bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene target discovery with network analysis in Toxoplasma gondii
Authors: Alonso Andres M. , Corvi Maria M. , Diambra Luis 
Published: January 2019

AbstractInfectious diseases are of great relevance for global health, but needed drugs and vaccines have not been developed yet or are not effective in many cases. In fact, traditional scientific approaches with intense focus on individual genes or proteins have not been successful in providing new treatments. Hence, innovations in technology and computational methods provide new tools to further understand complex biological systems such as pathogen biology. In this paper, we apply a gene regulatory network approach to analyze transcriptomic data of the parasite Toxoplasma gondii. By means of an optimization procedure, the phenotypic transitions between the stages associated with the life cycle of T. gondii were embedded into the dynamics of a gene regulatory network. Thus, through this methodology we were able to reconstruct a gene regulatory network able to emulate the life cycle of the pathogen. The community network analysis has revealed that nodes of the network can be organized in seven communities which allow us to assign putative functions to 338 previously uncharacterized genes, 25 of which are predicted as new pathogenic factors. Furthermore, we identified a small gene circuit that drives a series of phenotypic transitions that characterize the life cycle of this pathogen. These new findings can contribute to the understanding of parasite pathogenesis.
Rapid Oxidation of the Hole Transport Layer in Perovskite Solar Cells by A Low-Temperature Plasma
Authors: Wang Yumeng , Qu Hao , Zhang Chunmei , Chen Qiang 
Published: January 2019

AbstractHerein we report a strategy of rapid oxidation of the hole transport layer (HTL) in perovskite solar cells by using oxygen/argon mixture plasma. This strategy offers a promising approach for simple manufacturing, mass production, and industrial applications. Compared to the conventional process of overnight oxidation, only ~10 s of oxygen/argon mixture plasma treatment is enough for the solar cell devices with FTO/ETL/perovskite/HTL/Au structure demonstrating a high power conversion efficiency. It is found that the high concentration of atomic oxygen generated in plasma oxidizing the HTL improves the conductivity and mobility, and therefore the process time is considerably shortened. This novel approach is compatible with continuous mass production, and it is suitable for the fabrication of large-area perovskite solar cells in the future.
Constructive approach for synthesis of a functional IgG using a reconstituted cell-free protein synthesis system
Authors: Murakami Satoshi , Matsumoto Rena , Kanamori Takashi 
Published: January 2019

AbstractIgG is an indispensable biological experimental tool as well as a widely-used therapeutic protein. However, cell culture-based expression of monoclonal IgG is costly and time-consuming, making this process difficult to use for high-throughput screening in early-stage evaluation of biologics. With the goal of establishing a fast, simple, and robust high-throughput expression system for IgG, we implemented the synthesis of functional aglycosylated IgG by constructive approach based on a reconstituted prokaryotic cell-free protein synthesis system (PURE system). Optimization of the PURE system revealed that the following factors and reaction conditions were needed for IgG synthesis: (1) inclusion of the disulfide bond isomerase DsbC, (2) adjustment of the GSH/GSSG ratio, (3) inclusion of the molecular chaperone DnaK and its cofactors, and (4) use of an extended incubation time. Synthesis temperature and template DNA ratio (light chain-/heavy chain-encoding) also had been optimized for each IgG. Under optimal conditions, peak production of the anti-HER2 antibody trastuzumab reached 124 µg/mL. Furthermore, the active forms of other IgGs, including IgG1, IgG2, and IgG4 subclasses, also were synthesized. These results provide basic information for the development of novel high-throughput expression and functional screening systems for IgG, as well as useful information for understanding the IgG synthesis process.
Nebulized hypertonic saline triggers nervous system-mediated active liquid secretion in cystic fibrosis swine trachea
Authors: Luan Xiaojie , Tam Julian S. , Belev George , Jagadeeshan Santosh , Murray Brendan , Hassan Noman , Machen Terry E. , Chapman L. Dean , Ianowski Juan P. 
Published: January 2019

