bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 2,000-year-old specimen with intraerythrocyticBartonella quintana
Authors: Barbieri R , Mai B-H-A , Chenal T , Bassi M-L , Gandia D , Camoin-Jau L , Lepidi H , Aboudharam G , Drancourt M 
Published: March 2020

ABSTRACTPhotogrammetry and cascading microscopy investigations of dental pulp specimens collected from 2,000-year-old individuals buried in a Roman necropolis in Besançon, France, revealed unprecedented preserved tissular and cellular morphology. Photogrammetry yielded 3-D images of the smallest archaeological human remain ever recovered. Optical microscopy examinations after standard hematoxylin-phloxine-saffron staining and anti-glycophorin A immunohistochemistry exposed dental pulp cells, in addition erythrocytes were visualized by electron microscopy, which indicated that the ancient dental pulp trapped a blood drop. Fluorescencein situhybridization applied on red blood cells revealed the louse-borne pathogenBartonella quintana, a finding confirmed by polymerase chain reaction assays. Through paleohistology and paleocytology, we demonstrate that ancient dental pulp preserved intact blood cells at the time of the individual’s death, offering an unprecedented opportunity to engage in direct and indirect tests to diagnose pathogens in ancient buried individuals.
Impact of Cannabinoid Type 1 Receptor Modulation on Risky Decision-Making
Authors: Freels Timothy G. , Liley Anna E. , Gabriel Daniel B. K. , Simon Nicholas W. 
Published: March 2020

ABSTRACTRecent changes in policy regarding cannabis in the U.S. have been accompanied by an increase in the prevalence of cannabis use and a reduction in the perceived harms associated with consumption. However, little is understood regarding the effects of cannabinoids on cognitive processes. Given that deficient risk-taking is commonly observed in individuals suffering from substance use disorders (SUDs), we assessed the impact of manipulating cannabinoid type 1 receptors (CB1Rs; the primary target for Δ9-tetrahydrocannabinol in the brain) on punishment-based risk-taking using the risky decision-making task (RDT) in male Long-Evans rats. The RDT measures preference for small, safe rewards over large, risky rewards associated with an escalating chance of foot shock. Systemic bidirectional CB1R manipulation with a CB1R agonist, CB1R antagonist, and FAAH inhibitor (which increases overall endocannabinoid tone) did not alter overt risk-taking in the RDT. Interestingly, direct CB1R agonism, but not indirect CB1R stimulation or CB1R blockade, resulted in reduction in latency to make risky choices while not altering safe choice latency. Our findings suggest that CB1R activation expedites engagement in punishment based risk-taking without affecting overall preference for risky vs. safe options. This indicates that risk preference and rate of deliberation for risk-taking are influenced by distinct neural substrates, an important consideration for development of precise treatments targeting the aberrant risk-taking typical of SUD symptomology.
Five millennia ofBartonella quintanabacteremia
Authors: Mai Ba-Hoang-Anh , Barbieri Rémi , Chenal Thomas , Castex Dominique , Jonvel Richard , Tanasi Davide , Georges-Zimmerman Patrice , Dutour Olivier , Perissinotto David , Demangeot Coralie , Drancourt Michel , Aboudharam Gérard 
Published: March 2020

ABSTRACTBartonella quintanacaused trench fever in the framework of two World Wars and is now recognized as an agent of re-emerging infection. Many reports indicated the popularity ofB. quintanaexposure since the 90s. For evaluating its prevalence in ancient populations, we used real-time PCR to detectB. quintanaDNA in 400 teeth collected from 145 individuals dating from the 1st to 19th centuries in nine archeological sites with the presence of negative controls. Fisher’s exact test was used to compare the prevalence ofB. quintanadetection in civil and military populations.B. quintana DNAwas confirmed in a total of 28/145 (19.3%) individuals, comprising 78 citizens and 67 soldiers, 20.1% and 17.9% of which were positive forB. quintanabacteremia, respectively. This study collected previous studies on these ancient samples and showed that the presence ofB. quintanainfection followed the course of time in human history; a total of 14/15 sites from five European countries had a positive prevalence. The positive rate in soldiers was higher than those of citizens, with 20% and 18.8%, respectively, in the 18th - 19th centuries, but the difference in frequency was not significant. These results confirmed the role of dental pulp in diagnosingB. quintanabacteremia in ancient populations and showed the incidence ofB. quintanain both citizens and soldiers. Many recent findings contributed to understanding the coevolution of the relationship betweenB. quintanaand humans.
Synthesis of Glycoconjugates Utilizing the Regioselectivity of a Lytic Polysaccharide Monooxygenase
Authors: Westereng Bjørge , Kračun Stjepan K. , Leivers Shaun , Ø. Arntzen Magnus , Aachmann Finn L. , Eijsink Vincent G. H. 
Published: March 2020

