bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering selective competitors for the discrimination of highly conserved protein-protein interaction modules
Authors: Rimbault Charlotte , Maruthi Kashyap , Breillat Christelle , Genuer Camille , Crespillo Sara , Puente-Muñoz Virginia , Chamma Ingrid , Gauthereau Isabel , Antoine Ségolène , Thibaut Coraline , Tai Fabienne Wong Jun , Dartigues Benjamin , Grillo-Bosch Dolors , Claverol Stéphane , Poujol Christel , Choquet Daniel , Mackereth Cameron D. , Sainlos Matthieu 
Published: October 2019

AbstractDesigning highly specific modulators of protein-protein interactions (PPIs) is especially challenging in the context of multiple paralogs and conserved interaction surfaces. In this case, direct generation of selective and competitive inhibitors is hindered by high similarity within the evolutionary-related protein interfaces. We report here a strategy that uses a semi-rational approach to separate the modulator design into two functional parts. We first achieve specificity toward a region outside of the interface by using phage display selection coupled with molecular and cellular validation. Highly selective competition is then generated by appending the more degenerate interaction peptide to contact the target interface. We apply this approach to specifically bind a single PDZ domain within the postsynaptic protein PSD-95 over highly similar PDZ domains in PSD-93, SAP-97 and SAP-102. Our work provides a paralog-selective and domain specific inhibitor of PSD-95, and describes a method to efficiently target other conserved PPI modules.
Interplay and Targetome of the Two Conserved Cyanobacterial sRNAs Yfr1 and Yfr2 in Prochlorococcus MED4
Authors: Lambrecht S. Joke , Kanesaki Yu , Fuss Janina , Huettel Bruno , Reinhardt Richard , Steglich Claudia 
Published: October 2019

AbstractThe sRNA Yfr1 and members of the Yfr2 sRNA family are almost universally present within cyanobacteria. The conserved motifs of these sRNAs are nearly complementary to each other, suggesting their ability to participate in crosstalk. The conserved motif of Yfr1 is shared by members of the Yfr10 sRNA family, members of which are otherwise less conserved in sequence, structure, and synteny compared to Yfr1. The different structural properties enable the discrimination of unique targets of Yfr1 and Yfr10. Unlike most studied regulatory sRNAs, Yfr1 gene expression only slightly changes under the tested stress conditions and is present at high levels at all times. In contrast, cellular levels of Yfr10 increase during the course of acclimation to darkness, and levels of Yfr2 increase when cells are shifted to high light or nitrogen limitation conditions. In this study, we investigated the targetomes of Yfr2, Yfr1, and Yfr10 in Prochlorococcus MED4, establishing CRAFD-Seq as a new method for identifying direct targets of these sRNAs that is applicable to all bacteria, including those that are not amenable to genetic modification. The results suggest that these sRNAs are integrated within a regulatory network of unprecedented complexity in the adjustment of carbon and nitrogen-related primary metabolism.
Imaging Rheumatoid Arthritis in Mice Using Combined Near Infrared and 19F Magnetic Resonance Modalities
Authors: Vu-Quang Hieu , Vinding Mads Sloth , Jakobsen Maria , Song Ping , Dagnaes-Hansen Frederik , Nielsen Niels Chr. , Kjems Jørgen 
Published: October 2019

AbstractRheumatoid arthritis (RA) is an autoimmune disease that causes pain and tissue destruction in people worldwide. An accurate diagnosis is paramount in order to develop an effective treatment plan. This study demonstrates that combining near infrared (NIR) imaging and 19F MRI with the injection of labelled nanoparticles provides high diagnostic specificity for RA. The nanoparticles were made from poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (NP) or PLGA-PEG-Folate (Folate-NP), loaded with perfluorooctyl bromide (PFOB) and indocyanine green (ICG) and evaluated in vitro and in a collagen-induced arthritic (CIA) mouse model. The different particles had a similar size and a spherical shape according to dynamic light scattering (DLS) and transmission electron microscopy (TEM). Based on flow cytometry and 19F MRI analysis, Folate-NP yielded a higher uptake than NP in activated macrophages in vitro. The potential RA-targeting ability of the particles was studied in CIA mice using NIR and 19F MRI analysis. Both NP and Folate-NP accumulated in the RA tissues, where they were visible in NIR and 19F MRI for up to 24 hours. The presence of folate as a targeting ligand significantly improved the NIR signal from inflamed tissue at the early time point (2 hours), but not at later time points. Overall, these results suggest that our nanoparticles can be applied for combined NIR and 19F MRI imaging for improved RA diagnosis.
Early skeletal muscle pathology and disease progress in the dy3K/dy3K mouse model of congenital muscular dystrophy with laminin α2 chain-deficiency
Authors: Gawlik Kinga I. , Körner Zandra , Oliveira Bruno M. , Durbeej Madeleine 
Published: October 2019