AbstractInhaled hypertonic saline (HTS) treatment is used to improve lung health in patients with cystic fibrosis (CF). The current consensus is that the treatment generates an osmotic gradient that draws water into the airways and increases airway surface liquid (ASL) volume. However, there is evidence that HTS may also stimulate active secretion of ASL by airway epithelia through the activation of sensory neurons. We tested the contribution of the nervous system and airway epithelia on HTS-stimulated ASL height increase in CF and wild-type swine airway. We used synchrotron-based imaging to investigate whether airway neurons and epithelia are involved in HTS treatment-triggered ASL secretion in CFTR−/− and wild-type swine. We showed that blocking parasympathetic and sensory neurons in airway resulted in ~50% reduction of the effect of HTS treatment on ASL volume in vivo. Incubating tracheal preparations with inhibitors of epithelial ion transport across airway decreased secretory responses to HTS treatment. CFTR−/− swine ex-vivo tracheal preparations showed substantially decreased secretory response to HTS treatment after blockage of neuronal activity. Our results indicated that HTS-triggered ASL secretion is partially mediated by the stimulation of airway neurons and the subsequent activation of active epithelia secretion; osmosis accounts for only ~50% of the effect.
pH Regulation and Tissue Coordination Pathways Promote Calcium Carbonate Bioerosion by Excavating Sponges
Authors: Webb Alice E. , Pomponi Shirley A. , van Duyl Fleur C. , Reichart Gert-Jan , de Nooijer Lennart J. 
Published: January 2019

AbstractCoral reefs are threatened by a multitude of environmental and biotic influences. Among these, excavating sponges raise particular concern since they bore into coral skeleton forming extensive cavities which lead to weakening and loss of reef structures. Sponge bioerosion is achieved by a combination of chemical dissolution and mechanical chip removal and ocean acidification has been shown to accelerate bioerosion rates. However, despite the ecological relevance of sponge bioerosion, the exact chemical conditions in which dissolution takes place and how chips are removed remain elusive. Using fluorescence microscopy, we show that intracellular pH is lower at etching sites compared to ambient seawater and the sponge’s tissue. This is realised through the extension of filopodia filled with low intracellular pH vesicles suggesting that protons are actively transported into this microenvironment to promote CaCO3 dissolution. Furthermore, fusiform myocyte-like cells forming reticulated pathways were localised at the interface between calcite and sponge. Such cells may be used by sponges to contract a conductive pathway to remove chips possibly instigated by excess Ca2+ at the boring site. The mechanism underlying CaCO3 dissolution by sponges provides new insight into how environmental conditions can enhance dissolution and improves predictions of future rates of coral dissolution due to sponge activity.
Neuronal firing rates diverge during REM and homogenize during non-REM
Authors: Miyawaki Hiroyuki , Watson Brendon O. , Diba Kamran 
Published: January 2019

AbstractNeurons fire at highly variable intrinsic rates and recent evidence suggests that low- and high-firing rate neurons display different plasticity and dynamics. Furthermore, recent publications imply possibly differing rate-dependent effects in hippocampus versus neocortex, but those analyses were carried out separately and with potentially important differences. To more effectively synthesize these questions, we analyzed the firing rate dynamics of populations of neurons in both hippocampal CA1 and frontal cortex under one framework that avoids the pitfalls of previous analyses and accounts for regression to the mean (RTM). We observed several consistent effects across these regions. While rapid eye movement (REM) sleep was marked by decreased hippocampal firing and increased neocortical firing, in both regions firing rate distributions widened during REM due to differential changes in high- versus low-firing rate cells in parallel with increased interneuron activity. In contrast, upon non-REM (NREM) sleep, firing rate distributions narrowed while interneuron firing decreased. Interestingly, hippocampal interneuron activity closely followed the patterns observed in neocortical principal cells rather than the hippocampal principal cells, suggestive of long-range interactions. Following these undulations in variance, the net effect of sleep was a decrease in firing rates. These decreases were greater in lower-firing hippocampal neurons but also higher-firing frontal cortical neurons, suggestive of greater plasticity in these cell groups. Our results across two different regions, and with statistical corrections, indicate that the hippocampus and neocortex show a mixture of differences and similarities as they cycle between sleep states with a unifying characteristic of homogenization of firing during NREM and diversification during REM.
A cationic near infrared fluorescent agent and ethyl-cinnamate tissue clearing protocol for vascular staining and imaging
Authors: Huang Jiaguo , Brenna Cinzia , Khan Arif ul Maula , Daniele Cristina , Rudolf Rüdiger , Heuveline Vincent , Gretz Norbert 
Published: January 2019

