bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD+ depletion in experimental atrial fibrillation
Authors: Zhang Deli , Hu Xu , Li Jin , Liu Jia , Baks-te Bulte Luciënne , Wiersma Marit , Malik Noor-ul-Ann , van Marion Denise M. S. , Tolouee Marziyeh , Hoogstra-Berends Femke , Lanters Eva A. H. , van Roon Arie M. , de Vries Antoine A. F. , Pijnappels Daniël A. , de Groot Natasja M. S. , Henning Robert H. , Brundel Bianca J. J. M. 
Published: March 2019

AbstractAtrial fibrillation (AF) is the most common clinical tachyarrhythmia with a strong tendency to progress in time. AF progression is driven by derailment of protein homeostasis, which ultimately causes contractile dysfunction of the atria. Here we report that tachypacing-induced functional loss of atrial cardiomyocytes is precipitated by excessive poly(ADP)-ribose polymerase 1 (PARP1) activation in response to oxidative DNA damage. PARP1-mediated synthesis of ADP-ribose chains in turn depletes nicotinamide adenine dinucleotide (NAD+), induces further DNA damage and contractile dysfunction. Accordingly, NAD+ replenishment or PARP1 depletion precludes functional loss. Moreover, inhibition of PARP1 protects against tachypacing-induced NAD+ depletion, oxidative stress, DNA damage and contractile dysfunction in atrial cardiomyocytes and Drosophila. Consistently, cardiomyocytes of persistent AF patients show significant DNA damage, which correlates with PARP1 activity. The findings uncover a mechanism by which tachypacing impairs cardiomyocyte function and implicates PARP1 as a possible therapeutic target that may preserve cardiomyocyte function in clinical AF.
A highly selective and recyclable NO-responsive nanochannel based on a spiroring opening−closing reaction strategy
Authors: Sun Yao , Chen Sen , Chen Xiaoya , Xu Yuling , Zhang Siyun , Ouyang Qingying , Yang Guangfu , Li Haibing 
Published: March 2019

AbstractEndogenous nitric oxide (NO) is an important messenger molecule, which can directly activate K+ transmission and cause relaxation of vascular smooth muscle. Here, inspired by the K+ channel of smooth muscle cells, we report, a novel NO-regulated artificial nanochannel based on a spiro ring opening−closing reaction strategy. This nanofluidic diode system shows an outstanding NO selective response owing to the specific reaction between o-phenylenediamine (OPD) and NO on the channel surface with high ion rectification ratio (~6.7) and ion gating ratio (~4). Moreover, this NO gating system exhibits excellent reversibility and stability as well as high selectivity response. This system not only helps us understand the process of NO directly regulating biological ion channels, but also has potential application value in the field of biosensors.
A post-translational modification of human Norovirus capsid protein attenuates glycan binding
Authors: Mallagaray Alvaro , Creutznacher Robert , Dülfer Jasmin , Mayer Philipp H. O. , Grimm Lena Lisbeth , Orduña Jose Maria , Trabjerg Esben , Stehle Thilo , Rand Kasper D. , Blaum Bärbel S. , Uetrecht Charlotte , Peters Thomas 
Published: March 2019

AbstractAttachment of human noroviruses to histo blood group antigens (HBGAs) is essential for infection, but how this binding event promotes the infection of host cells is unknown. Here, we employ protein NMR experiments supported by mass spectrometry and crystallography to study HBGA binding to the P-domain of a prevalent virus strain (GII.4). We report a highly selective transformation of asparagine 373, located in an antigenic loop adjoining the HBGA binding site, into an iso-aspartate residue. This spontaneous post-translational modification (PTM) proceeds with an estimated half-life of a few days at physiological temperatures, independent of the presence of HBGAs but dramatically affecting HBGA recognition. Sequence conservation and the surface-exposed position of this PTM suggest an important role in infection and immune recognition for many norovirus strains.
Assessing the viability of transplanted gut microbiota by sequential tagging with D-amino acid-based metabolic probes
Authors: Wang Wei , Lin Liyuan , Du Yahui , Song Yanling , Peng Xiaoman , Chen Xing , Yang Chaoyong James 
Published: March 2019

