bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diverse hydrogen production and consumption pathways influence methane production in ruminants
Authors: Greening Chris , Geier Renae , Wang Cecilia , Woods Laura C , Morales Sergio E , McDonald Michael J , Rushton-Green Rowena , Morgan Xochitl C , Koike Satoshi , Leahy Sinead C , Kelly William J , Cann Isaac , Attwood Graeme T , Cook Gregory M , Mackie Roderick I 
Published: June 2019

Abstract
Farmed ruminants are the largest source of anthropogenic methane emissions globally. The methanogenic archaea responsible for these emissions use molecular hydrogen (H2), produced during bacterial and eukaryotic carbohydrate fermentation, as their primary energy source. In this work, we used comparative genomic, metatranscriptomic and co-culture-based approaches to gain a system-wide understanding of the organisms and pathways responsible for ruminal H2 metabolism. Two-thirds of sequenced rumen bacterial and archaeal genomes encode enzymes that catalyse H2 production or consumption, including 26 distinct hydrogenase subgroups. Metatranscriptomic analysis confirmed that these hydrogenases are differentially expressed in sheep rumen. Electron-bifurcating [FeFe]-hydrogenases from carbohydrate-fermenting Clostridia (e.g., Ruminococcus) accounted for half of all hydrogenase transcripts. Various H2 uptake pathways were also expressed, including methanogenesis (Methanobrevibacter), fumarate and nitrite reduction (Selenomonas), and acetogenesis (Blautia). Whereas methanogenesis-related transcripts predominated in high methane yield sheep, alternative uptake pathways were significantly upregulated in low methane yield sheep. Complementing these findings, we observed significant differential expression and activity of the hydrogenases of the hydrogenogenic cellulose fermenter Ruminococcus albus and the hydrogenotrophic fumarate reducer Wolinella succinogenes in co-culture compared with pure culture. We conclude that H2 metabolism is a more complex and widespread trait among rumen microorganisms than previously recognised. There is evidence that alternative hydrogenotrophs, including acetogenic and respiratory bacteria, can prosper in the rumen and effectively compete with methanogens for H2. These findings may help to inform ongoing strategies to mitigate methane emissions by increasing flux through alternative H2 uptake pathways, including through animal selection, dietary supplementation and methanogenesis inhibitors.
Long noncoding RNA Neat1 modulates myogenesis by recruiting Ezh2
Authors: Wang Shanshan , Zuo Hao , Jin Jianjun , Lv Wei , Xu Zaiyan , Fan Yonghui , Zhang Jiali , Zuo Bo 
Published: June 2019

AbstractNeat1 is widely expressed in many tissues and cells and exerts pro-proliferation effects on many cancer cells. However, little is known about the function of Neat1 in myogenesis. Here we characterized the roles of Neat1 in muscle cell formation and muscle regeneration. Gain- or loss-of-function studies in C2C12 cells demonstrated that Neat1 accelerates myoblast proliferation but suppresses myoblast differentiation and fusion. Further, knockdown of Neat1 in vivo increased the cross-sectional area of muscle fibers but impaired muscle regeneration. Mechanically, Neat1 physically interacted with Ezh2 mainly through the core binding region (1001–1540 bp) and recruited Ezh2 to target gene promoters. Neat1 promoted myoblast proliferation mainly by decreasing the expression of the cyclin-dependent kinase inhibitor P21 gene but inhibited myoblast differentiation by suppressing the transcription of myogenic marker genes, such as Myog, Myh4, and Tnni2. Altogether, we uncover a previously unknown function of Neat1 in muscle development and the molecular mechanism by which Neat1 regulates myogenesis.
Photocalorespirometry (Photo-CR): A Novel Method for Access to Photosynthetic Energy Conversion Efficiency
Authors: Maskow Thomas , Rothe Anne , Jakob Torsten , Paufler Sven , Wilhelm Christian 
Published: June 2019

