bluuebunny/crossref_metadata_2025 huggingface dataset:
Taking shortcuts with OWL using safe macros
Authors: Mungall Christopher , Ruttenberg Alan , Osumi-Sutherland David
Published: July 2019

Accurate representation of complex domains such as biology demands powerful and expressive ontology languages such as OWL. However, the complex nested class expressions required for modeling can be a hindrance to ontology authoring and adoption. These class expressions can appear opaque to domain experts, and even users proficient in OWL can benefit from some kind of syntactic sugar or "short-cut"strategy, especially when authoring large ontologies.One solution is to have domain experts fill in simple templates (for example, in Excel) and translate the results into more complex axioms,but this has the disadvantage of being disconnected from full ontology authoring and reasoning environment.We present here a method of specifying shortcut properties directly in OWL. These shortcut properties can be used in similar ways as object properties within the OWL environment, with the resulting simple axioms translated automatically to more complex axioms via macro expansion. We describe some example scenarios where this is of use in authoring existing bio-ontologies.One of the main implications of this work is a way to simplify the translation between OBO format and OWL, and the use of RDF triple-stores with complex OWL ontologies.
Screening for the optimal siRNA targeting a novel gene (HA117) and construction and evaluation of a derivative recombinant adenovirus
Authors: Xu Youhua , Zheng Gaihuan , Guo Yuxia , Jin Xianqing , Luo Qing
Published: July 2019

We found a novel gene named as HA117 in our previous research. At this study, we screened for an optimal siRNA targeting the novel gene HA117 using the pSOS-HUS method, verified the results of pSOS-HUS siRNA screening for optimal affinity for the target gene, and constructed and evaluated a recombinant adenovirus carrying the DNA template for transcription of the optimal HA117 siRNA. The pSOS-HUS vector method was successfully utilized as a rapid and effective screen for an optimal siRNA for a target gene. Among five pairs of DNA templates, siRNA transcribed from HAi5 gave the strongest interference with the novel gene HA117; a HAi5-carrying recombinant adenovirus (Ad-HAi5) was successfully constructed and evaluated, laying a foundation for the further study of HA117 gene function with RNAi technology.
Photoprotection in Southern Ocean phytoplankton: missing key to low primary productivity
Authors: Griffith Gary , Vennell Ross
Published: July 2019

The Southern Ocean is considered a zone of high nutrients and low chlorophyll (HNLC). Despite the year round availability of nutrients, phytoplankton biomass remains low. Key modes of control are now thought to be light, grazing, iron and supply of silicic acid^1^. Physiological photoprotective mechanisms used by phytoplankton to regulate photosynthesis versus rapid light fluctuations have not been considered important. In diatoms and haptophytes, which are the major component of phytoplankton biodiversity in the Southern Ocean, the one step de-epoxidation of diadinoxanthin (Dd) into diatoxanthin (Dt) of the Dd-cycle constitutes the main photoprotective mechanism^2,3^. Here we show that Southern Ocean diatoms and haptophytes have higher concentrations of cellular Dd-cycle pigments than other oceanic regions. The Dd-cycle is activated under low irradiance conditions and the pool of photoprotective pigments increases under intermittent light conditions. The high cellular concentration of Dd-cycle pigments and our observations of an increase of the pool size of Dd-cycle pigments towards the surface implies that the Dd-cycle pigments bind to light harvesting proteins other than with fucoxanthin and chlorophyll c. Within photosystem II, enrichment of Dd and the physiological acclimation to light changes constrains photosynthetic activity, efficiency and potentially growth rates^3-7^. These results raise important questions about the role of photoprotective mechanisms in limiting Southern Ocean primary productivity and how these mechanisms will respond to predicted climate change impacts^8^.
Parallel genome assembly from pre-biotic split-genes: A solution for the mosaic genome conundrum
Authors: Senapathy Periannan , Kumar Brajendra , Mattox Jeffrey , Senapathy Sudar
Published: July 2019

The classical concept that all complex life evolved from a simple bacterium-like life form has been questioned by comparative genomics and proteomics. Several discoveries, including the occurrence of entirely new genes in unexpected life forms without any precursors, and the random mosaic distribution of genes across organisms in higher taxa undermine the principal assertions of this theory. We present a new model of the pre-biotic parallel evolution of eukaryotic genomes starting with the structurally complex split genes, which are far more probable of supporting biological information and of occurring in random DNA sequences than contiguous genes. By comparing the mosaic patterns of simulated genomes and extant genomes, we show that genomes arising from simulated assembly of random split genes form the same gene distribution patterns observed in extant eukaryotes. This parallel genome origin model eliminates the post-genomic and classical conundrums faced by the linear branching evolution model.
Miraculous Survival of Three Trapping Miners by Drinking High Mineral Mine Water for 25
Authors: Liang Cheng , Sheng Deng , Lin Wang , Mao Mu
Published: July 2019

Little is known that how long a human been can survive a complete starvation. There were dozens of miners who lost their lives in a coal mine disaster at Qinglong,Guizhou,China in June 2009, only three of them were rescued 25 days later after they had been trapped in a coal mine 600 meters underground. They maintained their lives only by drinking mineral water in the mine, which created a miracle of life. We reported here on this life miracle in relation to high mineral mine water.
Fish play Minority Game as humans do
Authors: Liaw Sy-Sang , Liu Ruey-Tarng , Chung Fei Fang
Published: July 2019

