bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of TRIF-mediated innate immune response by K27-linked polyubiquitination and deubiquitination
Authors: Wu Xin , Lei Caoqi , Xia Tian , Zhong Xuan , Yang Qing , Shu Hong-Bing 
Published: September 2019

AbstractTIR domain-containing adaptor inducing interferon-β (TRIF) is an essential adaptor protein required for innate immune responses mediated by Toll-like receptor (TLR) 3- and TLR4. Here we identify USP19 as a negative regulator of TLR3/4-mediated signaling. USP19 deficiency increases the production of type I interferons (IFN) and proinflammatory cytokines induced by poly(I:C) or LPS in vitro and in vivo. Usp19-/- mice have more serious inflammation after poly(I:C) or LPS treatment, and are more susceptible to inflammatory damages and death following Salmonella typhimurium infection. Mechanistically, USP19 interacts with TRIF and catalyzes the removal of TRIF K27-linked polyubiquitin moieties, thereby impairing the recruitment of TRIF to TLR3/4. In addition, the RING E3 ubiquitin ligase complex Cullin-3-Rbx1-KCTD10 catalyzes K27-linked polyubiquitination of TRIF at K523, and deficiency of this complex inhibits TLR3/4-mediated innate immune signaling. Our findings thus reveal TRIF K27-linked polyubiquitination and deubiquitination as a critical regulatory mechanism of TLR3/4-mediated innate immune responses.
Effects of T-2 toxin on digestive enzyme activity, intestinal histopathology and growth in shrimp Litopenaeus vannamei
Authors: Huang Zhanrui , Wang Yaling , Qiu Mei , Sun Lijun , Deng Yijia , Wang Xiaobo , Bi Siyuan , Gooneratne Ravi , Zhao Jian 
Published: September 2019

AbstractT-2 toxin (T-2), a naturally occurring mycotoxin that often accumulates in aquatic animals via contaminated feed, is toxic to animals, including humans. In this study, six groups of shrimp (n = 30 shrimps/group) were given T-2 in feed at concentrations of 0–12.2 mg/kg for 20 days. T-2 accumulation, intestinal histopathology, digestive enzyme activities and subsequent effects on shrimp are reported. Compared to the control, T-2 significantly reduced weight gain, specific growth rate, and survival. The histopathology of shrimp intestine showed concentration-dependent degenerative and necrotic changes in response to dietary T-2. Progressive damage to the microstructures of shrimp intestine occurred with increasing dietary T-2 concentrations, with initial inflammation of the mucosal tissue at T-2 concentrations of 0.5 and 1.2 mg/kg, progressing to disappearance of intestinal villi and degeneration and necrosis of the submucosa at 12.2 mg/kg. Intestinal amylase and protease activities increased at low T-2 concentrations but showed significant inhibition at high concentrations; however, the opposite trend occurred for lipase activity. Collectively, these results indicate that digestive enzyme activities and mucosal structures are markedly affected by exposure to T-2, and these may have contributed to the lower survival rate of shrimp.
The interconnected wealth of nations: Shock propagation on global trade-investment multiplex networks
Authors: Starnini Michele , Boguñá Marián , Serrano M. Ángeles 
Published: September 2019

AbstractThe increasing integration of world economies, which organize in complex multilayer networks of interactions, is one of the critical factors for the global propagation of economic crises. We adopt the network science approach to quantify shock propagation on the global trade-investment multiplex network. To this aim, we propose a model that couples a spreading dynamics, describing how economic distress propagates between connected countries, with an internal contagion mechanism, describing the spreading of such economic distress within a given country. At the local level, we find that the interplay between trade and financial interactions influences the vulnerabilities of countries to shocks. At the large scale, we find a simple linear relation between the relative magnitude of a shock in a country and its global impact on the whole economic system, albeit the strength of internal contagion is country-dependent and the inter-country propagation dynamics is non-linear. Interestingly, this systemic impact can be associated to intra-layer and inter-layer scale factors that we name network multipliers, that are independent of the magnitude of the initial shock. Our model sets-up a quantitative framework to stress-test the robustness of individual countries and of the world economy.
csDMA: an improved bioinformatics tool for identifying DNA 6 mA modifications via Chou’s 5-step rule
Authors: Liu Ze , Dong Wei , Jiang Wei , He Zili 
Published: September 2019

