bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of a rifampicin pre-treatment on linezolid pharmacokinetics
Authors: Okazaki Fumiyasu , Tsuji Yasuhiro , Seto Yoshihiro , Ogami Chika , Yamamoto Yoshihiro , To Hideto 
Published: March 2019

AbstractLinezolid is an oxazolidinone antibiotic that effectively treats methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Since rifampicin induces other antibiotic effects, it is combined with linezolid in therapeutic regimes. However, linezolid blood concentrations are reduced by this combination, which increases the risk of the emergence of antibiotic-resistant bacteria. We herein demonstrated that the combination of linezolid with rifampicin inhibited its absorption and promoted its elimination, but not through microsomal enzymes. Our results indicate that the combination of linezolid with rifampicin reduces linezolid blood concentrations via metabolic enzymes.
Deriving Accurate Lipid Classification based on Molecular Formula
Authors: Mitchell Joshua M. , Moseley Hunter N.B. 
Published: March 2019

AbstractIntroductionAlthough Fourier-transform mass spectrometry has substantially improved our ability to detect lipids and other metabolites; the untargeted and accurate assignment of detected metabolites remains an unsolved problem in metabolomics. New assignment methods such as our SMIRFE algorithm can assign elemental molecular formula to observed spectral features in an untargeted manner without orthogonal information from tandem MS or chromatography. However, for many lipidomics applications, it is necessary to know at least the lipid category or class that is associated with a detected spectral feature in order to derive biochemical interpretation.ObjectivesOur goal is to develop a method for robustly classifying elemental molecular formula assignments into lipid categories for application to SMIRFE-generated assignments.ResultsUsing machine learning, we developed a method that can predict lipid category and class from SMIRFE molecular formula assignments. Our methods achieve high accuracy (>90%) and precision (>83%) for all eight of the lipid categories in the LIPIDMAPS database. Model performance was evaluated using sets of theoretical, data-derived, and artifactual molecular formulas. Our models were generalizable, applicable to real-world datasets, and very discriminating with most molecular formulas classified to the “not lipid” category. Lipid categories with the highest classification propensities were glycerophospholipids and sphingolipids, matching the highest category prevalence in LIPIDMAPS.ConclusionsOur methods enable the lipid classification of untargeted molecular formula assignments generated by SMIRFE without orthogonal information, facilitating biochemical interpretation of highly untargeted lipidomics experiments. However, this lipid classification appears insufficient for validating single-spectrum assignments, but could be useful in cross-spectrum assignment validation.
Affordable and robust phenotyping framework to analyse root system architecture of soil-grown plants
Authors: Bontpart Thibaut , Concha Cristobal , Giuffrida Valerio , Robertson Ingrid , Admkie Kassahun , Degefu Tulu , Girma Nigusie , Tesfaye Kassahun , Haileselassie Teklehaimanot , Fikre Asnake , Fetene Masresha , Tsaftaris Sotirios A. , Doerner Peter 
Published: March 2019

AbstractThe analysis of root system growth, root phenotyping, is important to inform efforts to enhance plant resource acquisition from soils. However, root phenotyping remains challenging due to soil opacity and requires systems that optimize root visibility and image acquisition. Previously reported systems require costly and bespoke materials not available in most countries, where breeders need tools to select varieties best adapted to local soils and field conditions. Here, we present an affordable soil-based growth container (rhizobox) and imaging system to phenotype root development in greenhouses or shelters. All components of the system are made from commodity components, locally available worldwide to facilitate the adoption of this affordable technology in low-income countries. The rhizobox is large enough (~6000 cm2visible soil) to not restrict vertical root system growth for at least seven weeks after sowing, yet light enough (~21 kg) to be routinely moved manually. Support structures and an imaging station, with five cameras covering the whole soil surface, complement the rhizoboxes. Images are acquiredviathe Phenotiki sensor interface, collected, stitched and analysed. Root system architecture (RSA) parameters are quantified without intervention. RSA of a dicot (chickpea,Cicer arietinumL.) and a monocot (barley,Hordeum vulgareL.) species, which exhibit contrasting root systems, were analysed. The affordable system is relevant for efforts in Ethiopia and elsewhere to enhance yields and climate resilience of chickpea and other crops for improved food security.Significance StatementAn affordable system to characterize root system architecture of soil-grown plants was developed. Using commodity components, this will enable local efforts world-wide to breed for enhanced root systems.
Massively Parallel Microwire Arrays Integrated with CMOS chips for Neural Recording
Authors: Obaid Abdulmalik , Hanna Mina-Elraheb , Wu Yu-Wei , Kollo Mihaly , Racz Romeo , Angle Matthew R , Müller Jan , Brackbill Nora , Wray William , Franke Felix , Chichilnisky E.J. , Hierlemann Andreas , Ding Jun B , Schaefer Andreas T , Melosh Nicholas A 
Published: March 2019