Previous computer simulations of the Minority Game (MG) have shown that the average agent number in the winning group (i.e., the minority group) had a maximal value such that the global gain was also maximal when an optimal amount of information was available to all agents . This property was further examined and its connection to financial markets has also been discussed . Here we report the results of an unprecedented real MG played by university staff members who clicked one of two identical buttons (A and B) on a computer screen while clocking in or out of work. We recorded the number of people who clicked button A for 1288 games, beginning on April 21, 2008 and ending on October 31, 2010, and calculated the variance among the people who clicked A as a function of time. We find that variance per person decreases to a minimum and rises to a value close to 1/4 which is the expected value when agents click buttons randomly. Our results are consistent with previous simulation results for the theoretical MG and suggest that our agents had employed more information for their strategies as their experience playing the game grew. We also carried out another experiment in which we forced 101 fish to enter one of the two symmetric chambers (A and B). We repeated the fish experiment 500 times and found that the variance of the number of fish that entered chamber A also decreased to a minimum and then increased to a saturated value, suggesting that fish have memory and can employ more strategies when facing the same situation again and again .
Shifting the balance of autophagy and proteasome activation reduces proteotoxic cell death: a novel therapeutic approach for restoring photoreceptor homeostasis
Authors: Qiu Yaoyan , Yao Jingyu , Jia Lin , Thompson Debra A. , Zacks David N.
Published: July 2019

The P23H variant of rhodopsin results in misfolding of the protein, and is a common cause of the blinding disease autosomal dominant retinitis pigmentosa (adRP). We have recently demonstrated that degeneration of photoreceptor cells in retinas of P23H mice is due to the endoplasmic reticulum stress (ERS)-induced activation of autophagy that leads to a secondary proteasome insufficiency and activation of cell death pathways. We propose that this increased level of autophagy flux relative to proteasome activity, which we term the A:P ratio, represents a marker of altered photoreceptor cell homeostasis, and that therapies aimed at normalizing this ratio will result in increased photoreceptor cell survival. To test this postulate, we treated P23H mice with a chemical chaperone (4-phenylbutyric acid) to improve rhodopsin folding, or with a selective phosphodiesterase-4 inhibitor (rolipram) to increase proteasome activity. P23H mice treated with either of these agents exhibited reduced ERS, decreased autophagy flux, increased proteasome activity, and decreased activation of cell death pathways. In addition, rates of retinal degeneration were decreased, and photoreceptor morphology and visual function were preserved. These findings support the conclusion that normalizing the A:P ratio, either by reducing the ERS-induced activation of autophagy, or by increasing proteasome activity, improves photoreceptor survival, and suggest a potential new therapeutic strategy for the treatment of adRP caused by protein folding defects.
Heterogeneous nuclear ribonucleoprotein L facilitates recruitment of 53BP1 and BRCA1 at the DNA break sites induced by oxaliplatin in colorectal cancer
Authors: Hu Wenjun , Lei Linping , Xie Xuqin , Huang Libin , Cui Qian , Dang Tang , Liu Gang Logan , Li Yuan , Sun Xiaofeng , Zhou Zongguang
Published: July 2019

Although oxaliplatin is an effective chemotherapeutic drug for treatment of colorectal cancer (CRC), tumor cells can develop mechanisms to evade oxaliplatin-induced cell death and show high tolerance and acquired resistance to this drug. Heterogeneous nuclear ribonucleoprotein L (hnRNP L) has been proved to play a critical role in DNA repair during IgH class switch recombination (CSR) in B lymphocytes, while, its role in CRC and chemotherapeutic resistance remain unknown. Our study aims to uncover an unidentified mechanism of regulating DNA double-strand breaks (DSBs) by hnRNP L in CRC cells treated by oxaliplatin. In present study, we observed that knockdown of hnRNP L enhanced the level of DNA breakage and sensitivity of CRC cells to oxaliplatin. The expression of key DNA repair factors (BRCA1, 53BP1, and ATM) was unaffected by hnRNP L knockdown, thereby excluding the likelihood of hnRNP L mediation via mRNA regulation. Moreover, we observed that phosphorylation level of ATM changed oppositely to 53BP1 and BRCA1 in the CRC cells (SW620 and HCT116) which exhibit synergistic effect by oxaliplatin plus hnRNP L impairment. And similar phenomenon was observed in the foci formation of these critical repair factors. We also found that hnRNP L binds directly with these DNA repair factors through its RNA-recognition motifs (RRMs). Analysis of cell death indicated that the RRMs of hnRNP L are required for cell survival under incubation with oxaliplatin. In conclusion, hnRNP L is critical for the recruitment of the DNA repair factors in oxaliplatin-induced DSBs. Targeting hnRNP L is a promising new clinical approach that could enhance the effectiveness of current chemotherapeutic treatment in patients with resistance to oxaliplatin.
MEG3-derived miR-493-5p overcomes the oncogenic feature of IGF2-miR-483 loss of imprinting in hepatic cancer cells
Authors: Gailhouste Luc , Liew Lee Chuen , Yasukawa Ken , Hatada Izuho , Tanaka Yasuhito , Kato Takashi , Nakagama Hitoshi , Ochiya Takahiro
Published: July 2019

