bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering protein assemblies with allosteric control via monomer fold-switching
Authors: Campos Luis A. , Sharma Rajendra , Alvira Sara , Ruiz Federico M. , Ibarra-Molero Beatriz , Sadqi Mourad , Alfonso Carlos , Rivas Germán , Sanchez-Ruiz Jose M. , Romero Garrido Antonio , Valpuesta José M. , Muñoz Victor 
Published: December 2019

AbstractThe macromolecular machines of life use allosteric control to self-assemble, dissociate and change shape in response to signals. Despite enormous interest, the design of nanoscale allosteric assemblies has proven tremendously challenging. Here we present a proof of concept of allosteric assembly in which an engineered fold switch on the protein monomer triggers or blocks assembly. Our design is based on the hyper-stable, naturally monomeric protein CI2, a paradigm of simple two-state folding, and the toroidal arrangement with 6-fold symmetry that it only adopts in crystalline form. We engineer CI2 to enable a switch between the native and an alternate, latent fold that self-assembles onto hexagonal toroidal particles by exposing a favorable inter-monomer interface. The assembly is controlled on demand via the competing effects of temperature and a designed short peptide. These findings unveil a remarkable potential for structural metamorphosis in proteins and demonstrate key principles for engineering protein-based nanomachinery.
Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4
Authors: Sato Yusuke , Tsuchiya Hikaru , Yamagata Atsushi , Okatsu Kei , Tanaka Keiji , Saeki Yasushi , Fukai Shuya 
Published: December 2019

AbstractNpl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast. Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase. Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4-binding motif of Ufd1. The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively. Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains. Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme. This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48–UN complex and its assembly.
Palladium-catalyzed Suzuki-Miyaura coupling of thioureas or thioamides
Authors: Mai Shaoyu , Li Wendong , Li Xue , Zhao Yingwei , Song Qiuling 
Published: December 2019

AbstractCross-coupling reactions involving metal carbene intermediates play an increasingly important role in C–C bond formation. Expanding the carbene precursors to a broader range of starting materials and more diverse products is an ongoing challenge in synthetic organic chemistry. Herein, we report a Suzuki-Miyaura coupling reaction of in situ-generated Pd–carbene complexes via desulfurization of thioureas or thioamides. This strategy enables the preparation of a broad array of substituted amidinium salts and unsymmetrical diaryl ketones. The reaction is readily scalable, compatible with bromo groups on aromatic rings, tolerant to moisture and air and has a broad substrate scope. Furthermore, a single crystal structure of Pd-diaminocarbene complex is obtained and proven to be the key intermediate in both catalytic and stoichiometric reactions. Preliminary mechanistic studies demonstrate the dual role of the silver salt as a desulfurating reagent assisting the elimination of sulfur and as oxidant facilitating the PdII/Pd0/PdII catalytic cycle.
Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients
Authors: Michalovich David , Rodriguez-Perez Noelia , Smolinska Sylwia , Pirozynski Michal , Mayhew David , Uddin Sorif , Van Horn Stephanie , Sokolowska Milena , Altunbulakli Can , Eljaszewicz Andrzej , Pugin Benoit , Barcik Weronika , Kurnik-Lucka Magdalena , Saunders Ken A. , Simpson Karen D. , Schmid-Grendelmeier Peter , Ferstl Ruth , Frei Remo , Sievi Noriane , Kohler Malcolm , Gajdanowicz Pawel , Graversen Katrine B. , Lindholm Bøgh Katrine , Jutel Marek , Brown James R. , Akdis Cezmi A. , Hessel Edith M. , O’Mahony Liam 
Published: December 2019

AbstractIn order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.
The effect of ω-3 polyunsaturated fatty acids on the liver lipidome, proteome and bile acid profile: parenteral versus enteral administration
Authors: Bechynska Kamila , Daskova Nikola , Vrzackova Nikola , Harant Karel , Heczková Marie , Podzimkova Katerina , Bratova Miriam , Dankova Helena , Berkova Zuzana , Kosek Vit , Zelenka Jaroslav , Hajslova Jana , Sedlacek Radislav , Suttnar Jiri , Hlavackova Alzbeta , Bartonova Lenka , Cahova Monika 
Published: December 2019