AbstractCurrently, there are more than 200 fecal microbiota transplantation (FMT) clinical trials worldwide. However, our knowledge of this microbial therapy is still limited. Here we develop a strategy using sequential tagging with D-amino acid-based metabolic probes (STAMP) for assessing the viabilities of transplanted microbiotas. A fluorescent D-amino acid (FDAA) is first administered to donor mice to metabolically label the gut microbiotas in vivo. The labeled microbiotas are transplanted to recipient mice, which receive a second FDAA with a different color. The surviving transplants should incorporate both FDAAs and can be readily distinguished by presenting two colors simultaneously. Isolation of surviving bacteria and 16S rDNA sequencing identify several enriched genera, suggesting the importance of specific bacteria in FMT. In addition, using STAMP, we evaluate the effects on transplant survival of pre-treating recipients using different antibiotics. We propose STAMP as a versatile tool for deciphering the complex biology of FMT, and potentially improving its treatment efficacy.
Mitochondrial origins of fractional control in regulated cell death
Authors: Santos Luís C. , Vogel Robert , Chipuk Jerry E. , Birtwistle Marc R. , Stolovitzky Gustavo , Meyer Pablo 
Published: March 2019

AbstractIndividual cells in clonal populations often respond differently to environmental changes; for binary phenotypes, such as cell death, this can be measured as a fractional response. These types of responses have been attributed to cell-intrinsic stochastic processes and variable abundances of biochemical constituents, such as proteins, but the influence of organelles is still under investigation. We use the response to TNF-related apoptosis inducing ligand (TRAIL) and a new statistical framework for determining parameter influence on cell-to-cell variability through the inference of variance explained, DEPICTIVE, to demonstrate that variable mitochondria abundance correlates with cell survival and determines the fractional cell death response. By quantitative data analysis and modeling we attribute this effect to variable effective concentrations at the mitochondria surface of the pro-apoptotic proteins Bax/Bak. Further, our study suggests that inhibitors of anti-apoptotic Bcl-2 family proteins, used in cancer treatment, may increase the diversity of cellular responses, enhancing resistance to treatment.
Large-scale network analysis reveals the sequence space architecture of antibody repertoires
Authors: Miho Enkelejda , Roškar Rok , Greiff Victor , Reddy Sai T. 
Published: March 2019

AbstractThe architecture of mouse and human antibody repertoires is defined by the sequence similarity networks of the clones that compose them. The major principles that define the architecture of antibody repertoires have remained largely unknown. Here, we establish a high-performance computing platform to construct large-scale networks from comprehensive human and murine antibody repertoire sequencing datasets (>100,000 unique sequences). Leveraging a network-based statistical framework, we identify three fundamental principles of antibody repertoire architecture: reproducibility, robustness and redundancy. Antibody repertoire networks are highly reproducible across individuals despite high antibody sequence dissimilarity. The architecture of antibody repertoires is robust to the removal of up to 50–90% of randomly selected clones, but fragile to the removal of public clones shared among individuals. Finally, repertoire architecture is intrinsically redundant. Our analysis provides guidelines for the large-scale network analysis of immune repertoires and may be used in the future to define disease-associated and synthetic repertoires.
The hammam effect or how a warm ocean enhances large scale atmospheric predictability
Authors: Faranda Davide , Alvarez-Castro M. Carmen , Messori Gabriele , Rodrigues David , Yiou Pascal 
Published: March 2019

AbstractThe atmosphere’s chaotic nature limits its short-term predictability. Furthermore, there is little knowledge on how the difficulty of forecasting weather may be affected by anthropogenic climate change. Here, we address this question by employing metrics issued from dynamical systems theory to describe the atmospheric circulation and infer the dynamical properties of the climate system. Specifically, we evaluate the changes in the sub-seasonal predictability of the large-scale atmospheric circulation over the North Atlantic for the historical period and under anthropogenic forcing, using centennial reanalyses and CMIP5 simulations. For the future period, most datasets point to an increase in the atmosphere’s predictability. AMIP simulations with 4K warmer oceans and 4 × atmospheric CO2 concentrations highlight the prominent role of a warmer ocean in driving this increase. We term this the hammam effect. Such effect is linked to enhanced zonal atmospheric patterns, which are more predictable than meridional configurations.
Dispersal homogenizes communities via immigration even at low rates in a simplified synthetic bacterial metacommunity
Authors: Fodelianakis Stilianos , Lorz Alexander , Valenzuela-Cuevas Adriana , Barozzi Alan , Booth Jenny Marie , Daffonchio Daniele 
Published: March 2019