AbstractMulti-channel electrical recordings of neural activity in the brain is an increasingly powerful method revealing new aspects of neural communication, computation, and prosthetics. However, while planar silicon-based CMOS devices in conventional electronics scale rapidly, neural interface devices have not kept pace. Here, we present a new strategy to interface silicon-based chips with three-dimensional microwire arrays, providing the link between rapidly-developing electronics and high density neural interfaces. The system consists of a bundle of microwires mated to large-scale microelectrode arrays, such as camera chips. This system has excellent recording performance, demonstrated via single unit and local-field potential recordings in isolated retina and in the motor cortex or striatum of awake moving mice. The modular design enables a variety of microwire types and sizes to be integrated with different types of pixel arrays, connecting the rapid progress of commercial multiplexing, digitisation and data acquisition hardware together with a three-dimensional neural interface.
Drug reformulation for a neglected disease. The NANOHAT project to develop a safer more effective sleeping sickness drug
Authors: Sanderson Lisa , da Silva Marcelo , Sekhar Gayathri N. , Brown Rachel C. , Burrell-Saward Hollie , Fidanboylu Mehmet , Liu Bo , Dailey Lea Ann , Dreiss Cécile A. , Lorenz Chris , Christie Mark , Persaud Shanta J. , Yardley Vanessa , Croft Simon L , Valero Margarita , Thomas Sarah A. 
Published: March 2019

AbstractHuman African trypanosomiasis (HAT or sleeping sickness) is caused by the parasite Trypanosoma brucei sspp. The disease has two stages, a haemolymphatic stage after the bite of an infected tsetse fly, followed by a central nervous system stage where the parasite penetrates the brain, causing death if untreated. Treatment is stage-specific, due to the blood-brain barrier, with less toxic drugs such as pentamidine used to treat stage 1. The objective of our research programme was to develop an intravenous formulation of pentamidine which increases CNS exposure by some 10-100 fold, leading to efficacy against a model of stage 2 HAT. This target candidate profile is in line with drugs for neglected diseases inititative recommendations. To do this, we evaluated the physicochemical and structural characteristics of formulations of pentamidine with Pluronic micelles (triblock-copolymers of polyethylene-oxide and polypropylene oxide), selected candidates for efficacy and toxicity evaluationin vitro, quantified pentamidine CNS delivery of a sub-set of formulationsin vitroandin vivo, and progressed one pentamidine-Pluronic formulation for further evaluation using anin vivosingle dose brain penetration study. Screening pentamidine against 40 CNS targets did not reveal any major neurotoxicity concerns, however, pentamidine had a high affinity for the imidazoline2receptor. The reduction in insulin secretion in MIN6 β-cells by pentamidine maybe secondary to pentamidine-mediated activation of β-cell imidazoline receptors and impairment of cell viability. Pluronic F68 (0.01%w/v)-pentamidine formulation had a similar inhibitory effect on insulin secretion as pentamidine alone and an additive trypanocidal effectin vitro. However, all Pluronics tested (P85, P105 and F68) did not significantly enhance brain exposure of pentamidine. These results are relevant to further developing block-copolymers as nanocarriers, improving BBB drug penetration and understanding the side effects of pentamidine.
Identification of DNA motifs that regulate DNA methylation
Authors: Wang Mengchi , Zhang Kai , Ngo Vu , Liu Chengyu , Fan Shicai , Whitaker John W , Chen Yue , Ai Rizi , Chen Zhao , Wang Jun , Zheng Lina , Wang Wei 
Published: March 2019

