bluuebunny/crossref_metadata_2025_split huggingface dataset:
Focal adhesion kinase activation limits efficacy of Dasatinib in c‐Myc driven hepatocellular carcinoma
Authors: Liu Xianqiong , Song Xinhua , Zhang Jie , Xu Zhong , Che Li , Qiao Yu , Ortiz Pedraza Yunuen , Cigliano Antonio , Pascale Rosa M. , Calvisi Diego F. , Liu Yanju , Chen Xin 
Published: October 2018

AbstractHepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options. Recently, it was found that Dasatinib treatment led to synthetic lethality in c‐Myc high‐expressing human cancer cells due to inhibition of p‐Lyn. Overexpression of c‐Myc is frequently seen in human HCC. We investigated the sensitivity to Dasatinib in vitro using HCC cell lines and in vivo using c‐Myc mouse HCC model. We found that HCC cell line responsiveness to Dasatinib varied significantly. However, there was no correlation between c‐Myc expression and IC50 to Dasatinib. In c‐Myc‐induced HCC in mice, tumors continued to grow despite Dasatinib treatment, although the eventual tumor burden was lower in Dasatinib treatment cohort. Molecular analyses revealed that Dasatinib was effective in inhibiting p‐Src, but not p‐Lyn, in HCC. Importantly, we found that in HCC cell lines as well as c‐Myc mouse HCC, Dasatinib treatment induced up regulation of activated/phosphorylated (p)‐focal adhesion kinase(FAK). Concomitant treatment of HCC cell lines with Dasatinib and FAK inhibitor prevented Dasatinib‐induced FAK activation, leading to stronger growth restraint. Altogether, our results suggest that Dasatinib may have limited efficacy as single agent for HCC treatment. Combined treatment with Dasatinib with FAK inhibitor might represent a novel therapeutic approach against HCC.
Antioxidant Defenses in Wild Growing Halophyte Crithmum maritimum from Inland and Coastline Populations
Authors: Gil Lorenzo , Pinya Samuel , Tejada Silvia , Capó Xavier , Sureda Antoni 
Published: October 2018

AbstractTraditional Mediterranean diet includes the halophyte Crithmum maritimum L. (Apiaceae) which can be found in the coastline of the Balearic Islands but also inland. Both areas differed in the environmental conditions, mainly in salinity which can affect the oxidative status of this species. The aim was to evaluate the antioxidant enzyme activities, polyphenols and the lipid peroxidation in leaves of wild C. maritimum growing in a natural coastal area influenced by marine salinity and an inland area without marine influence. The activities of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase as well as polyphenol and reduced glutathione content were significantly higher in the samples from coastline population, whereas no significant differences were found in glutathione reductase activity and in malondialdehyde levels. The production of H2O2 was also significantly higher in the population from coastline. In conclusion, C. maritimum adapt their antioxidant defense machinery to the different salinity conditions, avoiding the instauration of oxidative stress.
The Bacterial Extracellular Matrix Protein TapA Is a Two‐Domain Partially Disordered Protein
Authors: Abbasi Razan , Mousa Reem , Dekel Noa , Amartely Hadar , Danieli Tsafi , Lebendiker Mario , Levi‐Kalisman Yael , Shalev Deborah E. , Metanis Norman , Chai Liraz 
Published: October 2018

AbstractBiofilms are aggregates of microbial cells that form on surfaces and at interfaces, and are encased in an extracellular matrix. In biofilms made by the soil bacterium Bacillus subtilis, the protein TapA mediates the assembly of the functional amyloid protein TasA into extracellular fibers, and it anchors these fibers to the cell surface. We used circular dichroism and NMR spectroscopy to show that, unlike the structured TasA, TapA is disordered. In addition, TapA is composed of two weakly interacting domains: a disordered C‐terminal domain and a more structured N‐terminal domain. These two domains also exhibited different structural changes in response to changes in external conditions, such as increased temperatures and the presence of lipid vesicles. Although the two TapA domains weakly interacted in solution, their cooperative interaction with lipid vesicles prevented disruption of the vesicles. These findings therefore suggest that the two‐domain composition of TapA is important in its interaction with single or multiple partners in the extracellular matrix in biofilms.
Improving dry‐fractionated corn fermentation by supplementation of corn germ meal and pasta mill feed from agro‐food industries
Authors: Kumar Deepak , Singh Vijay 
Published: October 2018