ABSTRACTPolysaccharides from plant biomass are the most abundant renewable chemicals on Earth and can potentially be converted to a wide variety of useful glycoconjugates. While anomeric hydroxyl groups of carbohydrates are amenable to a variety of useful chemical modifications, selective cross-coupling to non-reducing ends has remained challenging. Several lytic polysaccharide monooxygenases (LPMOs), powerful enzymes known for their application in cellulose degradation, specifically oxidize non-reducing ends, introducing carbonyl groups that can be utilized for chemical coupling. This study provides a simple and highly specific approach to produce oxime-based glycoconjugates from LPMO-functionalized oligosaccharides. The products are evaluated by HPLC, mass spectrometry and NMR. Furthermore, we demonstrate potential biodegradability of these glycoconjugates using selective enzymes.
Methylphenidate normalizes aberrant beta oscillations and reduces alpha power during retention in children with ADHD
Authors: Mazzetti C. , ter Huurne N. , Buitelaar J.K. , Jensen O. 
Published: March 2020

AbstractAttention Deficit-Hyperactivity Disorder (ADHD) has been intensively studied in neurodevelopmental research, with the aim to identify the neural substrates of the disorder. Prior studies have established that brain oscillations in specific frequency ranges associated with attention and motor tasks are altered in ADHD patients as compared to typically developing (TD) peers. We hypothesized that the behavioral improvement following medication in ADHD patients should be accompanied by a normalization in the modulation of such oscillations. We hence implemented a double-blind placebo-controlled crossover design, where boys diagnosed with ADHD underwent behavioral and MEG measurements during a spatial attention task while on and off stimulant medication (methylphenidate, MPH). Results were compared with an age/IQ-matched TD group performing the same task, to assess the effect of MPH on oscillatory activity in the alpha (7 – 13Hz) and beta (15 – 30Hz) bands. We observed that depression of beta band oscillation over motor cortex in preparation to the response in ADHD boys on placebo were significantly lower as compared to the TD group. Importantly MPH resulted in a normalization of the beta depression, which then reached the same levels as in the control subjects. Furthermore, alpha power increased during the preparation interval in the ADHD control group, supposedly reflecting working memory maintenance of the cue information. This increase was significantly reduced in the ADHD group on MPH, reflecting a reduced impact on working memory load. This is the first MEG study showing task related changes in brain oscillations with MPH in children with ADHD.Significance statementBrain oscillations in the alpha (7-13Hz) and beta (15-30Hz) frequency bands are thought to underly different aspects of attentional processing and their aberrant modulation has been reported in ADHD. Here, we used a child-friendly adaptation of a Posner cueing paradigm to investigate such oscillations in children with and without a diagnosis of ADHD, and further examined the effects of methylphenidate (MPH) in the latter group. We showed that MPH restores aberrant patterns of beta desynchronization and reduces alpha power during retention in the ADHD group, concomitant to an improvement in behavioural performance.
Distinct neural mechanisms construct classical versus extraclassical inhibitory surrounds in an inhibitory nucleus in the midbrain attention network
Authors: Schryver Hannah M. , Lim Jing Xuan , Mysore Shreesh P. 
Published: March 2020

ABSTRACTInhibitory neurons in the midbrain spatial attention network, called isthmi pars magnocellularis (Imc), control stimulus selection by the sensorimotor and attentional hub, the optic tectum (OT). Here, we investigate in the barn owl how classical as well as extraclassical (global) inhibitory surrounds of Imc receptive fields (RFs), fundamental units of Imc computational function, are constructed. We find that focal, reversible blockade of GABAergic input onto Imc neurons disconnects their extraclassical inhibitory surrounds, but, surprisingly, leaves intact their classical surrounds. Subsequently, with paired recordings and iontophoresis, first at spatially aligned site-pairs in Imc and OT, and then, at mutually distant site-pairs within Imc, we demonstrate that classical inhibitory surrounds of Imc RFs are inherited from OT, but their extraclassical inhibitory surrounds are constructed within Imc. These results reveal key design principles of the midbrain spatial attention circuit, and attest to the critical importance of competitive interactions within Imc for its operation.
Evolutionary divergence of novel open reading frames in cichlids speciation
Authors: Puntambekar Shraddha , Newhouse Rachel , Navas Jaime San Miguel , Chauhan Ruchi , Vernaz Grégoire , Willis Thomas , Wayland Matthew T. , Urmania Yagnesh , Miska Eric A. , Prabakaran Sudhakaran 
Published: March 2020

