bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-molecule characterization of extrinsic transcription termination by Sen1 helicase
Authors: Wang S. , Han Z. , Libri D. , Porrua O. , Strick T. R. 
Published: April 2019

AbstractExtrinsic transcription termination typically involves remodeling of RNA polymerase by an accessory helicase. In yeast this is accomplished by the Sen1 helicase homologous to human senataxin (SETX). To gain insight into these processes we develop a DNA scaffold construct compatible with magnetic-trapping assays and from which S. cerevisiae RNA polymerase II (Pol II), as well as E. coli RNA polymerase (ecRNAP), can efficiently initiate transcription without transcription factors, elongate, and undergo extrinsic termination. By stalling Pol II TECs on the construct we can monitor Sen1-induced termination in real-time, revealing the formation of an intermediate in which the Pol II transcription bubble appears half-rewound. This intermediate requires ~40 sec to form and lasts ~20 sec prior to final dissociation of the stalled Pol II. The experiments enabled by the scaffold construct permit detailed statistical and kinetic analysis of Pol II interactions with a range of cofactors in a multi-round, high-throughput fashion.
High carbon emissions from thermokarst lakes of Western Siberia
Authors: Serikova S. , Pokrovsky O. S. , Laudon H. , Krickov I. V. , Lim A. G. , Manasypov R. M. , Karlsson J. 
Published: April 2019

AbstractThe Western Siberia Lowland (WSL), the world’s largest permafrost peatland, is of importance for understanding the high-latitude carbon (C) cycle and its response to climate change. Warming temperatures increase permafrost thaw and production of greenhouse gases. Also, permafrost thaw leads to the formation of lakes which are hotspots for atmospheric C emissions. Although lakes occupy ~6% of WSL, lake C emissions from WSL remain poorly quantified. Here we show high C emissions from lakes across all permafrost zones of WSL. The C emissions were especially high in shoulder seasons and in colder permafrost-rich regions. The total C emission from permafrost-affected lakes of WSL equals ~12 ± 2.6 Tg C yr−1 and is 2-times greater than region’s C export to the Arctic coast. The results show that C emission from WSL lakes is a significant component in the high-latitude C cycle, but also suggest that C emission may decrease with warming.
Identification of the kinase STK25 as an upstream activator of LATS signaling
Authors: Lim Sanghee , Hermance Nicole , Mudianto Tenny , Mustaly Hatim M. , Mauricio Ian Paolo Morelos , Vittoria Marc A. , Quinton Ryan J. , Howell Brian W. , Cornils Hauke , Manning Amity L. , Ganem Neil J. 
Published: April 2019

AbstractThe Hippo pathway maintains tissue homeostasis by negatively regulating the oncogenic transcriptional co-activators YAP and TAZ. Though functional inactivation of the Hippo pathway is common in tumors, mutations in core pathway components are rare. Thus, understanding how tumor cells inactivate Hippo signaling remains a key unresolved question. Here, we identify the kinase STK25 as an activator of Hippo signaling. We demonstrate that loss of STK25 promotes YAP/TAZ activation and enhanced cellular proliferation, even under normally growth-suppressive conditions both in vitro and in vivo. Notably, STK25 activates LATS by promoting LATS activation loop phosphorylation independent of a preceding phosphorylation event at the hydrophobic motif, which represents a form of Hippo activation distinct from other kinase activators of LATS. STK25 is significantly focally deleted across a wide spectrum of human cancers, suggesting STK25 loss may represent a common mechanism by which tumor cells functionally impair the Hippo tumor suppressor pathway.
Novel insights into gene expression regulation during meiosis revealed by translation elongation dynamics
Authors: Sabi Renana , Tuller Tamir 
Published: April 2019

