bluuebunny/crossref_metadata_2025 huggingface dataset:
The cartilage matrisome in adolescent idiopathic scoliosis
Authors: Wise Carol A. , Sepich Diane , Ushiki Aki , Khanshour Anas M. , Kidane Yared H. , Makki Nadja , Gurnett Christina A. , Gray Ryan S. , Rios Jonathan J. , Ahituv Nadav , Solnica-Krezel Lila
Published: March 2020

The human spinal column is a dynamic, segmented, bony, and cartilaginous structure that protects the neurologic system and simultaneously provides balance and flexibility. Children with developmental disorders that affect the patterning or shape of the spine can be at risk of neurologic and other physiologic dysfunctions. The most common developmental disorder of the spine is scoliosis, a lateral deformity in the shape of the spinal column. Scoliosis may be part of the clinical spectrum that is observed in many developmental disorders, but typically presents as an isolated symptom in otherwise healthy adolescent children. Adolescent idiopathic scoliosis (AIS) has defied understanding in part due to its genetic complexity. Breakthroughs have come from recent genome-wide association studies (GWAS) and next generation sequencing (NGS) of human AIS cohorts, as well as investigations of animal models. These studies have identified genetic associations with determinants of cartilage biogenesis and development of the intervertebral disc (IVD). Current evidence suggests that a fraction of AIS cases may arise from variation in factors involved in the structural integrity and homeostasis of the cartilaginous extracellular matrix (ECM). Here, we review the development of the spine and spinal cartilages, the composition of the cartilage ECM, the so-called “matrisome” and its functions, and the players involved in the genetic architecture of AIS. We also propose a molecular model by which the cartilage matrisome of the IVD contributes to AIS susceptibility.
Imatinib in combination with phosphoinositol kinase inhibitor buparlisib in patients with gastrointestinal stromal tumour who failed prior therapy with imatinib and sunitinib: a Phase 1b, multicentre study
Authors: Gelderblom Hans , Jones Robin L. , George Suzanne , Valverde Morales Claudia , Benson Charlotte , Jean-Yves Blay  , Renouf Daniel J. , Doi Toshihiko , Le Cesne Axel , Leahy Michael , Hertle Sabine , Aimone Paola , Brandt Ulrike , Schӧffski Patrick
Published: March 2020

Background

The majority of patients with advanced gastrointestinal stromal tumours (GISTs) develop resistance to imatinib and sunitinib, the standard of care for these patients. This study evaluated the combination of buparlisib, an oral phosphoinositide 3-kinase (PI3K) inhibitor, with imatinib in patients with advanced GIST, who have failed prior therapy with imatinib and sunitinib.

Methods

This Phase 1b, multicentre, open-label study aimed to determine the maximum tolerated dose (MTD) and/or a recommended Phase 2 dose of buparlisib in combination with 400 mg of imatinib through a dose-escalation part and a dose-expansion part, and also evaluated the clinical profile of the combination.

Results

Sixty patients were enrolled, including 25 in the dose-escalation part and 35 in the dose-expansion part. In the combination, MTD of buparlisib was established as 80 mg. No partial or complete responses were observed. The estimated median progression-free survival was 3.5 months in the expansion phase. Overall, 98.3% of patients had treatment-related adverse events (AEs), including 45% with grade 3 or 4 AEs.

Conclusions

Buparlisib in combination with imatinib provided no additional benefit compared with currently available therapies. Due to the lack of objective responses, further development of this combination was not pursued for third-line/fourth-line advanced/metastatic GIST.

Trial registration number

NCT01468688.
Resolving Dirac electrons with broadband high-resolution NMR
Authors: Papawassiliou Wassilios , Jaworski Aleksander , Pell Andrew J. , Jang Jae Hyuck , Kim Yeonho , Lee Sang-Chul , Kim Hae Jin , Alwahedi Yasser , Alhassan Saeed , Subrati Ahmed , Fardis Michael , Karagianni Marina , Panopoulos Nikolaos , Dolinšek Janez , Papavassiliou Georgios
Published: March 2020

Detecting the metallic Dirac electronic states on the surface of Topological Insulators (TIs) is critical for the study of important surface quantum properties (SQPs), such as Majorana zero modes, where simultaneous probing of the bulk and edge electron states is required. However, there is a particular shortage of experimental methods, showing at atomic resolution how Dirac electrons extend and interact with the bulk interior of nanoscaled TI systems. Herein, by applying advanced broadband solid-state 125Te nuclear magnetic resonance (NMR) methods on Bi2Te3 nanoplatelets, we succeeded in uncovering the hitherto invisible NMR signals with magnetic shielding that is influenced by the Dirac electrons, and we subsequently showed how the Dirac electrons spread inside the nanoplatelets. In this way, the spin and orbital magnetic susceptibilities induced by the bulk and edge electron states were simultaneously measured at atomic scale resolution, providing a pertinent experimental approach in the study of SQPs.
Diffuse X-ray scattering from correlated motions in a protein crystal
Authors: Meisburger Steve P. , Case David A. , Ando Nozomi
Published: March 2020