AbstractOne key parameter for assessing the CO2 fixation in aquatic ecosystems but also for the productivity of photobioreactors is the energy conversion efficiency (PE) by the photosynthetic apparatus. PE strictly depends on a range of different fluctuating environmental conditions and is therefore highly variable. PE is the result of complex metabolic control. At the moment PE can only be determined indirectly. Furthermore, the currently available techniques either capture only short time processes, thus reflecting only parts of the photosynthetic engine, or quantify the total process but only with limited time resolution. To close this gap, we suggest for the first time the direct measurement of the fixed energy combined with respirometry, called photocalorespirometry (Photo-CR). The proof of the principle of Photo-CR was established with the microalga Chlamydomonas reinhardtii. The simultaneous measurement of oxygen production and energy fixation provides an calorespirometric ratio of −(437.9 ± 0.7) kJ mol−1 under low light conditions. The elevated calorespirometric ratio under high light conditions provides an indication of photo-protective mechanisms. The Photo-CR delivers the PE in real time, depending on the light intensity. Energetic differences less than 0.14% at radiation densities of up to 800 μE m−2 s−1 can be quantified. Other photosynthetic growth parameters (e.g. the specific growth rate of 0.071 h−1, the cell specific energy conservation of 30.9 ± 1.3 pW cell−1 at 150 µE m−2 s−1 and the number of photons (86.8) required to fix one molecule of CO2) can easily be derived from the Photo-CR data.
Modelling the dynamics of EBV transmission to inform a vaccine target product profile and future vaccination strategy
Authors: Goscé Lara , Winter Joanne R. , Taylor Graham S. , Lewis Joanna E. A. , Stagg Helen R. 
Published: June 2019

AbstractEpstein-Barr virus (EBV) is one of the most common human viruses and the cause of pathologies such as infectious mononucleosis (IM) and certain cancers. No vaccine against EBV infection currently exists, but such vaccines are in development. Knowledge of how EBV is transmitted at the population level is critical to the development of target product profiles (TPPs) for such vaccines and future vaccination strategies. We present the first mathematical model of EBV transmission, parameterised using data from England, and use it to compare hypothetical prophylactic vaccines with different characteristics and the impact of vaccinating different age groups. We found that vaccine duration had more impact than vaccine efficacy on modelled EBV and IM prevalence. The age group vaccinated also had an important effect: vaccinating at a younger age led to a greater reduction in seroprevalence but an increase in IM cases associated with delayed infection. Vaccination had impact on cancer incidence only in the long run, because in England most EBV-related cancers arise in later life. Durability of protection should be a key factor to prioritise in EBV vaccine development and included in vaccine TPPs. These findings are timely and important for vaccine developers and policy-makers alike.
Characterization of four functional biocompatible pressure-sensitive adhesives for rapid prototyping of cell-based lab-on-a-chip and organ-on-a-chip systems
Authors: Kratz S. R. A. , Eilenberger C. , Schuller P. , Bachmann B. , Spitz S. , Ertl P. , Rothbauer M. 
Published: June 2019

AbstractIn the advent of affordable photo- and soft-lithography using polydimethylsiloxane (PDMS), low cost multi-step microfabrication methods have become available to a broad scientific community today. Although these methods are frequently applied for microfluidic prototype production in academic and industrial settings, fast design iterations and rapid prototyping within a few minutes with a high degree of flexibility are nearly impossible. To reduce microfluidic concept-to-chip time and costs, a number of alternative rapid prototyping techniques have recently been introduced including CNC micromachining, 3D printing and plotting out of numeric CAD designs as well as micro-structuring of thin PDMS sheets and pressure sensitive adhesives. Although micro-structuring of pressure sensitive adhesives promises high design flexibility, rapid fabrication and simple biochip assembly, most adhesives are toxic for living biological systems. Since an appropriate bio-interface and proper biology-material interaction is key for any cell chip and organ-on-a-chip system, only a limited number of medical-grade materials are available for microfluidic prototyping. In this study, we have characterized four functional biomedical-grade pressure sensitive adhesives for rapid prototyping (e.g. less than 1 hour) applications including structuring precision, physical and optical properties as well as biocompatibilities. While similar biocompatibility was found for all four adhesives, significant differences in cutting behavior, bonding strength to glass and polymers as well as gas permeability was observed. Practical applications included stability testing of multilayered, membrane-integrated organ-on-a-chip devices under standard cell culture conditions (e.g. 2–3 weeks at 37 °C and 100% humidity) and a shear-impact up to 5 dynes/cm2. Additionally, time- and shear-dependent uptake of non-toxic fluorescently labelled nanoparticles on human endothelial cells are demonstrated using micro-structured adhesive-bonded devices. Our results show that (a) both simple and complex microdevices can be designed, fabricated and tested in less than 1 hour, (b) these microdevices are stable for weeks even under physiological shear force conditions and (c) can be used to maintain cell monolayers as well as 3D cell culture systems.
Pancreatic human islets and insulin-producing cells derived from embryonic stem cells are rapidly identified by a newly developed Dithizone
Authors: Khiatah Bashar , Qi Meirigeng , Wu Youjun , Chen Kuan-Tsen , Perez Rachel , Valiente Luis , Omori Keiko , Isenberg Jeffrey S. , Kandeel Fouad , Yee Jiing-Kuan , Al-Abdullah Ismail H. 
Published: June 2019