AbstractDNA methylation is an important epigenetic mark but how its locus-specificity is decided in relation to DNA sequence is not fully understood. Here, we have analyzed 34 diverse whole-genome bisulfite sequencing datasets in human and identified 313 motifs, including 92 and 221 associated with methylation (methylation motifs, MMs) and unmethylation (unmethylation motifs, UMs), respectively. The functionality of these motifs is supported by multiple lines of evidences. First, the methylation levels at the MM and UM motifs are respectively higher and lower than the genomic background. Second, these motifs are enriched at the binding sites of methylation modifying enzymes including DNMT3A and TET1, indicating their possible roles of recruiting these enzymes. Third, these motifs significantly overlap with SNPs associated with gene expression and those with DNA methylation. Fourth, disruption of these motifs by SNPs is associated with significantly altered methylation level of the CpGs in the neighbor regions. Furthermore, these motifs together with somatic SNPs are predictive of cancer subtypes and patient survival. We revealed some of these motifs were also associated with histone modifications, suggesting possible interplay between the two types of epigenetic modifications. We also found some motifs form feed forward loops to contribute to DNA methylation dynamics.
Optimized Mucosal MVA Prime/ Soluble gp120 Boost Vaccination Regimen Induces Similar Antibody Responses as an Intramuscular Regimen
Authors: Jones Dorothy I. , Pollara Justin J. , Johnson-Weaver Brandi T. , LaBranche Celia C. , Montefiori David C. , Pickup David J. , Permar Sallie R. , Abraham Soman N. , Maddaloni Massimo , Pascual David W. , Staats Herman F. 
Published: March 2019

ABSTRACTThe benefits of mucosal vaccines over injected vaccines are difficult to ascertain since mucosally administered vaccines often induce serum antibody responses of lower magnitude than those induced by injected vaccines. This study aimed to determine if mucosal vaccination using a modified vaccinia Ankara expressing HIV-1 gp120 (MVA-g120) prime and HIV-1 gp120 protein boost could be optimized to induce serum antibody responses similar to those induced by an intramuscularly (IM) administered MVA prime/gp120 boost to allow comparison of an IM immunization regimen to a mucosal vaccination regimen for their ability to protect against a low dose rectal SHIV challenge while inducing similar serum anti-HIV-1 antibody responses. A 3-fold higher antigen dose was required for intranasal (IN) immunization with gp120 to induce serum anti-gp120 IgG responses not significantly different than those induced by IM immunization. Gp120 fused to the Adenovirus type 2 fiber binding domain (gp120-Ad2F), a mucosal targeting ligand, exhibited enhanced IN immunogenicity when compared to gp120 alone. MVA-gp120 was more immunogenic after IN delivery than gastric or rectal delivery, although serum antibodies induced by IN immunization were lower than those induced by intramuscular immunization. Using these optimized vaccines, an IN MVA-gp120 prime, combined IM (gp120) and IN (gp120-Ad2F) boost regimen (IN/IM+IN) induced serum anti-gp120 antibody titers similar to those induced by the intramuscular prime/boost regimen (IM/IM) in rabbits and non-human primates. Despite the induction of similar systemic anti-HIV-1 antibody responses, neither the IM/IM nor the IN/IM+IN regimen induced elevated anti-HIV-1 mucosal IgA responses nor protected against a repeated low-dose rectal SHIV challenge. These results demonstrate that immunization regimens utilizing the IN route are able to induce serum antigen-specific antibody responses similar to those induced by systemic immunizationIMPORTANCEMucosal vaccination is proposed as a method of immunization able to induce protection against mucosal pathogens that is superior to protection provided by parenteral immunization. However, mucosal vaccination often induces serum antigen-specific immune responses of lower magnitude than those induced by parenteral immunization, making the comparison of mucosal and parenteral immunization difficult. We identified vaccine parameters that allowed an immunization regimen consisting of an IN prime followed with boosters administered by both IN and IM routes to induce serum antibody responses similar to those induced by IM prime/boost vaccination. Additional studies are needed to determine the potential benefit of mucosal immunization for HIV-1 and other mucosally-transmitted pathogens.
Vertical niche definition of test-bearing protists (Rhizaria) into the twilight zone revealed by in situ imaging
Authors: Biard Tristan , Ohman Mark D. 
Published: March 2019