AbstractThe ability to dynamically control mRNA translation has a great impact on many intracellular processes. Whereas it is believed that translational control in eukaryotes occurs mainly at initiation, the condition-specific changes at the elongation level and their potential regulatory role remain unclear. Using computational approaches applied to ribosome profiling data, we show that elongation rate is dynamic and can change considerably during the yeast meiosis to facilitate the selective translation of stage-specific transcripts. We observed unique elongation changes during meiosis II, including a global inhibition of translation elongation at the onset of anaphase II accompanied by a sharp shift toward increased elongation for genes required at this meiotic stage. We also show that ribosomal proteins counteract the global decreased elongation by maintaining high initiation rates. Our findings provide new insights into gene expression regulation during meiosis and demonstrate that codon usage evolved, among others, to optimize timely translation.
Domestic cats (Felis catus) discriminate their names from other words
Authors: Saito Atsuko , Shinozuka Kazutaka , Ito Yuki , Hasegawa Toshikazu 
Published: April 2019

AbstractTwo of the most common nonhuman animals that interact with humans are domestic dogs (Canis familiaris) and cats (Felis catus). In contrast to dogs, the ability of domestic cats to communicate with humans has not been explored thoroughly. We used a habituation-dishabituation method to investigate whether domestic cats could discriminate human utterances, which consisted of cats’ own names, general nouns, and other cohabiting cats’ names. Cats from ordinary households and from a ‘cat café’ participated in the experiments. Among cats from ordinary households, cats habituated to the serial presentation of four different general nouns or four names of cohabiting cats showed a significant rebound in response to the subsequent presentation of their own names; these cats discriminated their own names from general nouns even when unfamiliar persons uttered them. These results indicate that cats are able to discriminate their own names from other words. There was no difference in discrimination of their own names from general nouns between cats from the cat café and household cats, but café cats did not discriminate their own names from other cohabiting cats’ names. We conclude that cats can discriminate the content of human utterances based on phonemic differences.
The asymmetry of plasma membranes and their cholesterol content influence the uptake of cisplatin
Authors: Rivel Timothée , Ramseyer Christophe , Yesylevskyy Semen 
Published: April 2019

AbstractThe composition of the plasma membrane of malignant cells is thought to influence the cellular uptake of cisplatin and to take part in developing resistance to this widespread anti-cancer drug. In this work we study the permeation of cisplatin through the model membranes of normal and cancer cells using molecular dynamics simulations. A special attention is paid to lipid asymmetry and cholesterol content of the membranes. The loss of lipid asymmetry, which is common for cancer cells, leads to a decrease in their permeability to cisplatin by one order of magnitude in comparison to the membranes of normal cells. The change in the cholesterol molar ratio from 0% to 33% also decreases the permeability of the membrane by approximately one order of magnitude. The permeability of pure DOPC membrane is 5–6 orders of magnitude higher than one of the membranes with realistic lipid composition, which makes it as an inadequate model for the studies of drug permeability.
Area-dependent change of response in the rat’s inferior colliculus to intracochlear electrical stimulation following neonatal cochlear damage
Authors: Hatano Miyako , Kelly Jack B. , Zhang Huiming 
Published: April 2019

AbstractTo understand brain changes caused by auditory sensory deprivation, we recorded local-field potentials in the inferior colliculus of young adult rats with neonatal cochlear damage produced by systemic injections of amikacin. The responses were elicited by electrical stimulation of the entire cochlea and recorded at various locations along a dorsolateral-ventromedial axis of the inferior colliculus. We found that hair cells were completely destroyed and spiral ganglion neurons were severely damaged in the basal cochleae of amikacin-treated animals. Hair cells as well as spiral ganglion neurons were damaged also in the middle and apical areas of the cochlea, with the damage being greater in the middle than the apical area. Amplitudes of local-field potentials were reduced in the ventromedial inferior colliculus, but enhanced in the dorsolateral inferior colliculus. Latencies of responses were increased over the entire structure. The enhancement of responses in the dorsolateral inferior colliculus was in contrast with the damage of hair cells and spiral ganglion cells in the apical part of the cochlea. This contrast along with the overall increase of latencies suggests that early cochlear damage can alter neural mechanisms within the inferior colliculus and/or the inputs to this midbrain structure.
Encapsulation of Lactobacillus fermentum K73 by Refractance Window drying
Authors: Aragón-Rojas Stephania , Quintanilla-Carvajal María Ximena , Hernández-Sánchez Humberto , Hernández-Álvarez Alan Javier , Moreno Fabian Leonardo 
Published: April 2019