AbstractBackground and objectivesSeparation of germ from corn using dry fractionation in modified dry‐grind processes results in the sluggish and incomplete fermentation of remaining corn because of nutrient deficiency for yeast. This study investigated the use of two low‐value co‐products, germ meal from corn wet milling and mill feed from pasta manufacturing, as additives to improve the fermentation of corn grits.FindingsAddition of 5% germ meal or 2.5% mill feed in corn grits resulted in the complete (no residual glucose) and faster fermentation, compared to 4.3% residual glucose during fermentation of only corn grits. Final ethanol yield (0.51 L/kg) was about 22% higher compared to control (0.42 L/kg). Increase in supplementation (10% of grits) further increased the fermentation rates, however, led to similar final ethanol concentrations and ethanol yields.ConclusionsBoth germ meal and pasta mill feed can improve fermentation rate and efficiency of dry‐fractionated grits and avoid the need for expensive supplements or enzymes.Significance and noveltyThis research provides an innovative solution to the challenge of inefficient fermentation of dry‐fractionated corn and also identifies new potential market for two low‐value co‐products from the agro‐food industries.
Microtube‐Membrane Methodology for Electrochemical Synthesis and Study of Electroactive and Ionically Conductive Materials, and the Conductivity of MnO2
Authors: Experton Juliette , Wu Xiaojian , Wang Gelan , Martin Charles R. 
Published: October 2018

AbstractA membrane‐based methodology for electrochemical synthesis and study of electroactive and ionically conductive materials is described. The Li+‐intercalation material MnO2 was used to demonstrate this methodology. The membrane was a polymeric support containing monodisperse gold microtubes (diameter 600 nm) that span the thickness of the membrane. Bipolar electrochemical synthesis of MnO2, from Mn2+ solutions, was conducted across this membrane, resulting in deposition of monodisperse, hemispherical MnO2 particles at the open ends of the tubes on one face of the membrane. The resulting microtube/MnO2 composite membrane makes a convenient construct for investigating the transport properties of the MnO2 particles. This was accomplished by mounting the membrane in a U‐tube cell, placing electrolyte solutions on either side, and driving an ionic current through the membrane. The ionic conductivity of MnO2 was measured in this way, and found to be 40±10 μS cm−1 when LiCl or LiClO4 solutions were used as the electrolyte. The mechanism of ionic conductivity through these MnO2 particles is discussed.
Strategies for the Design of Donors and Precursors of Reactive Sulfur Species
Authors: Xu Shi , Hamsath Akil , Neill Deshka L. , Wang Yingying , Yang Chun‐tao , Xian Ming 
Published: October 2018

AbstractReactive sulfur species (RSS) play regulatory roles in biological systems. Many RSS are highly reactive and transient molecules, making their study difficult. RSS donors or precursors, which are used to specifically produce or deliver RSS, are useful research tools, as well as possible therapeutic agents. In this Minireview, we summarized the chemical strategies that have been used in the design of donors/precursors of hydrogen sulfide relevant RSS (including hydrogen sulfide, hydrogen polysulfides, persulfides, and S‐nitroso‐hydrogen sulfide). The potential problems of applying these strategies in biological settings are also discussed.
Designing Two‐Dimensional Nanosheets for Improving Drug Delivery to Fucose‐Receptor‐Overexpressing Cancer Cells
Authors: Gupta Nitin , Jangid Ashok Kumar , Singh Mandeep , Pooja Deep , Kulhari Hitesh 
Published: October 2018

AbstractTargeted drug delivery has shown promise in improving the therapeutic efficacy of anticancer drugs. Gemcitabine hydrochloride (GEM) is a broad‐range chemotherapeutic agent for the treatment of various cancers. However, systemic use of free GEM is restricted because of its poor physicochemical properties and nonspecific drug delivery, resulting in dose‐dependent adverse effects. In this study, a fucose‐conjugated graphene oxide (GO)‐based smart targeted nanocarrier system was designed to provide high loading, sustained release, and targeted high concentrations of GEM to cancer cells. Fucose‐conjugated GO nanosheets (FGONS) and GEM‐loaded fucose‐conjugated GO nanosheets (GEM‐FGONS) were prepared and characterized by various techniques. About 36.2 % of GEM was loaded to the FGONS, which showed a pH‐dependent release over a period of 48 h. A colloidal suspension of GEM‐FGONS was found to be physiochemically stable for up to 96 h. In cytotoxicity studies, GEM‐FGONS demonstrated time‐ and dose‐dependent high toxicities on fucose‐receptor‐overexpressing MDA‐MB‐231 human breast cancer cells and A549 human lung cancer cells. Moreover, targeted formulations were more efficacious than non‐targeted or free GEM. Overall, bioconjugation of fucose helps in the stabilizing and targeting of graphene oxide nanosheets.
Thyrotropin‐releasing hormone (TRH) in the brain and pituitary of the teleost, Clarias batrachus and its role in regulation of hypophysiotropic dopamine neurons
Authors: Singh Omprakash , Pradhan Dipti R. , Nagalakashmi B. , Kumar Santosh , Mitra Saptarsi , Sagarkar Sneha , Sakharkar Amul J. , Lechan Ronald M. , Singru Praful S. 
Published: October 2018

