase its specificity
Authors: Lee Jungjoon K. , Jeong Euihwan , Lee Joonsun , Jung Minhee , Shin Eunji , Kim Young-hoon , Lee Kangin , Jung Inyoung , Kim Daesik , Kim Seokjoong , Kim Jin-Soo 
Published: July 2018

AbstractThe use of CRISPR-Cas9 as a therapeutic reagent is hampered by its off-target effects. Although rationally designed S. pyogenes Cas9 (SpCas9) variants that display higher specificities than the wild-type SpCas9 protein are available, these attenuated Cas9 variants are often poorly efficient in human cells. Here, we develop a directed evolution approach in E. coli to obtain Sniper-Cas9, which shows high specificities without killing on-target activities in human cells. Unlike other engineered Cas9 variants, Sniper-Cas9 shows WT-level on-target activities with extended or truncated sgRNAs with further reduced off-target activities and works well in a preassembled ribonucleoprotein (RNP) format to allow DNA-free genome editing.
A stochastic assembly model for Nipah virus revealed by super-resolution microscopy
Authors: Liu Qian , Chen Lei , Aguilar Hector C. , Chou Keng C. 
Published: July 2018

AbstractUnderstanding virus assembly mechanisms is important for developing therapeutic interventions. Nipah virus (NiV) is of interest because of its high mortality rate and efficient human–human transmissions. The current model for most enveloped viruses suggests that matrix proteins (M) recruit attachment glycoproteins (G) and fusion glycoproteins (F) to the assembly site at the plasma membrane. Here we report an assembly model that differs in many aspects from the current one. Examining NiV proteins on the cell plasma membrane using super-resolution microscopy reveals that clusters of F and G are randomly distributed on the plasma membrane regardless of the presence or absence of M. Our data suggests a model in which the M molecules assemble at the plasma membrane to form virus-like particles (VLPs), while the incorporation of F and G into the nascent VLPs is stochastic.
Vibration hotspots reveal longitudinal funneling of sound-evoked motion in the mammalian cochlea
Authors: Cooper Nigel P. , Vavakou Anna , van der Heijden Marcel 
Published: July 2018

AbstractThe micromechanical mechanisms that underpin tuning and dynamic range compression in the mammalian inner ear are fundamental to hearing, but poorly understood. Here, we present new, high-resolution optical measurements that directly map sound-evoked vibrations on to anatomical structures in the intact, living gerbil cochlea. The largest vibrations occur in a tightly delineated hotspot centering near the interface between the Deiters’ and outer hair cells. Hotspot vibrations are less sharply tuned, but more nonlinear, than basilar membrane vibrations, and behave non-monotonically (exhibiting hyper-compression) near their characteristic frequency. Amplitude and phase differences between hotspot and basilar membrane responses depend on both frequency and measurement angle, and indicate that hotspot vibrations involve longitudinal motion. We hypothesize that structural coupling between the Deiters’ and outer hair cells funnels sound-evoked motion into the hotspot region, under the control of the outer hair cells, to optimize cochlear tuning and compression.
A widespread alternate form of cap-dependent mRNA translation initiation
Authors: de la Parra Columba , Ernlund Amanda , Alard Amandine , Ruggles Kelly , Ueberheide Beatrix , Schneider Robert J. 
Published: July 2018

AbstractTranslation initiation of most mammalian mRNAs is mediated by a 5′ cap structure that binds eukaryotic initiation factor 4E (eIF4E). However, inactivation of eIF4E does not impair translation of many capped mRNAs, suggesting an unknown alternate mechanism may exist for cap-dependent but eIF4E-independent translation. We show that DAP5, an eIF4GI homolog that lacks eIF4E binding, utilizes eIF3d to facilitate cap-dependent translation of approximately 20% of mRNAs. Genome-wide transcriptomic and translatomic analyses indicate that DAP5 is required for translation of many transcription factors and receptor capped mRNAs and their mRNA targets involved in cell survival, motility, DNA repair and translation initiation, among other mRNAs. Mass spectrometry and crosslinking studies demonstrate that eIF3d is a direct binding partner of DAP5. In vitro translation and ribosome complex studies demonstrate that DAP5 and eIF3d are both essential for eIF4E-independent capped-mRNA translation. These studies disclose a widespread and previously unknown mechanism for cap-dependent mRNA translation by DAP5-eIF3d complexes.
Regulation of miR-181a expression in T cell aging
Authors: Ye Zhongde , Li Guangjin , Kim Chulwoo , Hu Bin , Jadhav Rohit R. , Weyand Cornelia M. , Goronzy Jörg J. 
Published: July 2018