Protein dynamics are integral to biological function, yet few techniques are sensitive to collective atomic motions. A long-standing goal of X-ray crystallography has been to combine structural information from Bragg diffraction with dynamic information contained in the diffuse scattering background. However, the origin of macromolecular diffuse scattering has been poorly understood, limiting its applicability. We present a finely sampled diffuse scattering map from triclinic lysozyme with unprecedented accuracy and detail, clearly resolving both the inter- and intramolecular correlations. These correlations are studied theoretically using both all-atom molecular dynamics and simple vibrational models. Although lattice dynamics reproduce most of the diffuse pattern, protein internal dynamics, which include hinge-bending motions, are needed to explain the short-ranged correlations revealed by Patterson analysis. These insights lay the groundwork for animating crystal structures with biochemically relevant motions.
A progesterone biosensor derived from microbial screening
Authors: Grazon Chloé , Baer R C. , Kuzmanović Uroš , Nguyen Thuy , Chen Mingfu , Zamani Marjon , Chern Margaret , Aquino Patricia , Zhang Xiaoman , Lecommandoux Sébastien , Fan Andy , Cabodi Mario , Klapperich Catherine , Grinstaff Mark W. , Dennis Allison M. , Galagan James E.
Published: March 2020

Bacteria are an enormous and largely untapped reservoir of biosensing proteins. We describe an approach to identify and isolate bacterial allosteric transcription factors (aTFs) that recognize a target analyte and to develop these TFs into biosensor devices. Our approach utilizes a combination of genomic screens and functional assays to identify and isolate biosensing TFs, and a quantum-dot Förster Resonance Energy Transfer (FRET) strategy for transducing analyte recognition into real-time quantitative measurements. We use this approach to identify a progesterone-sensing bacterial aTF and to develop this TF into an optical sensor for progesterone. The sensor detects progesterone in artificial urine with sufficient sensitivity and specificity for clinical use, while being compatible with an inexpensive and portable electronic reader for point-of-care applications. Our results provide proof-of-concept for a paradigm of microbially-derived biosensors adaptable to inexpensive, real-time sensor devices.
Nanocrystal facet modulation to enhance transferrin binding and cellular delivery
Authors: Qi Yu , Zhang Tong , Jing Chuanyong , Liu Sijin , Zhang Chengdong , Alvarez Pedro J. J. , Chen Wei
Published: March 2020

Binding of biomolecules to crystal surfaces is critical for effective biological applications of crystalline nanomaterials. Here, we present the modulation of exposed crystal facets as a feasible approach to enhance specific nanocrystal–biomolecule associations for improving cellular targeting and nanomaterial uptake. We demonstrate that facet-engineering significantly enhances transferrin binding to cadmium chalcogenide nanocrystals and their subsequent delivery into cancer cells, mediated by transferrin receptors, in a complex biological matrix. Competitive adsorption experiments coupled with theoretical calculations reveal that the (100) facet of cadmoselite and (002) facet of greenockite preferentially bind with transferrin via inner-sphere thiol complexation. Molecular dynamics simulation infers that facet-dependent transferrin binding is also induced by the differential affinity of crystal facets to water molecules in the first solvation shell, which affects access to exposed facets. Overall, this research underlines the promise of facet engineering to improve the efficacy of crystalline nanomaterials in biological applications.
Divergent receptor proteins confer responses to different karrikins in two ephemeral weeds
Authors: Sun Yueming Kelly , Yao Jiaren , Scaffidi Adrian , Melville Kim T. , Davies Sabrina F. , Bond Charles S. , Smith Steven M. , Flematti Gavin R. , Waters Mark T.
Published: March 2020

Wildfires can encourage the establishment of invasive plants by releasing potent germination stimulants, such as karrikins. Seed germination of Brassica tournefortii, a noxious weed of Mediterranean climates, is strongly stimulated by KAR1, the archetypal karrikin produced from burning vegetation. In contrast, the closely-related yet non-fire-associated ephemeral Arabidopsisthaliana is unusual because it responds preferentially to KAR2. The α/β-hydrolase KARRIKIN INSENSITIVE 2 (KAI2) is the putative karrikin receptor identified in Arabidopsis. Here we show that B. tournefortii expresses three KAI2 homologues, and the most highly-expressed homologue is sufficient to confer enhanced responses to KAR1 relative to KAR2 when expressed in Arabidopsis. We identify two amino acid residues near the KAI2 active site that explain the ligand selectivity, and show that this combination has arisen independently multiple times within dicots. Our results suggest that duplication and diversification of KAI2 proteins could confer differential responses to chemical cues produced by environmental disturbance, including fire.
Hyperoxia induces glutamine-fuelled anaplerosis in retinal Müller cells
Authors: Singh Charandeep , Tran Vincent , McCollum Leah , Bolok Youstina , Allan Kristin , Yuan Alex , Hoppe George , Brunengraber Henri , Sears Jonathan E.
Published: March 2020

Although supplemental oxygen is required to promote survival of severely premature infants, hyperoxia is simultaneously harmful to premature developing tissues such as in the retina. Here we report the effect of hyperoxia on central carbon metabolism in primary mouse Müller glial cells and a human Müller glia cell line (M10-M1 cells). We found decreased flux from glycolysis entering the tricarboxylic acid cycle in Müller cells accompanied by increased glutamine consumption in response to hyperoxia. In hyperoxia, anaplerotic catabolism of glutamine by Müller cells increased ammonium release two-fold. Hyperoxia induces glutamine-fueled anaplerosis that reverses basal Müller cell metabolism from production to consumption of glutamine.
Enhanced optical path and electron diffusion length enable high-efficiency perovskite tandems
Authors: Chen Bin , Baek Se-Woong , Hou Yi , Aydin Erkan , De Bastiani Michele , Scheffel Benjamin , Proppe Andrew , Huang Ziru , Wei Mingyang , Wang Ya-Kun , Jung Eui-Hyuk , Allen Thomas G. , Van Kerschaver Emmanuel , García de Arquer F. Pelayo , Saidaminov Makhsud I. , Hoogland Sjoerd , De Wolf Stefaan , Sargent Edward H.
Published: March 2020