AbstractThe purpose of this work was to model the survival of the microorganism and the kinetics of drying during the encapsulation ofLactobacillus fermentumK73 by Refractance Window drying. A whey culture medium with and without addition of maltodextrin were used as encapsulation matrices. The microorganism with the encapsulation matrices was dried at three water temperatures (333, 343 and 353 K) until reaching balanced moisture. Microorganism survival and thin layer drying kinetics were studied by using mathematical models. Results showed that modified Gompertz model and Midilli model described the survival of the microorganism and the drying kinetics, respectively. The most favorable process conditions found with the mathematical modelling were a drying time of 2460 s, at a temperature of 353 K. At these conditions, a product with 9.1 Log CFU/g and a final humidity of 10% [wet basis] using the culture medium as encapsulation matrix was obtained. The result shows that Refractance Window can be applied to encapsulate the microorganism probiotic with a proper survival of the microorganism.
Inhibition of the thioredoxin system by PX-12 (1-methylpropyl 2-imidazolyl disulfide) impedes HIV-1 infection in TZM-bl cells
Authors: Lundberg Mathias , Mattsson Åse , Reiser Kathrin , Holmgren Arne , Curbo Sophie 
Published: April 2019

AbstractHuman immunodeficiency virus (HIV-1) entry is initiated by the binding between the viral envelope glycoprotein gp120 and the host receptor CD4, and followed by reduction of structural disulfides of gp120 and CD4. The host thioredoxin-1 (Trx1) efficiently reduces disulfides of gp120 and CD4 in vitro, and recently CD4-dependent HIV-1 entry was shown to be inhibited by anti-Trx1-antibodies, indicating a central role for Trx1. 1-methylpropyl-2-imidazolyl disulfide (PX-12) is a reversible inhibitor of the Trx1 system that may also cause a slow irreversible thioalkylation of Trx1. It was developed as an antitumor agent, however, the current study aimed to determine if it also has an anti-HIV-1 effect. We show that PX-12 has anti-HIV-1(IIIB) activity in TZM-bl cells, in fact, no virus was detected inside the cells in the presence of 10 µM PX-12. Moreover, PX-12 inhibited the enzymatic activity of Trx1 and the Trx1-dependent disulfide reduction of gp120. Microtubule polymerization and formation of acetylated microtubules were also inhibited, activities shown to be required for HIV-1 life cycle propagation. In conclusion, our data strengthens the notion that the early steps of the HIV-1 life cycle depends on the Trx1 system and indicate that the Trx1 system may be a rational drug target for HIV-1 treatment.
Ocean acidification causes mortality in the medusa stage of the cubozoan Carybdea xaymacana
Authors: Chuard Pierre J. C. , Johnson Maggie D. , Guichard Frédéric 
Published: April 2019

AbstractOcean pH is decreasing due to anthropogenic activities, and the consequences of this acidification on marine fauna and ecosystems are the subject of an increasing number of studies. Yet, the impact of ocean acidification (OA) on several abundant and ecologically important taxa, such as medusozoans, is poorly documented. To date there have been no studies on the effect of post-2050 OA projections on the medusa stage of jellyfish. As medusae represent the reproductive stage of cnidarians, negative impacts on adult jellyfish could severely impact the long-term survival of this group. Using a laboratory experiment, we investigated the effect of 2300 OA projections (i.e. pH of 7.5) on the mortality rate of the medusa-stage of the cubozoan species Carybdea xaymacana, compared to ambient seawater pH conditions (i.e. pH of 8.1). After a 12-h exposure to OA, C. xaymacana medusae suffered higher mortality rates compared to ambient conditions. This study represents the first evidence of the potential lethal effects of post-2050 OA projections on jellyfish. The higher metabolic rates of cubozoans compared to other cnidarians might make box jellyfish more vulnerable to OA. A decrease in the density of cnidarians could lead to harmful ecological events, such as algal blooms.
Supervised machine learning of ultracold atoms with speckle disorder
Authors: Pilati S. , Pieri P. 
Published: April 2019