AbstractParenteral nutrition (PN) is often associated with the deterioration of liver functions (PNALD). Omega-3 polyunsaturated fatty acids (PUFA) were reported to alleviate PNALD but the underlying mechanisms have not been fully unraveled yet. Using omics´ approach, we determined serum and liver lipidome, liver proteome, and liver bile acid profile as well as markers of inflammation and oxidative stress in rats administered either ω-6 PUFA based lipid emulsion (Intralipid) or ω-6/ω-3 PUFA blend (Intralipid/Omegaven) via the enteral or parenteral route. In general, we found that enteral administration of both lipid emulsions has less impact on the liver than the parenteral route. Compared with parenterally administered Intralipid, PN administration of ω-3 PUFA was associated with 1. increased content of eicosapentaenoic (EPA)- and docosahexaenoic (DHA) acids-containing lipid species; 2. higher abundance of CYP4A isoenzymes capable of bioactive lipid synthesis and the increased content of their potential products (oxidized EPA and DHA); 3. downregulation of enzymes involved CYP450 drug metabolism what may represent an adaptive mechanism counteracting the potential negative effects (enhanced ROS production) of PUFA metabolism; 4. normalized anti-oxidative capacity and 5. physiological BAs spectrum. All these findings may contribute to the explanation of ω-3 PUFA protective effects in the context of PN.
Development of Aedes aegypti (Diptera: Culicidae) mosquito larvae in high ammonia sewage in septic tanks causes alterations in ammonia excretion, ammonia transporter expression, and osmoregulation
Authors: Durant Andrea C. , Donini Andrew 
Published: December 2019

AbstractLarvae of the disease vector mosquito, Aedes aegypti (L.) readily develop in ammonia rich sewage in the British Virgin Islands. To understand how the larvae survive in ammonia levels that are lethal to most animals, an examination of ammonia excretory physiology in larvae collected from septic-water and freshwater was carried out. A. aegypti larvae were found to be remarkably plastic in dealing with high external ammonia through the modulation of NH4+ excretion at the anal papillae, measured using the scanning ion-selective electrode technique (SIET), and NH4+ secretion in the primary urine by the Malpighian tubules when developing in septicwater. Ammonia transporters, Amt and Rh proteins, are expressed in ionoregulatory and excretory organs, with increases in Rh protein, Na+-K+-ATPase, and V-type-H+-ATPase expression observed in the Malpighian tubules, hindgut, and anal papillae in septic-water larvae. A comparative approach using laboratory A. aegypti larvae reared in high ammonia septic-water revealed similar responses to collected A. aegypti with regard to altered ammonia secretion and hemolymph ion composition. Results suggest that the observed alterations in excretory physiology of larvae developing in septic-water is a consequence of the high ammonia levels and that A. aegypti larvae may rely on ammonia transporting proteins coupled to active transport to survive in septic-water.
Genetic variations in olfactory receptor gene OR2AG2 in a large multigenerational family with asthma
Authors: Chakraborty Samarpana , Dakle Pushkar , Sinha Anirban , Vishweswaraiah Sangeetha , Nagori Aditya , Salimath Shivalingaswamy , Prakash Y. S. , Lodha R. , Kabra S. K. , Ghosh Balaram , Faruq Mohammed , Mahesh P. A. , Agrawal Anurag 
Published: December 2019