Numerous studies have described the critical role played by microRNAs (miRNAs) in cancer progression and the potential of these small non-coding RNAs for diagnostic or therapeutic applications. However, the mechanisms responsible for the altered expression of miRNAs in malignant cells remain poorly understood. Herein, via epigenetic unmasking, we identified a group of miRNAs located in the imprinted delta like non-canonical Notch ligand 1 (DLK1)-maternally expressed 3 (MEG3) locus that were repressed in hepatic tumor cells. Notably, miR-493-5p epigenetic silencing was correlated with hypermethylation of the MEG3 differentially regulated region (DMR) in liver cancer cell lines and tumor tissues from patients. Experimental rescue of miR-493-5p promoted an anti-cancer response by hindering hepatocellular carcinoma (HCC) cell growth in vitro and tumor progression in vivo. We found that miR-493-5p mediated part of its tumor-suppressor activity by abrogating overexpression of insulin-like growth factor 2 (IGF2) and the IGF2-derived intronic oncomir miR-483-3p in HCC cells characterized by IGF2 loss of imprinting (LOI). In summary, this study describes an unknown miRNA-dependent regulatory mechanism between two distinct imprinted loci and a possible therapeutic window for liver cancer patients exhibiting IGF2-miR-483 LOI and amplification.
Fundamentals and applications of photocatalytic CO2 methanation
Authors: Ulmer Ulrich , Dingle Thomas , Duchesne Paul N. , Morris Robert H. , Tavasoli Alexandra , Wood Thomas , Ozin Geoffrey A.
Published: July 2019

The extraction and combustion of fossil natural gas, consisting primarily of methane, generates vast amounts of greenhouse gases that contribute to climate change. However, as a result of recent research efforts, “solar methane” can now be produced through the photocatalytic conversion of carbon dioxide and water to methane and oxygen. This approach could play an integral role in realizing a sustainable energy economy by closing the carbon cycle and enabling the efficient storage and transportation of intermittent solar energy within the chemical bonds of methane molecules. In this article, we explore the latest research and development activities involving the light-assisted conversion of carbon dioxide to methane.
Towards integrated tunable all-silicon free-electron light sources
Authors: Roques-Carmes Charles , Kooi Steven E. , Yang Yi , Massuda Aviram , Keathley Phillip D. , Zaidi Aun , Yang Yujia , Joannopoulos John D. , Berggren Karl K. , Kaminer Ido , Soljačić Marin
Published: July 2019

Extracting light from silicon is a longstanding challenge in modern engineering and physics. While silicon has underpinned the past 70 years of electronics advancement, a facile tunable and efficient silicon-based light source remains elusive. Here, we experimentally demonstrate the generation of tunable radiation from a one-dimensional, all-silicon nanograting. Light is generated by the spontaneous emission from the interaction of these nanogratings with low-energy free electrons (2–20 keV) and is recorded in the wavelength range of 800–1600 nm, which includes the silicon transparency window. Tunable free-electron-based light generation from nanoscale silicon gratings with efficiencies approaching those from metallic gratings is demonstrated. We theoretically investigate the feasibility of a scalable, compact, all-silicon tunable light source comprised of a silicon Field Emitter Array integrated with a silicon nanograting that emits at telecommunication wavelengths. Our results reveal the prospects of a CMOS-compatible electrically-pumped silicon light source for possible applications in the mid-infrared and telecommunication wavelengths.
Strong and selective isotope effect in the vacuum ultraviolet photodissociation branching ratios of carbon monoxide
Authors: Jiang Pan , Chi Xiaoping , Zhu Qihe , Cheng Min , Gao Hong
Published: July 2019

Rare isotope (13C, 17O and 18O) substitutions can substantially change absorption line positions, oscillator strengths and photodissociation rates of carbon monoxide (CO) in the vacuum ultraviolet (VUV) region, which has been well accounted for in recent photochemical models for understanding the large isotopic fractionation effects that are apparent in carbon and oxygen in the solar system and molecular clouds. Here, we demonstrate a strong isotope effect associated with the VUV photodissociation of CO by measuring the branching ratios of 12C16O and 13C16O in the Rydberg 4p(2), 5p(0) and 5s(0) complex region. The measurements show that the quantum yields of electronically excited C atoms in the photodissociation of 13C16O are dramatically different from those of 12C16O, revealing strong isotope effect. This isotope effect strongly depends on specific quantum states of CO being excited, which implies that such effect must be considered in the photochemical models on a state by state basis.
Reconstitution of recombinant human CCR4-NOT reveals molecular insights into regulated deadenylation
Authors: Raisch Tobias , Chang Chung-Te , Levdansky Yevgen , Muthukumar Sowndarya , Raunser Stefan , Valkov Eugene
Published: July 2019