AbstractWe analyze how accurately supervised machine learning techniques can predict the lowest energy levels of one-dimensional noninteracting ultracold atoms subject to the correlated disorder due to an optical speckle field. Deep neural networks with different numbers of hidden layers and neurons per layer are trained on large sets of instances of the speckle field, whose energy levels have been preventively determined via a high-order finite difference technique. The Fourier components of the speckle field are used as the feature vector to represent the speckle-field instances. A comprehensive analysis of the details that determine the possible success of supervised machine learning tasks, namely the depth and the width of the neural network, the size of the training set, and the magnitude of the regularization parameter, is presented. It is found that ground state energies of previously unseen instances can be predicted with an essentially negligible error given a computationally feasible number of training instances. First and second excited state energies can be predicted too, albeit with slightly lower accuracy and using more layers of hidden neurons. We also find that a three-layer neural network is remarkably resilient to Gaussian noise added to the training-set data (up to 10% noise level), suggesting that cold-atom quantum simulators could be used to train artificial neural networks.
Lp-PLA2 activity and mass and CRP are associated with incident symptomatic peripheral arterial disease
Authors: Fatemi Shahab , Gottsäter Anders , Zarrouk Moncef , Engström Gunnar , Melander Olle , Persson Margaretha , Acosta Stefan 
Published: April 2019

AbstractLong follow up is needed in prospective cohort study evaluation of plasma biomarkers for incident peripheral arterial disease (PAD) Middle-aged PAD-free individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (n = 5550; 1991–94) were followed prospectively for a median time of 23.4 years. The plasma biomarkers lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and mass, proneurotensin, and CRP, were studied in relation to incidence of PAD until December 31st, 2016. The diagnosis of PAD could be validated and confirmed in 98%. Cox regression was used to calculate hazard ratios (HR) per 1 standard deviation increment of each respective log transformed plasma biomarker. Cumulative incidence of PAD was 4.4% (men 5.9%, women 3.3%). Adjusting for age, gender, smoking, body mass index, hypertension, diabetes mellitus, Lp-PLA2 activity (HR 1.33; 95% CI 1.17–1.52), Lp-PLA2 mass (HR 1.20; 95% CI 1.05–1.37) and CRP (HR 1.55; 95% CI 1.36–1.76) remained independently associated with incident PAD. The plasma biomarkers Lp-PLA2 activity and mass, and CRP were markers of PAD risk, implying that they might be useful biomarkers for subclinical atherosclerosis and atherosclerotic disease.
Structural basis of translation inhibition by cadazolid, a novel quinoxolidinone antibiotic
Authors: Scaiola Alain , Leibundgut Marc , Boehringer Daniel , Caspers Patrick , Bur Daniel , Locher Hans H. , Rueedi Georg , Ritz Daniel 
Published: April 2019

AbstractOxazolidinones are synthetic antibiotics used for treatment of infections caused by Gram-positive bacteria. They target the bacterial protein synthesis machinery by binding to the peptidyl transferase centre (PTC) of the ribosome and interfering with the peptidyl transferase reaction. Cadazolid is the first member of quinoxolidinone antibiotics, which are characterized by combining the pharmacophores of oxazolidinones and fluoroquinolones, and it is evaluated for treatment of Clostridium difficile gastrointestinal infections that frequently occur in hospitalized patients. In vitro protein synthesis inhibition by cadazolid was shown in Escherichia coli and Staphylococcus aureus, including an isolate resistant against linezolid, the prototypical oxazolidinone antibiotic. To better understand the mechanism of inhibition, we determined a 3.0 Å cryo-electron microscopy structure of cadazolid bound to the E. coli ribosome in complex with mRNA and initiator tRNA. Here we show that cadazolid binds with its oxazolidinone moiety in a binding pocket in close vicinity of the PTC as observed previously for linezolid, and that it extends its unique fluoroquinolone moiety towards the A-site of the PTC. In this position, the drug inhibits protein synthesis by interfering with the binding of tRNA to the A-site, suggesting that its chemical features also can enable the inhibition of linezolid-resistant strains.
Silencing an insulin-induced lncRNA, LncASIR, impairs the transcriptional response to insulin signalling in adipocytes
Authors: Degirmenci Ufuk , Li Jia , Lim Yen Ching , Siang Diana Teh Chee , Lin Shibo , Liang Hui , Sun Lei 
Published: April 2019