AbstractIt is estimated from twin studies that heritable factors account for at-least half of asthma-risk, of which genetic variants identified through population studies explain only a small fraction. Multi-generation large families with high asthma prevalence can serve as a model to identify highly penetrant genetic variants in closely related individuals that are missed by population studies. To achieve this, a four-generation Indian family with asthma was identified and recruited for examination and genetic testing. Twenty subjects representing all generations were selected for whole genome genotyping, of which eight were subjected to exome sequencing. Non-synonymous and deleterious variants, segregating with the affected individuals, were identified by exome sequencing. A prioritized deleterious missense common variant in the olfactory receptor gene OR2AG2 that segregated with a risk haplotype in asthma, was validated in an asthma cohort of different ethnicity. Phenotypic tests were conducted to verify expected deficits in terms of reduced ability to sense odors. Pathway-level relevance to asthma biology was tested in model systems and unrelated human lung samples. Our study suggests that OR2AG2 and other olfactory receptors may contribute to asthma pathophysiology. Genetic studies on large families of interest can lead to efficient discovery.
17α Estradiol promotes plasticity of spared inputs in the adult amblyopic visual cortex
Authors: Sengupta Deepali C. , Lantz Crystal L. , Rumi M. A. Karim , Quinlan Elizabeth M. 
Published: December 2019

AbstractThe promotion of structural and functional plasticity by estrogens is a promising approach to enhance central nervous system function in the aged. However, how the sensitivity to estrogens is regulated across brain regions, age and experience is poorly understood. To ask if estradiol treatment impacts structural and functional plasticity in sensory cortices, we examined the acute effect of 17α-Estradiol in adult Long Evans rats following chronic monocular deprivation, a manipulation that reduces the strength and selectivity of deprived eye vision. Chronic monocular deprivation decreased thalamic input from the deprived eye to the binocular visual cortex and accelerated short-term depression of the deprived eye pathway, but did not change the density of excitatory synapses in primary visual cortex. Importantly, we found that the classical estrogen receptors ERα and ERβ were robustly expressed in the adult visual cortex, and that a single dose of 17α-Estradiol reduced the expression of the calcium-binding protein parvalbumin, decreased the integrity of the extracellular matrix and increased the size of excitatory postsynaptic densities. Furthermore, 17α-Estradiol enhanced experience-dependent plasticity in the amblyopic visual cortex, by promoting response potentiation of the pathway served by the non-deprived eye. The promotion of plasticity at synapses serving the non-deprived eye may reflect selectivity for synapses with an initially low probability of neurotransmitter release, and may inform strategies to remap spared inputs around a scotoma or a cortical infarct.
Selective synthesis of spirobiindanes, alkenyl chlorides, and monofluoroalkenes from unactivated gem-difluoroalkanes controlled by aluminum-based Lewis acids
Authors: Wang Jiandong , Ogawa Yuta , Shibata Norio 
Published: December 2019

AbstractThe highly selective synthesis of spirobiindanes, alkenyl chlorides, and monofluoroalkenes via the cleavage of inert C(sp3)–F bonds in unactivated gem-difluoroalkanes using readily available and inexpensive aluminum-based Lewis acids of low toxicity is reported. The selectivity of this reaction can be controlled by modifying the substituents on the central aluminum atom of the promoter. An intramolecular cascade Friedel-Crafts alkylation of unactivated gem-difluorocarbons can be achieved using a stoichiometric amount of AlCl3. The subsequent synthesis of alkenyl chlorides via F/Cl exchange followed by an elimination can be accomplished using AlEt2Cl as a fluoride scavenger and halogen source. The defluorinative elimination of acyclic and cyclic gem-difluorocarbons to give monofluoroalkenes can be achieved using AlEt3.
Tunable High Spatio-Spectral Purity Undulator Radiation from a Transported Laser Plasma Accelerated Electron Beam
Authors: Ghaith A. , Oumbarek D. , Roussel E. , Corde S. , Labat M. , André T. , Loulergue A. , Andriyash I. A. , Chubar O. , Kononenko O. , Smartsev S. , Marcouillé O. , Kitégi C. , Marteau F. , Valléau M. , Thaury C. , Gautier J. , Sebban S. , Tafzi A. , Blache F. , Briquez F. , Tavakoli K. , Carcy A. , Bouvet F. , Dietrich Y. , Lambert G. , Hubert N. , El Ajjouri M. , Polack F. , Dennetière D. , Leclercq N. , Rommeluère P. , Duval J.-P. , Sebdaoui M. , Bourgoin C. , Lestrade A. , Benabderrahmane C. , Vétéran J. , Berteaud P. , De Oliveira C. , Goddet J. P. , Herbeaux C. , Szwaj C. , Bielawski S. , Malka V. , Couprie M.-E. 
Published: December 2019