AbstractSelection and dispersal are ecological processes that have contrasting roles in the assembly of communities. Variable selection diversifies and strong dispersal homogenizes them. However, we do not know whether dispersal homogenizes communities directly via immigration or indirectly via weakening selection across habitats due to physical transfer of material, e.g., water mixing in aquatic ecosystems. Here we examine how dispersal homogenizes a simplified synthetic bacterial metacommunity, using a sequencing-independent approach based on flow cytometry and mathematical modeling. We show that dispersal homogenizes the metacommunity via immigration, not via weakening selection, and even when immigration is four times slower than growth. This finding challenges the current view that dispersal homogenizes communities only at high rates and explains why communities are homogeneous at small spatial scales. It also offers a benchmark for sequence-based studies in natural microbial communities where immigration rates can be inferred solely by using neutral models.
Different adsorption-degradation behavior of methylene blue and Congo red in nanoceria/H2O2 system under alkaline conditions
Authors: Wei Xiaoshu , Wang Yi , Feng Yuqian , Xie Xiaomin , Li Xiaofeng , Yang Sen 
Published: March 2019

AbstractThe Fenton-like activity of nanoceria has attracted intensive attention for wastewater treatment in recent years. During the Fenton-like reaction, the adsorption of organic pollutants on catalyst surface plays a key role in their degradation. In this work, the adsorption-degradation of methylene blue (MB) and Congo red (CR) in nanoceria/H2O2 system was investigated under alkaline conditions. The MB exhibited weak adsorption on nanoceria surface via electrostatic attraction, while strong Lewis acid–base interactions between CR and cerium ions was observed. Moreover, the adsorption of MB was enhanced in the presence of H2O2 by the formation of surface peroxide species, but an adsorption competition existed between H2O2 and CR. With more Ce3+, CeO2 nanorods could degrade CR efficiently as Fenton-like catalyst. But the degradation of MB catalyzed by ceria was much lower than that of CR in the presence of H2O2.
Machine learning-powered antibiotics phenotypic drug discovery
Authors: Zoffmann Sannah , Vercruysse Maarten , Benmansour Fethallah , Maunz Andreas , Wolf Luise , Blum Marti Rita , Heckel Tobias , Ding Haiyuan , Truong Hoa Hue , Prummer Michael , Schmucki Roland , Mason Clive S. , Bradley Kenneth , Jacob Asha Ivy , Lerner Christian , Araujo del Rosario Andrea , Burcin Mark , Amrein Kurt E. , Prunotto Marco 
Published: March 2019

AbstractIdentification of novel antibiotics remains a major challenge for drug discovery. The present study explores use of phenotypic readouts beyond classical antibacterial growth inhibition adopting a combined multiparametric high content screening and genomic approach. Deployment of the semi-automated bacterial phenotypic fingerprint (BPF) profiling platform in conjunction with a machine learning-powered dataset analysis, effectively allowed us to narrow down, compare and predict compound mode of action (MoA). The method identifies weak antibacterial hits allowing full exploitation of low potency hits frequently discovered by routine antibacterial screening. We demonstrate that BPF classification tool can be successfully used to guide chemical structure activity relationship optimization, enabling antibiotic development and that this approach can be fruitfully applied across species. The BPF classification tool could be potentially applied in primary screening, effectively enabling identification of novel antibacterial compound hits and differentiating their MoA, hence widening the known antibacterial chemical space of existing pharmaceutical compound libraries. More generally, beyond the specific objective of the present work, the proposed approach could be profitably applied to a broader range of diseases amenable to phenotypic drug discovery.
Multi-Modal Haptic Feedback for Grip Force Reduction in Robotic Surgery
Authors: Abiri Ahmad , Pensa Jake , Tao Anna , Ma Ji , Juo Yen-Yi , Askari Syed J. , Bisley James , Rosen Jacob , Dutson Erik P. , Grundfest Warren S. 
Published: March 2019