Tandem solar cells involving metal-halide perovskite subcells offer routes to power conversion efficiencies (PCEs) that exceed the single-junction limit; however, reported PCE values for tandems have so far lain below their potential due to inefficient photon harvesting. Here we increase the optical path length in perovskite films by preserving smooth morphology while increasing thickness using a method we term boosted solvent extraction. Carrier collection in these films – as made – is limited by an insufficient electron diffusion length; however, we further find that adding a Lewis base reduces the trap density and enhances the electron-diffusion length to 2.3 µm, enabling a 19% PCE for 1.63 eV semi-transparent perovskite cells having an average near-infrared transmittance of 85%. The perovskite top cell combined with solution-processed colloidal quantum dot:organic hybrid bottom cell leads to a PCE of 24%; while coupling the perovskite cell with a silicon bottom cell yields a PCE of 28.2%.
Intermolecular [3+3] ring expansion of aziridines to dehydropiperi-dines through the intermediacy of aziridinium ylides
Authors: Eshon Josephine , Nicastri Kate A. , Schmid Steven C. , Raskopf William T. , Guzei Ilia A. , Fernández Israel , Schomaker Jennifer M.
Published: March 2020

The importance of N-heterocycles in drugs has stimulated diverse methods for their efficient syntheses. Methods that introduce significant stereochemical complexity are attractive for identifying new bioactive amine chemical space. Here, we report a [3 + 3] ring expansion of bicyclic aziridines and rhodium-bound vinyl carbenes to form complex dehydropiperidines in a highly stereocontrolled rearrangement. Mechanistic studies and DFT computations indicate that the reaction proceeds through formation of a vinyl aziridinium ylide; this reactive intermediate undergoes a pseudo-[1,4]-sigmatropic rearrangement to directly furnish heterocyclic products with net retention at the new C-C bond. In combination with asymmetric silver-catalyzed aziridination, enantioenriched scaffolds with up to three contiguous stereocenters are rapidly delivered. The mild reaction conditions, functional group tolerance, and high stereospecificity of this method are well-suited for appending piperidine motifs to natural product and complex molecules. Ultimately, our work establishes the value of underutilized aziridinium ylides as key intermediates for converting small, strained rings to larger N-heterocycles.
Quantifying bone marrow fat using standard T1-weighted magnetic resonance images in children with typical development and in children with cerebral palsy
Authors: Zhang Chuan , Slade Jill M. , Miller Freeman , Modlesky Christopher M.
Published: March 2020

Excess bone marrow adiposity may have a negative effect on bone growth and development. The aim of this study was to determine whether a procedure using standard T1-weighted magnetic resonance images provides an accurate estimate of bone marrow fat in children with typical development and in children with mild spastic cerebral palsy (CP; n = 15/group; 4–11 y). Magnetic resonance imaging was used to acquire T1-weighted images. It was also used to acquire fat and water images using an iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) technique. Bone marrow fat volume and fat fraction in the middle-third of the tibia were determined using the standard T1-weighted images (BMFVT1 and BMFFT1, respectively) and the fat and water images (BMFVIDEAL and BMFFIDEAL, respectively). In both groups, BMFVT1 was highly correlated with (both r > 0.99, p < 0.001) and not different from (both p > 0.05) BMFVIDEAL. In both groups, BMFFT1 was moderately correlated with (both r = 0.71, p < 0.01) and not different from (both p > 0.05) BMFFIDEAL. There was no group difference in BMFVT1 or BMFVIDEAL (both p > 0.05). BMFFIDEAL was higher in children with CP (p < 0.05), but there was no group difference in BMFFT1 (p > 0.05). We conclude that a procedure using standard T1-weighted magnetic resonance images can produce estimates of bone marrow fat volume similar to estimates from the IDEAL technique in children. However, it is less sensitive to variation in the bone marrow fat fraction.
Efficiency and irreversibility of movements in a city
Authors: Biazzo Indaco , Ramezanpour Abolfazl
Published: March 2020

We know that maximal efficiency in physical systems is attained by reversible processes. It is then interesting to see how irreversibility affects efficiency in other systems, e.g., in a city. In this study, we focus on a cyclic process of movements (home to workplace and back to home) in a city to investigate the above question. To this end, we present a minimal model of the movements, along with plausible definitions for the efficiency and irreversibility of the process; more precisely, we take the inverse of the total travel time per number of trips for efficiency and the relative entropy of the forward and backward flow distributions for the process irreversibility. We perform numerical simulations of the model for reasonable choices of the population distribution, the mobility law, and the movement strategy. The results show that the efficiency of movements is indeed negatively correlated with the above measure of irreversibility. The structure of the network and the impact of the flows on the travel times are the main factors here that affect the time intervals of arriving to destinations and returning to origins, which are usually larger than the time interval of the departures. This in turn gives rise to diverging of the backward flows from the forward ones and results to entropy (disorder or uncertainty) production in the system. The findings of this study might be helpful in characterizing more accurately the city efficiency and in better understanding of the main working principles of these complex systems.
Three-dimensional observation and analysis of remineralization in dentinal caries lesions
Authors: Yoshihara Kumiko , Nagaoka Noriyuki , Nakamura Akiko , Hara Toru , Hayakawa Satoshi , Yoshida Yasuhiro , Van Meerbeek Bart
Published: March 2020