AbstractDeficiency of laminin α2 chain leads to a severe form of congenital muscular dystrophy (LAMA2-CMD), and dystrophic symptoms progress rapidly in early childhood. Currently, there is no treatment for this detrimental disorder. Development of therapies is largely hindered by lack of understanding of mechanisms involved in the disease initiation and progress, both in patients but also in mouse models that are commonly used in the preclinical setup. Here, we unveil the first pathogenic events and characterise the disease development in a mouse model for LAMA2-CMD (dy3K/dy3K), by analysing muscles at perinatal, neonatal and postnatal stages. We found that apoptotic muscle fibres were present as early as postnatal day 1. Other typical dystrophic hallmarks (muscle degeneration, inflammation, and extensive production of the extracellular matrix proteins) were clearly evident already at postnatal day 4, and the highest degree of muscle deterioration was reached by day 7. Interestingly, the severe phenotype of limb muscles partially recovered on days 14 and 21, despite worsening of the general condition of the dy3K/dy3K mouse by that age. We found that masticatory muscles were severely affected in dy3K/dy3K mice and this may be an underlying cause of their malnutrition, which contributes to death around day 21. We also showed that several signalling pathways were affected already in 1-day-old dy3K/dy3K muscle. Therapeutic tests in the dy3K/dy3K mouse model should therefore be initiated shortly after birth, but should also take into account timing and correlation between regenerative and pathogenic events.
Digitizable therapeutics for decentralized mitigation of global pandemics
Authors: Hacohen Adar , Cohen Reuven , Efroni Sol , Barzel Baruch , Bachelet Ido 
Published: October 2019

AbstractWhen confronted with a globally spreading epidemic, we seek efficient strategies for drug dissemination, creating a competition between supply and demand at a global scale. Propagating along similar networks, e.g., air-transportation, the spreading dynamics of the supply vs. the demand are, however, fundamentally different, with the pathogens driven by contagion dynamics, and the drugs by commodity flow. We show that these different dynamics lead to intrinsically distinct spreading patterns: while viruses spread homogeneously across all destinations, creating a concurrent global demand, commodity flow unavoidably leads to a highly uneven spread, in which selected nodes are rapidly supplied, while the majority remains deprived. Consequently, even under ideal conditions of extreme production and shipping capacities, due to the inherent heterogeneity of network-based commodity flow, efficient mitigation becomes practically unattainable, as homogeneous demand is met by highly heterogeneous supply. Therefore, we propose here a decentralized mitigation strategy, based on local production and dissemination of therapeutics, that, in effect, bypasses the existing distribution networks. Such decentralization is enabled thanks to the recent development of digitizable therapeutics, based on, e.g., short DNA sequences or printable chemical compounds, that can be distributed as digital sequence files and synthesized on location via DNA/3D printing technology. We test our decentralized mitigation under extremely challenging conditions, such as suppressed local production rates or low therapeutic efficacy, and find that thanks to its homogeneous nature, it consistently outperforms the centralized alternative, saving many more lives with significantly less resources.
An Internally Quenched Fluorescent Peptide Substrate for Protealysin
Authors: Karaseva Maria A. , Chukhontseva Ksenia N. , Lemeskina Irina S. , Pridatchenko Marina L. , Kostrov Sergey V. , Demidyuk Ilya V. 
Published: October 2019