AbstractWe developed an optimized Dipheylthiocarbazone or Dithizone (DTZ) with improved physical and chemical properties to characterize human islets and insulin-producing cells differentiated from embryonic stem cells. Application of the newly formulated iDTZ (i stands for islet) over a range of temperatures, time intervals and cell and tissue types found it to be robust for identifying these cells. Through high transition zinc binding, the iDTZ compound concentrated in insulin-producing cells and proved effective at delineating zinc levels in vitro.
Neural networks versus Logistic regression for 30 days all-cause readmission prediction
Authors: Allam Ahmed , Nagy Mate , Thoma George , Krauthammer Michael 
Published: June 2019

AbstractHeart failure (HF) is one of the leading causes of hospital admissions in the US. Readmission within 30 days after a HF hospitalization is both a recognized indicator for disease progression and a source of considerable financial burden to the healthcare system. Consequently, the identification of patients at risk for readmission is a key step in improving disease management and patient outcome. In this work, we used a large administrative claims dataset to (1) explore the systematic application of neural network-based models versus logistic regression for predicting 30 days all-cause readmission after discharge from a HF admission, and (2) to examine the additive value of patients’ hospitalization timelines on prediction performance. Based on data from 272,778 (49% female) patients with a mean (SD) age of 73 years (14) and 343,328 HF admissions (67% of total admissions), we trained and tested our predictive readmission models following a stratified 5-fold cross-validation scheme. Among the deep learning approaches, a recurrent neural network (RNN) combined with conditional random fields (CRF) model (RNNCRF) achieved the best performance in readmission prediction with 0.642 AUC (95% CI, 0.640–0.645). Other models, such as those based on RNN, convolutional neural networks and CRF alone had lower performance, with a non-timeline based model (MLP) performing worst. A competitive model based on logistic regression with LASSO achieved a performance of 0.643 AUC (95% CI, 0.640–0.646). We conclude that data from patient timelines improve 30 day readmission prediction, that a logistic regression with LASSO has equal performance to the best neural network model and that the use of administrative data result in competitive performance compared to published approaches based on richer clinical datasets.
Simulated microgravity modulates the mesenchymal stromal cell response to inflammatory stimulation
Authors: Ratushnyy Andrey , Yakubets Danila , Andreeva Elena , Buravkova Ludmila 
Published: June 2019

AbstractThe duration and distance of manned space flights emphasizes the importance of advanced elucidation of space flight factors and their effects on human beings. The exposure to inflammatory mediators under microgravity may contribute to the activity of different cells, perivascular stromal cells (MSCs) in particular. Inflammatory activation is now considered as a principal cue of MSC engagement in reparative remodeling. In the present paper, the effect of simulated microgravity (sµg) on TNFα-mediated priming of adipose tissue-derived MSC (ASCs) was examined. Sµg per se did not induce inflammatory-related changes, such as elevation of ICAM-1 and HLA-ABC expression, soluble mediator production, or shifting of the transcription profile in ASCs. Moreover, the attenuated ASC response to TNFα priming under sµg was manifested in decreased production of TNFα-dependent pleiotropic cytokines (IL-8 and MCP-1), matrix remodeling proteases, and downregulation of some genes encoding growth factors and cytokines. Time-dependent analysis detected the first signs of priming attenuation after 48 hours of 3D-clinorotation. A reduced response of MSCs to priming under sµg can be a negative factor in terms of MSC involvement in tissue remodeling processes.
Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR
Authors: Zwarts Irene , van Zutphen Tim , Kruit Janine K. , Liu Weilin , Oosterveer Maaike H. , Verkade Henkjan J. , Uhlenhaut N. Henriette , Jonker Johan W. 
Published: June 2019