AbstractUnderstanding vascular structures and dysfunction is a fundamental challenge. This task has been approached by using traditional methodologies such as microscopic computed tomography and magnetic resonance imaging. Both techniques are not only expensive but also time-consuming. Here, we present a new method for visualizing vascular structures in different organs in an efficient manner. A cationic near infrared (NIR) fluorescent dye was developed with attractive features to specifically stain blood vessels. Furthermore, we refined the process of organ staining and harvesting by retrograde perfusion and optimized the subsequent dehydration and clearing process by the use of an automatic tissue processor and a non-toxic substance, ethyl-cinnamate. Using this approach, the time interval between organ harvesting and microscopic analysis can be reduced from day(s) or weeks to 4 hours. Finally, we have demonstrated that the new NIR fluorescent agent in combination with confocal or light-sheet microscopy can be efficiently used for visualization of vascular structures, such as the blood vessels in different organs e.g. glomeruli in kidneys, with an extremely high resolution. Our approach facilitates the development of automatic image processing and the quantitative analysis to study vascular and kidney diseases.
The effects of drought and nutrient addition on soil organisms vary across taxonomic groups, but are constant across seasons
Authors: Siebert Julia , Sünnemann Marie , Auge Harald , Berger Sigrid , Cesarz Simone , Ciobanu Marcel , Guerrero-Ramírez Nathaly R. , Eisenhauer Nico 
Published: January 2019

AbstractAnthropogenic global change alters the activity and functional composition of soil communities that are responsible for crucial ecosystem functions and services. Two of the most pervasive global change drivers are drought and nutrient enrichment. However, the responses of soil organisms to interacting global change drivers remain widely unknown. We tested the interactive effects of extreme drought and fertilization on soil biota ranging from microbes to invertebrates across seasons. We expected drought to reduce the activity of soil organisms and fertilization to induce positive bottom-up effects via increased plant productivity. Furthermore, we hypothesized fertilization to reinforce drought effects through enhanced plant growth, resulting in even drier soil conditions. Our results revealed that drought had detrimental effects on soil invertebrate feeding activity and simplified nematode community structure, whereas soil microbial activity and biomass were unaffected. Microbial biomass increased in response to fertilization, whereas invertebrate feeding activity substantially declined. Notably, these effects were consistent across seasons. The dissimilar responses suggest that soil biota differ vastly in their vulnerability to global change drivers. Thus, important ecosystem processes like decomposition and nutrient cycling, which are driven by the interdependent activity of soil microorganisms and invertebrates, may be disrupted under future conditions.
Tap water is one of the drivers that establish and assembly the lactic acid bacterium biota during sourdough preparation
Authors: Minervini Fabio , Dinardo Francesca Rita , De Angelis Maria , Gobbetti Marco 
Published: January 2019

AbstractThis study aimed at assessing the effect of tap water on the: (i) lactic acid bacteria (LAB) population of a traditional and mature sourdough; and (ii) establishment of LAB community during sourdough preparation. Ten tap water, collected from Italian regions characterized by cultural heritage in leavened baked goods, were used as ingredient for propagating or preparing firm (type I) sourdoughs. The same type and batch of flour, recipe, fermentation temperature and time were used for propagation/preparation, being water the only variable parameter. During nine days of propagation of a traditional and mature Apulian sourdough, LAB cell density did not differ, and the LAB species/strain composition hardly changed, regardless of the water. When the different tap water were used for preparing the corresponding sourdoughs, the values of pH became lower than 4.5 after two to four fermentations. The type of water affected the assembly of the LAB biome. As shown by Principal Components Analysis, LAB population in the sourdoughs and chemical and microbiological features of water used for their preparation partly overlapped. Several correlations were found between sourdough microbiota and water features. These data open the way to future researches about the use of various types of water in bakery industry.
Carbonic Anhydrase 6 Gene Variation influences Oral Microbiota Composition and Caries Risk in Swedish adolescents
Authors: Esberg A. , Haworth S. , Brunius C. , Lif Holgerson P. , Johansson I. 
Published: January 2019