CCR4-NOT is a conserved multiprotein complex which regulates eukaryotic gene expression principally via shortening of poly(A) tails of messenger RNA or deadenylation. Here, we reconstitute a complete, recombinant human CCR4-NOT complex. Our reconstitution strategy permits strict compositional control to test mechanistic hypotheses with purified component variants. CCR4-NOT is more active and selective for poly(A) than the isolated exonucleases, CCR4a and CAF1, which have distinct deadenylation profiles in vitro. The exonucleases require at least two out of three conserved non-enzymatic modules (CAF40, NOT10:NOT11 or NOT) for full activity in CCR4-NOT. CAF40 and the NOT10:NOT11 module both bind RNA directly and stimulate deadenylation in a partially redundant manner. Linear motifs from different RNA-binding factors that recruit CCR4-NOT to specific mRNAs via protein-protein interactions with CAF40 can inhibit bulk deadenylation. We reveal an additional layer of regulatory complexity to the human deadenylation machinery, which may prime it either for general or target-specific degradation.
Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets
Authors: Newell Felicity , Kong Yan , Wilmott James S. , Johansson Peter A. , Ferguson Peter M. , Cui Chuanliang , Li Zhongwu , Kazakoff Stephen H. , Burke Hazel , Dodds Tristan J. , Patch Ann-Marie , Nones Katia , Tembe Varsha , Shang Ping , van der Weyden Louise , Wong Kim , Holmes Oliver , Lo Serigne , Leonard Conrad , Wood Scott , Xu Qinying , Rawson Robert V. , Mukhopadhyay Pamela , Dummer Reinhard , Levesque Mitchell P. , Jönsson Göran , Wang Xuan , Yeh Iwei , Wu Hong , Joseph Nancy , Bastian Boris C. , Long Georgina V. , Spillane Andrew J. , Shannon Kerwin F. , Thompson John F. , Saw Robyn P. M. , Adams David J. , Si Lu , Pearson John V. , Hayward Nicholas K. , Waddell Nicola , Mann Graham J. , Guo Jun , Scolyer Richard A.
Published: July 2019

Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity of comprehensive mutation data on this rare tumor type. To better understand the genomic landscape of mucosal melanoma, here we describe whole genome sequencing analysis of 67 tumors and validation of driver gene mutations by exome sequencing of 45 tumors. Tumors have a low point mutation burden and high numbers of structural variants, including recurrent structural rearrangements targeting TERT, CDK4 and MDM2. Significantly mutated genes are NRAS, BRAF, NF1, KIT, SF3B1, TP53, SPRED1, ATRX, HLA-A and CHD8. SF3B1 mutations occur more commonly in female genital and anorectal melanomas and CTNNB1 mutations implicate a role for WNT signaling defects in the genesis of some mucosal melanomas. TERT aberrations and ATRX mutations are associated with alterations in telomere length. Mutation profiles of the majority of mucosal melanomas suggest potential susceptibility to CDK4/6 and/or MEK inhibitors.
Identifying surface reaction intermediates with photoemission tomography
Authors: Yang Xiaosheng , Egger Larissa , Hurdax Philipp , Kaser Hendrik , Lüftner Daniel , Bocquet François C. , Koller Georg , Gottwald Alexander , Tegeder Petra , Richter Mathias , Ramsey Michael G. , Puschnig Peter , Soubatch Serguei , Tautz F. Stefan
Published: July 2019

The determination of reaction pathways and the identification of reaction intermediates are key issues in chemistry. Surface reactions are particularly challenging, since many methods of analytical chemistry are inapplicable at surfaces. Recently, atomic force microscopy has been employed to identify surface reaction intermediates. While providing an excellent insight into the molecular backbone structure, atomic force microscopy is less conclusive about the molecular periphery, where adsorbates tend to react with the substrate. Here we show that photoemission tomography is extremely sensitive to the character of the frontier orbitals. Specifically, hydrogen abstraction at the molecular periphery is easily detected, and the precise nature of the reaction intermediates can be determined. This is illustrated with the thermally induced reaction of dibromo-bianthracene to graphene which is shown to proceed via a fully hydrogenated bisanthene intermediate. We anticipate that photoemission tomography will become a powerful companion to other techniques in the study of surface reaction pathways.
Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors
Authors: Jönsson Marie E , Ludvik Brattås Per , Gustafsson Charlotte , Petri Rebecca , Yudovich David , Pircs Karolina , Verschuere Shana , Madsen Sofia , Hansson Jenny , Larsson Jonas , Månsson Robert , Meissner Alexander , Jakobsson Johan
Published: July 2019

DNA methylation contributes to the maintenance of genomic integrity in somatic cells, in part through the silencing of transposable elements. In this study, we use CRISPR-Cas9 technology to delete DNMT1, the DNA methyltransferase key for DNA methylation maintenance, in human neural progenitor cells (hNPCs). We observe that inactivation of DNMT1 in hNPCs results in viable, proliferating cells despite a global loss of DNA CpG-methylation. DNA demethylation leads to specific transcriptional activation and chromatin remodeling of evolutionarily young, hominoid-specific LINE-1 elements (L1s), while older L1s and other classes of transposable elements remain silent. The activated L1s act as alternative promoters for many protein-coding genes involved in neuronal functions, revealing a hominoid-specific L1-based transcriptional network controlled by DNA methylation that influences neuronal protein-coding genes. Our results provide mechanistic insight into the role of DNA methylation in silencing transposable elements in somatic human cells, as well as further implicating L1s in human brain development and disease.
Author Correction: Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface
Authors: Tang HaoRan , Leung Leo , Saturno Grazia , Viros Amaya , Smith Duncan , Leva Gianpiero Di , Morrison Eamonn , Niculescu-Duvaz Dan , Lopes Filipa , Johnson Louise , Dhomen Nathalie , Springer Caroline , Marais Richard
Published: July 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Airway response to respiratory syncytial virus has incidental antibacterial effects
Authors: Sande Charles J. , Njunge James M. , Ngoi Joyce Mwongeli , Mutunga Martin N. , Chege Timothy , Gicheru Elijah T. , Gardiner Elizabeth M. , Gwela Agnes , Green Christopher A. , Drysdale Simon B. , Berkley James A. , Nokes D. James , Pollard Andrew J.
Published: July 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Signal integration and information transfer in an allosterically regulated network
Authors: Shockley Erin M. , Rouzer Carol A. , Marnett Lawrence J. , Deeds Eric J. , Lopez Carlos F.
Published: July 2019