AbstractThe Rhizaria is a super-group of ameoboid protists with ubiquitous distributions, from the euphotic zone to the twilight zone and beyond. While rhizarians have been recently described as important contributors to both silica and carbon fluxes, we lack the most basic information about their ecological preferences. Here, using the in situ imaging (Underwater Vision Profiler 5), we characterize the vertical ecological niches of different test-bearing rhizarian taxa in the southernCalifornia Current Ecosystem. We define three vertical layers between 0-500 m occupied, respectively, by 1) surface dwelling and mostly symbiont-bearing rhizarians (Acantharia and Collodaria), 2) flux-feeding phaeodarians in the lower epipelagic (100-200 m), and 3) Foraminifera and Phaeodaria populations adjacent to the Oxygen Minimum Zone. We then use Generalized Additive Models to analyze the response of each rhizarian category to a suite of environmental variables. The models explain between 13 and 93% of the total variance observed for the different groups. While temperature and the depth of the deep chlorophyll maximum, appear as the main factors influencing populations in the upper 200 m, silicic acid concentration is the most important variable related to the abundance of mesopelagic phaeodarians. The relative importance of biotic interactions (e.g., predation, parasitism) is still to be considered, in order to fully incorporate the dynamics of test-bearing pelagic rhizarians in ecological and biogeochemical models.
High-speed multifocal plane fluorescence microscopy for three-dimensional visualisation of beating flagella
Authors: Wheeler Richard J. 
Published: March 2019

AbstractAnalysis of flagellum beating in three dimensions is important for understanding how cells can undergo complex flagellum-driven motility and the ability to use fluorescence microscopy for such three-dimensional analysis would be extremely powerful. Trypanosoma and Leishmania are unicellular parasites which undergo complex cell movements in three dimensions as they swim and would particularly benefit from such an analysis. Here, high-speed multifocal plane fluorescence microscopy, a technique in which a light path multi-splitter is used to visualise 4 focal planes simultaneously, was used to reconstruct the flagellum beating of Trypanosoma brucei and Leishmania mexicana in three dimensions. It was possible to use either an organic fluorescent stain or a genetically-encoded fluorescence fusion protein to visualise flagellum and cell movement in three dimensions at a 200 Hz frame rate. This high-speed multifocal plane fluorescence microscopy approach was used to address two open questions regarding Trypanosoma and Leishmania swimming: To quantify the planarity of the L. mexicana flagellum beat and analyse the nature of flagellum beating during T. brucei ‘tumbling’.
Genome-wide sequencing uncovers cryptic diversity and mito-nuclear discordance in theOctopus vulgarisspecies complex
Authors: Amor Michael D. , Doyle Stephen R. , Norman Mark D. , Roura Alvaro , Hall Nathan E. , Robinson Andrew J. , Leite Tatiana S. , Strugnell Jan M. 
Published: March 2019

ABSTRACTMany marine species once considered to be cosmopolitan are now recognised as cryptic species complexes. Mitochondrial markers are ubiquitously used to address phylogeographic questions, and have been used to identify some cryptic species complexes; however, their efficacy in inference of evolutionary processes in the nuclear genome has not been thoroughly investigated. We used double digest restriction site-associated DNA sequencing (ddRADseq) markers to quantify species boundaries in the widely distributed and high value common octopus,Octopus vulgaris, comparing genome-wide phylogenetic signal to that obtained from mitochondrial markers. Phylogenetic analyses, genome-wide concordance and species tree estimation based on 604 genome-wide ddRADseq loci revealed six species within theO. vulgarisgroup. Divergence time estimates suggested modern-day species evolved over the last 2.5 ma, during a period of global cooling. Importantly, our study identified significant phylogenetic discordance between mitochondrial and nuclear markers; genome-wide nuclear loci supportedO. vulgarissensu stricto and Type III (South Africa) as distinct species, which mtDNA failed to recognise. Our finding of conflicting phylogenetic signal between mitochondrial and nuclear markers has broad implications for many taxa. Improved phylogenetic resolution ofO. vulgarishas significant implications for appropriate management of the group and will allow greater accuracy in global fisheries catch statistics.
Universal trends of post-duplication evolution revealed by the genomes of 13Parameciumspecies sharing an ancestral whole-genome duplication
Authors: Gout Jean-Francois , Johri Parul , Arnaiz Olivier , Doak Thomas G. , Bhullar Simran , Couloux Arnaud , Guérin Fréderic , Malinsky Sophie , Sperling Linda , Labadie Karine , Meyer Eric , Duharcourt Sandra , Lynch Michael 
Published: March 2019