AbstractProtealysin, a metalloprotease of Serratia proteamaculans, is the prototype of a subgroup of the M4 peptidase family. Protealysin-like proteases (PLPs) are widely spread in bacteria but also occur in fungi and certain archaea. The interest in PLPs is primarily due to their putative involvement in the bacterial pathogenesis in animals and plants. Studying PLPs requires an efficient quantitative assay for their activity; however, no such assay has been reported so far. Here, we used the autoprocessing site sequence of the protealysin precursor to construct an internally quenched fluorescent peptide substrate 2-aminobenzoyl-L-arginyl-L-seryl-L-valyl-L-isoleucyl-L-(ε-2,4-dinitrophenyl)lysine. Protealysin and thermolysin, the prototype of the M4 family, proved to hydrolyze only the Ser-Val bond of the substrate. The substrate exhibited a KM = 35 ± 4 μM and kcat = 21 ± 1 s−1 for protealysin as well as a KM = 33 ± 8 μM and kcat = 7 ± 1 s−1 for thermolysin at 37 °C. Comparison of the effect of different enzymes (thermolysin, trypsin, chymotrypsin, savinase, and pronase E) on the substrate has demonstrated that it is not strictly specific for protealysin; however, this enzyme has higher molar activity even compared to the closely related thermolysin. Thus, the proposed substrate can be advantageous for quantitative studies of protealysin as well as for activity assays of other M4 peptidases.
Interactions of a medicinal climber Tinospora cordifolia with supportive interspecific plants trigger the modulation in its secondary metabolic profiles
Authors: Sharma Bhawana , Yadav Aarti , Dabur Rajesh 
Published: October 2019

AbstractTinospora cordifolia (TC) is scientifically proven immunomodulatory drug being used for centuries. Ancient literature reported that inter-specific interactions change medicinal properties of TC. Thus, the current study is aimed to understand the influence of interspecific biotic interactions on chemo-profiles of TC. To explore it, TC samples collected from six co-occurring plants, i.e. Azarditchita indica, Acacia nilotica, Albezia lebbeck, Ficus benghalensis, Tamarandus indica and Acacia leucophloea were analyzed by HPLC-ESI-QTOF-MS. Mass data were subjected to multivariate analysis. Support vector machines (SVMs) was found to be best classifier (r2 < 0.93). Data analysis showed the specific compounds in all TC due to inter-specific interactions. Data were further analyzed with SNK post-hoc test followed by permutative (n = 50) Bonferroni FDR multiple testing correction. The compound without any missing values reduced the number of variables to 133 (p < 0.01). Statistical analysis revealed that TC having interactions with A.lebbeck and A. nilotica formed the most distant groups. However, TC co-occurred with A. indica showed the highest number of up-regulated metabolites, including jatrorrhizine, chrysin, peonidin, 6-methylcoumarin and some terpenoids. Some metabolites, including jatrorrhizine and magnoflorine were quantified to confirm the accuracy of qualitative analysis. Results demonstrated the influence of inter-specific biotic interactions on TC chemo-profiles, hence its medicinal properties.
Sex differences in risk factors for stroke in patients with hypertension and hyperhomocysteinemia
Authors: Pang Hui , Fu Qiang , Cao Qiumei , Hao Lin , Zong Zhenkun 
Published: October 2019

AbstractData on the sex-specific differences in risk of stroke among patients with H-type hypertension are limited. We aimed to analyze interactions between sex and other risk factors on stroke, including the sex-methylenetetrahydrofolate reductase (MTHFR) interaction. A retrospective analysis of baseline data from 2040 patients with hypertension and hyperhomocysteinemia (HHcy) included demographic characteristics, biomarkers, history of chronic diseases and lifestyle factors. Polymerase chain reaction-restriction fragment length polymorphism method was used to investigate the C677T polymorphism of MTHFR gene. We examined independent effects and interactions between sex and stratified factors on the risk of stroke by logistic regression model. A total of 1412 patients suffered stroke, and the prevalence of stroke was 70.65% in men and 66.53% in women. Both men and women had independent risk factors for stroke, including diabetes mellitus, atrial fibrillation, smoking, increased level of systolic blood pressure (SBP) and plasma total homocysteine (tHcy), as well as the decreased level of high-density lipoprotein cholesterol. Diastolic blood pressure (DBP) -specific risk of stroke was unique to men. Interactions between sex and other risk factors on stroke risk were statistically significant: age, fasting plasma glucose (FPG), SBP, DBP, triglycerides (TG) and tHcy. Furthermore, tHcy interacted with age, SBP and DBP in men, and age, SBP, DBP, FPG, and TG in women to modulate the risk of stroke. Although TT genotype did not have an independent effect on stroke, it could interact with sex and FPG, TG and SBP to increase stroke. In conclusion, sex-specific differences are useful to stratify the risk of stroke and assist clinicians in the decision to select a reasonable therapeutic option for high-risk patients.
Automated Platform for Long-Term Culture and High-Content Phenotyping of Single C. elegans Worms
Authors: Atakan H. B. , Xiang R. , Cornaglia M. , Mouchiroud L. , Katsyuba E. , Auwerx J. , Gijs M. A. M. 
Published: October 2019