The remineralization mechanism in dental caries lesions is not completely understood. This study reports on ultrastructural and chemical changes observed within arrested caries lesions. Carious human teeth were observed using scanning electron microscopy (SEM) and focused-ion-beam (FIB)-SEM. The crystals detected in the caries lesions were characterized by transmission electron microscopy (TEM), along with chemical element mapping using energy-dispersive spectroscopy (EDS)-STEM. FIB-SEM 3D reconstructions revealed a severely damaged dentin surface abundantly covered by bacteria. Although the dentin tubules were clogged up to a depth of 100 μm, bacterial invasion into dentin tubules was not observed. TEM crystal analysis and EDS-STEM revealed the presence of Ca and P, as well as of Mg within the HAp crystals deposited inside the dentin tubules. It was concluded that extensive remineralization with deposition of Mg-HAp crystals had occurred in dentin tubules of caries-arrested dentin. Understanding the natural remineralization process is thought to be helpful for developing clinical biomimetic remineralization protocols.
Biocompatible Mesoporous Hollow Carbon Nanocapsules for High Performance Supercapacitors
Authors: Wang Lijian , Liu Fenghua , Ning Yuesheng , Bradley Robert , Yang Chengbin , Yong Ken-Tye , Zhao Binyuan , Wu Weiping
Published: March 2020

A facile and general method for the controllable synthesis of N-doped hollow mesoporous carbon nanocapsules (NHCNCs) with four different geometries has been developed. The spheres (NHCNC-1), low-concaves (NHCNC-2), semi-concaves (NHCNC-3) and wrinkles (NHCNC-4) shaped samples were prepared and systematically investigated to understand the structural effects of hollow particles on their supercapacitor performances. Compared with the other three different shaped samples (NHCNC-1, NHCNC-2, and NHCNC-4), the as-synthesized semi-concave structured NHCNC-3 demonstrated excellent performance with high gravimetric capacitance of 326 F g−1 (419 F cm−3) and ultra-stable cycling stability (96.6% after 5000 cycles). The outstanding performances achieved are attributed to the unique semi-concave structure, high specific surface area (1400 m2 g−1), hierarchical porosity, high packing density (1.41 g cm−3) and high nitrogen (N) content (up to 3.73%) of the new materials. These carbon nanocapsules with tailorable structures and properties enable them as outstanding carriers and platforms for various emerging applications, such as nanoscale chemical reactors, catalysis, batteries, solar energy harvest, gas storage and so on. In addition, these novel carbons have negligible cytotoxicity and high biocompatibility for human cells, promising a wide range of bio applications, such as biomaterials, drug delivery, biomedicine, biotherapy and bioelectronic devices.
Electrochemical and thermodynamic study on the corrosion performance of API X120 steel in 3.5% NaCl solution
Authors: Shahzad Khuram , Sliem Mostafa H. , Shakoor R. A. , Radwan A. Bahgat , Kahraman Ramazan , Umer Malik Adeel , Manzoor Umair , Abdullah Aboubakr M.
Published: March 2020

The present work studied the effect of temperature on the corrosion behavior of API X120 steel in a saline solution saturated with CO2 in absence and presence of polyethyleneimine (PEI) as an environmentally safe green inhibitor. The effect of PEI on the corrosion behavior of API X120 steel was investigated using destructive and non-destructive electrochemical techniques. The overall results revealed that PEI significantly decreases the corrosion rate of API X120 steel with inhibition efficiency of 94% at a concentration of 100 μmol L−1. The adsorption isotherm, activation energy and the thermodynamic parameters were deduced from the electrochemical results. It is revealed that the adsorption of PEI on API X120 steel surface follows Langmuir adsorption isotherm adopting a Physi-chemisorption mechanism. Finally, the samples were characterized using scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques to elucidate the effect of aggressiveness of corrosive media on the surface morphology and the corrosion performance of API X120 steel. The surface topography result indicates that the API X120 steel interface in PEI presence is smoother than CO2 with Cl− ions or Cl− ions only. This is attributed to the compact protective film limits the aggressive ions transfer towards the metallic surface and reduces the corrosion rate. Moreover, PEI inhibition mechanism is based on its CO2 capturing ability and the PEI adsorption on the steel surface beside the siderite layer which give the PEI molecules the ability to reduce the scale formation and increase the corrosion protection due to capturing the CO2 from the brine solution.
The Value of Cardiopulmonary Exercise Testing in Determining Severity in Patients with both Systolic Heart Failure and COPD
Authors: Goulart Cássia da Luz , dos Santos Polliana Batista , Caruso Flávia Rossi , Arêas Guilherme Peixoto Tinoco , Marinho Renan Shida , Camargo Patricia de Faria , Alexandre Tiago da Silva , Oliveira Claudio R. , da Silva Andréa Lúcia Gonçalves , Mendes Renata Gonçalves , Roscani Meliza Goi , Borghi-Silva Audrey
Published: March 2020

