bluuebunny/crossref_metadata_2025_split huggingface dataset:
Piscine orthoreovirus demonstrates high infectivity but low virulence in Atlantic salmon of Pacific Canada
Authors: Polinski Mark P. , Marty Gary D. , Snyman Heindrich N. , Garver Kyle A. 
Published: March 2019

AbstractPiscine orthoreovirus (PRV) is ubiquitous in farmed Atlantic salmon and sometimes associated with disease – most notably, Heart and Skeletal Muscle Inflammation (HSMI). However, PRV is also widespread in non-diseased fish, particularly in Pacific Canada, where few cases of severe heart inflammation have been documented. To better understand the mechanisms behind PRV-associated disease, this study investigated the infection dynamics of PRV from Pacific Canada and the potential for experimental passage of putatively associated heart inflammation in Pacific-adapted Mowi-McConnell Atlantic salmon. Regardless of the PRV source (fish with or without HSMI-like heart inflammation), infections led to high-load viremia that induced only minor focal heart inflammation without significant transcriptional induction of inflammatory cytokines. Repeated screening of PRV dsRNA/ssRNA along with histopathology and gene expression analysis of host blood and heart tissues identified three distinct phases of infection: (1) early systemic dissemination and replication without host recognition; (2) peak replication, erythrocyte inclusion body formation and load-dependent host recognition; (3) long-term, high-load viral persistence with limited replication or host recognition sometimes accompanied by minor heart inflammation. These findings contrast previous challenge trials with PRV from Norway that induced severe heart inflammation and indicate that strain and/or host specific factors are necessary to initiate PRV-associated disease.
Crystal structures of multidrug efflux pump MexB bound with high-molecular-mass compounds
Authors: Sakurai Keisuke , Yamasaki Seiji , Nakao Kaori , Nishino Kunihiko , Yamaguchi Akihito , Nakashima Ryosuke 
Published: March 2019

AbstractRND-type multidrug efflux pumps have two voluminous multisite drug-binding pockets named the proximal and distal binding pocket. High- and low-molecular-mass drugs bind to these proximal and distal pocket, respectively. Here, we report the crystal structures of MexB of Pseudomonas aeruginosa bound with high-molecular-mass compounds. Contrary to the expectations, lauryl maltose neopentyl glycol (LMNG, MW 1,005), which is a surfactant larger than the proximal pocket-binding drugs, was found to bind to the distal pocket: one of the two hydrophobic alkyl chains was inserted into the hydrophobic pit, which is the binding site of the efflux pump inhibitor ABI-PP. LMNG is a substrate of the MexAB-OprM system and competitively inhibits the export of other substrates by this system. However, LMNG does not inhibit the export of other substrates by the inhibitor-binding-pit mutant F178W, which retains the export activity of LMNG. The crystal structure of this mutant suggested that the alkyl chain of LMNG could no longer be inserted into the pit because of steric hindrance. We also determined the crystal structure of MexB containing the high-molecular-mass compound neopentyl glycol derivative C7NG (MW 1,028), the binding site of which overlapped with LMNG in the distal pocket, indicating that whether a substrate binds to the distal or proximal pockets is controlled not only by its molecular weight but also by its individual molecular characteristic.
Unexpected Non-acid Drainage from Sulfidic Rock Waste
Authors: Gerson Andrea R. , Rolley Peter J. , Davis Catherine , Feig Sandrin T. , Doyle Stephen , Smart Roger St. C. 
Published: March 2019

AbstractMost rock extraction sites, including mine sites and building construction sites, require a plan to assess, and mitigate if present, the risk of acid mine drainage (AMD). AMD is typically the major environmental concern where sulfide minerals are present in the excavated material and AMD prediction and remediation is based on internationally-accepted acid-base accounting (ABA) tests of representative field samples. This paper demonstrates that standardized ABA tests may not always be provide the correct AMD classification for commonly occurring waste rocks containing low-pyrite and -carbonate due to mineralogic assumptions inherent in their design. The application of these standard ABA tests at a copper mine site in South Australia resulted in the classification of a portion of its waste material as potentially acid forming in apparent contradiction to long term field measurements. Full definition of the sulfide and silicate minerals enabled re-evaluation of the weathering reactions occurring. The overall rate of neutralisation due to silicate dissolution was found to always exceed the rate of acid generation, in agreement with field observations. Consequently, the waste rock was redefined as non-acid forming. The methods developed represent a significant advance in AMD prediction and more strategic, cost-effective environmental planning, with potential for reclassification of wastes with similar characteristics.
A global assessment of freshwater mollusk shell oxygen isotope signatures and their relation to precipitation and stream water
Authors: Pfister L. , Grave C. , Beisel J.-N. , McDonnell J. J. 
Published: March 2019

