bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical development of a miR-132 inhibitor for heart failure treatment
Authors: Foinquinos Ariana , Batkai Sandor , Genschel Celina , Viereck Janika , Rump Steffen , Gyöngyösi Mariann , Traxler Denise , Riesenhuber Martin , Spannbauer Andreas , Lukovic Dominika , Weber Natalie , Zlabinger Katrin , Hašimbegović Ena , Winkler Johannes , Fiedler Jan , Dangwal Seema , Fischer Martin , de la Roche Jeanne , Wojciechowski Daniel , Kraft Theresia , Garamvölgyi Rita , Neitzel Sonja , Chatterjee Shambhabi , Yin Xiaoke , Bär Christian , Mayr Manuel , Xiao Ke , Thum Thomas 
Published: January 2020

AbstractDespite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators and essential drivers of disease progression. We previously demonstrated that miR-132 is both necessary and sufficient to drive the pathological cardiomyocytes growth, a hallmark of adverse cardiac remodelling. Therefore, miR-132 may serve as a target for HF therapy. Here we report further mechanistic insight of the mode of action and translational evidence for an optimized, synthetic locked nucleic acid antisense oligonucleotide inhibitor (antimiR-132). We reveal the compound’s therapeutic efficacy in various models, including a clinically highly relevant pig model of HF. We demonstrate favourable pharmacokinetics, safety, tolerability, dose-dependent PK/PD relationships and high clinical potential for the antimiR-132 treatment scheme.
Quasiparticle tunnel electroresistance in superconducting junctions
Authors: Rouco V. , Hage R. El , Sander A. , Grandal J. , Seurre K. , Palermo X. , Briatico J. , Collin S. , Trastoy J. , Bouzehouane K. , Buzdin A. I. , Singh G. , Bergeal N. , Feuillet-Palma C. , Lesueur J. , Leon C. , Varela M. , Santamaría J. , Villegas Javier E. 
Published: January 2020

AbstractThe term tunnel electroresistance (TER) denotes a fast, non-volatile, reversible resistance switching triggered by voltage pulses in ferroelectric tunnel junctions. It is explained by subtle mechanisms connected to the voltage-induced reversal of the ferroelectric polarization. Here we demonstrate that effects functionally indistinguishable from the TER can be produced in a simpler junction scheme—a direct contact between a metal and an oxide—through a different mechanism: a reversible redox reaction that modifies the oxide’s ground-state. This is shown in junctions based on a cuprate superconductor, whose ground-state is sensitive to the oxygen stoichiometry and can be tracked in operando via changes in the conductance spectra. Furthermore, we find that electrochemistry is the governing mechanism even if a ferroelectric is placed between the metal and the oxide. Finally, we extend the concept of electroresistance to the tunnelling of superconducting quasiparticles, for which the switching effects are much stronger than for normal electrons. Besides providing crucial understanding, our results provide a basis for non-volatile Josephson memory devices.
Network-based diffusion analysis reveals context-specific dominance of dance communication in foraging honeybees
Authors: Hasenjager Matthew J. , Hoppitt William , Leadbeater Ellouise 
Published: January 2020

AbstractThe honeybee (Apis mellifera) dance communication system is a marvel of collective behaviour, but the added value it brings to colony foraging efficiency is poorly understood. In temperate environments, preventing communication of foraging locations rarely decreases colony food intake, potentially because simultaneous transmission of olfactory information also plays a major role in foraging. Here, we employ social network analyses that quantify information flow across multiple temporally varying networks (each representing a different interaction type) to evaluate the relative contributions of dance communication and hive-based olfactory information transfer to honeybee recruitment events. We show that virtually all successful recruits to novel locations rely upon dance information rather than olfactory cues that could otherwise guide them to the same resource. Conversely, during reactivation to known sites, dances are relatively less important, as foragers are primarily guided by olfactory information. By disentangling the contributions of multiple information networks, the contexts in which dance communication truly matters amid a complex system full of redundancy can now be identified.
Structural basis of proton-coupled potassium transport in the KUP family
Authors: Tascón Igor , Sousa Joana S. , Corey Robin A. , Mills Deryck J. , Griwatz David , Aumüller Nadine , Mikusevic Vedrana , Stansfeld Phillip J. , Vonck Janet , Hänelt Inga 
Published: January 2020