AbstractNovel open reading frames (nORFs) with coding potential may arise from noncoding DNA. Not much is known about their emergence, functional role, fixation in a population or contribution to adaptive radiation. Cichlids fishes exhibit extensive phenotypic diversification and speciation. Encounters with new environments alone are not sufficient to explain this striking diversity of cichlid radiation because other taxa coexistent with the Cichlidae demonstrate lower species richness. Wagner et al analyzed cichlid diversification in 46 African lakes and reported that both extrinsic environmental factors and intrinsic lineage-specific traits related to sexual selection have strongly influenced the cichlid radiation1, which indicates the existence of unknown molecular mechanisms responsible for rapid phenotypic diversification, such as emergence of novel open reading frames (nORFs). In this study, we integrated transcriptomic and proteomic signatures from two tissues of two cichlids species, identified nORFs and performed evolutionary analysis on these nORF regions. Our results suggest that the time scale of speciation of the two species and evolutionary divergence of these nORF genomic regions are similar and indicate a potential role for these nORFs in speciation of the cichlid fishes.
MetaGenomic analysis of short and long reads
Authors: Manske Felix , Grundmann Norbert , Makalowski Wojciech 
Published: March 2020

AbstractIdentifying single organisms in environmental samples is one of the key tasks of metagenomics. During the last few years, third generation sequencing technologies have enabled researchers to sequence much longer molecules, but at the expense of sequencing accuracy. Thus, new algorithms needed to be developed to cope with this new type of data. With this in mind, we developed a tool called MetaG. An intuitive web interface makes the software accessible to a vast range of users, including those without extensive bioinformatic expertise. Evaluation of MetaG’s performance showed that it makes nearly perfect classifications of viral isolates using simulated short and long reads. MetaG also outperformed current state-of-the-art algorithms on data from targeted sequencing of the 16S and 28S rRNA genes. Since MetaG’s output is also supplemented with information about hosts and antibiotic resistances of pathogens, we expect it to be especially useful to the healthcare sector. Moreover, the outstanding accuracy of the taxonomic assignments will make MetaG a serious alternative for anyone working with metagenomic sequences. MetaG can be accessed athttp://bioinformatics.uni-muenster.de/tools/metag/.
Spectral harmonicity distinguishes two types of ictal phase-amplitude cross frequency couplings in patients candidate to epilepsy surgery
Authors: Dellavale Damián , Urdapilleta Eugenio , Cámpora Nuria , Velarde Osvaldo Matías , Kochen Silvia , Mato Germán 
Published: March 2020

AbstractObjectiveSpectral harmonicity of the ictal activity was analyzed regarding two clinically relevant aspects, (1) as a confounding factor producing ‘spurious’ phase-amplitude couplings (PAC) which may lead to wrong conclusions about the underlying ictal mechanisms, and (2) its role in how good PAC is in correspondence to the seizure onset zone (SOZ) classification performed by the epileptologists.MethodsPAC patterns observed in intracerebral electroencephalography (iEEG) recordings were retrospectively studied during seizures of seven patients with pharmacoresistant focal epilepsy. The time locked index (TLI) measure was introduced to quantify the degree of harmonicity between frequency bands associated to the emergence of PAC during epileptic seizures.Results(1) Harmonic and non harmonic PAC patterns coexist during the seizure dynamics in iEEG recordings with macroelectrodes. (2) Harmonic PAC patterns are an emergent property of the periodic non sinusoidal waveform constituting the epileptiform activity. (3) The TLI metric allows to distinguish the non harmonic PAC pattern, which has been previously associated with the ictal core through the paroxysmal depolarizing shifts mechanism of seizure propagation.ConclusionsOur results suggest that the spectral harmonicity of the ictal activity plays a relevant role in the visual analysis of the iEEG recordings performed by the epileptologists to define the SOZ, and that it should be considered for the proper interpretation of ictal mechanisms.SignificanceThe proposed harmonicity analysis can be used to improve the delineation of the SOZ by reliably identifying non harmonic PAC patterns emerging from fully recruited cortical and subcortical areas.HighlightsHarmonic and non harmonic phase-amplitude couplings coexist in epileptiform local field potentials.The time locked index quantitatively differentiates harmonic and non harmonic ictal PAC patterns.Spectral harmonicity plays a relevant role in the interpretation of underlying ictal mechanisms.
Efficient Generation of Isogenic Primary Human Myeloid Cells using CRISPR-Cas9 Ribonucleoproteins
Authors: Hiatt Joseph , Cavero Devin A. , McGregor Michael J. , Gordon David E. , Zheng Weihao , Budzik Jonathan M. , Roth Theodore L. , Haas Kelsey M. , Rathore Ujjwal , Meyer-Franke Anke , Bouzidi Mohamed S. , Hultquist Judd F. , Wojcechowskyj Jason A. , Fontaine Krystal A. , Pillai Satish K. , Cox Jeffery S. , Ernst Joel D. , Krogan Nevan J. , Marson Alexander 
Published: March 2020