AbstractRecords of δ18O in stream flow are critical for understanding and modeling hydrological, ecological, biogeochemical and atmospheric processes. However, the number of such records are extremely limited globally and the length of such time series are usually less than a decade. This situation severely handicaps their use in model testing and evaluation. Here we present a global assessment of freshwater mollusk (bivalves & gastropods) isotope data from 25 river basins that have stream water isotope values, water temperature data and shell material isotope signatures. Our data span a latitude range of 37.50°S to 52.06°N. We show that δ18O signatures in freshwater mollusks are able to explain 95% of the variance of stream water δ18O. We use shell δ18O values and water temperature data to reconstruct stream water δ18O signatures. With freshwater mussel life expectancy ranging from a few years up to 200 years, this translation of mollusk metabolic properties into long term stream water isotope records is a promising approach for substantially extending global stream water isotope records in time and space.
Learning Unicycling Evokes Manifold Changes in Gray and White Matter Networks Related to Motor and Cognitive Functions
Authors: Weber Bernhard , Koschutnig Karl , Schwerdtfeger Andreas , Rominger Christian , Papousek Ilona , Weiss Elisabeth M. , Tilp Markus , Fink Andreas 
Published: March 2019

AbstractA three-week unicycling training was associated with (1) reductions of gray matter volume in regions closely linked to visuospatial processes such as spatial awareness, (2) increases in fractional anisotropy primarily in the right corticospinal tract and in the right forceps major of the corpus callosum, and (3) a slowly evolving increase in cortical thickness in the left motor cortex. Intriguingly, five weeks later, during which participants were no longer regularly engaged in unicycling, a re-increase in gray matter was found in the very same region of the rSTG. These changes in gray and white matter morphology were paralleled by increases in unicycling performance, and by improvements in postural control, which diminished until the follow-up assessments. Learning to ride a unicycle results in reorganization of different types of brain tissue facilitating more automated postural control, clearly demonstrating that learning a complex balance task modulates brain structure in manifold and highly dynamic ways.
Cationic gold nanoparticles elicit mitochondrial dysfunction: a multi-omics study
Authors: Gallud Audrey , Klöditz Katharina , Ytterberg Jimmy , Östberg Nataliya , Katayama Shintaro , Skoog Tiina , Gogvadze Vladimir , Chen Yu-Zen , Xue Ding , Moya Sergio , Ruiz Jaime , Astruc Didier , Zubarev Roman , Kere Juha , Fadeel Bengt 
Published: March 2019

AbstractSystems biology is increasingly being applied in nanosafety research for observing and predicting the biological perturbations inflicted by exposure to nanoparticles (NPs). In the present study, we used a combined transcriptomics and proteomics approach to assess the responses of human monocytic cells to Au-NPs of two different sizes with three different surface functional groups,i.e., alkyl ammonium bromide, alkyl sodium carboxylate, or poly(ethylene glycol) (PEG)-terminated Au-NPs. Cytotoxicity screening using THP-1 cells revealed a pronounced cytotoxicity for the ammonium-terminated Au-NPs, while no cell death was seen after exposure to the carboxylated or PEG-modified Au-NPs. Moreover, Au-NR3+ NPs, but not the Au-COOH NPs, were found to trigger dose-dependent lethalityin vivoin the model organism,Caenorhabditis elegans. RNA sequencing combined with mass spectrometry-based proteomics predicted that the ammonium-modified Au-NPs elicited mitochondrial dysfunction. The latter results were validated by using an array of assays to monitor mitochondrial function. Au-NR3+ NPs were localized in mitochondria of THP-1 cells. Moreover, the cationic Au-NPs triggered autophagy in macrophage-like RFP-GFP-LC3 reporter cells, and cell death was aggravated upon inhibition of autophagy. Taken together, these studies have disclosed mitochondria-dependent effects of cationic Au-NPs resulting in the rapid demise of the cells.
Frequency and clinical features of hearing loss caused by STRC deletions
Authors: Yokota Yoh , Moteki Hideaki , Nishio Shin-ya , Yamaguchi Tomomi , Wakui Keiko , Kobayashi Yumiko , Ohyama Kenji , Miyazaki Hiromitsu , Matsuoka Rina , Abe Satoko , Kumakawa Kozo , Takahashi Masahiro , Sakaguchi Hirofumi , Uehara Natsumi , Ishino Takashi , Kosho Tomoki , Fukushima Yoshimitsu , Usami Shin-ichi 
Published: March 2019