A biological reaction network may serve multiple purposes, processing more than one input and impacting downstream processes via more than one output. These networks operate in a dynamic cellular environment in which the levels of network components may change within cells and across cells. Recent evidence suggests that protein concentration variability could explain cell fate decisions. However, systems with multiple inputs, multiple outputs, and changing input concentrations have not been studied in detail due to their complexity. Here, we take a systems biochemistry approach, combining physiochemical modeling and information theory, to investigate how cyclooxygenase-2 (COX-2) processes simultaneous input signals within a complex interaction network. We find that changes in input levels affect the amount of information transmitted by the network, as does the correlation between those inputs. This, and the allosteric regulation of COX-2 by its substrates, allows it to act as a signal integrator that is most sensitive to changes in relative input levels.
Simulation of heterosis in a genome-scale metabolic network provides mechanistic explanations for increased biomass production rates in hybrid plants
Authors: Vacher Michael , Small Ian
Published: July 2019

Heterosis, or hybrid vigour, is said to occur when F1 individuals exhibit increased performance for a number of traits compared to their parental lines. Improved traits can include increased size, better yield, faster development and a higher tolerance to pathogens or adverse conditions. The molecular basis for the phenomenon remains disputed, despite many decades of theorising and experimentation. In this study, we add a genetics layer to a constraint-based model of plant (Arabidopsis) primary metabolism and show that we can realistically reproduce and quantify heterosis in a highly complex trait (the rate of biomass production). The results demonstrate that additive effects coupled to the complex patterns of epistasis generated by a large metabolic network are sufficient to explain most or all the heterosis seen in typical F1 hybrids. Such models provide a simple approach to exploring and understanding heterosis and should assist in designing breeding strategies to exploit this phenomenon in the future.
Transcriptome analysis and codominant markers development in caper, a drought tolerant orphan crop with medicinal value
Authors: Mercati Francesco , Fontana Ignazio , Gristina Alessandro Silvestre , Martorana Adriana , El Nagar Mahran , De Michele Roberto , Fici Silvio , Carimi Francesco
Published: July 2019

Caper (Capparis spinosa L.) is a xerophytic shrub cultivated for its flower buds and fruits, used as food and for their medicinal properties. Breeding programs and even proper taxonomic classification of the genus Capparis has been hampered so far by the lack of reliable genetic information and molecular markers. Here, we present the first genomic resource for C. spinosa, generated by transcriptomic approach and de novo assembly. The sequencing effort produced nearly 80 million clean reads assembled into 124,723 unitranscripts. Careful annotation and comparison with public databases revealed homologs to genes with a key role in important metabolic pathways linked to abiotic stress tolerance and bio-compounds production, such purine, thiamine and phenylpropanoid biosynthesis, α-linolenic acid and lipid metabolism. Additionally, a panel of genes involved in stomatal development/distribution and encoding for Stress Associated Proteins (SAPs) was also identified. We also used the transcriptomic data to uncover novel molecular markers for caper. Out of 50 SSRs tested, 14 proved polymorphic and represent the first set of SSR markers for the genus Capparis. This transcriptome will be an important contribution to future studies and breeding programs for this orphan crop, aiding to the development of improved varieties to sustain agriculture in arid conditions.
Host specificity drives genetic structure in a freshwater mussel
Authors: Wacker Sebastian , Larsen Bjørn Mejdell , Karlsson Sten , Hindar Kjetil
Published: July 2019

Parasites often depend on their hosts for long distance transport, and genetic population structure can be strongly affected by host specificity and dispersal. Freshwater pearl mussel (Margaritifera margaritifera) populations have previously been found to naturally infest either primarily Atlantic salmon (‘salmon-mussel’) or exclusively brown trout (‘trout-mussel’) across a wide geographic range. Here, we experimentally test whether this intraspecific variation in natural infestation can be explained by host specificity in freshwater pearl mussel. Our experiments show that when both host species were exposed to larvae from salmon- and trout-mussel respectively, salmon-mussel larvae almost never infested brown trout and vice versa. This suggests that host specificity can explain variation in natural infestation among the studied freshwater pearl mussel populations. Host specificity provides a link to the species’ variable population genetic structure, as mussel populations limited to Atlantic salmon, the host with stronger dispersal, show higher genetic diversity and weaker differentiation than populations limited to brown trout as host.
Insufficient evidence for BMAA transfer in the pelagic and benthic food webs in the Baltic Sea
Authors: Zguna Nadezda , Karlson Agnes M. L. , Ilag Leopold L. , Garbaras Andrius , Gorokhova Elena
Published: July 2019