AbstractDNA N6-methyldeoxyadenosine (6 mA) modifications were first found more than 60 years ago but were thought to be only widespread in prokaryotes and unicellular eukaryotes. With the development of high-throughput sequencing technology, 6 mA modifications were found in different multicellular eukaryotes by using experimental methods. However, the experimental methods were time-consuming and costly, which makes it is very necessary to develop computational methods instead. In this study, a machine learning-based prediction tool, named csDMA, was developed for predicting 6 mA modifications. Firstly, three feature encoding schemes, Motif, Kmer, and Binary, were used to generate the feature matrix. Secondly, different algorithms were selected into the prediction model and the ExtraTrees model received the best AUC of 0.878 by using 5-fold cross-validation on the training dataset. Besides, the ExtraTrees model also received the best AUC of 0.893 on the independent testing dataset. Finally, we compared our method with state-of-the-art predictors and the results shown that our model achieved better performance than existing tools.
Prion protein modulates endothelial to mesenchyme-like transition in trabecular meshwork cells: Implications for primary open angle glaucoma
Authors: Ashok Ajay , Kang Min H. , Wise Aaron S. , Pattabiraman P. , Johnson William M. , Lonigro Michael , Ravikumar Ranjana , Rhee Douglas J. , Singh Neena 
Published: September 2019

AbstractEndothelial-to-mesenchyme-like transition (Endo-MT) of trabecular meshwork (TM) cells is known to be associated with primary open angle glaucoma (POAG). Here, we investigated whether the prion protein (PrPC), a neuronal protein known to modulate epithelial-to-mesenchymal transition in a variety of cell types, is expressed in the TM, and plays a similar role at this site. Using a combination of primary human TM cells and human, bovine, and PrP-knock-out (PrP−/−) mouse models, we demonstrate that PrPC is expressed in the TM of all three species, including endothelial cells lining the Schlemm’s canal. Silencing of PrPC in primary human TM cells induces aggregation of β1-integrin and upregulation of α-smooth muscle actin, fibronectin, collagen 1A, vimentin, and laminin, suggestive of transition to a mesenchyme-like phenotype. Remarkably, intraocular pressure is significantly elevated in PrP−/− mice relative to wild-type controls, suggesting reduced pliability of the extracellular matrix and increased resistance to aqueous outflow in the absence of PrPC. Since PrPC is cleaved by members of the disintegrin and matrix-metalloprotease family that are increased in the aqueous humor of POAG arising from a variety of conditions, it is likely that concomitant cleavage of PrPC exaggerates and confounds the pathology by inducing Endo-MT-like changes in the TM.
Spatio-temporal expression of ANK2 promotes cytokinesis in oocytes
Authors: Tetkova Anna , Jansova Denisa , Susor Andrej 
Published: September 2019

AbstractIn the absence of transcription, the regulation of gene expression in oocytes is controlled almost exclusively at the level of transcriptome and proteome stabilization, and translation. A subset of maternal transcripts is stored in a translationally dormant state in the oocyte, and temporally driven translation of specific mRNAs propel meiotic progression, oocyte-to-embryo transition and early embryo development. We identified Ank2.3 as the only transcript variant present in the mouse oocyte and discovered that it is translated after nuclear envelope breakdown. Here we show that Ank2.3 mRNA is localized in higher concentration in the oocyte nucleoplasm and, after nuclear envelope breakdown, in the newly forming spindle where its translation occurs. Furthermore, we reveal that Ank2.3 mRNA contains an oligo-pyrimidine motif at 5′UTR that predetermines its translation through a cap-dependent pathway. Lastly, we show that prevention of ANK2 translation leads to abnormalities in oocyte cytokinesis.
Using Atomic Force Microscopy to Measure Thickness of Passive Film on Stainless Steel Immersed in Aqueous Solution
Authors: Wang Rongguang , Li Yunhui , Xiao Tian , Cong Li , Ling Yunhan , Lu Zhaoxia , Fukushima Chiharu , Tsuchitori Isao , Bazzaoui Mohammed 
Published: September 2019