SummaryGenome engineering of primary human cells with CRISPR-Cas9 has revolutionized experimental and therapeutic approaches to cell biology, but human myeloid-lineage cells have remained largely genetically intractable. We present a method for delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes by nucleofection directly into CD14+ human monocytes purified from peripheral blood, leading to high rates of precise gene knockout. These cells can be efficiently differentiated into monocyte-derived macrophages or dendritic cells. This process yields genetically-edited cells that retain critical markers of both myeloid differentiation and phagocytic function. Genetic ablation of the restriction factor SAMHD1 increased HIV-1 infection more than fifty-fold, demonstrating the power of this system for genotype-phenotype interrogation. This fast, flexible and scalable platform can be used for genetic studies of human myeloid cells in immune signaling, inflammation, cancer immunology, host-pathogen interactions, and beyond, and could facilitate development of novel myeloid cellular therapies.
Discrimination amongCryptococcus deneoformans, C. neoformansand interspecies hybrids using MALDI-TOF Mass Spectrometry
Authors: Zvezdanova Margarita Estreya , Arroyo Manuel J. , Méndez Gema , Guinea Jesús , Mancera Luis , Muñoz Patricia , Rodríguez-Sánchez Belén , Escribano Pilar 
Published: March 2020

ABSTRACTBackgroundDifferentiation of the species within theCryptococcus neoformanscomplex (C. deneoformans, C. neoformansandC. neoformansinterspecies hybrids –C. deneoformansxC. neoformans-) is important to define the epidemiology of the infection.ObjectivesIn this study we attempted the discrimination of threeC. neoformansspecies using MALDI-TOF MS coupled with an in-house library.MethodsAllCryptococcusspp. isolates were identified by AFLP markers. An in-house database was constructed 26 well characterizedC. deneoformans, C. neoformansand interspecies hybrids. Forty-fourCryptococcusspp. isolates were blindly identified using MALDI-TOF MS (Bruker Daltonics) and the expanded library. Their protein spectra were also submitted to hierarchical clustering and the resulting species were verified via Partial Least Squares Differential Analysis (PLS-DA) and Support-Vector Machine (SVM).ResultsMALDI-TOF MS coupled with the in-house library allowed 100% correct identification ofC. deneoformansandC. neoformansbut misidentified the interspecies hybrids. The same level of discrimination amongC. deneoformansandC. neoformanswas achieved applying SVM. The application of the PLS-DA and SVM algorithms in a two-step analysis allowed 96.95% and 96.55% correct discrimination ofC. neoformansfrom the interspecies hybrids, respectively. Besides, PCA analysis prior to SVM provided 98.45% correct discrimination of the 3 species analysed in a one-step analysis.ConclusionsOur results indicate that MALDI-TOF MS could be a rapid and reliable tool for the correct discrimination ofC. deneoformansandC. neoformans. The correct identification of the interspecies hybrids could only be achieved by hierarchical clustering with other protein spectra from the same species.
Increased severity of closed head injury or repetitive subconcussive head impacts enhances post-traumatic headache-like behaviors in a rat model
Authors: Bree Dara , Stratton Jennifer , Levy Dan 
Published: March 2020