The evidence regarding BMAA occurrence in the Baltic Sea is contradictory, with benthic sources appearing to be more important than pelagic ones. The latter is counterintuitive considering that the identified sources of this compound in the food webs are pelagic primary producers, such as diatoms, dinoflagellates, and cyanobacteria. To elucidate BMAA distribution, we analyzed BMAA in the pelagic and benthic food webs in the Northern Baltic Proper. As potential sources, phytoplankton communities were used. Pelagic food chain was represented by zooplankton, mysids and zooplanktivorous fish, whereas benthic invertebrates and benthivorous fish comprised the benthic chain. The trophic structure of the system was confirmed by stable isotope analysis. Contrary to the reported ubiquitous occurrence of BMAA in the Baltic food webs, only phytoplankton, zooplankton and mysids tested positive, whereas no measurable levels of this compound occurred in the benthic invertebrates and any of the tested fish species. These findings do not support the widely assumed occurrence and transfer of BMAA to the top consumers in the Baltic food webs. More controlled experiments and field observations are needed to understand the transfer and possible transformation of BMAA in the food web under various environmental settings.
Ferromagnetic-like behavior of Bi0.9La0.1FeO3–KBr nanocomposites
Authors: Karpinsky Dmitry V. , Fesenko Olena M. , Silibin Maxim V. , Dubkov Sergei V. , Chaika Mykola , Yaremkevich Andrii , Lukowiak Anna , Gerasymchuk Yuri , Stręk Wiesław , Pakalniškis Andrius , Skaudzius Ramunas , Kareiva Aivaras , Fomichov Yevhen M. , Shvartsman Vladimir V. , Kalinin Sergei V. , Morozovsky Nicholas V. , Morozovska Anna N.
Published: July 2019

We studied magnetostatic response of the Bi0.9La0.1FeO3– KBr composites (BLFO-KBr) consisting of nanosized (≈100 nm) ferrite Bi0.9La0.1FeO3(BLFO) conjugated with fine grinded ionic conducting KBr. When the fraction of KBr is rather small (less than 15 wt%) the magnetic response of the composite is very weak and similar to that observed for the BLFO (pure KBr matrix without Bi1-xLaxFeO3has no magnetic response as anticipated). However, when the fraction of KBr increases above 15%, the magnetic response of the composite changes substantially and the field dependence of magnetization reveals ferromagnetic-like hysteresis loop with a remanent magnetization about 0.14 emu/g and coercive field about 1.8 Tesla (at room temperature). Nothing similar to the ferromagnetic-like hysteresis loop can be observed in Bi1-zLazFeO3ceramics with z ≤ 0.15, which magnetization quasi-linearly increases with magnetic field. Different physical mechanisms were considered to explain the unusual experimental results for BLFO-KBr nanocomposites, but only those among them, which are highly sensitive to the interaction of antiferromagnetic Bi0.9La0.1FeO3with ionic conductor KBr, can be relevant.
Role of intravenous immunoglobulin therapy in the survival rate of pediatric patients with acute myocarditis: A systematic review and meta-analysis
Authors: Yen Chun-Yu , Hung Miao-Chiu , Wong Ying-Chi , Chang Chia-Yuan , Lai Chou-Cheng , Wu Keh-Gong
Published: July 2019

The treatment of pediatric myocarditis is controversial, and the benefits of intravenous immunoglobulin (IVIG) are inconclusive due to limited data. We searched studies from PubMed, MEDLINE, Embase, and Cochrane Library databases since establishment until October 1st, 2018. Thirteen studies met the inclusion criteria. We included a total of 812 patients with IVIG treatment and 592 patients without IVIG treatment. The meta-analysis showed that the survival rate in the IVIG group was higher than that in the non-IVIG group (odds ratio = 2.133, 95% confidence interval (CI): 1.32–3.43, p = 0.002). There was moderate statistical heterogeneity among the included studies (I2 = 35%, p = 0.102). However, after adjustment using Duval and Tweedie’s trim and fill method, the point estimate of the overall effect size was 1.40 (95% CI 0.83, 2.35), which became insignificant. Moreover, the meta-regression revealed that age (coefficient = −0.191, 95% CI (−0.398, 0.015), p = 0.069) and gender (coefficient = 0.347, 95% CI (−7.586, 8.279), p = 0.93) were not significantly related to the survival rate. This meta-analysis showed that IVIG treatment was not associated with better survival. The use of IVIG therapy in acute myocarditis in children cannot be routinely recommended based on current evidence. Further prospective and randomized controlled studies are needed to elucidate the effects of IVIG treatment.
Systematic Review of Somatic Mutations in Splenic Marginal Zone Lymphoma
Authors: Jaramillo Oquendo Carolina , Parker Helen , Oscier David , Ennis Sarah , Gibson Jane , Strefford Jonathan C.
Published: July 2019

The aims of this systematic review are to refine the catalogue of somatic variants in splenic marginal zone lymphoma (SMZL) and to provide a well-annotated, manually curated database of high-confidence somatic mutations to facilitate variant interpretation for further biological studies and future clinical implementation. Two independent reviewers systematically searched PubMed and Ovid in January 2019 and included studies that sequenced SMZL cases with confirmed diagnosis. The database included fourteen studies, comprising 2817 variants in over 1000 genes from 475 cases. We confirmed the high prevalence of NOTCH2, KLF2 and TP53 mutations and analysis of targeted genes further implicated TNFAIP3, KMT2D, and TRAF3 as recurrent targets of somatic mutation based on their high incidence across studies. The major limitations we encountered were the low number of patients with whole-genome, unbiased analysis and the relative sensitivities of differing sequencing approaches. Overall, we showed that there is little concordance between whole exome sequencing studies of SMZL. We strongly support the continuing unbiased analysis of the SMZL genome for mutations in all protein-coding genes and provide a valuable database resource to facilitate this endeavour that will ultimately improve our understanding of SMZL pathobiology.
Emergence of hierarchical organization in memory for random material
Authors: Naim Michelangelo , Katkov Mikhail , Recanatesi Stefano , Tsodyks Misha
Published: July 2019