AbstractUndulator based synchrotron light sources and Free Electron Lasers (FELs) are valuable modern probes of matter with high temporal and spatial resolution. Laser Plasma Accelerators (LPAs), delivering GeV electron beams in few centimeters, are good candidates for future compact light sources. However the barriers set by the large energy spread, divergence and shot-to-shot fluctuations require a specific transport line, to shape the electron beam phase space for achieving ultrashort undulator synchrotron radiation suitable for users and even for achieving FEL amplification. Proof-of-principle LPA based undulator emission, with strong electron focusing or transport, does not yet exhibit the full specific radiation properties. We report on the generation of undulator radiation with an LPA beam based manipulation in a dedicated transport line with versatile properties. After evidencing the specific spatio-spectral signature, we tune the resonant wavelength within 200–300 nm by modification of the electron beam energy and the undulator field. We achieve a wavelength stability of 2.6%. We demonstrate that we can control the spatio-spectral purity and spectral brightness by reducing the energy range inside the chicane. We have also observed the second harmonic emission of the undulator.
A reporter mouse for non-invasive detection of toll-like receptor ligands induced acute phase responses
Authors: Huang Chun-Fang , Chiu Shang-Yi , Huang Hung-Wen , Cheng Bing-Ho , Pan Hsiu-Min , Huang Wei-Lun , Chang Hsiao-Hui , Liao Chia-Chi , Jiang Si-Tse , Su Yu-Chia 
Published: December 2019

AbstractThe acute phase response (APR) is a systemic first-line defense against challenges including infection, trauma, stress, and neoplasia. Alteration of acute phase protein (APP) levels in plasma is the most important change during acute phase response. C-reactive protein (CRP), which increases dramatically during inflammation onset, is an indicator of inflammation. To monitor the process of APR, we generated human CRP promoter-driven luciferase transgenic (hCRP-Luc) mice to quantify the hCRP promoter activationin vivo. The naïve female hCRP-Luc mice express low basal levels of liver bioluminescence, but the naïve male hCRP-Luc mice do not. Thus, female hCRP-Luc mice are suitable for monitoring the process of APR. The liver bioluminescence of female hCRP-Luc mice can be induced by several toll-like receptor (TLR) ligands. The expression of liver bioluminescence was highly sensitive to endotoxin stimulation in a dose-dependent manner. On-off-on bioluminescence response was noted in female hCRP-Luc mice upon two endotoxin stimulations one month apart. The LPS-induced bioluminescence of the female hCRP-Luc mice was IL-6-mediated and associated with APP alpha-1-acid glycoprotein expression. In conclusion, the female hCRP-Luc mouse is a non-invasive, sensitive and reusable reporter tool for APR.
Unsupervised Pre-training of a Deep LSTM-based Stacked Autoencoder for Multivariate Time Series Forecasting Problems
Authors: Sagheer Alaa , Kotb Mostafa 
Published: December 2019

AbstractCurrently, most real-world time series datasets are multivariate and are rich in dynamical information of the underlying system. Such datasets are attracting much attention; therefore, the need for accurate modelling of such high-dimensional datasets is increasing. Recently, the deep architecture of the recurrent neural network (RNN) and its variant long short-term memory (LSTM) have been proven to be more accurate than traditional statistical methods in modelling time series data. Despite the reported advantages of the deep LSTM model, its performance in modelling multivariate time series (MTS) data has not been satisfactory, particularly when attempting to process highly non-linear and long-interval MTS datasets. The reason is that the supervised learning approach initializes the neurons randomly in such recurrent networks, disabling the neurons that ultimately must properly learn the latent features of the correlated variables included in the MTS dataset. In this paper, we propose a pre-trained LSTM-based stacked autoencoder (LSTM-SAE) approach in an unsupervised learning fashion to replace the random weight initialization strategy adopted in deep LSTM recurrent networks. For evaluation purposes, two different case studies that include real-world datasets are investigated, where the performance of the proposed approach compares favourably with the deep LSTM approach. In addition, the proposed approach outperforms several reference models investigating the same case studies. Overall, the experimental results clearly show that the unsupervised pre-training approach improves the performance of deep LSTM and leads to better and faster convergence than other models.
Advanced P Wave Detection in Ecg Signals During Pathology: Evaluation in Different Arrhythmia Contexts
Authors: Maršánová Lucie , Němcová Andrea , Smíšek Radovan , Vítek Martin , Smital Lukáš 
Published: December 2019