AbstractThe nematodeCaenorhabditis elegansis a suitable model organism in drug screening. Traditionally worms are grown on agar plates, posing many challenges for long-term culture and phenotyping of animals under identical conditions. Microfluidics allows for ‘personalized’ phenotyping, as microfluidic chips permit collecting individual responses over worms’ full life. Here, we present a multiplexed, high-throughput, high-resolution microfluidic approach to cultureC.elegansfrom embryo to the adult stage at single animal resolution. We allocated single embryos to growth chambers, for observing the main embryonic and post-embryonic development stages and phenotypes, while exposing worms to up to 8 different well-controlled chemical conditions. Our approach allowed eliminating bacteria aggregation and biofilm formation-related clogging issues, which enabled us performing up to 80 hours of automated single worm culture studies. Our microfluidic platform is linked with an automated phenotyping code that registers organism-associated phenotypes at high-throughput. We validated our platform with a dose-response study of the anthelmintic drug tetramisole by studying its influence through the life cycle of the nematodes. In parallel, we could observe development effects and variations in single embryo and worm viability due to the bleaching procedure that is standardly used for harvesting the embryos from a worm culture agar plate.
Cryo-EM structure of the bacterial Ton motor subcomplex ExbB–ExbD provides information on structure and stoichiometry
Authors: Celia Herve , Botos Istvan , Ni Xiaodan , Fox Tara , De Val Natalia , Lloubes Roland , Jiang Jiansen , Buchanan Susan K. 
Published: October 2019

AbstractThe TonB–ExbB–ExbD molecular motor harnesses the proton motive force across the bacterial inner membrane to couple energy to transporters at the outer membrane, facilitating uptake of essential nutrients such as iron and cobalamine. TonB physically interacts with the nutrient-loaded transporter to exert a force that opens an import pathway across the outer membrane. Until recently, no high-resolution structural information was available for this unique molecular motor. We published the first crystal structure of ExbB–ExbD in 2016 and showed that five copies of ExbB are arranged as a pentamer around a single copy of ExbD. However, our spectroscopic experiments clearly indicated that two copies of ExbD are present in the complex. To resolve this ambiguity, we used single-particle cryo-electron microscopy to show that the ExbB pentamer encloses a dimer of ExbD in its transmembrane pore, and not a monomer as previously reported. The revised stoichiometry has implications for motor function.
Above-below surface interactions mediate effects of seagrass disturbance on meiobenthic diversity, nematode and polychaete trophic structure
Authors: Nascimento Francisco J. A. , Dahl Martin , Deyanova Diana , Lyimo Liberatus D. , Bik Holly M. , Schuelke Taruna , Pereira Tiago José , Björk Mats , Creer Simon , Gullström Martin 
Published: October 2019

AbstractEcological interactions between aquatic plants and sediment communities can shape the structure and function of natural systems. Currently, we do not fully understand how seagrass habitat degradation impacts the biodiversity of belowground sediment communities. Here, we evaluated indirect effects of disturbance of seagrass meadows on meiobenthic community composition, with a five-month in situ experiment in a tropical seagrass meadow. Disturbance was created by reducing light availability (two levels of shading), and by mimicking grazing events (two levels) to assess impacts on meiobenthic diversity using high-throughput sequencing of 18S rRNA amplicons. Both shading and simulated grazing had an effect on meiobenthic community structure, mediated by seagrass-associated biotic drivers and sediment abiotic variables. Additionally, shading substantially altered the trophic structure of the nematode community. Our findings show that degradation of seagrass meadows can alter benthic community structure in coastal areas with potential impacts to ecosystem functions mediated by meiobenthos in marine sediments.
Comprehensive modeling of bloodstain aging by multivariate Raman spectral resolution with kinetics
Authors: Takamura Ayari , Watanabe Daisuke , Shimada Rintaro , Ozawa Takeaki 
Published: October 2019