AbstractFructose has become a major constituent of our modern diet and is implicated as an underlying cause in the development of metabolic diseases. The fructose transporter GLUT5 (SLC2A5) is required for intestinal fructose absorption. GLUT5 expression is induced in the intestine and skeletal muscle of type 2 diabetes (T2D) patients and in certain cancers that are dependent on fructose metabolism, indicating that modulation of GLUT5 levels could have potential in the treatment of these diseases. Using an unbiased screen for transcriptional control of the human GLUT5 promoter we identified a strong and specific regulation by liver X receptor α (LXRα, NR1H3). Using promoter truncations and site-directed mutagenesis we identified a functional LXR response element (LXRE) in the human GLUT5 promoter, located at −385 bp relative to the transcriptional start site (TSS). Finally, mice treated with LXR agonist T0901317 showed an increase in Glut5 mRNA and protein levels in duodenum and adipose tissue, underscoring the in vivo relevance of its regulation by LXR. Together, our findings show that LXRα regulates GLUT5 in mice and humans. As a ligand-activated transcription factor, LXRα might provide novel pharmacologic strategies for the selective modulation of GLUT5 activity in the treatment of metabolic disease as well as cancer.
Proactive and retroactive interference with associative memory consolidation in the snail Lymnaea is time and circuit dependent
Authors: Crossley Michael , Lorenzetti Frederick D. , Naskar Souvik , O’Shea Michael , Kemenes György , Benjamin Paul R. , Kemenes Ildikó 
Published: June 2019

AbstractInterference-based forgetting occurs when new information acquired either before or after a learning event attenuates memory expression (proactive and retroactive interference, respectively). Multiple learning events often occur in rapid succession, leading to competition between consolidating memories. However, it is unknown what factors determine which memory is remembered or forgotten. Here, we challenge the snail, Lymnaea, to acquire two consecutive similar or different memories and identify learning-induced changes in neurons of its well-characterized motor circuits. We show that when new learning takes place during a stable period of the original memory, proactive interference only occurs if the two consolidating memories engage the same circuit mechanisms. If different circuits are used, both memories survive. However, any new learning during a labile period of consolidation promotes retroactive interference and the acquisition of the new memory. Therefore, the effect of interference depends both on the timing of new learning and the underlying neuronal mechanisms.
Interpreting and integrating big data in the life sciences
Authors: Mangul Serghei 
Published: June 2019

Abstract
Recent advances in omics technologies have led to the broad applicability of computational techniques across various domains of life science and medical research. These technologies provide an unprecedented opportunity to collect the omics data from hundreds of thousands of individuals and to study the gene–disease association without the aid of prior assumptions about the trait biology. Despite the many advantages of modern omics technologies, interpretations of big data produced by such technologies require advanced computational algorithms. I outline key challenges that biomedical researches are facing when interpreting and integrating big omics data. I discuss the reproducibility aspect of big data analysis in the life sciences and review current practices in reproducible research. Finally, I explain the skills that biomedical researchers need to acquire to independently analyze big omics data.
The high-energy radiation environment of the habitable-zone super-Earth LHS 1140b
Authors: Spinelli R. , Borsa F. , Ghirlanda G. , Ghisellini G. , Campana S. , Haardt F. , Poretti E. 
Published: June 2019

Context.In the last few years many exoplanets in the habitable zone (HZ) of M-dwarfs have been discovered, but the X-ray/UV activity of cool stars is very different from that of our Sun. The high-energy radiation environment influences the habitability, plays a crucial role for abiogenesis, and impacts the chemistry and evolution of planetary atmospheres. LHS 1140b is one of the most interesting exoplanets discovered. It is a super-Earth-size planet orbiting in the HZ of LHS 1140, an M4.5 dwarf at ~15 parsecs.Aims.In this work, we present the results of the analysis of aSwiftX-ray/UV observing campaign. We characterize for the first time the X-ray/UV radiation environment of LHS 1140b.Methods.We measure the variability of the near ultraviolet (NUV) flux and estimate the far ultraviolet (FUV) flux with a correlation between FUV1344−1786Åand NUV1771−2831Åflux obtained using the sample of low-mass stars in the GALEX archive. We highlight the presence of a dominating X-ray source close to the J2000 coordinates of LHS 1140, characterize its spectrum, and derive an X-ray flux upper limit for LHS 1140. We find that this contaminant source could have influenced the previously estimated spectral energy distribution.Results.No significant variation of the NUV1771−2831Åflux of LHS 1140 is found over 3 months, and we do not observe any flare during the 38 ks on the target. LHS 1140 is in the 25th percentile of least variable M4-M5 dwarfs of the GALEX sample. Analyzing the UV flux experienced by the HZ planet LHS 1140b, we find that outside the atmosphere it receives a NUV1771−2831Åflux <2% with respect to that of the present-day Earth, while the FUV1344−1786Å/NUV1771−2831Åratio is ~100–200 times higher. This represents a lower limit to the true FUV/NUV ratio since the FUV1344−1786Åband does not include Lyman-alpha, which dominates the FUV output of low-mass stars. This is a warning for future searches for biomarkers, which must take into account this high ratio.Conclusions.The relatively low level and stability of UV flux experienced by LHS 1140b should be favorable for its present-day habitability.
Défauts primaires d’éruption : état des lieux auprès des spécialistes en orthopédie dento-faciale des régions Grand Est et Bourgogne-Franche-Comté
Authors: Strub Marion , Kramer Elie , Manière Marie-Cécile , Wagner Delphine 
Published: June 2019