Our aim was to identify optimal cardiopulmonary exercise testing (CPET) threshold values that distinguish disease severity progression in patients with co-existing systolic heart failure (HF) and chronic obstructive pulmonary disease (COPD), and to evaluate the impact of the cut-off determined on the prognosis of hospitalizations. We evaluated 40 patients (30 men and 10 woman) with HF and COPD through pulmonary function testing, doppler echocardiography and maximal incremental CPET on a cycle ergometer. Several significant CPET threshold values were identified in detecting a forced expiratory volume in 1 second (FEV1) < 1.6 L: 1) oxygen uptake efficiency slope (OUES) < 1.3; and 2) circulatory power (CP) < 2383 mmHg.mlO2.kg−1. CPET significant threshold values in identifying a left ventricular ejection fraction (LVEF) < 39% were: 1) OUES: < 1.3; 2) CP < 2116 mmHg.mlO2.kg−1.min−1 and minute ventilation/carbon dioxide production (V̇E/V̇CO2) slope>38. The 15 (38%) patients hospitalized during follow-up (8 ± 2 months). In the hospitalizations analysis, LVEF < 39% and FEV1 < 1.6, OUES < 1.3, CP < 2116 mmHg.mlO2.kg−1.min−1 and V̇E/V̇CO2 > 38 were a strong risk predictor for hospitalization (P ≤ 0.050). The CPET response effectively identified worsening disease severity in patients with a HF-COPD phenotype. LVEF, FEV1, CP, OUES, and the V̇E/V̇CO2 slope may be particularly useful in the clinical assessment and strong risk predictor for hospitalization.
Comparison of several Real-Time PCR Kits versus a Culture-dependent Algorithm to Identify Enteropathogens in Stool Samples
Authors: Valledor Silvia , Valledor Inés , Gil-Rodríguez María Concepción , Seral Cristina , Castillo Javier
Published: March 2020

This study aims to validate the current diagnostic method for the clinical detection of gastroenteritis. We analyzed 400 stool samples to detect three of the most common enteropathogens: Salmonella spp., Campylobacter spp., and Yersinia enterocolitica. All specimens were tested with a routine clinical diagnosis algorithm and with five real-time PCR assays. A total of 98 specimens (24.5%) were positive for enteropathogens. We found 24 samples positive for Salmonella enterica, 71 positive for Campylobacter spp., and 4 positive for Yersinia enterocolitica. All evaluated methods exhibited a good performance in identifying Salmonella and Yersinia enterocolitica, being the highest positive percent agreement (PPA) value of 95.8% and 100%, respectively. The clinical algorithm showed the highest PPA value identifying Salmonella, due to the enrichment in selenite broth. However, the evaluated methods showed notable differences in the identification of Campylobacter species, obtaining a wide range of PPA values: 59.2%–100%. The clinical algorithm showed the lowest PPA value since it was only able to detect Campylobacter jejuni and Campylobacter coli species. This study revealed the importance of implementing the real-time PCR technique in a clinical algorithm: it improved the accuracy of the diagnosis and provided results in a shorter time compared to routine clinical methods.
Neighborhood Preference of Amino Acids in Protein Structures and its Applications in Protein Structure Assessment
Authors: Liu Siyuan , Xiang Xilun , Gao Xiang , Liu Haiguang
Published: March 2020

Amino acids form protein 3D structures in unique manners such that the folded structure is stable and functional under physiological conditions. Non-specific and non-covalent interactions between amino acids exhibit neighborhood preferences. Based on structural information from the protein data bank, a statistical energy function was derived to quantify amino acid neighborhood preferences. The neighborhood of one amino acid is defined by its contacting residues, and the energy function is determined by the neighboring residue types and relative positions. The neighborhood preference of amino acids was exploited to facilitate structural quality assessment, which was implemented in the neighborhood preference program NEPRE. The source codes are available via https://github.com/LiuLab-CSRC/NePre.
X-ray Crystallography and Electron Paramagnetic Resonance Spectroscopy Reveal Active Site Rearrangement of Cold-Adapted Inorganic Pyrophosphatase
Authors: Horitani Masaki , Kusubayashi Kazuki , Oshima Kyoka , Yato Akane , Sugimoto Hiroshi , Watanabe Keiichi
Published: March 2020

Inorganic pyrophosphatase (PPase) catalyses the hydrolysis reaction of inorganic pyrophosphate to phosphates. Our previous studies showed that manganese (Mn) activated PPase from the psychrophilic bacterium Shewanella sp. AS-11 (Mn-Sh-PPase) has a characteristic temperature dependence of the activity with an optimum at 5 °C. Here we report the X-ray crystallography and electron paramagnetic resonance (EPR) spectroscopy structural analyses of Sh-PPase in the absence and presence of substrate analogues. We successfully determined the crystal structure of Mn-Sh-PPase without substrate and Mg-activated Sh-PPase (Mg-Sh-PPase) complexed with substrate analogue (imidodiphosphate; PNP). Crystallographic studies revealed a bridged water placed at a distance from the di-Mn centre in Mn-Sh-PPase without substrate. The water came closer to the metal centre when PNP bound. EPR analysis of Mn-Sh-PPase without substrate revealed considerably weak exchange coupling, whose magnitude was increased by binding of substrate analogues. The data indicate that the bridged molecule has weak bonds with the di-Mn centre, which suggests a ‘loose’ structure, whereas it comes closer to di-Mn centre by substrate binding, which suggests a ‘well-tuned’ structure for catalysis. Thus, we propose that Sh-PPase can rearrange the active site and that the ‘loose’ structure plays an important role in the cold adaptation mechanism.
The effect of synbiotic preparations on the intestinal microbiota and her metabolism in broiler chickens
Authors: Śliżewska Katarzyna , Markowiak-Kopeć Paulina , Żbikowski Artur , Szeleszczuk Piotr
Published: March 2020