AbstractEmploying atomic force microscopy (AFM) to measure passive film thickness on stainless steel (SS) in aqueous solution is proposed. SUS304 austenite and SUS329J4L duplex SS samples partly covered by gold were set in a minicell. To remove the original film, the SS surface but gold was etched using dilute sulfuric acid. After cleaning, open circuit potential (OCP), and distance from the sample surface to the top of the gold were measured. They were then immersed in either 1.0% NaCl; 5.0% NaCl; or aqueous solution with pH ranging from 1.0 to 10.0 and measured again. Differences between the first and subsequent measures of OCP suggested a passive film had formed in solution with pH ranging from 2.8 to 10.0. Similarly, differences among AFM measures revealed the observed film thickness increased with increase in pH and with decrease in chloride ions. Also, film thickness in water was greater than that in a vacuum. Comparison of AFM measurements of passive film on the austenite and sigma phases in sensitized SUS329J4L duplex SS revealed the film was thinner on the sigma phase containing more chromium. Taken together, these findings suggest the proposed method is applicable for measuring the thickness of passive films in aqueous solution.
On the escape from potentials with two exit channels
Authors: Navarro Juan F. 
Published: September 2019

AbstractThe aim of this paper is to investigate the escape dynamics in a Hamiltonian system describing the motion of stars in a galaxy with two exit channels through the analysis of the successive intersections of the stable and unstable manifolds to the main unstable periodic orbits with an adequate surface of section. We describe in detail the origin of the spirals shapes of the windows through which stars escape.
Systems pharmacology-based approach for dissecting the mechanisms of pyrazine components in Maotai liquor
Authors: Zhou Wei , Chen Ziyi , Zhang Guohao , Liu Zhigang 
Published: September 2019

Abstract
Maotai liquor is a typical representative of sauce aroma-style flavor liquors and has been considered to be a precious cultural heritage of the oriental spirit culture. Aroma components are largely responsible for the characteristic aroma of liquor. Pyrazine compound is one of the most important categories of aroma components that affect the flavor of Maotai liquor. However, limited information is available regarding the systemic analysis of pyrazine compounds, especially the pharmacological effects of bioactive pyrazine components. Therefore, in the current study, a systemic analysis approach was provided by integrating absorption, distribution, metabolism, and excretion (ADME) screening, target identification, pharmacological evaluation and pathway analysis to explore the pharmacological mechanism of pyrazine compounds in Maotai liquor. As a result, 17 pyrazine components with adequate pharmacokinetic properties were filtered out using ADME models. Thirty eight potential targets of these active compounds were identified through target prediction. The pharmacological evaluation was proposed to uncover the pharmacological effect of pyrazine compounds in Maotai liquor from the holistic perspective. Finally, the pharmacological effects of the pathways perturbed by potential targets were interpreted based on the pathway analysis. Our study lays the foundation for formulating a comprehensive understanding of the pyrazine compounds in Maotai liquor, which would contribute to the development of Chinese liquor.
Trockene altersabhängige Makuladegeneration – Epidemiologie und Klassifikation
Authors: Fleckenstein Monika , Thiele Sarah , Pfau Maximilian , Schmitz-Valckenberg Steffen , Holz Frank G. 
Published: September 2019