AbstractThyrotropin‐releasing hormone (TRH) regulates the hypothalamic–pituitary–thyroid axis in mammals and also regulates prolactin secretion, directly or indirectly via tuberoinfundibular dopamine neurons. Although TRH is abundantly expressed in teleost brain and believed to mediate neuronal communication, empirical evidence is lacking. We analyzed pro‐TRH‐mRNA expression, mapped TRH‐immunoreactive elements in the brain and pituitary, and explored its role in regulation of hypophysiotropic dopamine (DA) neurons in the catfish, Clarias batrachus. Partial pro‐TRH transcript from C. batrachus transcriptome showed six TRH progenitors repeats. Quantitative real‐time polymerase chain reaction (qRT‐PCR) identified pro‐TRH transcript in a number of different brain regions and immunofluorescence showed TRH‐immunoreactive cells/fibers in the olfactory bulb, telencephalon, preoptic area (POA), hypothalamus, midbrain, hindbrain, and spinal cord. In the pituitary, TRH‐immunoreactive fibers were seen in the neurohypophysis, proximal pars distalis, and pars intermedia but not rostral pars distalis. In POA, distinct TRH‐immunoreactive cells/fibers were seen in nucleus preopticus periventricularis anterior (NPPa) that demonstrated a significant increase in TRH‐immunoreactivity when collected during preparatory and prespawning phases, reaching a peak in the spawning phase. Although tyrosine hydroxylase (TH)‐immunoreactive neurons in NPPa are hypophysiotropic, none of the TRH‐immunoreactive neurons in NPPa accumulated neuronal tracer DiI following implants into the pituitary. However, 87 ± 1.6% NPPa TH‐immunoreactive neurons were surrounded by TRH‐immunoreactive axons that were seen in close proximity to the somata. Superfused POA slices treated with TRH (0.5–2 μM) significantly reduced TH concentration in tissue homogenates and the percent TH‐immunoreactive area in the NPPa. We suggest that TRH in the brain of C. batrachus regulates a range of physiological functions but in particular, serves as a potential regulator of hypophysiotropic DA neurons and reproduction.
Terabit encryption in a second: Performance evaluation of block ciphers in GPU with Kepler, Maxwell, and Pascal architectures
Authors: Lee Wai‐Kong , Goi Bok‐Min , Phan Raphael C.‐W. 
Published: October 2018

SummaryWith the emergence of IoT and cloud computing technologies, massive data are generated from various applications everyday and communicated through the Internet. Secure communication is essential to protect these data from malicious attacks. Block ciphers are one mechanism to offer such protection but unfortunately involve intensive computations that can be performance bottlenecks to the servers, especially when the data center needs to handle thousands of concurrent transactions. In this paper, we investigate the feasibility of the GPU as an accelerator to perform high‐speed encryption in server environments. We present optimized implementations of a conventional block cipher (AES) and new lightweight block ciphers (LEA, Chaskey, SIMON, SPECK, and SIMECK) across three new GPU architectures (Kepler, Maxwell, and Pascal). For AES, we improve the fine‐grain implementation by utilizing the warp shuffle instruction available in these three new GPU architectures, which yield a 6%‐16% improvement over the previous implementations. For LEA, Chaskey, SIMON, SPECK, and SIMECK, we first analyze why they cannot have efficient fine‐grain implementations in the GPU and then present our optimization techniques, which are able to achieve impressive encryption speeds of 1.912, 637, 1.485, 2.291, and 1.478 Tb/s, respectively, in GTX1080.
Hydroxyl Groups of Exceptionally High Acidity in Desilicated Zeolites Y
Authors: Gackowski Mariusz , Kuterasiński Łukasz , Podobiński Jerzy , Datka Jerzy 
Published: October 2018