AbstractWhole-Genome Duplications (WGDs) have shaped the gene repertoire of many eukaryotic lineages. The redundancy created by WGDs typically results in a phase of massive gene loss. However, some WGD-derived paralogs are maintained over long evolutionary periods and the relative contributions of different selective pressures to their maintenance is still debated. Previous studies have revealed a history of three successive WGDs in the lineage of the ciliateParamecium tetraureliaand two of its sister species from theP. aureliacomplex. Here, we report the genome sequence and analysis of 10 additionalP. aureliaspecies and one additional outgroup, allowing us to track post-WGD evolution in 13 species that share a common ancestral WGD. We found similar biases in gene retention compatible with dosage constraints playing a major role opposing post-WGD gene loss across all 13 species. Interestingly we found that post-WGD gene loss was slower inParameciumthan in other species having experienced genome duplication, suggesting that the selective pressures against post-WGD gene loss are especially strong inParamecium. We also report a lack of recent segmental duplications inParamecium, which we interpret as additional evidence for strong selective pressures against individual genes dosage changes. Finally, we hope that this exceptional dataset of 13 species sharing an ancestral WGD and two closely related outgroup species will be a useful resource for future studies and will help establishParameciumas a major model organism in the study of post-WGD evolution.
Metabolic constraints drive self-organization of specialized cell groups
Authors: Varahan Sriram , Walvekar Adhish , Sinha Vaibhhav , Krishna Sandeep , Laxman Sunil 
Published: March 2019

AbstractHow phenotypically distinct states in isogenic cell populations appear and stably co-exist remains an unresolved question. We find that within a clonal yeast colony developing in low glucose, cells arrange into metabolically disparate cell groups. Using this system, we model and experimentally identify metabolic constraints sufficient to drive such assembly. Beginning in a gluconeogenic state, cells in a contrary state, exhibiting high pentose phosphate pathway activity, spontaneously appear and proliferate, in a spatially constrained manner. The gluconeogenic cells in the developing colony produce a resource, which we identify as trehalose. At threshold concentrations of trehalose, cells in the new metabolic state emerge and proliferate. A self-organized system establishes, where cells in this new state are sustained by trehalose consumption, which thereby restrains other cells in the trehalose producing, gluconeogenic state. Our work suggests simple physico-chemical principles that determine how isogenic cells spontaneously self-organize into structured assemblies in complimentary, specialized states.
A systematic review of MERS-CoV (Middle East Respiratory Syndrome Coronavirus) seroprevalence and viral RNA prevalence in dromedary camels: implications for animal vaccination
Authors: Dighe Amy , Jombart Thibaut , Van Kerkhove Maria D. , Ferguson Neil 
Published: March 2019

AbstractHuman infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is driven by recurring dromedary-to-human spill-over events, leading decision-makers to consider dromedary vaccination. Dromedary vaccine candidates in the development pipeline are showing hopeful results, but gaps in our understanding of the epidemiology of MERS-CoV in dromedaries must be addressed to design and evaluate potential vaccination strategies. We systematically reviewed the published literature reporting seroprevalence and/or prevalence of active MERS-CoV infection in dromedary populations from both cross-sectional and longitudinal studies, including 60 studies in our qualitative syntheses. MERS-CoV seroprevalence increased with age up to 80-100% in adult dromedaries supporting geographically wide spread endemicity of MERS-CoV in dromedaries in both the Arabian Peninsula and countries exporting dromedaries from Africa. The high prevalence of active infection measured in juveniles and at sites where dromedary populations mix should guide further investigation – particularly of dromedary movement – and inform vaccination strategy design.