ZusammenfassungKlinisch wird die altersabhängige Makuladegeneration (AMD) in Früh- und Spätstadien eingeteilt. Der Begriff „trockene“ AMD wird häufig verwendet, wenn keine „exsudativen“ Veränderungen am Augenhintergrund vorliegen. Es existiert eine Vielzahl von Studien zur Epidemiologie der AMD. Dabei wird in den meisten Studien zwischen AMD-Früh- und -Spätformen unterschieden, allerdings ohne eine weitere Differenzierung der „trockenen“ AMD-Spätform. Zudem stellt sich die Herausforderung unterschiedlicher Klassifikationen der AMD in verschiedenen Studien, was zwangsläufig zu Abweichungen in den epidemiologischen Daten bei der AMD führt. Neue Klassifikationssysteme berücksichtigen mikrostrukturelle Veränderungen, die mittels hochauflösender In-vivo-Bildgebung der Netzhaut detektiert werden können. Eine neue Konsensusklassifikation der AMD-assoziierten Atrophie soll ermöglichen, zukünftige Studien nach einheitlichen Definitionen durchzuführen.
Behandlung von Patientinnen mit frühem Mammakarzinom: Evidenz, Kontroversen, Konsens
Authors: Untch Michael , Thomssen Christoph , Bauerfeind Ingo , Braun Michael , Brucker Sara Y. , Felberbaum Ricardo , Hagemann Friederike , Haidinger Renate , Hönig Arnd , Huober Jens , Jackisch Christian , Kolberg Hans-Christian , Kolberg-Liedtke Cornelia , Kühn Thorsten , Lüftner Diana , Maass Nicolai , Reimer Toralf , Schneeweiss Andreas , Schumacher-Wulf Eva , Schütz Florian , Thill Marc , Wuerstlein Rachel , Fasching Peter A. , Harbeck Nadia 
Published: September 2019

ZusammenfassungDie Ergebnisse der internationalen St.-Gallen-Konsensus-Konferenz zur Behandlung des primären Mammakarzinoms wurden auch dieses Jahr von einer Arbeitsgruppe führender Brustkrebsexperten vor dem Hintergrund der Therapieempfehlungen für den Klinikalltag in Deutschland diskutiert. Drei der Brustkrebsexperten sind zugleich Mitglieder des diesjährigen St.-Gallen-Panels. Der Vergleich der St.-Gallen-Empfehlungen mit den jährlich aktualisierten Therapieempfehlungen der Arbeitsgemeinschaft Gynäkologische Onkologie (AGOMamma 2019) sowie der S3-Leitlinie ist sinnvoll, da die Empfehlungen des St.-Gallen-Panels ein Meinungsbild von Experten unterschiedlicher Länder und Fachdisziplinen darstellen. Die Empfehlungen der S3-Leitlinie und AGO basieren dagegen auf einer evidenzbasierten Literaturrecherche. Die diesjährige 16. St.-Gallen-Konferenz stand unter dem Motto „Magnitude of clinical benefit“. Neben der evidenzbasierten Grundlage muss jede Therapieentscheidung auch einer Nutzen-Risiko-Abwägung für die individuelle Situation einer Patientin unterzogen und mit der Patientin besprochen werden.
Diagnostik und Therapie des triple-negativen Mammakarzinoms (TNBC) – Empfehlungen für die tägliche Routine
Authors: Schneeweiss Andreas , Denkert Carsten , Fasching Peter A. , Fremd Carlo , Gluz Oleg , Kolberg-Liedtke Cornelia , Loibl Sibylle , Lück Hans-Joachim 
Published: September 2019