AbstractCarbonic anhydrase VI (CA6) catalyses the reversible hydration of carbon dioxide in saliva with possible pH regulation, taste perception, and tooth formation effects. This study assessed effects of variation in the CA6 gene on oral microbiota and specifically the acidophilic and caries-associated Streptococcus mutans in 17-year old Swedish adolescents (n = 154). Associations with caries status and secreted CA6 protein were also evaluated. Single Nucleotide Polymorphisms (27 SNPs in 5 haploblocks) and saliva and tooth biofilm microbiota from Illumina MiSeq 16S rDNA (V3-V4) sequencing and culturing were analysed. Haploblock 4 (rs10864376, rs3737665, rs12138897) CCC associated with low prevalence of S. mutans (OR (95% CI): 0.5 (0.3, 0.8)), and caries (OR 0.6 (0.3, 0.9)), whereas haploblock 4 TTG associated with high prevalence of S. mutans (OR: 2.7 (1.2, 5.9)) and caries (OR: 2.3 (1.2, 4.4)). The TTG-haploblock 4 (represented by rs12138897(G)) was characterized by S. mutans, Scardovia wiggsiae, Treponema sp. HOT268, Tannerella sp. HOT286, Veillonella gp.1 compared with the CCC-haploblock 4 (represented by rs12138897(C)). Secreted CA6 in saliva was weakly linked to CA6 gene variation. In conclusion, the results indicate that CA6 gene polymorphisms influence S. mutans colonization, tooth biofilm microbiota composition and risk of dental caries in Swedish adolescents.
Stem cell exosomes inhibit angiogenesis and tumor growth of oral squamous cell carcinoma
Authors: Rosenberger Leonie , Ezquer Marcelo , Lillo-Vera Fernando , Pedraza Paulina L. , Ortúzar María Ignacia , González Paz L. , Figueroa-Valdés Aliosha I. , Cuenca Jimena , Ezquer Fernando , Khoury Maroun , Alcayaga-Miranda Francisca 
Published: January 2019

AbstractRecently, exosomes secreted by menstrual mesenchymal stem cells have been identified as inhibitory agents of tumor angiogenesis and modulators of the tumor cell secretome in prostate and breast cancer. However, their direct effect on endothelial cells and paracrine mediators have not yet been investigated. Using a carrier-based cell culture system to test the scalability for exosome production, we showed that different types of endothelial cells present specific kinetics for exosomes internalization. Exosome-treatment of endothelial cells increased cytotoxicity and reduced VEGF secretion and angiogenesis in a dose-dependent manner. Using the hamster buccal pouch carcinoma as a preclinical model for human oral squamous cell carcinoma, we demonstrated a significant antitumor effect of intra-tumoral injection of exosomes associated with a loss of tumor vasculature. These results address up-scaling of exosome production, a relevant issue for their clinical application, and also assess menstrual stem cell exosomes as potential anti-angiogenic agents for the treatment of neoplastic conditions.
Curcumin inhibits the TGF-β1-dependent differentiation of lung fibroblasts via PPARγ-driven upregulation of cathepsins B and L
Authors: Saidi Ahlame , Kasabova Mariana , Vanderlynden Lise , Wartenberg Mylène , Kara-Ali Ghania Hounana , Marc Daniel , Lecaille Fabien , Lalmanach Gilles 
Published: January 2019

AbstractPulmonary fibrosis is a progressive disease characterized by a widespread accumulation of myofibroblasts and extracellular matrix components. Growing evidences support that cysteine cathepsins, embracing cathepsin B (CatB) that affects TGF-β1-driven Smad pathway, along with their extracellular inhibitor cystatin C, participate in myofibrogenesis. Here we established that curcumin, a potent antifibrotic drug used in traditional Asian medicine, impaired the expression of both α-smooth muscle actin and mature TGF-β1 and inhibited the differentiation of human lung fibroblasts (CCD-19Lu cells). Curcumin induced a compelling upregulation of CatB and CatL. Conversely cystatin C was downregulated, which allowed the recovery of the peptidase activity of secreted cathepsins and the restoration of the proteolytic balance. Consistently, the amount of both insoluble and soluble type I collagen decreased, reaching levels similar to those observed for undifferentiated fibroblasts. The signaling pathways activated by curcumin were further examined. Curcumin triggered the expression of nuclear peroxisome proliferator-activated receptor γ (PPARγ). Contrariwise PPARγ inhibition, either by an antagonist (2-chloro-5-nitro-N-4-pyridinyl-benzamide) or by RNA silencing, restored TGF-β1-driven differentiation of curcumin-treated CCD-19Lu cells. PPARγ response element (PPRE)-like sequences were identified in the promoter regions of both CatB and CatL. Finally, we established that the transcriptional induction of CatB and CatL depends on the binding of PPARγ to PPRE sequences as a PPARγ/Retinoid X Receptor-α heterodimer.
Speed-Selectivity in Retinal Ganglion Cells is Sharpened by Broad Spatial Frequency, Naturalistic Stimuli
Authors: Ravello César R. , Perrinet Laurent U. , Escobar María-José , Palacios Adrián G. 
Published: January 2019