AbstractThe desilication of dealuminated zeolite Y in NaOH/tetrabutylammonium hydroxide mixtures produces hierarchical zeolite Y containing a micropore system as well as mesopores of significant volume and surface. IR studies evidenced that a new kind of hydroxyls was formed if desilication was realized above 318 K. This new kind of acidic hydroxyls is characterized by IR band at 3600 cm−1. IR studies showed, that these new hydroxyls showed extremely high acidity. This was evidenced by very high frequency shifts of IR bands of OH interacting with probe molecules: CO and N2:
=411 cm−1 and
=164 cm−1, resp. These frequency shift are the highest in all the chemistry of zeolites including very strongly acidic dealuminated mazzite and steamed zeolite USY (
=ca. 380 cm−1) indicating that 3600 cm−1 hydroxyls are the most acidic in all the zeolites.
Antibiotics as both friends and foes of the human gut microbiome: The microbial community approach
Authors: Nogueira Teresa , David Pedro H. C. , Pothier Joël 
Published: October 2018

AbstractThe exposure of the human gut to antibiotics can have a great impact on human health. Antibiotics pertain to the preservation of human health and are useful tools for fighting bacterial infections. They can be used for curing infections and can play a critical role in immunocompromised or chronic patients, or in fighting childhood severe malnutrition. Yet, the genomic and phylogenetic diversity of the human gut changes under antibiotic exposure. Antibiotics can also have severe side effects on human gut health, due to the spreading of potential antibiotic resistance genetic traits and to their correlation with virulence of some bacterial pathogens. They can shape, and even disrupt, the composition and functioning diversity of the human gut microbiome. Traditionally bacterial antibiotic resistances have been evaluated at clone or population level. However, the understanding of these two apparently disparate perspectives as both friends and foes may come from the study of microbiomes as a whole and from the evaluation of both positive and negative effects of antibiotics on microbial community dynamics and diversity. In this review we present some metagenomic tools and databases that enable the studying of antibiotic resistance in human gut metagenomes, promoting the development of personalized medicine strategies, new antimicrobial therapy protocols and patient follow‐up.
Marine bacteria and fungi as promising source for new antibiotics
Authors: Wiese Jutta , Imhoff Johannes F. 
Published: October 2018

AbstractNatural products and derivatives thereof are of considerable importance in the discovery of new pharmaceuticals, for example, for the treatment of cancer, diabetes, inflammation diseases, and infection diseases caused by bacteria, fungi, viruses, or parasites. The great biodiversity of marine microorganisms is reflected in their huge chemical diversity, which provides a rich source of biologically active compounds. An increasing interest in marine microorganisms as promising producers of new compounds with potential medical applications has raised increasing interest in the sustainable exploration of marine microbial resources for the discovery of new antibiotics, which is highlighted. The bottlenecks in the development of drugs using the large marine natural product pipeline are also discussed.
Association with outcomes and response to treatment of trimethylamine N‐oxide in heart failure: results from BIOSTAT‐CHF
Authors: Suzuki Toru , Yazaki Yoshiyuki , Voors Adriaan A. , Jones Donald J.L. , Chan Daniel C.S. , Anker Stefan D. , Cleland John G. , Dickstein Kenneth , Filippatos Gerasimos , Hillege Hans L. , Lang Chim C. , Ponikowski Piotr , Samani Nilesh J. , van Veldhuisen Dirk J. , Zannad Faiez , Zwinderman Aeilko H. , Metra Marco , Ng Leong L. 
Published: October 2018

AimsAssociation of elevated circulating levels of trimethylamine N‐oxide (TMAO) with adverse outcomes in patients with heart failure (HF) has been described. However, response of TMAO levels to treatment and medications has not been investigated. Therefore, we investigated whether TMAO levels are responsive to guideline‐recommended treatment and medications, and further reflect changes in outcomes.Methods and resultsTMAO levels were investigated in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT‐CHF), which addressed response to guideline‐recommended pharmacological treatment. TMAO levels in 2234 patients with new‐onset or progressively worsening HF showed strong associations with adverse events (mortality and/or rehospitalisation) at 1, 2 and 3 years [hazard ratio (HR) 1.37–1.51, P ≤ 0.019). Analysis of 972 patients with plasma available at both enrolment and follow‐up visit showed reductions of B‐type natriuretic peptide (BNP) levels with guideline‐based treatment (P < 0.001), but not for TMAO levels. Moreover, patients with higher TMAO levels than median before and after treatment showed increased association with adverse outcomes [HR 2.21, 95% confidence interval (CI) 1.43–3.43, P < 0.001] compared to patients with lower than median levels either before or after treatment (HR 1.13, 95% CI 0.63–2.04, P = 0.684 and HR 1.14, 95% CI 0.64–2.03, P = 0.662, respectively).ConclusionTMAO levels were associated with adverse outcomes (mortality and/or rehospitalisation) in BIOSTAT‐CHF, and did not respond to guideline‐based pharmacological treatment in contrast to BNP levels which did as expected. Lower TMAO levels were associated with favourable outcome regardless of treatment.
Treatment of early life status epilepticus: What can we learn from animal models?
Authors: Thompson Kerry W. , Suchomelova Lucie , Wasterlain Claude G. 
Published: October 2018