AbstractIntroductionPosttraumatic headache (PTH) is one of the most common, debilitating and difficult symptoms to manage after a traumatic head injury. The development of novel therapeutic approaches is nevertheless hampered by the paucity of preclinical models and poor understanding of the mechanisms underlying PTH. To address these shortcomings, we previously characterized the development of PTH-like pain behaviors in rats subjected to a single mild closed head injury using a 250 g weight drop. Here, we conducted a follow-up study to further develop this preclinical model by exploring the development of headache-like pain behaviors in male rats subjected to a single, but more severe head trauma (450 g) as well as following repetitive, subconcussive head impacts (150 g). In addition, we tested whether these behaviors involve peripheral CGRP signaling by testing the effect of systemic anti-CGRP monoclonal antibody (anti-CGRP mAb).MethodsAdult male Sprague Dawley rats (total n=138) were subjected to diffuse closed head injury using a weight-drop device, or a sham procedure. Three injury paradigms were employed: a single hit, using 450 g or 150 g weight drop, and three successive 150 g weight drop events conducted 72 hours apart. Changes in open field activity and development of headache-related cephalic and extracephalic mechanical pain hypersensitivity were assessed up to 42 days post head trauma. Treatment included systemic administration of a mouse anti-calcitonin-gene-related peptide monoclonal antibody (30 mg/kg.).ResultsRats subjected to 450 g closed head injury displayed an acute decrease in rearing and increased thigmotaxis, together with cephalic and extracephalic mechanical pain hypersensitivity that resolved by 6 weeks post-injury. Repetitive subconcussive head impacts using the 150 g weight drop, but not a single event, led to decreased vertical rearing as well as prolonged cephalic and extracephalic mechanical pain hypersensitivity. Early and prolonged anti-CGRP mAb treatment inhibited the development of the cephalic, but not extracephalic pain hypersensitivities in both the severe and repetitive subconcussive head impact models.ConclusionsWhen compared to the data obtained from male rats in the previous study, a more severe head injury gives rise to a prolonged state of cephalic and extracephalic hyperalgesia. Such enhanced headache-like behaviors also occur following repetitive, subconcussive head impacts. Extended headache-like behaviors following severe and repetitive mild closed head injury are ameliorated by early and prolonged anti-CGRP mAb treatment, suggesting a mechanism linked to peripheral CGRP signaling.
Escherichia colimetabolism under short-term repetitive substrate dynamics: Adaptation and trade-offs
Authors: Vasilakou Eleni , van Loosdrecht Mark C. M. , Wahl S. Aljoscha 
Published: March 2020

AbstractBackgroundMicrobial metabolism is highly dependent on the environmental conditions. Especially, the substrate concentration, as well as oxygen availability, determine the metabolic rates. In large-scale bioreactors, microorganisms encounter dynamic conditions in substrate and oxygen availability (mixing limitations), which influence their metabolism and subsequently their physiology. Earlier, single substrate pulse experiments were not able to explain the observed physiological changes generated under large-scale industrial fermentation conditions.ResultsIn this study we applied a repetitive feast-famine regime in an aerobicEscherichia coliculture in a time-scale of seconds. The regime was applied for several generations, allowing cells to adapt to the (repetitive) dynamic environment. The observed response was highly reproducible over the cycles, indicating that cells were indeed fully adapted to the regime. We observed an increase of the specific substrate and oxygen consumption (average) rates during the feast-famine regime, compared to a steady-state (chemostat) reference environment. The increased rates at same (average) growth rate led to a reduced biomass yield (30% lower). Interestingly, this drop was not followed by increased by-product formation, pointing to the existence of energy-spilling reactions and/or less effective ATP synthesis. During the feast-famine cycle, the cells rapidly increased their uptake rate. Within 10 seconds after the beginning of the feeding, the substrate uptake rate was higher (4.68 μmol/gCDW/s) than reported during batch growth (3.3 μmol/gCDW/s). The high uptake led to an accumulation of several intracellular metabolites, during the feast phase, accounting for up to 34 % of the carbon supplied. Although the metabolite concentrations changed rapidly, the cellular energy charge remained unaffected, suggesting well-controlled balance between ATP producing and ATP consuming reactions. The role of inorganic polyphosphate as an energy buffer is discussed.ConclusionsThe adaptation of the physiology and metabolism ofEscherichia coliunder substrate dynamics, representative for large-scale fermenters, revealed the existence of several cellular mechanisms coping with stress. Changes in the substrate uptake system, storage potential and energy-spilling processes resulted to be of great importance. These metabolic strategies consist a meaningful step to further tackle reduced microbial performance, observed under large-scale cultivations.