The aim of the research was to determine the effect of newly elaborated synbiotic preparations on the count of dominant intestinal microorganisms, on the profile of fatty acids (short chain – SCFA and branched chain – BCFA), the lactic acid produced and the performance of chickens. The studies determined the composition of the dominant intestinal microbiota with use of the culture method. The fatty acid profile was also determined using the high-performance liquid chromatography method (HPLC). Moreover, the performance of chickens was determined such as the daily cumulative mortality rate, the feed conversion ratio (FCR) and the European Production Efficiency Factor (EPEF). It was found that synbiotics had a beneficial effect on parameters of the performance of chickens, and also resulted in increase in the count of beneficial bacteria and to the restriction in growth of potential pathogens in the gastrointestinal tract. Synbiotics caused an increase in the concentration of lactic acid and SCFA and a decrease in the concentration of BCFA in the broiler’s excreta. These results showed a beneficial effect of the tested synbiotics on the intestinal microbiota, their metabolism and the performance of broiler chickens. The elaborated synbiotics can be successfully used as feed additives for broiler chickens.
Replicative conditioning of Herpes simplex type 1 virus by Survivin promoter, combined to ERBB2 retargeting, improves tumour cell-restricted oncolysis
Authors: Sasso Emanuele , Froechlich Guendalina , Cotugno Gabriella , D’Alise Anna Morena , Gentile Chiara , Bignone Veronica , De Lucia Maria , Petrovic Biljana , Campadelli-Fiume Gabriella , Scarselli Elisa , Nicosia Alfredo , Zambrano Nicola
Published: March 2020

Oncolytic virotherapy is emerging as a promising therapeutic option for solid tumours. Several oncolytic vectors in clinical testing are based on attenuated viruses; thus, efforts are being taken to develop a new repertoire of oncolytic viruses, based on virulent viral genomes. This possibility, however, raises concerns dealing with the safety features of the virulent phenotypes. We generated a double regulatedHerpes simplextype-1 virus (HSV-1), in which tumour cell restricted replicative potential was combined to selective entry via ERBB2 receptor retargeting. The transcriptional control of the viral alpha4 gene encoding for the infected cell protein-4 (ICP4) by the cellular Survivin/BIRC5promoter conferred a tumour cell-restricted replicative potential to a virulent HSV-1 genome. The combination of the additional ERBB2 retargeting further improved the selectivity for tumour cells, conferring to the double regulated virus a very limited ability to infect and propagate in non-cancerous cells. Accordingly, a suitable replicative and cytotoxic potential was maintained in tumour cell lines, allowing the double regulated virus to synergizein vivowith immune checkpoint (anti-PD-1) blockade in immunocompetent mice. Thus, restricting the replicative spectrum and tropism of virulent HSV-1 genomes by combination of conditional replication and retargeting provides an improved safety, does not alter the oncolytic strength, and is exploitable for its therapeutic potential with immune checkpoint blockade in cancer.
DJ-1 is indispensable for the S-nitrosylation of Parkin, which maintains function of mitochondria
Authors: Ozawa Kentaro , Tsumoto Hiroki , Miura Yuri , Yamaguchi Junji , Iguchi-Ariga Sanae M. M. , Sakuma Tetsushi , Yamamoto Takashi , Uchiyama Yasuo
Published: March 2020

The DJ-1 gene, a causative gene for familial Parkinson’s disease (PD), has been reported to have various functions, including transcriptional regulation, antioxidant response, and chaperone and protease functions; however, the molecular mechanism associated with the pathogenesis of PD remains elusive. To further explore the molecular function of DJ-1 in the pathogenesis of PD, we compared protein expression profiles in brain tissues from wild-type and DJ-1-deficient mice. Two-dimensional difference gel electrophoresis analysis and subsequent analysis using data mining methods revealed alterations in the expression of molecules associated with energy production. We demonstrated that DJ-1 deletion inhibited S-nitrosylation of endogenous Parkin as well as overexpressed Parkin in neuroblastoma cells and mouse brain tissues. Thus, we used genome editing to generate neuroblastoma cells with DJ-1 deletion or S-nitrosylated cysteine mutation in Parkin and demonstrated that these cells exhibited similar phenotypes characterized by enhancement of cell death under mitochondrial depolarization and dysfunction of mitochondria. Our data indicate that DJ-1 is required for the S-nitrosylation of Parkin, which positively affects mitochondrial function, and suggest that the denitrosylation of Parkin via DJ-1 inactivation might contribute to PD pathogenesis and act as a therapeutic target.
Leaf structure and seed histochemistry analyses provided structural insights into the improved yield and quality of tree peony seed under light shading conditions
Authors: Han Chenjing , Yu Mei , Wang Qi , Wang Lei , Yang Haiping , Zhao Yongjun , Dong Hezhong
Published: March 2020

In biology, structure is the basis of function. For plants, changes in their physiological and ecological functions are usually caused by structural changes. To understand how shading conditions change the plant structures, thereby providing structural insights into the improved yield and quality, oilseed tree peony were shaded with different densities of polyethylene nets from 28 days after pollination (DAP) until harvesting. The thickness of the leaf (LT), vein (VT), upper epidermis (UET), lower epidermis (LET), palisade tissue (PT), sponge tissue (ST), as well as the accumulation and distribution of starch, protein, and fat, were observed at 14-day intervals. The results showed that shading had a significant effect on the anatomical structure of the leaves. In the rapid growth period (before 70 DAP), the LT, ET, and VT under shading were significantly lower than under non-shading. During this period, the accumulation of starch and protein under shading was lower than that under non-shading. At the maturation period (99–112 DAP), the LT and PT under shading were higher than under non-shading, indicating that light shading delayed leaf senescence and increased photosynthetic capacity. Shading delayed the degradation of the integument cells and prolonged seed development and nutrient accumulation.
Edgetic perturbation signatures represent known and novel cancer biomarkers
Authors: Kataka Evans , Zaucha Jan , Frishman Goar , Ruepp Andreas , Frishman Dmitrij
Published: March 2020