AbstractSensorineural hearing loss is a common deficit and mainly occurs due to genetic factors. Recently, copy number variants (CNVs) in the STRC gene have also been recognized as a major cause of genetic hearing loss. We investigated the frequency of STRC deletions in the Japanese population and the characteristics of associated hearing loss. For CNV analysis, we employed a specialized method of Ion AmpliSeqTM sequencing, and confirmed the CNV results via custom array comparative genomic hybridization. We identified 17 probands with STRC homozygous deletions. The prevalence of STRC homozygous deletions was 1.7% in the hearing loss population overall, and 4.3% among mild-to-moderate hearing loss patients. A 2.63% carrier deletion rate was identified in both the hearing loss and the control population with normal hearing. In conclusion, our results show that STRC deletions are the second most common cause of mild-to-moderate hearing loss after the GJB2 gene, which accounts for the majority of genetic hearing loss. The phenotype of hearing loss is congenital and appears to be moderate, and is most likely to be stable without deterioration even after the age of 50. The present study highlights the importance of the STRC gene as a major cause of mild-to-moderate hearing loss.
Designing novel possible kinase inhibitor derivatives as therapeutics against Mycobacterium tuberculosis: An in silico study
Authors: Shahbaaz Mohd , Nkaule Anati , Christoffels Alan 
Published: March 2019

AbstractRv2984 is one of the polyphosphate kinases present in Mycobacterium tuberculosis involved in the catalytic synthesis of inorganic polyphosphate, which plays an essential role in bacterial virulence and drug resistance. Consequently, the structure of Rv2984 was investigated and an 18 membered compound library was designed by altering the scaffolds of computationally identified inhibitors. The virtual screening of these altered inhibitors was performed against Rv2984 and the top three scoring inhibitors were selected, exhibiting the free energy of binding between 8.2–9 kcal mol−1 and inhibition constants in the range of 255–866 nM. These selected molecules showed relatively higher binding affinities against Rv2984 compared to the first line drugs Isoniazid and Rifampicin. Furthermore, the docked complexes were further analyzed in explicit water conditions using 100 ns Molecular Dynamics simulations. Through the assessment of obtained trajectories, the interactions between the protein and selected inhibitors including first line drugs were evaluated using MM/PBSA technique. The results validated the higher efficiency of the designed molecules compared to 1st line drugs with total interaction energies observed between −100 kJ mol−1 and −1000 kJ mol−1. This study will facilitate the process of drug designing against M. tuberculosis and can be used in the development of potential therapeutics against drug-resistant strains of bacteria.
Thermodynamic and structural contributions of the 6-thioguanosine residue to helical properties of RNA
Authors: Gładysz Michał , Andrałojć Witold , Czapik Tomasz , Gdaniec Zofia , Kierzek Ryszard 
Published: March 2019

AbstractThionucleotides, especially 4-thiouridine and 6-thioguanosine, are photosensitive molecules that photocrosslink to both proteins and nucleic acids, and this feature is a major reason for their application in various investigations. To get insight into the thermodynamic and structural contributions of 6-thioguanosine to the properties of RNA duplexes a systematic study was performed. In a series of RNA duplexes, selected guanosine residues located in G-C base pairs, mismatches (G-G, G-U, and G-A), or 5′ and 3′-dangling ends were replaced with 6-thioguanosine. Generally, the presence of 6-thioguanosine diminishes the thermodynamic stability of RNA duplexes. This effect depends on its position within duplexes and the sequence of adjacent base pairs. However, when placed at a dangling end a 6-thioguanosine residue actually exerts a weak stabilizing effect. Furthermore, the structural effect of 6-thioguanosine substitution appears to be minimal based on NMR and Circular Dichroism (CD) data.
The contraceptive medroxyprogesterone acetate, unlike norethisterone, directly increases R5 HIV-1 infection in human cervical explant tissue at physiologically relevant concentrations
Authors: Ray Roslyn M. , Maritz Michelle F. , Avenant Chanel , Tomasicchio Michele , Dlamini Sigcinile , van der Spuy Zephne , Hapgood Janet P. 
Published: March 2019