AbstractMotion detection represents one of the critical tasks of the visual system and has motivated a large body of research. However, it remains unclear precisely why the response of retinal ganglion cells (RGCs) to simple artificial stimuli does not predict their response to complex, naturalistic stimuli. To explore this topic, we use Motion Clouds (MC), which are synthetic textures that preserve properties of natural images and are merely parameterized, in particular by modulating the spatiotemporal spectrum complexity of the stimulus by adjusting the frequency bandwidths. By stimulating the retina of the diurnal rodent, Octodon degus with MC we show that the RGCs respond to increasingly complex stimuli by narrowing their adjustment curves in response to movement. At the level of the population, complex stimuli produce a sparser code while preserving movement information; therefore, the stimuli are encoded more efficiently. Interestingly, these properties were observed throughout different populations of RGCs. Thus, our results reveal that the response at the level of RGCs is modulated by the naturalness of the stimulus - in particular for motion - which suggests that the tuning to the statistics of natural images already emerges at the level of the retina.
Stratification of amyotrophic lateral sclerosis patients: a crowdsourcing approach
Authors: Kueffner Robert , Zach Neta , Bronfeld Maya , Norel Raquel , Atassi Nazem , Balagurusamy Venkat , Di Camillo Barbara , Chio Adriano , Cudkowicz Merit , Dillenberger Donna , Garcia-Garcia Javier , Hardiman Orla , Hoff Bruce , Knight Joshua , Leitner Melanie L. , Li Guang , Mangravite Lara , Norman Thea , Wang Liuxia ,   The ALS Stratification Consortium, Alkallas Rached , Anghel Catalina , Avril Jeanne , Bacardit Jaume , Balser Barbara , Balser John , Bar-Sinai Yoav , Ben-David Noa , Ben-Zion Eyal , Bliss Robin , Cai Jialu , Chernyshev Anatoly , Chiang Jung-Hsien , Chicco Davide , Corriveau Bhavna Ahuja Nicole , Dai Junqiang , Deshpande Yash , Desplats Eve , Durgin Joseph S. , Espiritu Shadrielle Melijah G. , Fan Fan , Fevrier Philippe , Fridley Brooke L. , Godzik Adam , Golińska Agnieszka , Gordon Jonathan , Graw Stefan , Guo Yuelong , Herpelinck Tim , Hopkins Julia , Huang Barbara , Jacobsen Jeremy , Jahandideh Samad , Jeon Jouhyun , Ji Wenkai , Jung Kenneth , Karanevich Alex , Koestler Devin C. , Kozak Michael , Kurz Christoph , Lalansingh Christopher , Larrieu Thomas , Lazzarini Nicola , Lerner Boaz , Lesinski Wojciech , Liang Xiaotao , Lin Xihui , Lowe Jarrett , Mackey Lester , Meier Richard , Min Wenwen , Mnich Krzysztof , Nahmias Violette , Noel-MacDonnell Janelle , O’Donnell Adrienne , Paadre Susan , Park Ji , Polewko-Klim Aneta , Raghavan Rama , Rudnicki Witold , Saghapour Ehsan , Salomond Jean-Bernard , Sankaran Kris , Sendorek Dorota , Sharan Vatsal , Shiah Yu-Jia , Sirois Jean-Karl , Sumanaweera Dinithi N. , Usset Joseph , Vang Yeeleng S. , Vens Celine , Wadden Dave , Wang David , Wong Wing Chung , Xie Xiaohui , Xu Zhiqing , Yang Hsih-Te , Yu Xiang , Zhang Haichen , Zhang Li , Zhang Shihua , Zhu Shanfeng , Xiao Jinfeng , Fang Wen-Chieh , Peng Jian , Yang Chen , Chang Huan-Jui , Stolovitzky Gustavo 
Published: January 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease where substantial heterogeneity in clinical presentation urgently requires a better stratification of patients for the development of drug trials and clinical care. In this study we explored stratification through a crowdsourcing approach, the DREAM Prize4Life ALS Stratification Challenge. Using data from >10,000 patients from ALS clinical trials and 1479 patients from community-based patient registers, more than 30 teams developed new approaches for machine learning and clustering, outperforming the best current predictions of disease outcome. We propose a new method to integrate and analyze patient clusters across methods, showing a clear pattern of consistent and clinically relevant sub-groups of patients that also enabled the reliable classification of new patients. Our analyses reveal novel insights in ALS and describe for the first time the potential of a crowdsourcing to uncover hidden patient sub-populations, and to accelerate disease understanding and therapeutic development.