AbstractPotassium homeostasis is vital for all organisms, but is challenging in single-celled organisms like bacteria and yeast and immobile organisms like plants that constantly need to adapt to changing external conditions. KUP transporters facilitate potassium uptake by the co-transport of protons. Here, we uncover the molecular basis for transport in this widely distributed family. We identify the potassium importer KimA from Bacillus subtilis as a member of the KUP family, demonstrate that it functions as a K+/H+ symporter and report a 3.7 Å cryo-EM structure of the KimA homodimer in an inward-occluded, trans-inhibited conformation. By introducing point mutations, we identify key residues for potassium and proton binding, which are conserved among other KUP proteins.
Global meta-analysis shows pervasive phosphorus limitation of aboveground plant production in natural terrestrial ecosystems
Authors: Hou Enqing , Luo Yiqi , Kuang Yuanwen , Chen Chengrong , Lu Xiankai , Jiang Lifen , Luo Xianzhen , Wen Dazhi 
Published: January 2020

AbstractPhosphorus (P) limitation of aboveground plant production is usually assumed to occur in tropical regions but rarely elsewhere. Here we report that such P limitation is more widespread and much stronger than previously estimated. In our global meta-analysis, almost half (46.2%) of 652 P-addition field experiments reveal a significant P limitation on aboveground plant production. Globally, P additions increase aboveground plant production by 34.9% in natural terrestrial ecosystems, which is 7.0–15.9% higher than previously suggested. In croplands, by contrast, P additions increase aboveground plant production by only 13.9%, probably because of historical fertilizations. The magnitude of P limitation also differs among climate zones and regions, and is driven by climate, ecosystem properties, and fertilization regimes. In addition to confirming that P limitation is widespread in tropical regions, our study demonstrates that P limitation often occurs in other regions. This suggests that previous studies have underestimated the importance of altered P supply on aboveground plant production in natural terrestrial ecosystems.
Direct C–H difluoromethylation of heterocycles via organic photoredox catalysis
Authors: Zhang Wei , Xiang Xin-Xin , Chen Junyi , Yang Chen , Pan Yu-Liang , Cheng Jin-Pei , Meng Qingbin , Li Xin 
Published: January 2020

AbstractThe discovery of modern medicine relies on the sustainable development of synthetic methodologies to meet the needs associated with drug molecular design. Heterocycles containing difluoromethyl groups are an emerging but scarcely investigated class of organofluoro molecules with potential applications in pharmaceutical, agricultural and material science. Herein, we developed an organophotocatalytic direct difluoromethylation of heterocycles using O2 as a green oxidant. The C–H oxidative difluoromethylation obviates the need for pre-functionalization of the substrates, metals and additives. The operationally straightforward method enriches the efficient synthesis of many difluoromethylated heterocycles in moderate to excellent yields. The direct difluoromethylation of pharmaceutical moleculars demonstrates the practicability of this methodology to late-stage drug development. Moreover, 2′-deoxy-5-difluoromethyluridine (F2TDR) exhibits promising activity against some cancer cell lines, indicating that the difluoromethylation methodology might provide assistance for drug discovery.
Neuronal ensemble-specific DNA methylation strengthens engram stability
Authors: Gulmez Karaca Kubra , Kupke Janina , Brito David V. C. , Zeuch Benjamin , Thome Christian , Weichenhan Dieter , Lutsik Pavlo , Plass Christoph , Oliveira Ana M. M. 
Published: January 2020

AbstractMemories are encoded by memory traces or engrams, represented within subsets of neurons that are synchronously activated during learning. However, the molecular mechanisms that drive engram stabilization during consolidation and consequently ensure its reactivation by memory recall are not fully understood. In this study we manipulate, during memory consolidation, the levels of the de novo DNA methyltransferase 3a2 (Dnmt3a2) selectively within dentate gyrus neurons activated by fear conditioning. We found that Dnmt3a2 upregulation enhances memory performance in mice and improves the fidelity of reconstitution of the original neuronal ensemble upon memory retrieval. Moreover, similar manipulation in a sparse, non-engram subset of neurons does not bias engram allocation or modulate memory strength. We further show that neuronal Dnmt3a2 overexpression changes the DNA methylation profile of synaptic plasticity-related genes. Our data implicates DNA methylation selectively within neuronal ensembles as a mechanism of stabilizing engrams during consolidation that supports successful memory retrieval.
Stabilizing lithium metal anode by octaphenyl polyoxyethylene-lithium complexation
Authors: Dai Hongliu , Gu Xingxing , Dong Jing , Wang Chao , Lai Chao , Sun Shuhui 
Published: January 2020