AbstractReliable P wave detection is necessary for accurate and automatic electrocardiogram (ECG) analysis. Currently, methods for P wave detection in physiological conditions are well-described and efficient. However, methods for P wave detection during pathology are not generally found in the literature, or their performance is insufficient. This work introduces a novel method, based on a phasor transform, as well as innovative rules that improve P wave detection during pathology. These rules are based on the extraction of a heartbeats’ morphological features and knowledge of heart manifestation during both physiological and pathological conditions. To properly evaluate the performance of the proposed algorithm in pathological conditions, a standard database with a sufficient number of reference P wave positions is needed. However, such a database did not exist. Thus, ECG experts annotated 12 chosen pathological records from the MIT-BIH Arrhythmia Database. These annotations are publicly available via Physionet. The algorithm performance was also validated using physiological records from the MIT-BIH Arrhythmia and QT databases. The results for physiological signals were Se = 98.42% and PP = 99.98%, which is comparable to other methods. For pathological signals, the proposed method reached Se = 96.40% and PP = 85.84%, which greatly outperforms other methods. This improvement represents a huge step towards fully automated analysis systems being respected by ECG experts. These systems are necessary, particularly in the area of long-term monitoring.
Differential impedance spectra analysis reveals optimal actuation frequency in bulk mode acoustophoresis
Authors: Vitali Valentina , Core Giulia , Garofalo Fabio , Laurell Thomas , Lenshof Andreas 
Published: December 2019

AbstractThis work reports a method to select the optimal working frequency in transversal bulk resonator acoustophoretic devices by electrical impedance measurements. The impedance spectra of acoustophoretic devices are rich in spurious resonance peaks originating from different resonance modes in the system not directly related to the channel resonance, why direct measurement of the piezoelectric transducer impedance spectra is not a viable strategy. This work presents, for the first time, that the resonance modes of microchip integrated acoustophoresis channels can be identified by sequentially measuring the impedance spectra of the acoustophoretic device when the channel is filled with two different fluids and subsequently calculate the Normalized Differential Spectrum (NDS). Seven transversal bulk resonator acoustophoretic devices of different materials and designs were tested with successful results. The developed method enables a rapid, reproducible and precise determination of the optimal working frequency.
The amount of available food affects diurnal locomotor activity in migratory songbirds during stopover
Authors: Ferretti Andrea , Maggini Ivan , Lupi Sara , Cardinale Massimiliano , Fusani Leonida 
Published: December 2019

AbstractMigratory passerine birds fly long distances twice a year alternating nocturnal flights with stopovers to rest and replenish energy stores. The duration of each stopover depends on several factors including internal clocks, meteorological conditions, and environmental factors such as availability of food. Foraging entails energetic costs, and if birds need to refuel efficiently, they should modulate their activity in relation to food availability. We investigated how food availability influences locomotor activity in migrating birds of six passerine species at a spring stopover site in the central Mediterranean Sea. We selected birds with low fat scores which we expected to be strongly motivated to refuel. We simulated stopover sites of different quality by providing temporarily caged birds with different amounts of food to simulate scarce to abundant food. We analysed the diurnal locomotory activity as a proxy for food searching effort. Low food availability resulted in an increased diurnal locomotor activity in almost all species, while all birds showed low intensity of nocturnal migratory restlessness. In conclusion, our study shows that food availability in an important determinant of behaviour of migratory birds at stopover sites.