AbstractThe intramuscular progestin-only injectable contraceptive, depo-medroxyprogesterone acetate (DMPA-IM), is more widely used in Sub-Saharan Africa than another injectable contraceptive, norethisterone enanthate (NET-EN). Epidemiological data show a significant 1.4-fold increased risk of HIV-1 acquisition for DMPA-IM usage, while no such association is shown from limited data for NET-EN. We show that MPA, unlike NET, significantly increases R5-tropic but not X4-tropic HIV-1 replication ex vivo in human endocervical and ectocervical explant tissue from pre-menopausal donors, at physiologically relevant doses. Results support a mechanism whereby MPA, unlike NET, acts via the glucocorticoid receptor (GR) to increase HIV-1 replication in cervical tissue by increasing the relative frequency of CD4+ T cells and activated monocytes. We show that MPA, unlike NET, increases mRNA expression of the CD4 HIV-1 receptor and CCR5 but not CXCR4 chemokine receptors, via the GR. However, increased density of CD4 on CD3+ cells was not observed with MPA by flow cytometry of digested tissue. Results suggest that DMPA-IM may increase HIV-1 acquisition in vivo at least in part via direct effects on cervical tissue to increase founder R5-tropic HIV-1 replication. Our findings support differential biological mechanisms and disaggregation of DMPA-IM and NET-EN regarding HIV-1 acquisition risk category for use in high risk areas.
Adverse effects of routine bovine health treatments containing triclabendazole and synthetic pyrethroids on the abundance of dipteran larvae in bovine faeces
Authors: Gilbert Gillian , MacGillivray Fiona S. , Robertson Helen L. , Jonsson Nicholas N. 
Published: March 2019

AbstractMacrocyclic lactone treatments for livestock can have detrimental effects on the arthropod populations in livestock faeces. For the last twenty years, avoidance of these products has been a standard recommendation on livestock farms that are managed for wildlife by the Royal Society for Protection of Birds (RSPB). However, the continued decline in the populations of birds (in particular the red-billed choughPyrrhocorax pyrrhocorax) that are dependent on dung invertebrates on islands in the Inner Hebrides of Scotland prompted us to investigate the effects of livestock treatments that are commonly used on these islands. We conducted a replicated field plot study over two years to quantify the effects of livestock treatments containing copper, deltamethrin and triclabendazole on invertebrate density in pooled, artificial faecal pats on the island of Islay. We found that the density of arthropod larvae was significantly reduced by the triclabendazole and deltamethrin treatments in both years and by as much as 86% when the treatments were combined. Copper-containing boluses did not consistently affect abundance of arthropod larvae. These results suggest that veterinary treatment of livestock might contribute to a reduction in the food supply of chough.
The influence of the host microbiome on 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperthermia and vice versa
Authors: Ridge Emily A. , Pachhain Sudhan , Choudhury Sayantan Roy , Bodnar Sara R. , Larsen Ray A. , Phuntumart Vipaporn , Sprague Jon E. 
Published: March 2019

AbstractHyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) can be life-threatening. Here, we investigate the role of the gut microbiome and TGR5 bile acid receptors in MDMA-mediated hyperthermia. Fourteen days prior to treatment with MDMA, male Sprague-Dawley rats were provided water or water treated with antibiotics. Animals that had received antibiotics displayed a reduction in gut bacteria and an attenuated hyperthermic response to MDMA. MDMA treated animals showed increased uncoupling protein 1 (UCP1) and TGR5 expression levels in brown adipose tissue and skeletal muscle while increased expression of UCP3 was observed only in skeletal muscle. Antibiotics prior to MDMA administration significantly blunted these increases in gene expression. Furthermore, inhibition of the TGR5 receptor with triamterene or of deiodinase II downstream of the TGR5 receptor with iopanoic acid also resulted in the attenuation of MDMA-induced hyperthermia. MDMA-treatment enriched the relative proportion of a Proteus mirabilis strain in the ceca of animals not pre-treated with antibiotics. These findings suggest a contributing role for the gut microbiota in MDMA-mediated hyperthermia and that MDMA treatment can trigger a rapid remodeling of the composition of the gut microbiome.
In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases
Authors: Shey Robert Adamu , Ghogomu Stephen Mbigha , Esoh Kevin Kum , Nebangwa Neba Derrick , Shintouo Cabirou Mounchili , Nongley Nkemngo Francis , Asa Bertha Fru , Ngale Ferdinand Njume , Vanhamme Luc , Souopgui Jacob 
Published: March 2019