Structured information is easier to remember and recall than random one. In real life, information exhibits multi-level hierarchical organization, such as clauses, sentences, episodes and narratives in language. Here we show that multi-level grouping emerges even when participants perform memory recall experiments with random sets of words. To quantitatively probe brain mechanisms involved in memory structuring, we consider an experimental protocol where participants perform ‘final free recall’ (FFR) of several random lists of words each of which was first presented and recalled individually. We observe a hierarchy of grouping organizations of FFR, most notably many participants sequentially recalled relatively long chunks of words from each list before recalling words from another list. Moreover, participants who exhibited strongest organization during FFR achieved highest levels of performance. Based on these results, we develop a hierarchical model of memory recall that is broadly compatible with our findings. Our study shows how highly controlled memory experiments with random and meaningless material, when combined with simple models, can be used to quantitatively probe the way meaningful information can efficiently be organized and processed in the brain.
Interleukin-12 and -23 blockade mitigates elastase-induced abdominal aortic aneurysm
Authors: Yan Huimin , Hu Ying , Akk Antonina , Ye Karen , Bacon John , Pham Christine T. N.
Published: July 2019

Macrophages play an important role in the inflammatory process that contributes to the development of abdominal aortic aneurysm (AAA). Studies of human and mouse AAA tissue reveal expanded populations of macrophages producing an abundance of pro-inflammatory cytokines, including TNF-α, IL-12p40 and high level of metalloprotease 9 (MMP-9) at the late stages of disease. Herein, we show that blockade of IL-12p40 in the early phase of aneurysm development suppresses macrophage expansion, inflammatory cytokine and MMP-9 production and mitigates AAA development. Since IL-12 and IL-23 are related cytokines that share the common p40 subunit, we also evaluate the effect of direct IL-23 blockade on the development of AAA. Specific IL-23p19 blockade prevents AAA progression with the same efficiency as IL-12p40 antagonism, suggesting that the efficacy of anti-IL-12p40 treatment may reflect IL-23 blockade. IL-12p40 and IL-23p19 are also abundantly expressed in human AAA tissue. Our findings have potential translational value since IL-12p40 and IL-23p19 antagonists already exist as FDA-approved therapeutics for various chronic inflammatory conditions.
Differential responses of the soil microbial community in two pitaya orchards with different mulch types
Authors: Luo Juan , Xu Min , Qi Zhao , Xiong Rui , Cheng Yu , Liu Chengli , Wei Shuangshuang , Tang Hua
Published: July 2019

To prevent plants from being damaged due to extreme temperature and sunlight, the pitaya orchards in Hainan Province, China, are increasingly adopting living and black fabric cloth mulching. In this study, an Illumina Hiseq sequencer was employed to compare the soil microbial communities of two pitaya orchards, one covered by living mulching (LM) and the other covered by black fabric cloth (FC). Bacterial abundance was higher in the LM orchard than in the FC orchard (1.19 × 104versus 4.49 × 104 g−1 soil). In contrast, fungal abundance was higher in the FC orchard than in the LM orchard (2.71 × 106versus 2.97 × 105 g−1 soil). We also found that the most dominant species in the FC orchard were from the genus Neoscytalidium, which included species that could cause infection in a large variety of plant hosts. However, the LM orchard mainly harbored useful fungal species, such as Trichoderma and Chaetomium. Soil nutrients were positively correlated in the FC orchard, which potentially indicated that the FC orchard could demonstrate better fertilizer utilization efficiency. However, the LM and FC strategies have both advantages and disadvantages with regards to the cultivation management of pitaya orchards.
Discovering Links Between Side Effects and Drugs Using a Diffusion Based Method
Authors: Timilsina Mohan , Tandan Meera , d’Aquin Mathieu , Yang Haixuan
Published: July 2019

Identifying the unintended effects of drugs (side effects) is a very important issue in pharmacological studies. The laboratory verification of associations between drugs and side effects requires costly, time-intensive research. Thus, an approach to predicting drug side effects based on known side effects, using a computational model, is highly desirable. To provide such a model, we used openly available data resources to model drugs and side effects as a bipartite graph. The drug-drug network is constructed using the word2vec model where the edges between drugs represent the semantic similarity between them. We integrated the bipartite graph and the semantic similarity graph using a matrix factorization method and a diffusion based model. Our results show the effectiveness of this integration by computing weighted (i.e., ranked) predictions of initially unknown links between side effects and drugs.
The transporters SLC35A1 and SLC30A1 play opposite roles in cell survival upon VSV virus infection
Authors: Moskovskich Anna , Goldmann Ulrich , Kartnig Felix , Lindinger Sabrina , Konecka Justyna , Fiume Giuseppe , Girardi Enrico , Superti-Furga Giulio
Published: July 2019