AbstractMicroRNAs have emerged as key regulators in T cell development, activation, and differentiation, with miR-181a having a prominent function. By targeting several signaling pathways, miR-181a is an important rheostat controlling T cell receptor (TCR) activation thresholds in thymic selection as well as peripheral T cell responses. A decline in miR-181a expression, due to reduced transcription of pri-miR-181a, accounts for T cell activation defects that occur with older age. Here we examine the transcriptional regulation of miR-181a expression and find a putative pri-miR-181a enhancer around position 198,904,300 on chromosome 1, which is regulated by a transcription factor complex including YY1. The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Partial silencing of YY1 in T cells from young individuals reproduces the signaling defects seen in older T cells. In conclusion, YY1 controls TCR signaling by upregulating miR-181a and dampening negative feedback loops mediated by miR-181a targets.
Nature and nurture effects on the spatiality of the mental time line
Authors: Anelli Filomena , Peters-Founshtein Gregory , Shreibman Yaen , Moreh Elior , Forlani Chiara , Frassinetti Francesca , Arzy Shahar 
Published: July 2018

AbstractThe nature-nurture debate regarding the origin of mental lines is fundamental for cognitive neuroscience. We examined natural-nurture effects on the mental time line, applying three different challenges to the directionality of time representation. We tested (1) patients with left-neglect and healthy participants, who are (2) left-to-right or right-to-left readers/writers, using (3) a lateralized left-right button press or a vocal mode in response to a mental time task, which asks participants to judge whether events have already happened in the past or are still to happen in the future. Using lateralized responses, a spatial-temporal association of response code (STEARC) effect was found, in concordance with the cultural effects. With vocal responses (no lateralization), past and future events showed similar results in both cultures. In patients with neglect, who have a deficit of spatial attention in processing the left side of space, future events were processed more slowly and less accurately than past events in both cultures. Our results indicate the existence of a “natural” disposition to map past and future events along a horizontal mental time line, which is affected by the different ways in which spatial representation of time is introduced.
Oil-Impregnated Hydrocarbon-Based Polymer Films
Authors: Mukherjee Ranit , Habibi Mohammad , Rashed Ziad T. , Berbert Otacilio , Shi Xiangke , Boreyko Jonathan B. 
Published: July 2018

AbstractPorous surfaces impregnated with a liquid lubricant exhibit minimal contact angle hysteresis with immiscible test liquids, rendering them ideal as self-cleaning materials. Rather than roughening a solid substrate, an increasingly popular choice is to use an absorbent polymer as the “porous” material. However, to date the polymer choices have been limited to expensive silicone-based polymers or complex assemblies of polymer multilayers on functionalized surfaces. In this paper, we show that hydrocarbon-based polymer films such as polyethylene can be stably impregnated with chemically compatible vegetable oils, without requiring any surface treatment. These oil-impregnated hydrocarbon-based films exhibit minimal contact angle hysteresis for a wide variety of test products including water, ketchup, and yogurt. Our oil-impregnated films remain slippery even after several weeks of being submerged in ketchup, illustrating their extreme durability. We expect that the simple and cost-effective nature of our slippery hydrocarbon-based films will make them useful for industrial packaging applications.
Stormwater runoff driven phosphorus transport in an urban residential catchment: Implications for protecting water quality in urban watersheds
Authors: Yang Yun-Ya , Toor Gurpal S. 
Published: July 2018