AbstractLithium metal is an ideal anode for lithium batteries due to its low electrochemical potential and high theoretical capacity. However, safety issues arising from lithium dendrite growth have significantly reduced the practical applicability of lithium metal batteries. Here, we report the addition of octaphenyl polyoxyethylene as an electrolyte additive to enable a stable complex layer on the surface of the lithium anode. This surface layer not only promotes uniform lithium deposition, but also facilitates the formation of a robust solid-electrolyte interface film comprising cross-linked polymer. As a result, lithium|lithium symmetric cells constructed using the octaphenyl polyoxyethylene additive exhibit excellent cycling stability over 400 cycles at 1 mA cm−2, and outstanding rate performance up to 4 mA cm−2. Full cells assembled with a LiFePO4 cathode exhibit high rate capability and impressive cyclability, with capacity decay of only 0.023% per cycle.
Generation and symmetry control of quantum frequency combs
Authors: Maltese G. , Amanti M. I. , Appas F. , Sinnl G. , Lemaître A. , Milman P. , Baboux F. , Ducci S. 
Published: January 2020

AbstractQuantum frequency combs are a useful resource for parallel quantum communication and processing, given the robustness and easy handling offered by the frequency degree of freedom. In this work, we propose a method to generate broadband biphoton frequency combs and control their symmetry under particle exchange, based on purely passive optical components, such as a cavity and an optical delay line. We experimentally demonstrate our method using an integrated AlGaAs semiconductor platform producing quantum frequency combs, working at room temperature and compliant with electrical injection. We show the generation and manipulation of biphoton frequency combs, spreading over more the 500 peaks. These results open interesting perspectives for the development of massively parallel and reconfigurable systems for complex quantum operations.
Core gene-based molecular detection and identification of Acanthamoeba species
Authors: Chelkha Nisrine , Jardot Priscilla , Moussaoui Iness , Levasseur Anthony , La Scola Bernard , Colson Philippe 
Published: January 2020

AbstractAcanthamoeba spp. are predominant free-living amoebae of water and soil. They have been used as tools for the isolation and culture of microbes that resist after their phagocytosis, such as Legionella-like bacteria, and, more recently giant viruses for which differences in permissiveness have been reported. However, problems have been reported regarding their identification at the species level. The present work implemented specific PCR systems for the detection and identification of Acanthamoeba species through comparison of sequences and phylogenetic analyses. Thirty-three Acanthamoeba isolates were studied, including 20 reference strains and 13 isolates retrieved from water, soil or clinical samples. Previous delineation of a core genome encompassing 826 genes based on draft genome sequences from 14 Acanthamoeba species allowed designing PCR systems for one of these core genes that encodes an alanine-tRNA ligase. These primers allowed an efficient and specific screening to detect Acanthamoeba presence. In addition, they identified all 20 reference strains, while partial and complete sequences coding for 18S ribosomal RNA identified only 11 (55%). We found that four isolates may be considered as new Acanthamoeba species. Consistent with previous studies, we demonstrated that some Acanthamoeba isolates were incorrectly assigned to species using the 18S rDNA sequences. Our implemented tool may help determining which Acanthamoeba strains are the most efficient for the isolation of associated microorganisms.
Chemical-free and synergistic interaction of ultrasound combined with plasma-activated water (PAW) to enhance microbial inactivation in chicken meat and skin
Authors: Royintarat Tanitta , Choi Eun Ha , Boonyawan Dheerawan , Seesuriyachan Phisit , Wattanutchariya Wassanai 
Published: January 2020