ZusammenfassungDurch den raschen Erkenntnisgewinn zu Tumorbiologie und Tumorpathogenese des triple-negativen Mammakarzinoms (TNBC) ergeben sich neue Therapieansätze und neue Therapiekonzepte für die Behandlung. Seit Jahren gilt das TNBC wegen seiner in der Regel aggressiven Tumorbiologie und angesichts limitierter Therapieoptionen als schwierig zu behandelnder Tumor. Das Rezidiv- und Metastasierungsrisiko ist höher als bei anderen Mammakarzinom-Subtypen desselben Stadiums. Neben Operation und Bestrahlung in der kurativen Situation ist die systemische Chemotherapie mit Anthrazyklinen und/oder Taxanen nach wie vor die Therapie der Wahl. Neue Therapieansätze basieren auf der Erkenntnis, dass das TNBC eine molekular sehr heterogene Erkrankung ist. Forschungsgruppen arbeiten daran, das TNBC immer besser auf molekularer Ebene zu klassifizieren und diese molekulare Subtypisierung als Grundlage für neue therapeutische Strategien zu nutzen. Im Folgenden werden die vielversprechendsten neuen Ansätze und Überlegungen zur Therapie des TNBCs dargestellt. Anhand einer fiktiven Kasuistik werden zudem die derzeitigen Therapiestrategien unter Berücksichtigung der aktuellen Datenlage und den sich daraus ergebenden therapeutischen Konsequenz besprochen.
Antimicrobial Effect of Newly Formulated Toothpastes and a Mouthrinse on Specific Microorganisms: An In Vitro Study
Authors: Guven Yeliz , Ustun Nilufer , Tuna Elif Bahar , Aktoren Oya 
Published: September 2019

Abstract
Objective The aim of this in vitro study was to assess the antimicrobial properties of newly formulated toothpastes (four toothpastes for adults and two toothpastes for kids/babies) and a mouthrinse.
Materials and Methods Newly formulated six different toothpastes and one mouthrinse of a single brand and commercially available five toothpastes and three mouthrinse were investigated for their antimicrobial activity against two oral pathogens, Streptococcus mutans and Candida albicans, by agar well diffusion assay. After incubation, the inhibition zone diameters were measured in millimeters and statistical analyses were performed.
Results All experimental adult toothpastes exhibited good antimicrobial activity against S. mutans and C. albicans except the experimental toothpaste D. Experimental toothpaste B exhibited the highest antibacterial activity against C. albicans and S. mutans. Experimental toothpaste for kids showed the best antimicrobial activity against S. mutans when kids’ toothpastes were compared. None of the tested toothpastes for kids/babies showed antibacterial effects for C. albicans. Among the mouthrinse tested, Sensodyne mouthrinse showed the best results. Experimental mouthrinse showed significantly lower antibacterial activity against S. mutans then Sensodyne, Eludril, and chlorhexidine mouthrinse.
Conclusion Although experimental toothpaste and mouthrinse formulations revealed good results in terms of antimicrobial activity to some specific microorganisms, further studies involving more bacterial species or analyzing the quality and efficacy of these products by other in vitro or in vivo tests are needed.
Two Novel GATA1 Mutations in Transient Abnormal Myelopoiesis of Thai Neonates with Down Syndrome
Authors: Chukua Kanokporn , Netsawang Chayanont , Padungthai Kittipoom , Khetkham Thanitchet , Chokevittaya Piyaporn , Poonjearansilp Onapinya , Prachuktum Sariya , Kositamongkol Sudatip , Techasatit Wiliporn , Silapamongkolkul Phakatip , Satayasai Wallee , Pusongchai Tasama , Surapolchai Pacharapan , Rojnueangnit Kitiwan 
Published: September 2019

AbstractChildren with Down syndrome (DS) are 150 times more likely to develop acute myeloid leukemia (ML-DS), compared with those without. One risk factor is transient abnormal myelopoiesis (TAM). Somatic truncating GATA1 mutations are found in most TAM patients and are markers for future ML-DS. We identified two novel frameshift mutations in our seven newborns with DS and TAM: a heterozygous mutation of 17 nucleotide duplication (c.154_170 dup) and a heterozygous 9-nucleotide deletion combined with a 2-nucleotide insertion (c.150_158delins CT). Both mutations introduced a truncated GATA1 protein. Thus, neonates with DS and TAM require frequent ML-DS monitoring.
Significance of sunlight for organic matter degradation in aquatic systems
Authors: Hunting Ellard R , de Jong Sanne , Schrama Maarten 
Published: September 2019