AbstractLong noncoding RNA(lncRNA)s are new regulators governing the metabolism in adipose tissue. In this study, we aimed to understand how lncRNAs respond to insulin signalling and explore whether lncRNAs have a functional role in insulin signalling pathway. We treated primary adipocyte cultures with insulin and collected RNA for RNA-sequencing to profile the non-coding transcriptome changes, through which we identified a top Adipose Specific Insulin Responsive LncRNA (LncASIR). To determine its biological function, we knocked down LncASIR using dcas9-KRAB, followed by RNA-seq to examine the effect on insulin-induced gene expression program. We identified a set of lncRNAs regulated by insulin signalling pathway. LncASIR is transcribed from a super enhancer region and responds robustly to insulin treatment. Silencing LncASIR resulted in an impaired global insulin-responsive gene program. LncASIR is a novel and integral component in the insulin signalling pathway in adipocytes.
Deep learning enables robust assessment and selection of human blastocysts after in vitro fertilization
Authors: Khosravi Pegah , Kazemi Ehsan , Zhan Qiansheng , Malmsten Jonas E. , Toschi Marco , Zisimopoulos Pantelis , Sigaras Alexandros , Lavery Stuart , Cooper Lee A. D. , Hickman Cristina , Meseguer Marcos , Rosenwaks Zev , Elemento Olivier , Zaninovic Nikica , Hajirasouliha Iman 
Published: April 2019

AbstractVisual morphology assessment is routinely used for evaluating of embryo quality and selecting human blastocysts for transfer after in vitro fertilization (IVF). However, the assessment produces different results between embryologists and as a result, the success rate of IVF remains low. To overcome uncertainties in embryo quality, multiple embryos are often implanted resulting in undesired multiple pregnancies and complications. Unlike in other imaging fields, human embryology and IVF have not yet leveraged artificial intelligence (AI) for unbiased, automated embryo assessment. We postulated that an AI approach trained on thousands of embryos can reliably predict embryo quality without human intervention. We implemented an AI approach based on deep neural networks (DNNs) to select highest quality embryos using a large collection of human embryo time-lapse images (about 50,000 images) from a high-volume fertility center in the United States. We developed a framework (STORK) based on Google’s Inception model. STORK predicts blastocyst quality with an AUC of >0.98 and generalizes well to images from other clinics outside the US and outperforms individual embryologists. Using clinical data for 2182 embryos, we created a decision tree to integrate embryo quality and patient age to identify scenarios associated with pregnancy likelihood. Our analysis shows that the chance of pregnancy based on individual embryos varies from 13.8% (age ≥41 and poor-quality) to 66.3% (age <37 and good-quality) depending on automated blastocyst quality assessment and patient age. In conclusion, our AI-driven approach provides a reproducible way to assess embryo quality and uncovers new, potentially personalized strategies to select embryos.
GHET1 acts as a prognostic indicator and functions as an oncogenic lncRNA in cervical cancer
Authors: Zhang Qunchang , Zhang Yongtao , Wang Ying 
Published: April 2019

Abstract
Gastric carcinoma proliferation enhancing transcript 1 (GHET1) has been suggested to serve as a promising oncogenic lncRNA in various types of human cancer. However, the role of GHET1 remained unknown in cervical cancer. In our study, we found GHET1 expression was markedly elevated in cervical cancer tissue specimens and cell lines compared with adjacent normal cervical tissue specimens and human normal cervical cell line, respectively. Then, we found high expression of GHET1 is a useful biomarker to discriminate cervical cancer tissues from non-tumorous tissues, and associated with advanced clinical stage, lymph node metastasis, distant metastasis and poor histological grade in cervical cancer patients. The survival analysis showed high GHET1 expression was an independent unfavorable prognostic factor in cervical cancer patients. Knockdown of GHET1 expression markedly inhibits cervical cancer cell proliferation, migration, and invasion. The loss-of-function study indicated knockdown of GHET1 expression markedly inhibits cervical cancer cell proliferation, migration, and invasion. In conclusion, GHET1 acts as an oncogenic lncRNA in cervical cancer.