AbstractIncreased stormwater runoff in urban watersheds is a leading cause of nonpoint phosphorus (P) pollution. We investigated the concentrations, forms, and temporal trends of P in stormwater runoff from a residential catchment (31 low-density residential homes; 0.11 km2 drainage area) in Florida. Unfiltered runoff samples were collected at 5 min intervals over 29 storm events with an autosampler installed at the stormwater outflow pipe. Mean concentrations of orthophosphate (PO4–P) were 0.18 ± 0.065 mg/L and total P (TP) were  0.28 ± 0.062 mg/L in all runoff samples. The PO4–P was the dominant form in >90% of storm events and other–P (combination of organic P and particulate P) was dominant after a longer antecedent dry period. We hypothesize that in the stormwater runoff, PO4–P likely originated from soluble and desorbed pool of eroded soil and other–P likely originated from decomposing plant materials i.e. leaves and grass clippings and eroded soil. We found that the runoff was co-limited with nitrogen (N) and P in 34% of storm events and only N limited in 66% of storm events, implicating that management strategies focusing on curtailing both P and N transport would be more effective than focussing on only N or P in protecting water quality in residential catchments.
A new quinoline-based chemical probe inhibits the autophagy-related cysteine protease ATG4B
Authors: Bosc D. , Vezenkov L. , Bortnik S. , An J. , Xu J. , Choutka C. , Hannigan A. M. , Kovacic S. , Loo S. , Clark P. G. K. , Chen G. , Guay-Ross R. N. , Yang K. , Dragowska W. H. , Zhang F. , Go N. E. , Leung A. , Honson N. S. , Pfeifer T. A. , Gleave M. , Bally M. , Jones S. J. , Gorski S. M. , Young R. N. 
Published: July 2018

AbstractThe cysteine protease ATG4B is a key component of the autophagy machinery, acting to proteolytically prime and recycle its substrate MAP1LC3B. The roles of ATG4B in cancer and other diseases appear to be context dependent but are still not well understood. To help further explore ATG4B functions and potential therapeutic applications, we employed a chemical biology approach to identify ATG4B inhibitors. Here, we describe the discovery of 4–28, a styrylquinoline identified by a combined computational modeling, in silico screening, high content cell-based screening and biochemical assay approach. A structure-activity relationship study led to the development of a more stable and potent compound LV-320. We demonstrated that LV-320 inhibits ATG4B enzymatic activity, blocks autophagic flux in cells, and is stable, non-toxic and active in vivo. These findings suggest that LV-320 will serve as a relevant chemical tool to study the various roles of ATG4B in cancer and other contexts.
Addition of dairy lipids and probiotic Lactobacillus fermentum in infant formula programs gut microbiota and entero-insular axis in adult minipigs
Authors: Lemaire Marion , Dou Samir , Cahu Armelle , Formal Michèle , Le Normand Laurence , Romé Véronique , Nogret Isabelle , Ferret-Bernard Stéphanie , Rhimi Moez , Cuinet Isabelle , Canlet Cécile , Tremblay-Franco Marie , Le Ruyet Pascale , Baudry Charlotte , Gérard Philippe , Le Huërou-Luron Isabelle , Blat Sophie 
Published: July 2018

AbstractClinical and animal studies have demonstrated beneficial effects of early consumption of dairy lipids and a probiotic, Lactobacillus fermentum (Lf), on infant gut physiology. The objective of this study was to investigate their long-term effects on gut microbiota and host entero-insular axis and metabolism. Piglets were suckled with a milk formula containing only plant lipids (PL), a half-half mixture of plant lipids and dairy lipids (DL), or this mixture supplemented with Lf (DL + Lf). They were weaned on a standard diet and challenged with a high-energy diet until postnatal day 140. DL and DL + Lf modulated gut microbiota composition and metabolism, increasing abundance of several Clostridia genera. Moreover, DL + Lf specifically decreased the faecal content of 2-oxoglutarate and lysine compared to PL and 5-aminovalerate compared to PL and DL. It also increased short-chain fatty acid concentrations like propionate compared to DL. Furthermore, DL + Lf had a beneficial effect on the endocrine function, enhancing caecal GLP-1 and GLP-1 meal-stimulated secretion. Correlations highlighted the consistent relationship between microbiota and gut physiology. Together, our results evidence a beneficial programming effect of DL + Lf in infant formula composition on faecal microbiota and entero-insular axis function.
Microplastic in riverine fish is connected to species traits
Authors: McNeish R. E. , Kim L. H. , Barrett H. A. , Mason S. A. , Kelly J. J. , Hoellein T. J. 
Published: July 2018