Abstract
Degradation of organic matter (OM) is generally considered to be primarily governed by biotic factors in aquatic environments. However, a number of abiotic processes also play key roles in mediating OM-degradation. Sunlight can act as a principal abiotic driver of the degradation of terrestrial organic matter, but its importance for freshwater ecosystems and possible interactions with biotic drivers remains poorly understood. We carried out two microcosm experiments which focused on the role of sunlight on microbial and invertebrate-mediated OM degradation using two species of plant leaves and the aquatic invertebrate Asellus aquaticus. Results indicated that sunlight was the primary driver of leaf mass loss during the early stages of decomposition, whereas microbial communities had a negligible effect. Sunlight was observed to strongly affect invertebrate behavior as invertebrates avoided direct illumination. This alteration of behavior resulted in a reduction in the consumption of a leaf surrogate (DECOTAB) by A. aquaticus. Together, these results indicate that sunlight has the potential to strongly influence structural and functional attributes of shallow freshwater systems, and hence serve as an appraisal to consider sunlight as a significant direct and indirect physical driver governing OM degradation in shallow aquatic systems.
Practical Cost Analysis of Genomic Data in the Cloud
Authors: Krumm Niklas , Hoffman Noah 
Published: September 2019

Abstract

Background
The growth of clinical NGS testing, together with new CAP checklist items stating that read-level (raw) NGS data must be retained for a minimum of 2 years, has prompted laboratories to reevaluate their NGS data storage solutions. In this context, cloud-based storage has several advantages, such as low per-GB prices, scalability, and minimal fixed costs; nonetheless, several perceived disadvantages, including increased complexity and security/regulatory considerations, have hindered adoption. Furthermore, despite the ostensibly simple usage-based pricing plans, practical cost analysis of cloud storage for NGS data storage is not straightforward.

Methods
We developed an easy-to-use tool designed specifically for cost and usage estimation for laboratories performing clinical NGS testing (https://ngscosts.info). Our tool enables quick exploration of dozens of storage options across three major cloud providers and provides complex cost and usage forecasts over 10- to 20-year timeframes. Parameters include current test volumes (and customizable file sizes), expected test volume growth rate, data compression techniques, data retention times across storage tiers, and case reaccess rates. Outputs include an easy-to-visualize chart of total data stored, yearly and lifetime costs, and a “cost per test” estimate.

Results
The per-GB storage prices among major cloud providers have dropped ~6 to 7× over the past 10 years; in addition, there currently exists an up to 20× price difference between storage tiers. Lower prices are typically offset by either increased access/transfer costs or slower retrieval rates. Two factors were found to markedly affect the average cost per test: (1) total file size, including the use of NGS-specific file compression techniques, and (2) storage tiers and rapid transfer to “cold” or archival storage. In contrast, some factors were not found to affect total costs, including costs associated with reaccess from archival storage tiers, and discounts associated with increased volumes.
When data from NGS testing were stored in “hot” storage for 1 year, then archived for 9 years, typical costs per exome were ~$3/test and genomes ranged from $40/test to $66/test, depending on compression algorithms used. Overall, reaccess of data from cold storage added 2% or less to the total cost per test (with an estimated reaccess rate of 10% of cases per year).

Conclusions
Steady declines in cloud storage pricing, as well as new options for storage and retrieval, make storing clinical NGS data on the cloud economical and friendly to laboratory workflows. Taken together, laboratories should not be concerned about reaccess costs but rather should focus on data compression techniques and archival storage tiers for long-term data. Our web-based tool makes it possible to explore and compare cloud storage solutions and provide forecasts specifically for clinical NGS laboratories.