Isoform switching is a recently characterized hallmark of cancer, and often translates to the loss or gain of domains mediating protein interactions and thus, the re-wiring of the interactome. Recent computational tools leverage domain-domain interaction data to resolve the condition-specific interaction networks from RNA-Seq data accounting for the domain content of the primary transcripts expressed. Here, we used The Cancer Genome Atlas RNA-Seq datasets to generate 642 patient-specific pairs of interactomes corresponding to both the tumor and the healthy tissues across 13 cancer types. The comparison of these interactomes provided a list of patient-specific edgetic perturbations of the interactomes associated with the cancerous state. We found that among the identified perturbations, select sets are robustly shared between patients at the multi-cancer, cancer-specific and cancer sub-type specific levels. Interestingly, the majority of the alterations do not directly involve significantly mutated genes, nevertheless, they strongly correlate with patient survival. The findings (available at EdgeExplorer: “http://webclu.bio.wzw.tum.de/EdgeExplorer”) are a new source of potential biomarkers for classifying cancer types and the proteins we identified are potential anti-cancer therapy targets.
A systematic review of the applications of artificial intelligence and machine learning in autoimmune diseases
Authors: Stafford I. S. , Kellermann M. , Mossotto E. , Beattie R. M. , MacArthur B. D. , Ennis S.
Published: March 2020

Autoimmune diseases are chronic, multifactorial conditions. Through machine learning (ML), a branch of the wider field of artificial intelligence, it is possible to extract patterns within patient data, and exploit these patterns to predict patient outcomes for improved clinical management. Here, we surveyed the use of ML methods to address clinical problems in autoimmune disease. A systematic review was conducted using MEDLINE, embase and computers and applied sciences complete databases. Relevant papers included “machine learning” or “artificial intelligence” and the autoimmune diseases search term(s) in their title, abstract or key words. Exclusion criteria: studies not written in English, no real human patient data included, publication prior to 2001, studies that were not peer reviewed, non-autoimmune disease comorbidity research and review papers. 169 (of 702) studies met the criteria for inclusion. Support vector machines and random forests were the most popular ML methods used. ML models using data on multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease were most common. A small proportion of studies (7.7% or 13/169) combined different data types in the modelling process. Cross-validation, combined with a separate testing set for more robust model evaluation occurred in 8.3% of papers (14/169). The field may benefit from adopting a best practice of validation, cross-validation and independent testing of ML models. Many models achieved good predictive results in simple scenarios (e.g. classification of cases and controls). Progression to more complex predictive models may be achievable in future through integration of multiple data types.
Urolithin A attenuated ox-LDL-induced cholesterol accumulation in macrophages partly through regulating miR-33a and ERK/AMPK/SREBP1 signaling pathways
Authors: Han Qi-an , Su Dongfang , Shi Chao , Liu Peifeng , Wang Yue , Zhu Beiwei , Xia Xiaodong
Published: March 2020

Urolithin A attenuated cholesterol accumulation in macrophage cells possibly through interaction with ERK/AMPKα/SREBP1 signaling pathways and regulation of miR-33a expression.
Controlling layered Ruddlesden–Popper perovskites via solvent additives
Authors: Pan Han , Zhao Xiaojuan , Xiu Gong , Li Hao , Zhang Xiao Li , Liang Guijie , Shen Yan , Wang Mingkui
Published: March 2020

We report that a solvent additive-induced Ostwald ripening process effectively promotes the reduction of low-n phases and uniform Layered Ruddlesden–Popper perovskite composition.
Efficient defect passivation of perovskite solar cells via stitching of an organic bidentate molecule
Authors: Lee Moon-Soo , Sarwar Saad , Park Sunghyeok , Asmat Ullah , Thuy Dao Thi , Han Chi-hwan , Ahn SeJin , Jeong Inyoung , Hong Sungjun
Published: March 2020

A bidentate Lewis base, pyrazine, acting as an efficient passivation agent to improve the charge-carrier lifetime and the efficiency of perovskite solar cells.
Immobilized iridium complexes for hydrogen evolution from formic acid dehydrogenation
Authors: Shen Yangbin , Zhan Yulu , Bai Chuang , Ning Fandi , Wang Huihui , Wei Jun , Lv Guojun , Zhou Xiaochun
Published: March 2020

Formic acid dehydrogenation has attracted plenty of attention lately due to its atom-economical method for hydrogen production.
The natural critical current density limit for Li7La3Zr2O12 garnets
Authors: Flatscher Florian , Philipp Martin , Ganschow Steffen , Wilkening H. Martin R. , Rettenwander Daniel
Published: March 2020

The critical current density in symmetrical Li metal cells using Li7La3Zr2O12 single crystals is determined. The upper limit at room temperature without applying any external forces is below 300 μA cm−2.
Super-assembled core/shell fibrous frameworks with dual growth factors forin situcementum–ligament–bone complex regeneration
Authors: Ding Tian , Li Jianhua , Zhang Xingshuang , Du Lingqian , Li Yang , Li Dengwang , Kong Biao , Ge Shaohua
Published: March 2020

In this work, a super-assembled framework (SAF) was fabricated to achieve sequential delivery of bFGF and BMP-2 forin situcementum–ligament–bone complex regeneration.
Nutritional value, physicochemical characterization and bioactive properties of the Brazilian quinoaBRS Piabiru
Authors: Sampaio Shirley L. , Fernandes Ângela , Pereira Carla , Calhelha Ricardo C. , Sokovic Marina , Santos-Buelga Celestino , Barros Lillian , Ferreira Isabel C. F. R.
Published: March 2020