AbstractMicroplastic is a contaminant of concern worldwide. Rivers are implicated as major pathways of microplastic transport to marine and lake ecosystems, and microplastic ingestion by freshwater biota is a risk associated with microplastic contamination, but there is little research on microplastic ecology within freshwater ecosystems. Microplastic uptake by fish is likely affected by environmental microplastic abundance and aspects of fish ecology, but these relationships have rarely been addressed. We measured the abundance and composition of microplastic in fish and surface waters from 3 major tributaries of Lake Michigan, USA. Microplastic was detected in fish and surface waters from all 3 sites, but there was no correlation between microplastic concentrations in fish and surface waters. Rather, there was a significant effect of functional feeding group on microplastic concentration in fish.Neogobius melanostomus(round goby, a zoobenthivore) had the highest concentration of gut microplastic (19 particles fish−1) compared to 10 other fish taxa measured, and had a positive linear relationship between body size and number of microplastic particles. Surface water microplastic concentrations were lowest in the most northern, forested watershed, and highest in the most southern, agriculturally dominated watershed. Results suggest microplastic pollution is common in river food webs and is connected to species feeding characteristics. Future research should focus on understanding the movement of microplastic from point-source and diffuse sources and into aquatic ecosystems, which will support pollution management efforts on inland waters.
A New Approach to Compute the Porosity and Surface Roughness of Porous Coated Capillary-Assisted Low Pressure Evaporators
Authors: Cheppudira Thimmaiah Poovanna , Panda Asish Kumar , Pandey Upendra Kumar , McCague Claire , Dutta Pradip , Bahrami Majid 
Published: July 2018

AbstractThe fundamental characteristics of metal coatings that influence heat transfer are porosity and surface roughness. It is a challenge to analyze the porosity and surface roughness due to the inadequate amount of copper per coated area. In this study, a new approach to non-invasively determine the porosity of metal films utilizing a helium pycnometer and computed micro-tomography (CMT) is presented. Furthermore, a telescope-goniometer is used to measure the surface roughness. Experiments are conducted on four varieties of thin film samples coated with copper powder using wire flame and plasma thermal spray coating methods. The porosities of the thin films were determined to be between 39 and 43%. The thermal spray coating increased the hydrophobicity of the surface and the plasma coating created super-hydrophobic surfaces. The new approach establishes that the porosity of thin films can be non-invasively determined and may also be applied to a wide variety of coated surfaces.
An unusual association of hadrosaur and therizinosaur tracks within Late Cretaceous rocks of Denali National Park, Alaska
Authors: Fiorillo Anthony R. , McCarthy Paul J. , Kobayashi Yoshitsugu , Tomsich Carla S. , Tykoski Ronald S. , Lee Yuong-Nam , Tanaka Tomonori , Noto Christopher R. 
Published: July 2018

AbstractWe report details of a unique association of hadrosaur and therizinosaur tracks found in the Late Cretaceous lower Cantwell Formation, Denali National Park, central Alaska Range, Alaska. This rock unit is now well-documented as a source of thousands of fossil footprints of vertebrates such as fishes, pterosaurs, and avialan and non-avialan dinosaurs. The lower Cantwell Formation in this area consists of numerous fining-upward successions of conglomerates and pebbly sandstones, cross-stratified and massive sandstones, interbedded sandstones and siltstones, organic-rich siltstones and shales, and rare, thin, bentonites, typically bounded by thin coal seams, and it contains a diverse fossil flora. We report the first North American co-occurrence of tracks attributable to hadrosaurs and therizinosaurs in the lower Cantwell Formation. Although previously un-reported in North America, this association of hadrosaur and therizinosaur tracks is more characteristic of the correlative Nemegt Formation in central Asia, perhaps suggesting that parameters defining the continental ecosystem of central Asia were also present in this part of Alaska during the Latest Cretaceous.
An Expert Diagnostic System to Automatically Identify Asthma and Chronic Obstructive Pulmonary Disease in Clinical Settings
Authors: Badnjevic Almir , Gurbeta Lejla , Custovic Eddie 
Published: July 2018

AbstractRespiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD), are affecting a huge percentage of the world’s population with mortality rates exceeding those of lung cancer and breast cancer combined. The major challenge is the number of patients who are incorrectly diagnosed. To address this, we developed an expert diagnostic system that can differentiate among patients with asthma, COPD or a normal lung function based on measurements of lung function and information about patient’s symptoms. To develop accurate classification algorithms, data from 3657 patients were used and then independently verified using data from 1650 patients collected over a period of two years. Our results demonstrate that the expert diagnostic system can correctly identify patients with asthma and COPD with sensitivity of 96.45% and specificity of 98.71%. Additionally, 98.71% of the patients with a normal lung function were correctly classified, which contributed to a 49.23% decrease in demand for conducting additional tests, therefore decreasing financial cost.
Targeted next-generation sequencing as a comprehensive test for Mendelian diseases: a cohort diagnostic study
Authors: Sun Yan , Man Jianfen , Wan Yang , Pan Gao , Du Lique , Li Long , Yang Yun , Qiu Liru , Gao Qing , Dan Handong , Mao Liangwei , Cheng Zhengyu , Fan Chen , Yu Jing , Lin Mufei , Kristiansen Karsten , Shen Yin , Wei Xiaoming 
Published: July 2018

AbstractWith the development of next generation sequencing, more and more common inherited diseases have been reported. However, accurate and convenient molecular diagnosis cannot be achieved easily because of the enormous size of disease causing mutations. In this study, we introduced a new single-step method for the genetic analysis of patients and carriers in real clinical settings. All kinds of disease causing mutations can be detected at the same time in patients with Mendelian diseases or carriers. First, we evaluated this technology using YH cell line DNA and 9 samples with known mutations. Accuracy and stability of 99.80% and 99.58% were achieved respectively. Then, a total of 303 patients were tested using our targeted NGS approaches, 50.17% of which were found to have deleterious mutations and molecular confirmation of the clinical diagnosis. We identified 219 disease causing mutations, 43.84% (96/219) of which has never been reported before. Additionally, we developed a new deleteriousness prediction method for nonsynonymous SNVs, and an automating annotation and diagnosis system for Mendelian diseases, thus greatly assisting and enhancing Mendelian diseases diagnosis and helping to make a precise diagnosis for patients with Mendelian diseases.
Alteration in glucose homeostasis and persistence of the pancreatic clock in aged mPer2Luc mice
Authors: Novosadová Zuzana , Polidarová Lenka , Sládek Martin , Sumová Alena 
Published: July 2018

AbstractThe physiological function of the pancreas is controlled by the circadian clock. The aim of this study was to determine whether aging-induced changes in glucose homeostasis affect properties of the circadian clock in the pancreas and/or its sensitivity to disturbances in environmental lighting conditions. mPer2Luc mice aged 24–26 months developed hyperinsulinemic hypoglycaemia, which was likely due to the Pclo-mediated insulin hyper-secretion and Slc2a2-mediated glucose transport impairment in the pancreas, and due to the alterations in Pp1r3c-related glycogen storage and Sgk1-related glucose transport in the liver. In the pancreatic tissue, aging affected clock gene expression only marginally, it upregulated Bmal1 and downregulated Clock expression. Whereas aging significantly impaired the circadian clock in lung explants, which were used as a control tissue, the properties of the pancreatic clock in vitro were not affected. The data suggest a non-circadian role of Bmal1 in changes of pancreatic function that occur during aging. Additionally, the pancreatic clock was more sensitive to exposure of animals to constant light conditions. These findings provide an explanation for the previously demonstrated relationship between disturbances in the circadian system and disordered glucose homeostasis, including diabetes mellitus type 2, in subjects exposed to long-term shift work.