Host factor requirements for different classes of viruses have not been fully unraveled. Replication of the viral genome and synthesis of viral proteins within the human host cell are associated with an increased demand for nutrients and specific metabolites. With more than 400 acknowledged members to date in humans, solute carriers (SLCs) represent the largest family of transmembrane proteins dedicated to the transport of ions and small molecules such as amino acids, sugars and nucleotides. Consistent with their impact on cellular metabolism, several SLCs have been implicated as host factors affecting the viral life cycle and the cellular response to infection. In this study, we aimed at characterizing the role of host SLCs in cell survival upon viral infection by performing unbiased genetic screens using a focused CRISPR knockout library. Genetic screens with the cytolytic vesicular stomatitis virus (VSV) showed that the loss of two SLCs genes, encoding the sialic acid transporter SLC35A1/CST and the zinc transporter SLC30A1/ZnT1, affected cell survival upon infection. Further characterization of these genes suggests a role for both of these transporters in the apoptotic response induced by VSV, offering new insights into the cellular response to oncolytic virus infections.
An investigation into the diagnostic accuracy, reliability, acceptability and safety of a novel device for Continuous Ambulatory Vestibular Assessment (CAVA)
Authors: Phillips John S. , Newman Jacob L. , Cox Stephen J.
Published: July 2019

Dizziness is a common condition that is responsible for a significant degree of material morbidity and burden on health services. It is usually episodic and short-lived, so when a patient presents to their clinician, examination is normal. The CAVA (Continuous Ambulatory Vestibular Assessment) device has been developed to provide continuous monitoring of eye-movements, allowing insight into the physiological parameters present during a dizziness attack. This article describes the first clinical investigation into the medical and technical aspects of this new diagnostic system. Seventeen healthy subjects wore the device near continuously for up to thirty days, artificially inducing nystagmus on eight occasions. 405 days’ worth of data was captured, comprising around four billion data points. A computer algorithm developed to detect nystagmus demonstrated a sensitivity of 99.1% (95% CI: 95.13% to 99.98%) and a specificity of 98.6% (95% CI: 96.54% to 99.63%). Eighty-two percent of participants wore the device for a minimum of eighty percent of each day. Adverse events were self-limiting and mostly the consequence of skin stripping from the daily replacement of the electrodes. The device was shown to operate effectively as an ambulatory monitor, allowing the reliable detection of artificially induced nystagmus.
Both left upper lobectomy and left pneumonectomy are risk factors for postoperative stroke
Authors: Xie Nanchang , Meng Xianghe , Wu Chuanjie , Lian Yajun , Wang Cui , Yu Mengyan , Li Yingjiao , Wang Yali
Published: July 2019

Retrospective studies have found that left upper lobectomy (LUL) may be a new risk factor for stroke, and the potential mechanism is pulmonary vein thrombosis, which more likely develops in the left superior pulmonary vein (LSPV) stump. The LSPV remaining after left pneumonectomy is similar to that remaining after LUL. However, the association between left pneumonectomy, LUL, and postoperative stroke remains unclear. Thus, we sought to analyze whether both LUL and left pneumonectomy are risk factors for postoperative stroke. We prospectively included consecutive patients who underwent resection between November 2016 and March 2018 at our institution with 6 months of follow-up. Baseline demographic and clinical data were taken. A logistic regression model was used to determine independent predictors of postoperative stroke. In our study, 756 patients who underwent an isolated pulmonary lobectomy procedure were screened; of these, 637 patients who completed the 6-month follow-up were included in the analysis. Multivariable logistic regression analysis adjusted for common risk factors showed that the LUL and left pneumonectomy were independent predictors of stroke (odds ratio, 18.12; 95% confidence interval, 2.12–155.24; P = 0.008). Moreover, diabetes mellitus also was a predictor of postoperative stroke. In conclusion, both LUL and left pneumonectomy are significant risk factors for postoperative stroke.
Bedside-measurement of serum cholinesterase activity predicts patient morbidity and length of the intensive care unit stay following major traumatic injury
Authors: Zivkovic Aleksandar R. , Schmidt Karsten , Stein Thomas , Münzberg Matthias , Brenner Thorsten , Weigand Markus A. , Kleinschmidt Stefan , Hofer Stefan
Published: July 2019

Major traumatic injury (MTI), a life-threatening condition requiring prompt medical intervention, is associated with an extensive inflammatory response often resulting in multiple organ dysfunction. Early stratification of trauma severity and the corresponding inflammation may help optimize resources at the intensive care unit (ICU). The cholinergic system counters inflammation by quickly modulating the immune response. Serum cholinesterase (butyrylcholinesterase, BChE) is an enzyme that hydrolyses acetylcholine. We tested whether a change in the BChE activity correlates with the morbidity and the length of ICU stay. Blood samples from 10 healthy volunteers and 44 patients with MTI were gathered at hospital admission, followed by measurements 12, 24 and 48 hours later. Point-of-care approach was used to determine the BChE activity. Disease severity was assessed by clinical scoring performed within 24 hours following hospital admission. BChE activity, measured at hospital admission, showed a significant and sustained reduction and correlated with disease severity scores obtained 24 hours following admission. BChE activity, obtained at hospital admission, correlated with the length of ICU stay. Bedside measurement of BChE activity, as a complementary addition to established procedures, might prove useful in the primary assessment of the disease severity and might therefore optimize therapy in the ICU.
A Short Personal History of Micronuclei
Authors: Heddle John
Published: July 2019

A personal journey through micronucleus assays is described, including some new information. An important comment is made that the micronucleus assay is of greater validity than the cancer bioassay. Specifically, the cancer bioassay is internally inconsistent and can be misinterpreted statistically (a point that has been made by others). No assay in genetic toxicology can succeed when judged against the imperfect cancer bioassay.