AbstractIn general, the poultry industry uses 0.5–1 ppm chlorine solution in the meat sanitization process. However, chlorine can react with organic material and produce halogenated organic compounds, notably chloroform, which causes bladder and rectal cancer in humans. For this reason, many industries try to avoid chlorine. This study investigated the efficacy of ultrasound and plasma-activated water (PAW) on the inactivation ofEscherichia coliandStaphylococcus aureusin chicken muscle, rough skin, and smooth skin. Samples inoculated with bacteria suspension were treated by ultrasound alone and PAW–ultrasound. The Taguchi method and desirability function approach were used for the experimental design and optimization. Combined ultrasound and PAW inactivated up to 1.33 log CFU/ml ofE. coliK12 and 0.83 log CFU/ml ofS. aureusat a sample thickness of 4 mm, at 40 °C for 60 min, while PAW alone only reducedE. coliK12 by 0.46 log CFU/ml andS. aureusby 0.33 log CFU/ml under the same condition. The muscle topography showed a porous structure, which facilitated the penetration of PAW. The color measurements of muscle treated with ultrasound and PAW–ultrasound were dramatically different from the untreated sample, as also perceived by the sensory evaluation panel. Therefore, the synergistic interaction of combined PAW–ultrasound could be used to enhance microbial inactivation in meat.
Relationship between Intrinsically Photosensitive Ganglion Cell Function and Circadian Regulation in Diabetic Retinopathy
Authors: Reutrakul Sirimon , Crowley Stephanie J. , Park Jason C. , Chau Felix Y. , Priyadarshini Medha , Hanlon Erin C. , Danielson Kirstie K. , Gerber Ben S. , Baynard Tracy , Yeh Jade J. , McAnany J. Jason 
Published: January 2020

AbstractBackground: Intrinsically photosensitive retinal ganglion cells (ipRGCs) control non-visual light responses (e.g. pupillary light reflex and circadian entrainment). Patients with diabetic retinopathy (DR) show reduced ipRGC function, as inferred by abnormalities in the post illumination pupil response (PIPR). We explored whether ipRGC function in DR is associated with circadian outputs and sleep/wake behavior. Methods: Forty-five participants (15 without diabetes, 15 with type 2 diabetes (T2D) and no DR, 15 with T2D and DR) participated. ipRGC function was inferred from the PIPR (pupil size following stimulus offset). Circadian outputs were melatonin amplitude (overnight urinary 6-sulfatoxymelatonin (aMT6s)) and timing (dim light melatonin onset (DLMO)), and evening salivary cortisol levels. Sleep/wake patterns were measured with wrist actigraphy and insomnia symptoms were assessed subjectively. Results: Patients with T2D and DR had smaller PIPR and lower urinary aMT6s than other groups (p < 0.001). In adjusted regression models, smaller PIPR was associated with lower urinary aMT6s (β = 4.552, p = 0.005). Patients with DR were more likely to have no detectable DLMO (p = 0.049), higher evening salivary cortisol, greater insomnia symptoms and greater sleep variability compared to other groups. Sleep duration, efficiency and rest-activity rhythms were similar. Conclusion: Reduced ipRGC function in DR is associated with circadian dysregulation and sleep disturbances, although a causal relationship cannot be established in this cross-sectional study. Prospective mechanistic and intervention studies examining circadian and sleep health in these patients are warranted.
Repeated intramuscular transplantations of hUCB-MSCs improves motor function and survival in the SOD1 G93A mice through activation of AMPK
Authors: Kook Myung Geun , Lee SeungEun , Shin Nari , Kong Dasom , Kim Da-Hyun , Kim Min-Soo , Kang Hyun Kyoung , Choi Soon Won , Kang Kyung-Sun 
Published: January 2020

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by loss of motor neurons and degeneration of neuromuscular junctions. To improve disease progression, previous studies have suggested many options that have shown beneficial effects in diseases, especially stem cell therapy. In this study, we used repeated intramuscular transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) and observed positive effects on muscle atrophy and oxidative stress. In an in vivo study, motor function, body weight and survival rate were assessed, and skeletal muscle tissues were analyzed by western blotting and immunohistochemistry. After intramuscular transplantation, the hUCB-MSCs survived within the skeletal muscle for at least 1 week. Transplantation ameliorated muscle atrophy and the rate of neuromuscular degeneration in skeletal muscle through reductions in intracellular ROS levels. Both expression of skeletal muscle atrophy markers, muscle atrophy F-box (MAFbx)/atrogin1 and muscle RING finger 1 (MuRF1), were also reduced; however, the reductions were not significant. Moreover, transplantation of hUCB-MSCs improved protein synthesis and inhibited the iNOS/NO signaling pathway through AMPK activation. Our results suggest that repeated intramuscular transplantation of hUCB-MSCs can be a practical option for stem cell therapy for ALS.
Open-source, 3D-printed Peristaltic Pumps for Small Volume Point-of-Care Liquid Handling
Authors: Behrens Michael R. , Fuller Haley C. , Swist Emily R. , Wu Jingwen , Islam Md. Mydul , Long Zhicheng , Ruder Warren C. , Steward Robert 
Published: January 2020