Quinoa is a very interesting food due to its nutritional and chemical composition, as well as its bioactive properties, such as antioxidant and antimicrobial activity.
The inhibitory activity of alginate against allergic reactions in an ovalbumin-induced mouse model
Authors: Yu Boming , Bi Decheng , Yao Lijun , Li Tong , Gu Liang , Xu Hong , Li Xiuting , Li Hui , Hu Zhangli , Xu Xu
Published: March 2020

Marine seaweed polysaccharides have been considered as a potential resource for antiallergic therapy.
A small bimetallic Ag3Cu2 nanocluster with dual emissions within and against Kasha's rule
Authors: Anumula Rajini , Xiao Pin , Cui Chaonan , Wu Haiming , Cui Ganglong , Fang Wei-Hai , Luo Zhixun , Yao Jiannian
Published: March 2020

Single crystals of a small bimetallic Ag3Cu2 nanocluster protected by six ligands of 2,4-dimethylbenzene thiol are synthesized by a one-pot procedure of wet chemistry.
Surface functionalization of gold nanoclusters with arginine: a trade-off between microtumor uptake and radiotherapy enhancement
Authors: Broekgaarden Mans , Bulin Anne-Laure , Porret Estelle , Musnier Benjamin , Chovelon Benoit , Ravelet Corinne , Sancey Lucie , Elleaume Hélène , Hainaut Pierre , Coll Jean-Luc , Le Guével Xavier
Published: March 2020

Gold nanoclusters (AuNC) have strong potential for cancer imaging and therapy. We demonstrate that optimizing the surface chemistry of AuNCs for increased tumor uptake can significantly affect its potential to augment radiotherapy outcomes.
Enabling high performance n-type metal oxide semiconductors at low temperatures for thin film transistors
Authors: Tiwari Nidhi , Nirmal Amoolya , Kulkarni Mohit Rameshchandra , John Rohit Abraham , Mathews Nripan
Published: March 2020

The review highlights low temperature activation processes for high performance n-type metal oxide semiconductors for TFTs.
Recrystallized ice-templated electroless plating for fabricating flexible transparent copper meshes
Authors: Li Linhai , Fan Qingrui , Xue Han , Zhang Shizhong , Wu Shuwang , He Zhiyuan , Wang Jianjun
Published: March 2020

Herein, we report the fabrication of flexible copper meshes using recrystallized ice-crystal templates. The linewidth and mean size of the copper meshes can be tuned by adjusting the ice grains.
Low-spin cobalt(ii) redox shuttle by isocyanide coordination
Authors: Raithel Austin L. , Kim Tea-Yon , Nielsen Karl C. , Staples Richard J. , Hamann Thomas W.
Published: March 2020

The electron transfer kinetics in the DSSCs were tuned dramatically by coordination of the strong-field ligand 2,6-dimethyl isocyanide to induce a low-spin Co(ii) redox shuttle.
High-aspect-ratio deflection transducers inspired by the ultra-sensitive cantilever configuration of scorpion trichobothria
Authors: Zhang Changchao , Chen Daobing , Niu Shichao , Zhang Junqiu , Meng Xiancun , Liu Linpeng , Sun Tao , Wen Shifeng , Zhou Yan , Shi Yusheng , Han Zhiwu , Ren Luquan
Published: March 2020

Inspired by the high-aspect-ratio cantilever configuration of scorpion trichobothria, a deflection transducer was designed.
Extracellular DNA in blood products and its potential effects on transfusion
Authors: Yang Li , Yang Dongmei , Yang Qian , Cheng Fu , Huang Yuanshuai
Published: March 2020

Blood transfusions are sometimes necessary after a high loss of blood due to injury or surgery. Some people need regular transfusions due to medical conditions such as haemophilia or cancer. Studies have suggested that extracellular DNA including mitochondrial DNA present in the extracellular milieu of transfused blood products has biological actions that are capable of activating the innate immune systems and potentially contribute to some adverse reactions in transfusion. From the present work, it becomes increasingly clear that extracellular DNA encompassed mitochondrial DNA is far from being biologically inert in blood products. It has been demonstrated to be present in eligible blood products and thus can be transfused to blood recipients. Although the presence of extracellular DNA in human plasma was initially detected in 1948, some aspects have not been fully elucidated. In this review, we summarize the potential origins, clearance mechanisms, relevant structures, and potential role of extracellular DNA in the innate immune responses and its relationship with individual adverse reactions in transfusion.
Hydrogen ionization equilibrium in magnetic fields
Authors: Vera Rueda Matías , Rohrmann René D.
Published: March 2020

We assess the partition function and ionization degree of magnetized hydrogen atoms at thermodynamic equilibrium for a wide range of field intensities, B ≈ 105–1012 G. Evaluations include fitting formulae for an arbitrary number of binding energies, the coupling between the internal atomic structure and the center-of-mass motion across the magnetic field, and the formation of the so-called decentered states (bound states with the electron shifted from the Coulomb well). Non-ideal gas effects are treated within the occupational probability method. We also present general mathematical expressions for the bound state correspondence between the limits of zero-field and high-field. This let us evaluate the atomic partition function in a continuous way from the Zeeman perturbative regime to very strong fields. Results are shown for conditions found in atmospheres of magnetic white dwarf (MWD) stars, with temperatures T ≈ 5000–80 000 K and densities ρ ≈ 10−12–10−3 g cm3. Our evaluations show a marked reduction of the gas ionization due to the magnetic field in the atmospheres of strong MWDs. We also found that decentered states could be present in the atmospheres of currently known hot MWDs, giving a significant contribution to the partition function in the strongest magnetized atmospheres.