AbstractMinimally invasive robotic surgery allows for many advantages over traditional surgical procedures, but the loss of force feedback combined with a potential for strong grasping forces can result in excessive tissue damage. Single modality haptic feedback systems have been designed and tested in an attempt to diminish grasping forces, but the results still fall short of natural performance. A multi-modal pneumatic feedback system was designed to allow for tactile, kinesthetic, and vibrotactile feedback, with the aims of more closely imitating natural touch and further improving the effectiveness of HFS in robotic surgical applications and tasks such as tissue grasping and manipulation. Testing of the multi-modal system yielded very promising results with an average force reduction of nearly 50% between the no feedback and hybrid (tactile and kinesthetic) trials (p < 1.0E-16). The multi-modal system demonstrated an increased reduction over single modality feedback solutions and indicated that the system can help users achieve average grip forces closer to those normally possible with the human hand.
Interactions of newly synthesized platinum nanoparticles with ICR-191 and their potential application
Authors: Borowik Agnieszka , Banasiuk Rafal , Derewonko Natalia , Rychlowski Michal , Krychowiak-Masnicka Marta , Wyrzykowski Dariusz , Ziabka Magdalena , Woziwodzka Anna , Krolicka Aleksandra , Piosik Jacek 
Published: March 2019

AbstractOne of the greatest challenges of modern medicine is to find cheaper and easier ways to produce transporters for biologically active substances, which will provide selective and efficient drug delivery to the target cells, while causing low toxicity towards healthy cells. Currently, metal-based nanoparticles are considered a successful and viable solution to this problem. In this work, we propose the use of novel synthesis method of platinum nanoparticles (PtNPs) connected with their precise biophysical characterization and assessment of their potential toxicity. To work as an efficient nanodelivery platform, nanoparticles should interact with the desired active compounds spontaneously and non-covalently. We investigated possible direct interactions of PtNPs with ICR-191, a model acridine mutagen with well-established biophysical properties and mutagenic activity, by Dynamic Light Scattering, fluorescence spectroscopy, and Isothermal Titration Calorimetry. Moreover, to determine the biological activity of ICR-191-PtNPs aggregates, we employed Ames mutagenicity test, eukaryotic cell line analysis and toxicity test against the model organism Caenorhabditis elegans. PtNPs’ interesting physicochemical properties associated to the lack of toxicity in a tested range of concentrations, as well as their ability to modulate ICR-191 biological activity, suggest that these particles successfully work as potential delivery platforms for different biologically active substances.
Strain Engineering of Germanium Nanobeams by Electrostatic Actuation
Authors: Ayan Arman , Turkay Deniz , Unlu Buse , Naghinazhadahmadi Parisa , Oliaei Samad Nadimi Bavil , Boztug Cicek , Yerci Selcuk 
Published: March 2019

AbstractGermanium (Ge) is a promising material for the development of a light source compatible with the silicon microfabrication technology, even though it is an indirect-bandgap material in its bulk form. Among various techniques suggested to boost the light emission efficiency of Ge, the strain induction is capable of providing the wavelength tunability if the strain is applied via an external force. Here, we introduce a method to control the amount of the axial strain, and therefore the emission wavelength, on a suspended Ge nanobeam by an applied voltage. We demonstrate, based on mechanical and electrical simulations, that axial strains over 4% can be achieved without experiencing any mechanical and/or electrical failure. We also show that the non-uniform strain distribution on the Ge nanobeam as a result of the applied voltage enhances light emission over 6 folds as compared to a Ge nanobeam with a uniform strain distribution. We anticipate that electrostatic actuation of Ge nanobeams provides a suitable platform for the realization of the on-chip tunable-wavelength infrared light sources that can be monolithically integrated on Si chips.
Demonstration of End-to-End Automation of DNA Data Storage
Authors: Takahashi Christopher N. , Nguyen Bichlien H. , Strauss Karin , Ceze Luis 
Published: March 2019

AbstractSynthetic DNA has emerged as a novel substrate to encode computer data with the potential to be orders of magnitude denser than contemporary cutting edge techniques. However, even with the help of automated synthesis and sequencing devices, many intermediate steps still require expert laboratory technicians to execute. We have developed an automated end-to-end DNA data storage device to explore the challenges of automation within the constraints of this unique application. Our device encodes data into a DNA sequence, which is then written to a DNA oligonucleotide using a custom DNA synthesizer, pooled for liquid storage, and read using a nanopore sequencer and a novel, minimal preparation protocol. We demonstrate an automated 5-byte write, store, and read cycle with a modular design enabling expansion as new technology becomes available.
Unveiling the influence of device stiffness in single macromolecule unfolding
Authors: Florio G. , Puglisi G. 
Published: March 2019