AbstractBlood, as a cardinal biological system, is a challenging target for biochemical characterization because of sample complexity and a lack of analytical approaches. To reveal and evaluate aging process of blood compositions is an unexplored issue in forensic analysis, which is useful to elucidate the details of a crime. Here we demonstrate a spectral deconvolution model of near-infrared Raman spectra of bloodstain to comprehensively describe the aging process based on the chemical mechanism, particularly the kinetics. The bloodstain spectra monitored over several months at different temperatures are decomposed into significant spectral components by multivariate calculation. The kinetic schemes of the spectral components are explored and subsequently incorporated into the developed algorithm for the optimal spectral resolution. Consequently, the index of bloodstain aging is proposed, which can be used under different experimental conditions. This work provides a novel perspective on the chemical mechanisms in bloodstain aging and facilitates forensic applications.
Intelligent packaging for monitoring food quality.
Authors: Luchese C. L. 
Published: October 2019

Abstract
Synthetic plastics derived primarily from fossil carbon sources (such as crude oil and natural gas) are one of the main constituents of urban solid waste that present an increasing problem of disposal and environmental pollution due to its recalcitrant nature. Growing environmental concerns over the uncontrolled use of traditional synthetic plastics and a desire related to reducing the use of non-renewable resources have led to several looking for alternative packaging materials. An alternative to minimize the problem related to plastic waste disposal is the production of biodegradable films. Currently, dynamic information and constant monitoring of food quality, shelf life, safety and convenience are required for the most demanding consumer news. Intelligent packaging systems are those that monitor the condition of packaged foods to provide information about die quality of packaged food during transportation and storage. In the current context, smart (active and intelligent) packaging is a potential area for future research. The development and improvement of processing technologies and the raw materials used in the manufacture of this type of packaging can help to preserve products of animal origin (chicken meat, beef and pork) and vegetables (minimally processed), as the different characteristic of the material can be obtained.
DFT  +  U study of H2O adsorption and dissociation on stoichiometric and nonstoichiometric CuO(1 1 1) surfaces
Authors: Ahmad Faozan , Agusta Mohammad Kemal , Maezono Ryo , Dipojono Hermawan Kresno 
Published: October 2019

Abstract
Surface interaction through adsorption and dissociation between H2O and metal oxides plays an important role in many industrial as well as fundamental processes. To gain further insights on the interaction, this study performs dispersion-corrected Hubbard-corrected density functional theory calculations in H2O adsorption and dissociation on stoichiometric and nonstoichiometric CuO(1 1 1) surfaces. The nonstoichiometric surfaces consist of oxygen vacancy defect and oxygen-preadsorbed surfaces. This study finds that H2O is chemically adsorbed on the top of Cusub and Cusub–Cusub bridge due to the interaction of its p  orbital with d orbital of Cu. The adsorption is found to be the strongest on the surface with the oxygen vacancy defect, followed by the stoichiometric surface, and the oxygen-preadsorbed surface. The oxygen vacancy increases the reactivity for H2O adsorption and reduces the reaction energy required for H2O dissociation on the surface. However, the surface modification by the oxygen-preadsorbed significantly reduces the barrier energy for H2O dissociation when compared with the other surfaces.
Synthesis of nanosize manganese oxides from its ore using solvothermal method
Authors: Abi F D Y P , Kusumaningrum R , Widayatno W B , Wismogroho A S , Noviyanto A , Rochman N T , Amal M I 
Published: October 2019

Abstract
Nano-sized manganese oxide was successfully synthesized from local manganese ore using solvothermal method. The manganese ore were obtained from Jereweh District, Sumbawa, West of Nusa Tenggara, Indonesia. The aims of this research are to study the effects of temperature and time to the morphology, size and phase of manganese oxide obtained by solvothermal method. In the first step, we performed the extraction of manganese precursor from manganese ore. The method to extract the manganese precursor was hydrometallurgy. The second step, manganese precursor that obtained in the first step was used to synthesis manganese oxide using solvothermal method. NaOH was used as precipitating agent. The phase, morphologies and particle size of manganese oxides were examined by x-ray diffractometer and scanning electron microscopy.