Introduction : Les défauts primaires d’éruption (DPE) correspondent à l’échec partiel ou total d’éruption d’une ou de plusieurs dents, sans obstacle mécanique; des formes isolées et syndromiques de cette pathologie existent. Ils résultent d’une anomalie des processus d’éruption qui peut toucher les dents temporaires et/ou les dents permanentes. Les molaires sont les principales dents atteintes, provoquant des infraclusions postérieures. Pathologie rare, les DPE sont essentiellement pris en charge par les spécialistes en orthopédie dento-faciale (ODF). Les tentatives de traction chirurgico-orthodontiques se soldent généralement par un échec. Matériels et méthodes : Le but de ce travail était d’évaluer, par une enquête prospective basée sur un questionnaire anonyme, les connaissances des orthodontistes et la complexité de la prise en charge de cette anomalie de l’éruption. Les praticiens des régions Grand Est et Bourgogne-Franche-Comté ont été sollicités. Résultats : Le taux de participation était de 33,5 %. Les participants ont principalement obtenu leur qualification entre 1980 et 2009 (80 %), via le Certificat d’Études Cliniques Spécialisées Mention Orthodontie (CECSMO) (87 %). Quatre-vingt-six pour cent d’entre eux connaissaient les DPE mais 20 % seulement l’implication possible du gène PTHR1 (Parathyroid Hormone Receptor 1). Le vaste panel de thérapeutiques envisagées et les faibles taux de satisfaction soulignent les difficultés rencontrées par les praticiens. Discussion : La variabilité phénotypique complique le diagnostic et rend difficile toute systématisation de la prise en charge. Conclusion : De nouveaux projets de recherche clinique, notamment en matière de diagnostic moléculaire, amélioreront les connaissances sur les corrélations génotype-phénotype, et conditionneront éventuellement la prise en charge thérapeutique.
La place de l’ostéotomie courte en chirurgie orthognathique : avantages, inconvénients et perspectives
Authors: Bachelet Jean-Thomas , Adnot Jérôme , Termont Aurélien , Decaudaveine Suzanne , Paulus Christian 
Published: June 2019

Introduction : L’ostéotomie courte évoquée par Blair en 1907 a été décrite et caractérisée par Kater et Paulus en 2013. Il s’agit d’une ostéotomie sus-spigienne oblique de dedans en dehors de haut en bas d’arrière en avant, visant à séparer le ramus en portion articulaire et portion angulo-mandibulaire, les deux valves osseuses étant maintenues en contact par une surface proportionnelle à l’angulation de l’ostéotomie. Matériels et Méthodes : Nous présentons, à travers une série de 82 patients, les avantages en termes de stabilité et de préservation de la sensibilité de cette technique. Résultats : Au total, 82 patients ont été inclus, 74 patients (90 %) ont décrit une sensibilité normale et huit patients (10 %) une sensibilité modifiée deux ans après la chirurgie. Discussion : L’ostéotomie courte permet, par la nature et la hauteur du trait d’ostéotomie, l’éviction de la manipulation directe du nerf alvéolaire inférieur. Elle est associée à un taux de sensibilité post-opératoire identique au pré-opératoire dans plus de 90 % des cas. Pour de bonnes indications, cette technique pourrait être utilisée de manière préférentielle afin d’optimiser la récupération nerveuse post-opératoire. Nous discuterons également les limites actuelles de cette technique de chirurgie orthognathique, ainsi que les perspectives en lien avec le développement de l’impression 3D et la planification pré-opératoire.