AbstractSingle-molecule stretching experiments on DNA, RNA, and other biological macromolecules opened up the possibility of an impressive progress in many fields of life and medical sciences. The reliability of such experiments may be crucially limited by the possibility of determining the influence of the apparatus on the experimental outputs. Here we deduce a model that let us analytically evaluate such influence, fundamental for the interpretation of Single Molecule Force Spectroscopy experiments and intermolecular interactions phenomena. As we show, our model is coherent with previous numerical results and quantitively reproduce AFM experimental tests on titin macromolecules and P-selectin with variable probe stiffnesses.
In vitro micro-physiological model of the inflamed human adipose tissue for immune-metabolic analysis in type II diabetes
Authors: Kongsuphol Patthara , Gupta Shilpi , Liu Yunxiao , Bhuvanendran Nair Gourikutty Sajay , Biswas Subhra K. , Ramadan Qasem 
Published: March 2019

AbstractChronic inflammation mediated by the interaction of immune cells and adipocytes is a key underlying factor in obesity-associated type 2 diabetes mellitus (T2DM). Therefore, methods to investigate adipocyte-immune cells interaction and their immuno-metabolic status in obese/T2DM subjects not only serve as an early indicator of disease development but also provide an insight into disease mechanism. A microfluidic-basedin vitromodel of the human adipose that is interfaced with a co-culture of immune cell has been developed forin vitroimmune-metabolic analysis. This miniaturized system integrates a biologically activein vitrocellular system within a perfusion-based microfluidic device for mimicking the major processes that characterize the interaction of adipose tissue with immune cells. A viable immune competent model of the adipocytes/PBMCs co-culture has been demonstrated and characterized. Our testing results showed that the inflammatory cytokine profile obtained from the on-chip culture agrees with those from static transwell based co-culture with more intense responses observed in the chip-based system. The microfluidic chip also allows time-resolved measurement of cytokines that provide reliable data and detailed mechanisms of inflammation. In addition, glucose uptake by the adipocytes from the chip-based cultures showed correlated insulin responsivity/resistivity to the expression of the cytokine profile in different dynamic culture conditions. Testing of the known diabetic drug, metformin, and neutraceutical compound, omega-3, on-chip show agreeable results as compared to the previously reported data. This organotypic culture system offers a physiologically relevant model that exhibits a key characteristic of type 2 diabetic adipose tissues and can be used to study the T2DM mechanisms and diabetic drug screening.
Effect of planting patterns on yield, nutrient accumulation and distribution in maize and soybean under relay intercropping systems
Authors: Raza Muhammad Ali , Bin Khalid Muhammad Hayder , Zhang Xia , Feng Ling Yang , Khan Imran , Hassan Muhammad Jawad , Ahmed Mukhtar , Ansar Muhammad , Chen Yuan Kai , Fan Yuan Fang , Yang Feng , Yang Wenyu 
Published: March 2019

AbstractPlanting patterns affect nitrogen (N), phosphorus (P), and potassium (K) acquisition and distribution in maize and soybean under intercropping conditions. Here we reveal that strip relay-intercropping increases the N, P, and K uptake and distribution across plant organs (root, straw, and seed) of maize and soybean, accelerates the dry-matter production of intercrop-species, and compensates the slight maize yield loss by considerably increasing the soybean yield. In a two-year experiment, soybean was planted with maize in different planting patterns (SI, 50:50 cm and SII, 40:160 cm) of relay-intercropping, both planting patterns were compared with sole cropping of maize (SM) and soybean (SS). As compared to SI, SII increased the N, P, and K accumulation in each organ of soybean by 20, 32, and 18 (root) %, 71, 61, and 76 (straw) %, and 68, 65, and 62 (seed) %, respectively, whereas decreased the N, P, and K accumulation in each organ of maize by 1, 4, and 8 (root) %, 1, 10, and 3 (straw) %, and 5, 10, and 8 (seed) %, respectively. Overall, in SII, relay-cropped soybean accumulated 91% of total nutrient uptake (TNU) of sole soybean plants, and relay-cropped maize accumulated 94% of TNU of sole maize plants.