SummaryTreatment of status epilepticus (SE) in infants and children is challenging. There is a recognition that a broad set of developmental processes need to be considered to fully appreciate the physiologic complexity of severe seizures, and seizure outcomes, in infants and children. The development and use of basic models to elucidate important mechanisms will help further our understanding of these processes. Here we review some of the key experimental models and consider several areas relevant to treatment that could lead to productive translational research. Terminating seizures quickly is essential. Understanding pharmacoresistance of SE as it relates to receptor trafficking will be critical to seizure termination. Once a severe seizure is terminated, how will the developing brain respond? Basic studies suggest that there are important acute and long‐term histopathologic, and pathophysiologic, consequences that, if left unaddressed, will produce long‐lasting deficits on the form and function of the central nervous system. To fully utilize the evidence that basic models produce, age‐ and development‐ and model‐specific frameworks have to be considered carefully. Studies have demonstrated that severe seizures can cause perturbations to developmental processes during critical periods of development that lead to life‐long deficits. Unfortunately, some of the drugs that are commonly used to treat seizures may also produce negative outcomes by enhancing Cl‐‐mediated depolarization, or by accelerating programmed cell death. More research is needed to understand these phenomena and their relevance to the human condition, and to develop rational drugs that protect the developing brain from severe seizures to the fullest extent possible.
Autism spectrum disorder and cognitive profile in children with Dravet syndrome: Delineation of a specific phenotype
Authors: Ouss Lisa , Leunen Dorothee , Laschet Jacques , Chemaly Nicole , Barcia Giulia , Losito Emma M. , Aouidad Aveline , Barrault Zoe , Desguerre Isabelle , Breuillard Delphine , Nabbout Rima 
Published: October 2018

SummaryObjectiveWe aimed to assess a cohort of young patients with Dravet syndrome (DS) for intellectual disability (ID) and autism spectrum disorder (ASD) using standardized tools and parental questionnaires to delineate their specific profiles.MethodsWe included 35 patients with DS aged 24 months to 7 years, excluding patients with a developmental age (DA) <18 months (n = 5). We performed specific tests adapted for ID (Psychoeducational Profile, Third Edition [PEP‐3]), in addition to the Child Development Inventory (CDI) and Vineland Adaptive Behavior Scales, Second Edition (VABS‐II) questionnaires. We used 2 standardized tools for ASD: the Autism Diagnostic Observation Schedule, Second Edition (ADOS‐2) and the Autism Diagnostic Interview‐Revised (ADI‐R). We compared the with parental questionnaires and the VABS‐II, and with ASD characteristics.ResultsPEP‐3 subscales showed pathologic development in all but one patient (97%): ID in 23 of 30 (77%), and borderline cognitive functioning in 6 of 30 (22%). Eleven patients (39%) had ASD and 2 (7%) had a Social Communication Disorder (SCD) diagnosis. We found no difference between PEP‐3 and CDI categorization except for fine motor skills. We found significant negative correlations between ADOS‐2 and PEP‐3 for the majority of scores. For patients aged older than 50 months, 2 groups emerged (ASD/no ASD) with significant difference in DA. The logistic regression for ASD diagnosis explained by VABS‐II showed a significant effect for Socialization, Motor Skills, and Adaptive Behavior.SignificanceWe found a high prevalence of ID in patients with DS. ID is characterized by expressive and comprehensive communication deficits in addition to visuospatial difficulties. ASD showed a specific profile with a relative preservation of social skills, emphasizing a possible underdiagnosis. Parental questionnaires can provide a good assessment of cognitive profile and might allow the difficulty of addressing cognitive scales in DS to be overcome. The profile of ID and ASD should help to establish early adapted rehabilitation programs and emphasizes the global need for care beyond seizures in DS and other developmental epileptic encephalopathies.