AbstractOnchocerciasis is a parasitic disease with high socio-economic burden particularly in sub-Saharan Africa. The elimination plan for this disease has faced numerous challenges. A multi-epitope prophylactic/therapeutic vaccine targeting the infective L3 and microfilaria stages of the parasite’s life cycle would be invaluable to achieve the current elimination goal. There are several observations that make the possibility of developing a vaccine against this disease likely. For example, despite being exposed to high transmission rates of infection, 1 to 5% of people have no clinical manifestations of the disease and are thus considered as putatively immune individuals. An immuno-informatics approach was applied to design a filarial multi-epitope subunit vaccine peptide consisting of linear B-cell and T-cell epitopes of proteins reported to be potential novel vaccine candidates. Conservation of the selected proteins and predicted epitopes in other parasitic nematode species suggests that the generated chimera could be helpful for cross-protection. The 3D structure was predicted, refined, and validated using bioinformatics tools. Protein-protein docking of the chimeric vaccine peptide with the TLR4 protein predicted efficient binding. Immune simulation predicted significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-γ, and IL-2. Overall, the constructed recombinant putative peptide demonstrated antigenicity superior to current vaccine candidates.
Superior Electrochemical Performance of Thin-Film Thermoplastic Elastomer-Coated SnSb as an Anode for Li-ion Batteries
Authors: Tesfaye Alexander T. , Dumur Frédéric , Gigmes Didier , Maria Sébastien , Monconduit Laure , Djenizian Thierry 
Published: March 2019

AbstractThe high failure strain of thermoplastic elastomers (TPEs) is a very desirable feature for rechargeable Li-ion batteries by improving the lifetime of high specific capacity anode materials that undergo mechanical fractures induced by large volume variations. In this work, poly(styrene-b-2-hydroxyethyl acrylate) called PS-b-PHEA was synthesized by a nitroxide meditated polymerization method. Owing to the use of a specific polystyrene macroinitiator (SG1), a suitable TPE copolymer with long hydroxyethyl acrylate blocks to ensure good mechanical properties is obtained for the first time. We show that the electrochemical properties of the PS-b-PHEA-coated SnSb anode are drastically improved by suppressing the crack formation at the surface of the electrode. Indeed, electrochemical characterization revealed that a high and stable gravimetric capacity over 100 cycles could be achieved. Moreover, excellent capacity reversibility was achieved when cycled at multiple C-rates and fast kinetics confirming the strong protection role of the polymer. The advanced chemical and mechanical properties of PS-b-PHEA open up promising perspectives to significantly improve the electrochemical performance of all electrodes that are known to suffer from large volume variations.
PIP3-Phldb2 is crucial for LTP regulating synaptic NMDA and AMPA receptor density and PSD95 turnover
Authors: Xie Min-Jue , Ishikawa Yasuyuki , Yagi Hideshi , Iguchi Tokuichi , Oka Yuichiro , Kuroda Kazuki , Iwata Keiko , Kiyonari Hiroshi , Matsuda Shinji , Matsuzaki Hideo , Yuzaki Michisuke , Fukazawa Yugo , Sato Makoto 
Published: March 2019

AbstractThe essential involvement of phosphoinositides in synaptic plasticity is well-established, but incomplete knowledge of the downstream molecular entities prevents us from understanding their signalling cascades completely. Here, we determined that Phldb2, of which pleckstrin-homology domain is highly sensitive to PIP3, functions as a phosphoinositide-signalling mediator for synaptic plasticity. BDNF application caused Phldb2 recruitment toward postsynaptic membrane in dendritic spines, whereas PI3K inhibition resulted in its reduced accumulation. Phldb2 bound to postsynaptic scaffolding molecule PSD-95 and was crucial for localization and turnover of PSD-95 in the spine. Phldb2 also bound to GluA1 and GluA2. Phldb2 was indispensable for the interaction between NMDA receptors and CaMKII, and the synaptic density of AMPA receptors. Therefore, PIP3-responsive Phldb2 is pivotal for induction and maintenance of LTP. Memory formation was impaired in our Phldb2−/− mice.