AbstractMicrofluidic technologies are frequently employed as point-of-care diagnostic tools for improving time-to-diagnosis and improving patient outcomes in clinical settings. These microfluidic devices often are designed to operate with peripheral equipment for liquid handling that increases the cost and complexity of these systems and reduces their potential for widespread adoption in low resource healthcare applications. Here, we present a low-cost (~$120), open-source peristaltic pump constructed with a combination of three dimensional (3D)-printed parts and common hardware, which is amenable to deployment with microfluidic devices for point-of-care diagnostics. This pump accepts commonly available silicone rubber tubing in a range of sizes from 1.5 to 3 mm, and is capable of producing flow rates up to 1.6 mL min−1. This device is programmed with an Arduino microcontroller, allowing for custom flow profiles to fit a wide range of low volume liquid handling applications including precision liquid aliquoting, flow control within microfluidics, and generation of physiologically relevant forces for studying cellular mechanobiology within microfluidic systems.
Sensitive Readout for Microfluidic High-Throughput Applications using Scanning SQUID Microscopy
Authors: Wissberg Shai , Ronen Maria , Oren Ziv , Gerber Doron , Kalisky Beena 
Published: January 2020

AbstractMicrofluidic chips provide a powerful platform for high-throughput screening of diverse biophysical systems. The most prevalent detection methods are fluorescence based. Developing new readout techniques for microfluidics focusing on quantitative information in the low signal regime is desirable. In this work, we combine the well-established immunoassay approach, with magnetic nanoparticles, with a highly sensitive magnetic imaging technique. We offer to integrate a microfluidic array into a scanning superconducting quantum interference device (SQUID) microscope, to image nanoparticles that were moved through the microfluidic device. We demonstrate the technique on protein-protein interactions (PPI). We compare sensitivity to that of a conventional readout, quantify the amount of interactions, and demonstrate 0.1 atto-mole sensitivity. Our work serves as a proof of concept that will promote the development of a new set of eyes, a stable usable microfluidic-scanning SQUID microscopy.
Association between diabetes and cognitive function at baseline in the Brazilian Longitudinal Study of Adult Health (ELSA- Brasil)
Authors: Teixeira Mônica M. , Passos Valéria M. A. , Barreto Sandhi M. , Schmidt Maria I. , Duncan Bruce B. , Beleigoli Alline M. R. , Fonseca Maria J. M. , Vidigal Pedro G. , Araújo Larissa F. , Diniz Maria de Fátima H. S. 
Published: January 2020

AbstractDiabetes has been associated with cognitive changes and an increased risk of vascular dementia and Alzheimer’s disease, but it is unclear whether there are associations between diabetes and early alterations in cognitive performance. The present study consisted of a cross-section analysis of 14,444 participants aged 35–74 years and from a developing country at baseline in the Brazilian Longitudinal Study of Adult Health (ELSA–Brasil); these participants were recruited between 2008 and 2010. We investigated whether there was an association between diabetes and early changes in the cognitive performance of this Brazilian population. To assess cognitive domains, we used the word-list learning, word-list delayed recall and word recognition tests along. Phonemic verbal fluency tests included semantic phonemic test (animals) and a phonemic test (words beginning with the letter F). Executive functions associated with attention, concentration and psychomotor speed were evaluated using the Trail Making Test B. The exposure variable in the study was defined as diabetes. Multiple linear regression was used to estimate the association between diabetes and cognitive performance. The results were adjusted for age, sex, education, hypertension, coronary disease, depression, physical activity, smoking, alcohol consumption, and the cholesterol/HDL-C ratio. We found a significant association between diabetes and decreased memory, language and executive function (attention, concentration and psychomotor speed) performance in this population from a country with a distinct epidemiological profile, even after adjusting for the main intervening variables.